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Revised report to DG Environment
May 2007
Study on enhancing the Endocrine Disrupter priority list with a focus on low production volume chemicals
ENV.D.4/ETU/2005/0028r
Study on enhancing the Endocrine Disrupter priority list with a focus on low production volume chemicals ENV.D.4/ETU/2005/0028r
Agern Allé 5
DK-2970 Hørsholm, Denmark
Tel: +45 4516 9200
Fax: +45 4516 9292
e-mail: [email protected]
Web: www.dhigroup.com
Client
DG Environment
Client’s representative
Project
Study on enhancing the Endocrine Disrupter priority list with a focus on low production volume chemicals
Project No.
53559
Date 2007.06.04
Authors
Gitte Petersen Dorte Rasmussen Kim Gustavson
Approved by
Torben Madsen
03
02 Revised report GIP DOR TMA 2007.06.04
01 Final report GIP DOR TMA 2006.12.14
Revision Description By Checked Approved Date
Key words
Endocrine disrupter, priority list, low production volume chemicals
Classification
Open
Internal
Proprietary
Distribution No. of copies
DG Environment DHI: GIP/DOR/KIG/ERA
4
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 i
CONTENTS
1 PREFACE .....................................................................................................................1
2 EXECUTIVE SUMMARY...............................................................................................2
3 INTRODUCTION.........................................................................................................15 3.1 Background.................................................................................................................15 3.2 Objectives and scope of the current project.................................................................16 3.3 Study approach ...........................................................................................................18
4 METHODOLOGY........................................................................................................19 4.1 Identification of relevant stakeholders (Task 1)............................................................19 4.2 Identification of new candidate LPVC for further evaluation of their endocrine disrupting
properties (Task 2) ......................................................................................................19 4.3 Collection and evaluation of data/information on LPVC to establish priorities for further
evaluation of their role in endocrine disruption (Task 3)...............................................20 4.3.1 Data search strategy and data collection (Task 3.1) ....................................................20 4.3.2 Evaluation of endocrine potential (Task 3.2)................................................................22 4.3.3 Evaluation of exposure of humans and wildlife (Task 3.3) ...........................................22 4.4 Update of database and list (Task 4)...........................................................................29
5 RESULTS ...................................................................................................................30 5.1 Identification of relevant stakeholders (Task 1)............................................................30 5.2 Identification of new candidate LPVC for further evaluation of their endocrine disrupting
properties (Task 2) ......................................................................................................30 5.3 Collection and evaluation of data/information on LPVC to establish priorities for further
evaluation of their role in endocrine disruption (Task 3)...............................................32 5.3.1 Evaluation of endocrine potential (Task 3.2)................................................................32 5.3.2 Evaluation of exposure of humans and wildlife (Task 3.3) ...........................................76 5.4 Update of database and list (Task 4)...........................................................................93 Appendices A Minutes from the meeting: Kick-off meeting. 17 November 2005 B Minutes from the meeting: Discussion of list of substances. 15 March 2006 C Minutes from the meeting: Discussion of interim report. 29 June 2006 D Minutes from the meeting: Discussion of draft final deliverables, i.e. report, database
and list. 8 December 2006 E List of stakeholders contacted F The questionnaire for identification of new candidate LPVC with potential endocrine
disrupting effects G The request to CEFIC H Request for comments to the draft final deliverables I The revised list of priority substances for evaluation in the present study J References to studies and reports on endocrine disruption incorporated in the database K Manual for the VIEW version of the EDC Database L Updated ranked priority list
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 1
1 PREFACE
By letter of 10 November 2005, the European Commission, DG Environment (DG ENV) commissioned DHI Water & Environment (DHI) to conduct a study entitled “Study on enhancing the Endocrine Disrupter priority list with a focus on low produc-tion volume chemicals” (reference: ENV.D.4/ETU/2005/0028r). This study is a follow-up study for the establishment by the Commission of a priority list of substances for fur-ther evaluation of their role in endocrine disruption. Two studies in this area were pre-viously carried out by BKH in 2000 and by RPS BKH in 2002. The present study is thus the last of three evaluations going through the list of candidate substances from the EU candidate list including 553 substances. Project coordinator for the present project for the EC was Katharina Spens (DG ENV) from beginning of the project and until May 2006 and hereafter Reinhild Puergy (DG ENV) took over. The project coordinator for DHI is Gitte I. Petersen. A kick-off meeting with the Commission (DG ENV) on the set-up of the project was held on 15 November 2005. Furthermore, meetings with the Commission were held on 15 March 2006 (evaluation of the list of substances to be evaluated), on 29 June 2006 (interim report meeting) and on 8 December 2006 (discussion of final deliverables). It should be noted that the results of this study (as the results of the two previous stud-ies) will be used as a basis for the consultation process by the Commission. This consul-tation process constitutes the third step in the establishment of a priority list of sub-stances for further in depth evaluation of their role in endocrine disruption, as outlined in the Commission Communication to Council and European Parliament on a Commu-nity Strategy for Endocrine Disrupters COM(2001)262 of June 2001.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 2
2 EXECUTIVE SUMMARY
The present study “Study on enhancing the Endocrine Disrupter priority list with a fo-cus on low production volume chemicals” is a follow-up study for the establishment of a priority list of substances to be used for further in-depth evaluation of their role in en-docrine disruption. Two previous studies in this area were carried out by BKH in 2000 and by RPS BKH in 2002. The present study is thus the latest of three evaluations work-ing up the EU candidate list that included 553 substances in total. For reasons of consis-tency, as the present study is the last of three evaluations of the candidate substances, the methodology for substance evaluation used in the previous RPS-BKH 2002 project was applied. In the present study, the remaining substances (mainly Low Production Volume Chemi-cals (LPVC)) from the candidate list were evaluated. A priority list of substances was prepared. The ranked priority list is based on this evaluation together with the evalua-tions performed in the two previous studies. The compilation of the priority list was based on a screening of available literature and should therefore be regarded as a starting point for further in-depth evaluation of the substances placed on the priority list with highest priority given to substances placed in the Category 1 group (clear evidence for endocrine disrupting effects in an intact organ-ism). The evaluations shall be seen in line with the previous studies and are NOT con-sidered comprehensive risk assessments. In the future in-depth evaluations, a methodol-ogy needs to be developed to make the list iterative, i.e. that a substance can enter or be deleted from the list on the basis of an agreed approach. The subject of this project falls under the short-term priority actions in the current prior-ity of the implementation of the Community Strategy on EDS. The following study approach was applied: • Identification of relevant stakeholders • Identification of new candidate substances • Collection and evaluation of data/information on candidate substances • Evaluation of exposure to humans and wildlife • Update of database and priority list of substances
In the very beginning of the project, 160 stakeholders were identified and invited to go through the candidate list of substances to be evaluated in the project. Stakeholders were invited to forward potential information on the candidate substances as well as asked to identify new substances, if any, to the list. During this task, 22 new candidate sub-stances were identified. During a thorough evaluation of the compiled candidate list (173 substances from the ordinary list + 22 new candidate substances), it was found that, most probably, several substances were no longer in use. It was also found that few of the substances were High Production Volume Chemicals (HPVC) and that the majority of the substances
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 3
were neither HPVC nor LPVC. They are existing substances but they are produced or imported in amounts ≤10 tons per year. Based on this information, it was decided that the present study should only include HPVC and LPVC plus existing substances registered in the ECB-ESIS database al-though they were produced or imported in amounts ≤10 tons per year. Based on a close examination of the candidate substances list including the 22 new substances added by the invited stakeholders (195 substances), it turned out that 73 substances could not be found on the ESIS database and no CAS No. were identified for 15 substances. In total, 107 substances remained for the present evaluation. As already outlined, the outcome of the present study shall be consistent with the out-come of the previous studies and end up in a ranked priority list of substances. The categorisation of the substances was performed according to the following evalua-tion criteria:
CAT 1 At least one in-vivo study providing clear evidence for endocrine disruption in an intact organism.
CAT 2 Potential for endocrine disruption. In-vitro data indicating potential for endocrine disruption in intact organisms. Also includes effects in-vivo that may, or may not, be ED-mediated.
CAT 3a No scientific basis for inclusion in list (ED studies available but no indications of ED effects)
CAT 3b Substances with no or insufficient data gathered
Several studies were included and evaluated in accordance with screening criteria but only one study was selected as the key study and the categorisation of the substance was thus mainly based on the key study. All evaluated studies are reflected in the database. However, it should be emphasized that the amount of evidence provided by other stud-ies not selected key studies (all of which are included in the database) has influenced the conclusions as to categorisation as well. The choice of catetories was made solely by the consultant, and apart from the clear evaluation criteria for the categories given above, it may thus be regarded as subjective. For all Category 1 substances, monitoring data were searched. However, only a few monitoring data were found and it was thus decided to base the exposure evaluations on EUSES calculations. EUSES is designed to be a decision support system for the evalua-tion of the exposure of chemicals to man and the environment. The overall results and output from the EUSES modelling include among other things: • Release to the environment on local, regional and continental scale • Concentration in water, soil and sediment on local scale (highest concentration) • Concentration in water and sediment local, regional and continental • Concentration in fish for secondary poisoning (fresh water) • Concentration in fish-eating marine top predators • Concentration in earthworms from agricultural soil
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 4
Based on an evaluation of the results of the EUSES calculations together with an evaluation of the Use Category (e.g. cosmetics, pesticide etc.), a subjective evaluation of exposure concern (high, medium, low) was performed. E.g., if a substance turned out to be readily biodegradable but used in cosmetics, a relatively high human exposure can be foreseen and the substance was rated as ‘high concern’. It shall be clearly empha-sized that the exposure evaluation is not a risk assessment and that the choice of catego-ries (high, medium, low concern) was made solely by the consultant. A brief overview, the historical evaluation process of the candidate substances and the number of priority substances (CAT 1 substances) is presented in Table 2.1. Table 2.1 Overview of candidate list substances
Selection criteria Number of substances
Number of substances
CAT 1 substances
Original candidate list of substances with ED effects
565 565
Excluded at the ED expert meeting of 1999 12 Candidate list of substances with ED effects, 2000
553 553
HPV already restricted or banned (109) + WRc evaluation (9)
118 66
Remaining substances 435 435 HPV and/or persistent and/or high exposure (evaluation by RPS BKH 2002)
204 94
Group names (not to be evaluated) 13 Mixtures or polymers (not to be evaluated) 41 Substances twice in list (not to be evaluated) 4 Remaining substances on the candidate list to be evaluated in the DHI 2006 project
173 173
New substances identified by stakeholders 22 Total number of substances to be evaluated in the DHI 2006 project
195 195
Not in ESIS database (excluded from the evalua-tion)
73
No CAS No (excluded from the evaluation) 15 Final number of substances evaluated in the DHI 2006 project
107 107 34
Total number of priority substances (Category 1)
194
A brief overview (CAS No, substance name, Use Category; exposure evaluation and le-gal status) of CAT 1 substances identified in the present study is given in Table 2.2.
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
5
Tab
le 2
.2
Brie
f ove
rvie
w o
f eva
luat
ed s
ubst
ance
s w
hich
hav
e sh
owed
evi
denc
e of
end
ocrin
e di
srup
ting
effe
cts
in a
n in
tact
org
anis
m (
CA
T 1
su
bsta
nces
)
CA
SN
R
NA
ME
C
oncl
usio
n 10
043-
35-3
B
oric
aci
d B
ori
c ac
id is
use
d in
con
sum
er p
rodu
cts
as e
.g. c
osm
etic
s an
d is
acc
ordi
ng to
the
ES
IS d
atab
ase
a H
PV
sub
stan
ce.
For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 5
0000
tone
s pe
r ye
ar h
as b
een
used
. Bor
ic a
cid
is n
ot b
ioac
cu-
mul
ativ
e an
d is
rea
dily
bio
degr
adab
le in
the
envi
ronm
ent.
EU
SE
S c
alcu
latio
ns fo
r se
cond
ary
pois
onin
g sh
ows
that
th
e su
bsta
nce
is n
ot a
ccum
ulat
ed in
sig
nific
ant a
mou
nts
in fi
sh a
nd to
p pr
edat
ors.
A r
elat
ivel
y hi
gh h
uman
exp
osur
e is
how
ever
exp
ecte
d du
e to
the
defin
ed u
se o
f the
sub
stan
ce. B
ased
on
thes
e ev
alua
tions
Bor
ic a
cid
is c
onsi
dere
d as
bei
ng o
f Med
ium
Co
nce
rn. P
rese
ntly
no
EU
cla
ssifi
catio
n is
app
lied
to B
oric
aci
d. A
ris
k as
sess
men
t on
Bor
ic
acid
is a
t the
mom
ent b
eing
per
form
ed b
y A
ustr
ia. P
ropo
sed
clas
sific
atio
n: R
62; R
63
104-
40-5
4-
Non
ylph
enol
(4-
NP
) N
on
ylp
hen
ol (
NP
) is
wid
ely
used
as
a co
mpo
nent
of d
eter
gent
s, p
aint
s, p
estic
ides
, and
man
y ot
her
form
ulat
ed
prod
ucts
. 4-N
onyl
phen
ol is
pro
duce
d is
low
am
ount
and
is a
ccor
ding
to th
e E
SIS
dat
abas
e ne
ither
a H
PV
or
LPV
su
bsta
nce.
4-N
onyl
phen
ol is
not
rea
dily
bio
degr
adab
le a
nd h
as a
hig
h po
tent
ial t
o bi
oacc
umul
ate
(log
Kow
=5.
76).
4-
Non
ylph
enol
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
as
wel
l as
sedi
men
ts a
nd a
gric
ultu
ral s
oils
. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
pois
onin
g 4-
Non
ylph
enol
is e
xpec
ted
to b
e fo
und
both
in fi
sh a
nd to
p pr
edat
ors
in c
once
ntra
tions
up
to 1
000
mg/
kg w
et w
eigh
t. Lo
cal d
aily
hum
an in
take
is e
stim
ated
to b
e up
to 2
50
mg/
kg b
ody
wei
ght p
er d
ay. D
ue to
an
expe
cted
clo
se h
uman
con
tact
to 4
-Non
ylph
enol
via
det
erge
nts
and
pain
ts, 4
-N
onyl
phen
ol is
con
side
red
as b
eing
of H
igh
Co
nce
rn. I
n th
e E
U th
ere
is a
res
tric
tion
on th
e us
e of
non
ylph
enol
and
its
eth
oxyl
ates
(A
nnex
I of
Dire
ctiv
e 76
/769
/EE
C)
limiti
ng th
e in
clus
ion
of th
ese
subs
tanc
es in
a v
arie
ty o
f pro
duct
s to
no
mor
e th
an 0
.1%
. Pro
pose
d cl
assi
ficat
ion:
Rep
.3;R
62 R
ep.3
;R63
Xn;
R22
C;R
34 N
;R50
/53
1113
-02-
6 O
met
hoat
e O
met
ho
ate
is u
sed
as a
pes
ticid
e. O
met
hoat
e is
acc
ordi
ng to
the
ES
IS d
atab
ase
a LP
V s
ubst
ance
. For
the
EU
SE
S
calc
ulat
ions
a p
rodu
ctio
n vo
lum
e of
500
tone
s pe
r ye
ar h
as b
een
used
. Om
etho
ate
is n
ot r
eadi
ly b
iode
grad
able
, but
ha
s a
low
pot
entia
l to
bioa
ccum
ulat
e (lo
g K
ow=
-0.7
5).
Bas
ed o
n E
US
ES
est
imat
ions
Om
etho
ate
expe
cted
to b
e fo
und
in lo
cal s
urfa
ce w
ater
in c
once
ntra
tions
up
to 4
mg/
L. A
s O
met
hoat
e is
not
pot
entia
l bio
accu
mul
ativ
e th
e su
b-st
ance
is n
ot e
xpec
ted
to g
ive
any
prob
lem
s in
rel
atio
n to
sec
onda
ry p
oiso
ning
. Om
etho
ate
is c
onsi
dere
d as
bei
ng o
f L
ow
Co
nce
rn. C
over
ed b
y C
ounc
il D
irect
ive
91/4
14/E
EC
. No
RA
R h
as b
een
prov
ided
and
the
subs
tanc
e is
not
in-
clud
ed in
the
list f
or p
estic
ides
to b
e re
view
ed. C
lass
ifica
tion:
XN
;R21
T;R
25 N
;R50
11
31-6
0-8
4-C
yclo
hexy
lphe
nol
4-C
yclo
hex
ylp
hen
ol i
s us
ed in
the
form
atio
n of
res
in. R
esin
is w
idel
y us
ed p
rodu
ct. 4
-Cyc
lohe
xylp
heno
l is
acco
rdin
g to
the
ES
IS d
atab
ase
prod
uced
in lo
w a
mou
nt a
nd is
nei
ther
a H
PV
or
LPV
sub
stan
ce. F
or th
e E
US
ES
cal
cula
tions
a
prod
uctio
n vo
lum
e of
10
tone
s pe
r ye
ar h
as b
een
used
. 4-C
yclo
hexy
lphe
nol i
s no
t rea
dily
bio
degr
adab
le a
nd h
as a
hi
gh p
oten
tial t
o bi
oacc
umul
ate
in th
e en
viro
nmen
t (lo
g ko
w=
4.22
). 4
-Cyc
lohe
xylp
heno
l is
in th
e en
viro
nmen
t mai
nly
dist
ribut
ed to
sur
face
wat
er a
s w
ell a
s se
dim
ents
and
agr
icul
tura
l soi
ls. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
pois
onin
g 4-
Cyc
lohe
xylp
heno
l is
expe
cted
to b
e fo
und
in fi
sh a
nd to
p pr
edat
ors
in m
inor
am
ount
. A m
ediu
m h
uman
ex
posu
re is
exp
ecte
d. 4
-Cyc
lohe
xylp
heno
l is
cons
ider
ed a
s be
ing
of M
ediu
m C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
was
foun
d, h
owev
er th
e su
bsta
nce
is r
elat
ed to
non
ylph
enol
.
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
6
CA
SN
R
NA
ME
C
oncl
usio
n 12
0-47
-8
eth
yl 4
-hy
drox
yben
zoat
e E
thyl
4-h
ydro
xyb
enzo
ate
is u
sed
as p
rese
rvat
ives
in fo
od, p
harm
aceu
tical
and
cos
met
ic fo
rmul
atio
ns. E
thyl
4-
hydr
oxyb
enzo
ate
is p
rodu
ced
in a
mou
nts
up to
50
tone
s pe
r ye
ar a
nd th
us a
LP
V s
ubst
ance
. Eth
yl 4
-hy
drox
yben
zoat
e is
rea
dily
bio
degr
adab
le a
nd h
as a
med
ium
pot
entia
l for
bio
accu
mul
atio
n. B
ased
EU
SE
S c
alcu
la-
tions
Eth
yl 4
-hyd
roxy
benz
oate
is e
xpec
ted
to b
e re
leas
ed to
the
envi
ronm
ent i
n in
sign
ifica
nt a
mou
nts
and
is n
ot e
x-pe
cted
to g
ive
any
prob
lem
s in
rel
atio
n to
sec
onda
ry p
oiso
ning
. How
ever
, as
ethy
l 4-h
ydro
xybe
nzoa
te a
s a
pres
erva
-tiv
e in
food
and
cos
met
ics
a hi
gh h
uman
exp
osur
e is
exp
ecte
d. E
thyl
4-h
ydro
xybe
nzoa
te is
thus
con
side
red
as b
eing
of
Med
ium
Co
nce
rn. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
13
1-18
-0
Di-n
-pen
tylp
htha
late
(D
PP
) =
D
ipen
tylp
htha
late
Con
sum
er a
nd in
dust
rial a
pplic
atio
ns fo
r ph
thal
ates
are
num
erou
s an
d ra
nge
from
mak
ing
nail
polis
h fle
xibl
e an
d sc
rew
driv
er h
andl
es le
ss b
rittle
to h
elpi
ng m
ake
the
time-
rele
ase
coat
ings
on
num
erou
s ph
arm
aceu
tical
pro
duct
s.
Dip
enty
lph
thal
ate
is a
ccor
ding
to th
e E
SIS
dat
abas
e a
LPV
sub
stan
ce. F
or th
e E
US
ES
cal
cula
tions
a p
rodu
ctio
n vo
lum
e of
50
tone
s pe
r ye
ar h
as b
een
used
. Dip
enty
lpht
hala
te is
inhe
rent
ly b
iode
grad
able
and
has
a h
igh
pote
ntia
l to
bioa
ccum
ulat
e (lo
g K
ow=
5.62
). B
ased
on
EU
SE
S c
alcu
latio
ns d
ipen
tylp
htha
late
is n
ot e
xpec
ted
to b
e fo
und
in s
ig-
nific
ant a
mou
nts
in th
e en
viro
nmen
t (su
rfac
e w
ater
s an
d se
dim
ents
). H
owev
er a
s D
ipen
tylp
htha
late
is o
f med
ium
co
ncer
n in
rel
atio
n to
sec
onda
ry p
oiso
ning
. Dip
enty
lpht
hala
te is
thus
con
side
red
as b
eing
of M
ediu
m C
on
cern
. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
13
1-55
-5
Ben
zoph
enon
e-2
(Bp-
2), 2
,2',4
,4'-
tetr
ahyd
roxy
benz
o-ph
enon
e
Ben
zop
hen
on
e-2
(Bp
-2),
2,2
',4,4
'-tet
rah
ydro
xyb
enzo
ph
eno
ne
is u
sed
as a
UV
sun
scre
en in
cos
met
ics.
Ben
zo-
phen
one-
2 (B
p-2)
, 2,2
',4,4
'-tet
rahy
drox
yben
zoph
enon
e is
acc
ordi
ng to
the
ES
IS d
atab
ase
a LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 5
0 to
nes
per
year
has
bee
n us
ed. B
enzo
phen
one-
2 (B
p-2)
, 2,2
',4,4
'-te
trah
ydro
xybe
nzop
heno
ne is
not
rea
dily
bio
degr
adab
le a
nd h
as a
med
ium
pot
entia
l to
bioa
ccum
ulat
e. B
enzo
phe-
none
-2 (
Bp-
2), 2
,2',4
,4'-t
etra
hydr
oxyb
enzo
phen
one
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
as
wel
l as
sed
imen
ts a
nd a
gric
ultu
ral s
oils
. Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
Ben
zoph
enon
e-2
(Bp-
2),
2,2'
,4,4
'-tet
rahy
drox
yben
zoph
enon
e is
not
exp
ecte
d to
be
foun
d in
fish
and
top
pred
ator
s. A
hig
h hu
man
exp
osur
e is
ex
pect
ed m
ainl
y du
e to
the
fact
that
the
subs
tanc
e is
use
d as
a U
V s
cree
n in
cos
met
ics.
Ben
zoph
enon
e-2
(Bp-
2),
2,2'
,4,4
'-tet
rahy
drox
yben
zoph
enon
e is
ther
efor
e co
nsid
ered
as
bein
g of
Hig
h C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
was
foun
d.
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
-no
n =
Res
benz
ophe
-no
ne
2,4-
Dih
ydro
xyb
enzo
ph
eno
n is
use
d as
a U
V s
unsc
reen
in c
osm
etic
s. 2
,4-D
ihyd
roxy
benz
ophe
non
is a
ccor
ding
to
the
ES
IS d
atab
ase
a LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 5
0 to
nes
per
year
has
be
en u
sed.
2,4
-Dih
ydro
xybe
nzop
heno
n is
not
rea
dily
bio
degr
adab
le a
nd h
as a
pot
entia
l to
bioa
ccum
ulat
e in
the
envi
-ro
nmen
t (lo
g ko
w=
2.96
). 2
,4-D
ihyd
roxy
benz
ophe
non
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
as
wel
l as
sed
imen
ts a
nd a
gric
ultu
ral s
oils
. Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
2,4-
Dih
ydro
xybe
nzop
heno
n is
not
exp
ecte
d to
be
foun
d in
fish
and
top
pred
ator
s. A
hig
h hu
man
exp
osur
e is
exp
ecte
d m
ainl
y du
e to
the
fact
that
the
subs
tanc
e is
use
d as
a U
V s
cree
n in
cos
met
ics.
2,4
-Dih
ydro
xybe
nzop
heno
n is
ther
e-fo
re c
onsi
dere
d as
bei
ng o
f Hig
h C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
was
foun
d.
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
7
CA
SN
R
NA
ME
C
oncl
usio
n 13
1-70
-4
Mon
o-n-
buty
lpht
hala
te
Con
sum
er a
nd in
dust
rial a
pplic
atio
ns fo
r ph
thal
ates
are
num
erou
s an
d ra
nge
from
mak
ing
nail
polis
h fle
xibl
e an
d sc
rew
driv
er h
andl
es le
ss b
rittle
to h
elpi
ng m
ake
the
time-
rele
ase
coat
ings
on
num
erou
s ph
arm
aceu
tical
pro
duct
s.
Mo
no
-n-b
uty
lph
thal
ate
is a
ccor
ding
to th
e E
SIS
dat
abas
e pr
oduc
ed in
am
ount
s <
10
tone
s/ye
ar a
nd th
us n
ot a
LP
V
subs
tanc
e. F
or th
e E
US
ES
cal
cula
tions
a p
rodu
ctio
n vo
lum
e of
10
tone
s pe
r ye
ar h
as b
een
used
. Mon
o-n-
buty
lpht
hala
te is
rea
dily
bio
degr
adab
le a
nd h
as a
med
ium
pot
entia
l to
bioa
ccum
ulat
e (lo
g K
ow=
2.84
). B
ased
on
EU
SE
S c
alcu
latio
ns M
ono-
n-bu
tylp
htha
late
is n
ot e
xpec
ted
to b
e fo
und
in s
igni
fican
t am
ount
s in
the
envi
ronm
ent
(sur
face
wat
ers
and
sedi
men
ts)
and
is n
ot e
xpec
ted
to g
ive
any
prob
lem
s in
rel
atio
n to
sec
onda
ry p
oiso
ning
and
hu-
man
inta
ke. M
ono-
n-bu
tylp
htha
late
is c
onsi
dere
d as
bei
ng o
f Lo
w C
on
cern
. Non
e sp
ecifi
cally
reu
lato
ry o
r le
gal
stat
us fo
r th
is s
ubst
ance
was
foun
d. T
he r
elat
ed s
ubst
ance
Dib
utyl
phth
alat
is o
n th
e lis
t of d
ange
rous
sub
stan
ces
(Ann
ex I
to D
irect
ive
67/5
48/E
EC
) 13
593-
03-8
Q
uina
lpho
s =
Chi
-na
lpho
s Q
uin
alp
ho
s is
use
d as
a in
sect
icid
e. Q
uina
lpho
s is
acc
ordi
ng t
o th
e E
SIS
dat
abas
e a
LPV
sub
stan
ce. Q
uina
lpho
s is
no
t rea
dily
bio
degr
adab
le a
nd h
as a
hig
h po
tent
ial t
o bi
oacc
umul
ate
(log
Kow
=4.
44).
Bas
ed o
n E
US
ES
est
imat
ions
Q
uina
lpho
s ex
pect
ed to
be
foun
d in
loca
l sur
face
wat
er in
con
cent
ratio
ns u
p to
2 m
g/L.
Due
to th
e pe
rsis
tenc
y of
the
subs
tanc
e an
d th
e hi
gh p
oten
tial b
ioac
cum
ulat
ion
Qui
nalp
hos
is o
f med
ium
con
cern
in r
elat
ion
to s
econ
dary
poi
son-
ing
and
daily
hum
an in
take
. Qui
nalp
hos
is c
onsi
dere
d as
bei
ng o
f Med
ium
Co
nce
rn. Q
uina
lpho
s is
cov
ered
by
Cou
ncil
Dire
ctiv
e 91
/414
/EE
C. N
o R
AR
has
bee
n pr
ovid
ed a
nd th
e su
bsta
nce
is n
ot in
clud
ed in
the
list f
or p
estic
ides
to
be
revi
ewed
. Cla
ssifi
catio
n: X
N;R
21 T
;R25
N;R
50/5
3 15
087-
24-8
3-
Ben
zylid
ene
cam
-ph
or (
3-B
C)
3-B
enzy
liden
e ca
mp
ho
r is
use
d as
a U
V s
unsc
reen
in c
osm
etic
s. 3
-Ben
zylid
ene
cam
phor
is a
ccor
ding
to th
e E
SIS
da
taba
se a
LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 5
0 to
nes
per
year
has
bee
n us
ed. 3
-B
enzy
liden
e ca
mph
or is
not
rea
dily
bio
degr
adab
le a
nd h
as a
hig
h po
tent
ial t
o bi
oacc
umul
ate
in th
e en
viro
nmen
t (lo
g ko
w=
4.67
). 3
-Ben
zylid
ene
cam
phor
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
as
wel
l as
sedi
men
ts
and
agric
ultu
ral s
oils
. Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
3-B
enzy
liden
e ca
mph
or is
exp
ecte
d to
be
foun
d in
fish
and
top
pred
ator
s in
min
or a
mou
nt. A
hig
h hu
man
exp
osur
e is
exp
ecte
d m
ainl
y du
e to
the
fact
that
th
e su
bsta
nce
is u
sed
as a
UV
scr
een
in c
osm
etic
s. 2
,4-3
-Ben
zylid
ene
cam
phor
is th
eref
ore
cons
ider
ed a
s be
ing
of
Hig
h C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
was
foun
d.
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
8
CA
SN
R
NA
ME
C
oncl
usio
n 15
82-0
9-8
Trif
lura
lin
Tri
flu
ralin
is u
sed
as a
pes
ticid
e an
d is
acc
ordi
ng to
the
ES
IS d
atab
ase
a H
PV
sub
stan
ce. F
or th
e E
US
ES
cal
cula
-tio
ns a
pro
duct
ion
volu
me
of 1
0000
tone
s pe
r ye
ar h
as b
een
used
. Trif
lura
lin is
not
rea
dily
bio
degr
adab
le a
nd h
as a
hi
gh p
oten
tial t
o bi
oacc
umul
ate
in th
e en
viro
nmen
t (lo
g ko
w=
5.34
). T
riflu
ralin
is in
the
env
ironm
ent m
ainl
y di
strib
uted
to
sur
face
wat
er a
s w
ell a
s se
dim
ents
and
agr
icul
tura
l soi
ls. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
pois
onin
g 2,
4- T
riflu
ralin
is e
xpec
ted
to b
e fo
und
in fi
sh a
nd to
p pr
edat
ors
in e
xtre
mel
y hi
gh a
mou
nts.
A h
igh
hum
an e
xpos
ure
up to
70
mg/
kg/d
ay is
exp
ecte
d. T
riflu
ralin
is in
the
pres
ent e
valu
atio
n co
nsid
ered
as
bein
g of
Hig
h C
on
cern
. Trif
lu-
ralin
is c
over
ed b
y C
ounc
il D
irect
ive
91/4
14/E
EC
. No
RA
R h
as b
een
prov
ided
and
the
subs
tanc
e is
not
incl
uded
in
the
list f
or p
estic
ides
to b
e re
view
ed. C
lass
ifica
tion:
XI;R
36 R
43 N
;R50
/53.
Fin
alis
ed a
sses
smen
ts r
evie
w b
y E
FS
A.
Agr
eem
ent t
hat t
here
is o
nly
limite
d ev
iden
ce fo
r en
docr
ine
effe
cts
and
that
this
was
rec
orde
d at
hig
h do
se le
vels
an
d w
as h
ard
to d
istin
guis
h fr
om s
yste
mic
toxi
city
. 16
34-0
4-4
met
hyl t
ertia
ry b
utyl
et
her
(MT
BE
) M
eth
yl t
erti
ary
bu
tyl e
ther
is u
sed
as a
pet
rol a
dditi
ve a
nd is
acc
ordi
ng to
the
ES
IS d
atab
ase
a H
PV
sub
stan
ce. F
or
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 5
0000
tone
s pe
r ye
ar h
as b
een
used
. Met
hyl t
ertia
ry b
utyl
eth
er is
no
t rea
dily
bio
degr
adab
le a
nd h
as a
low
pot
entia
l to
bioa
ccum
ulat
e in
the
envi
ronm
ent (
log
kow
=1.
06).
Met
hyl t
erti-
ary
buty
l eth
er is
in th
e en
viro
nmen
t mai
nly
dist
ribut
ed t
o su
rfac
e w
ater
s. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
con-
dary
poi
soni
ng 2
,4-
Met
hyl t
ertia
ry b
utyl
eth
er is
exp
ecte
d to
be
foun
d in
fish
and
top
pred
ator
s in
min
or a
mou
nt. A
re
lativ
ely
low
dai
ly h
uman
inta
ke is
exp
ecte
d. D
ue to
the
fact
that
Met
hyl t
ertia
ry b
utyl
eth
er is
a h
igh
volu
me
sub-
stan
ce a
nd n
ot r
eadi
ly b
iode
grad
able
rel
ativ
ely
high
con
cent
ratio
ns in
sur
face
wat
ers
can
be e
xpec
ted
and
Met
hyl
tert
iary
but
yl e
ther
is th
us c
onsi
dere
d as
bei
ng o
f Med
ium
Co
nce
rn. R
AR
from
200
2 is
ava
ilabl
e on
ES
IS. C
lass
ifica
-tio
n: F
;R11
XI;R
38
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le
(BH
A)
Ter
t.-B
uty
lhyd
roxy
anis
ole
(B
HA
) is
use
d as
an
antio
xida
nt to
pre
serv
e an
d st
abili
ze th
e fr
eshn
ess
of fo
od a
nd fe
ed
and
is a
ccor
ding
to th
e E
SIS
dat
abas
e a
LPV
sub
stan
ce. B
HA
is n
ot r
eadi
ly b
iode
grad
able
and
has
a h
igh
pote
ntia
l to
bio
accu
mul
ate
in th
e en
viro
nmen
t (lo
g ko
w=
3.29
). B
HA
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
pois
onin
g B
HA
is n
ot e
xpec
ted
to b
e of
sig
nific
ant c
once
rn. A
rel
ativ
ely
low
dai
ly h
uman
inta
ke is
exp
ecte
d. H
owev
er, a
s B
HA
is a
dded
dire
ctly
to fo
od it
ems
to p
rese
rve
and
stab
ilize
the
fres
hnes
s of
food
and
feed
a d
irect
hum
an e
xpos
ure
is o
bvio
us. B
HA
is th
us c
onsi
dere
d as
bei
ng o
f Hig
h C
on
cern
. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
9
CA
SN
R
NA
ME
C
oncl
usio
n 27
193-
28-8
P
heno
l, (1
,1,3
,3-
tetr
amet
hylb
utyl
)- =
O
ctyl
phen
ol
Oct
ylp
hen
ol i
s us
ed a
s a
prec
urso
r to
pro
duce
sur
fact
ants
(et
hoxy
late
s) a
nd in
pla
stic
pro
duct
s. O
ctyl
phen
ol is
ac-
cord
ing
to th
e E
SIS
dat
abas
e no
t a L
PV
sub
stan
ce. F
or th
e E
US
ES
cal
cula
tions
a p
rodu
ctio
n vo
lum
e of
10
tone
s pe
r ye
ar h
as b
een
used
. Oct
ylph
enol
is n
ot r
eadi
ly b
iode
grad
able
and
has
a h
igh
pote
ntia
l to
bioa
ccum
ulat
e in
the
envi
-ro
nmen
t (lo
g ko
w=
5.5)
. Oct
ylph
enol
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
as
wel
l as
sedi
men
ts
and
agric
ultu
ral s
oils
. Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
Oct
ylph
enol
is e
xpec
ted
to b
e of
me-
dium
con
cern
. A h
igh
loca
l dai
ly h
uman
inta
ke is
exp
ecte
d (u
p to
app
rox.
170
mg/
kg/d
ay).
Oct
ylph
enol
is c
onsi
dere
d as
bei
ng o
f Hig
h C
on
cern
. The
PB
T p
rope
rtie
s ha
ve b
een
asse
ssed
by
the
EU
and
it w
as c
oncl
uded
that
Oct
ylph
e-no
l doe
s no
t ful
fil th
e P
BT
crit
eria
. T
he d
atab
ase
for
p-te
rt.-
octy
lphe
nol i
s ve
ry c
ompr
ehen
sive
, inc
ludi
ng a
hig
h qu
al-
ity m
ulti-
gene
ratio
n st
udy.
The
EU
CM
R g
roup
rec
ently
dec
ided
that
Oct
ylph
enol
sho
uld
not b
e cl
assi
fied
for
repr
o-to
xic
effe
cts.
33
204-
76-1
2,
6-ci
s-D
iphe
nylh
exam
ethy
l-cy
clot
etra
silo
xane
-
2,6-
cis-
[(P
hMe-
SiO
)2(M
e2S
iO)2
][
Dip
hen
ylh
exam
eth
ylcy
clo
tetr
asilo
xan
e is
use
d fo
r va
rious
pur
pose
s as
e.g
. bre
ast i
mpl
ants
and
bea
ring
grea
se.
Dip
heny
lhex
amet
hylc
yclo
tetr
asilo
xane
is a
ccor
ding
to th
e E
SIS
dat
abas
e no
t a L
PV
sub
stan
ce. F
or th
e E
US
ES
cal
-cu
latio
ns a
pro
duct
ion
volu
me
of 1
0 to
nes
per
year
has
bee
n us
ed. D
iphe
nylh
exam
ethy
lcyc
lote
tras
iloxa
ne is
not
re
adily
bio
degr
adab
le a
nd h
as a
hig
h po
tent
ial t
o bi
oacc
umul
ate
in th
e en
viro
nmen
t (lo
g ko
w=
7.52
). D
iphe
nylh
exa-
met
hylc
yclo
tetr
asilo
xane
is in
the
envi
ronm
ent d
istr
ibut
ed to
sur
face
wat
er a
s w
ell a
s se
dim
ents
and
agr
icul
tura
l so
ils. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
pois
onin
g D
iphe
nylh
exam
eth
ylcy
clot
etra
silo
xane
is e
xpec
ted
to b
e of
med
ium
con
cern
. A h
igh
loca
l dai
ly h
uman
inta
ke is
exp
ecte
d (u
p to
app
rox.
275
mg/
kg/d
ay).
Dip
heny
lhex
ame-
thyl
cycl
otet
rasi
loxa
ne is
con
side
red
as b
eing
of H
igh
Co
nce
rn. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
su
bsta
nce
was
foun
d.
3686
1-47
-9
3-(4
-M
ethy
lben
-zy
liden
e)ca
mph
or
3-(4
-Met
hyl
ben
zylid
ene)
cam
ph
or
is u
sed
as a
UV
sun
scre
en in
cos
met
ics.
3-(
4-M
ethy
lben
zylid
ene)
cam
phor
is a
c-co
rdin
g to
the
ES
IS d
atab
ase
a LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 5
0 to
nes
per
year
has
bee
n us
ed. 3
-(4-
Met
hylb
enzy
liden
e)ca
mph
or is
not
rea
dily
bio
degr
adab
le a
nd h
as a
hig
h po
tent
ial t
o bi
oac-
cum
ulat
e in
the
envi
ronm
ent (
log
kow
=5.
22).
3-(
4-M
ethy
lben
zylid
ene)
cam
phor
is in
the
envi
ronm
ent m
ainl
y di
strib
-ut
ed to
sur
face
wat
er a
s w
ell a
s se
dim
ents
and
agr
icul
tura
l soi
ls. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
poi-
soni
ng 3
-(4-
Met
hylb
enzy
liden
e)ca
mph
or is
exp
ecte
d to
be
foun
d in
fish
and
top
pred
ator
s in
am
ount
s up
to a
ppro
x.
2000
mg/
kg w
w. A
hig
h hu
man
exp
osur
e is
exp
ecte
d m
ainl
y du
e to
the
fact
that
the
sub
stan
ce is
use
d as
a U
V
scre
en in
cos
met
ics.
3-(
4-M
ethy
lben
zylid
ene)
cam
phor
is th
eref
ore
cons
ider
ed a
s be
ing
of H
igh
Co
nce
rn. N
one
spe-
cific
ally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
was
foun
d.
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
10
CA
SN
R
NA
ME
C
oncl
usio
n 43
76-2
0-9
Mon
o 2
eth
yl h
exyl
-ph
thal
ate
(ME
HP
) M
on
o 2
eth
yl h
exyl
ph
thal
ate
(ME
HP
) is
the
maj
or D
EH
P m
etab
olite
. ME
HP
is a
ccor
ding
to th
e E
SIS
dat
abas
e pr
o-du
ced
in a
mou
nts
< 1
0 to
nes/
year
and
thus
not
a L
PV
sub
stan
ce. F
or th
e E
US
ES
cal
cula
tions
a p
rodu
ctio
n vo
lum
e of
10
tone
s pe
r ye
ar h
as b
een
used
. ME
HP
is n
ot r
eadi
ly b
iode
grad
able
and
has
a h
igh
pote
ntia
l to
bioa
ccum
ulat
e (lo
g K
ow=
4.73
). M
EH
P is
in th
e en
viro
nmen
t mai
nly
dist
ribut
ed to
sur
face
wat
er a
s w
ell a
s se
dim
ents
and
agr
icul
-tu
ral s
oils
. Bas
ed o
n E
US
ES
cal
cula
tions
ME
HP
is e
xpec
ted
to g
ive
min
or p
robl
ems
in r
elat
ion
to s
econ
dary
poi
son-
ing
and
hum
an in
take
. Due
to th
e pe
rsis
tenc
y an
d hi
gh b
ioac
cum
ulat
ion
pote
ntia
l Mon
o-n-
buty
lpht
hala
te is
con
sid-
ered
as
bein
g of
Med
ium
Co
nce
rn. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
50
-18-
0 C
yclo
phos
pham
ide
Cyc
lop
ho
sph
amid
e is
use
d as
a in
sect
icid
e as
wel
l as
in c
hem
othe
rap
y. C
yclo
phos
pham
ide
is a
ccor
ding
to th
e E
SIS
dat
abas
e pr
oduc
ed in
am
ount
s <
10
tone
s/ye
ar a
nd th
us n
ot a
LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pr
oduc
tion
volu
me
of 1
0 to
nes
per
year
has
bee
n us
ed. C
yclo
phos
pham
ide
is n
ot r
eadi
ly b
iode
grad
able
and
has
a
low
pot
entia
l to
bioa
ccum
ulat
e (lo
g K
ow=
0.63
). B
ased
on
EU
SE
S e
stim
atio
ns C
yclo
phos
pham
ide
is e
xpec
ted
to b
e fo
und
in lo
cal s
urfa
ce w
ater
in c
once
ntra
tions
up
to a
ppro
x. 1
mg/
L. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
poi-
soni
ng a
nd h
uman
inta
ke C
yclo
phos
pham
ide
is e
xpec
ted
to b
e fo
und
in fi
sh, p
reda
tors
and
hum
an fo
od in
min
or
amou
nts.
Chl
ordi
mef
orm
is c
onsi
dere
d as
bei
ng o
f Lo
w C
on
cern
. The
sub
stan
ce is
cov
ered
by
Cou
ncil
Dire
ctiv
e 91
/414
/EE
C. N
o R
AR
has
bee
n pr
ovid
ed a
nd th
e su
bsta
nce
is n
ot in
clud
ed in
the
list f
or p
estic
ides
to b
e re
view
ed.
5466
-77-
3 2-
ethy
l-hex
yl-4
-m
etho
xyci
nnam
ate
2-et
hyl
-hex
yl-4
-met
ho
xyci
nn
amat
e is
use
d as
a U
V s
unsc
reen
in c
osm
etic
s. 2
-eth
yl-h
exyl
-4-m
etho
xyci
nnam
ate
is
acco
rdin
g to
the
ES
IS d
atab
ase
a H
PV
sub
stan
ce. F
or th
e E
US
ES
cal
cula
tions
a p
rodu
ctio
n vo
lum
e of
500
0 to
nes
per
year
has
bee
n us
ed. 2
-eth
yl-h
exyl
-4-m
etho
xyci
nnam
ate
is r
eadi
ly b
iode
grad
able
and
has
a h
igh
pote
ntia
l to
bio-
accu
mul
ate
in th
e en
viro
nmen
t (lo
g ko
w=
5.8)
. 2-e
thyl
-hex
yl-4
-met
hoxy
cinn
amat
e is
in th
e en
viro
nmen
t mai
nly
dis-
trib
uted
to s
urfa
ce w
ater
as
wel
l as
sedi
men
ts a
nd a
gric
ultu
ral s
oils
. Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
2-et
hyl
-hex
yl-4
-met
hoxy
cinn
amat
e is
exp
ecte
d to
be
foun
d in
fish
and
top
pred
ator
s in
am
ount
s up
to
appr
ox. 7
0000
mg/
kg w
w. F
urth
erm
ore
a hi
gh r
egio
nal h
uman
exp
osur
e is
exp
ecte
d. B
esid
es a
hig
h hu
man
exp
o-su
re is
exp
ecte
d m
ainl
y du
e to
the
fact
that
the
subs
tanc
e is
use
d as
a U
V s
cree
n in
cos
met
ics.
2-e
thyl
-hex
yl-4
-m
etho
xyci
nnam
ate
is th
eref
ore
cons
ider
ed a
s be
ing
of H
igh
Co
nce
rn. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
55
6-67
-2
Cyc
lote
tras
iloxa
ne
Cyc
lote
tras
iloxa
ne
has
num
erou
s in
dust
rial a
nd c
onsu
mer
app
licat
ions
and
is a
ccor
ding
to th
e E
SIS
dat
abas
e a
HP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 5
0000
tone
s pe
r ye
ar h
as b
een
used
. Cyc
lote
t-ra
silo
xane
is n
ot r
eadi
ly b
iode
grad
able
and
has
a h
igh
pote
ntia
l to
bioa
ccum
ulat
e in
the
envi
ronm
ent (
log
kow
=5.
45).
C
yclo
tetr
asilo
xane
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
. Bas
ed o
n E
US
ES
est
imat
ions
for
sec-
onda
ry p
oiso
ning
Cyc
lote
tras
iloxa
ne is
exp
ecte
d to
be
foun
d in
fish
and
top
pred
ator
s in
min
or a
mou
nts.
Cyc
lote
tras
i-lo
xane
has
a p
oten
tial f
or h
uman
exp
osur
e as
it is
use
d in
num
erou
s in
dust
rial a
nd c
onsu
mer
. App
licat
ions
. C
yclo
tet-
rasi
loxa
ne is
con
side
red
as b
eing
of H
igh
Co
nce
rn. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce
was
foun
d. C
lass
ifica
tion:
R
EP
3;R
62 R
53
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
11
CA
SN
R
NA
ME
C
oncl
usio
n 61
1-99
-4
4,4'
-D
ihyd
roxy
benz
ophe
-no
n
4,4'
-Dih
ydro
xyb
enzo
ph
eno
n is
use
d as
a U
V s
unsc
reen
in c
osm
etic
s. 4
,4'-D
ihyd
roxy
benz
ophe
non
is a
ccor
ding
to
the
ES
IS d
atab
ase
prod
uced
in a
mou
nts
< 1
0 to
nes/
year
and
thus
not
a L
PV
sub
stan
ce. F
or th
e E
US
ES
cal
cula
tions
a
prod
uctio
n vo
lum
e of
10
tone
s pe
r ye
ar h
as b
een
used
. 4,4
'-Dih
ydro
xybe
nzop
heno
n is
not
rea
dily
bio
degr
adab
le
and
has
a m
ediu
m p
oten
tial t
o bi
oacc
umul
ate
in th
e en
viro
nmen
t (lo
g ko
w=
2.19
). 4
,4'-D
ihyd
roxy
benz
ophe
non
is in
th
e en
viro
nmen
t mai
nly
dist
ribut
ed to
sur
face
wat
er. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
pois
onin
g 4,
4-D
ihyd
roxy
benz
ophe
non
is e
xpec
ted
to b
e fo
und
in fi
sh a
nd to
p pr
edat
ors
in m
inor
am
ount
s. A
hig
h hu
man
exp
osur
e is
exp
ecte
d m
ainl
y du
e to
the
fact
that
the
subs
tanc
e is
use
d as
a U
V s
cree
n in
cos
met
ics.
4,4
-D
ihyd
roxy
benz
ophe
non
is th
eref
ore
cons
ider
ed a
s be
ing
of M
ediu
m C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or le
gal
stat
us fo
r th
is s
ubst
ance
was
foun
d.
6164
-98-
3 C
hlor
dim
efor
m
Ch
lord
imef
orm
is u
sed
as a
inse
ctic
ide.
Chl
ordi
mef
orm
is a
ccor
ding
to th
e E
SIS
dat
abas
e pr
oduc
ed in
am
ount
s <
10
tone
s/ye
ar a
nd th
us n
ot a
LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 1
0 to
nes
per
year
ha
s be
en u
sed.
Chl
ordi
mef
orm
is n
ot r
eadi
ly b
iode
grad
able
and
has
a m
ediu
m p
oten
tial t
o bi
oacc
umul
ate
(log
Kow
=2.
89).
Bas
ed o
n E
US
ES
est
imat
ions
Chl
ordi
mef
orm
is e
xpec
ted
to b
e fo
und
in lo
cal s
urfa
ce w
ater
s in
con
cen-
trat
ions
up
to a
ppro
x. 1
mg/
L. B
ased
on
EU
SE
S e
stim
atio
ns fo
r se
cond
ary
pois
onin
g an
d hu
man
inta
ke C
hlor
dim
e-fo
rm is
exp
ecte
d to
be
foun
d in
fish
, pre
dato
rs a
nd h
uman
food
in m
inor
am
ount
s. C
hlor
dim
efor
m is
con
side
red
as
bein
g of
Lo
w C
on
cern
. Cov
ered
by
Cou
ncil
Dire
ctiv
e 91
/414
/EE
C. N
o R
AR
has
bee
n pr
ovid
ed a
nd th
e su
bsta
nce
is
not i
nclu
ded
in th
e lis
t for
pes
ticid
es to
be
revi
ewed
. 74
00-0
8-0
p-C
oum
aric
aci
d (P
CA
) p
-Co
um
aric
aci
d (
PC
A)
is a
nat
ural
phe
nolic
aci
d. P
CA
is a
ccor
ding
to th
e E
SIS
dat
abas
e pr
oduc
ed in
am
ount
s <
10
tone
s/ye
ar a
nd th
us n
ot a
LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 1
0 to
nes
per
year
ha
s be
en u
sed.
PC
A is
rea
dily
bio
degr
adab
le a
nd h
as a
low
pot
entia
l to
bioa
ccum
ulat
e (lo
g K
ow=
1.79
). B
ased
on
EU
SE
S e
stim
atio
ns P
CA
is e
xpec
ted
to b
e fo
und
in lo
cal s
urfa
ce w
ater
in c
once
ntra
tions
up
to a
ppro
x. 1
mg/
L.
Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
and
hum
an in
take
PC
A is
exp
ecte
d to
be
foun
d in
fish
, pre
da-
tors
and
hum
an fo
od in
insi
gnifi
cant
am
ount
s. P
CA
is c
onsi
dere
d as
bei
ng o
f Lo
w C
on
cern
. Non
e sp
ecifi
cally
reg
u-la
tory
or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
77
-09-
8 3,
3'-B
is(4
-hy
drox
y-ph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e
Ph
eno
lph
thal
ein
is u
sed
as a
labo
rato
ry r
eage
nt a
nd a
cid-
base
indi
cato
r an
d in
ove
r-th
e-co
unte
r la
xativ
e pr
epar
a-tio
ns. P
heno
lpht
hale
in is
acc
ordi
ng to
the
ES
IS d
atab
ase
prod
uced
in a
mou
nts
< 1
0 to
nes/
year
and
thus
not
a L
PV
su
bsta
nce.
For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 1
0 to
nes
per
year
has
bee
n us
ed. P
heno
lpht
hale
in is
no
t rea
dily
bio
degr
adab
le a
nd h
as p
oten
tial t
o bi
oacc
umul
ate
(log
Kow
=3.
06).
Bas
ed o
n E
US
ES
est
imat
ions
Phe
nol-
phth
alei
n is
exp
ecte
d to
be
foun
d in
loca
l sur
face
wat
er in
rel
ativ
ely
high
con
cent
ratio
ns (
appr
ox. 1
0 m
g/L)
as
wel
l as
sedi
men
ts a
nd a
gric
ultu
ral s
oils
. Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
and
hum
an in
take
Chl
ordi
-m
efor
m is
exp
ecte
d to
be
foun
d in
fish
, pre
dato
rs a
nd h
uman
food
in in
sign
ifica
nt a
mou
nts.
Bas
ed o
n th
e ex
pect
ed
high
con
cent
ratio
ns in
sur
face
wat
ers
PC
A is
con
side
red
as b
eing
of
Med
ium
Co
nce
rn. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
12
CA
SN
R
NA
ME
C
oncl
usio
n 77
-40-
7 2,
2-B
is(4
-hy
drox
yphe
nyl)-
n-bu
tan
= B
isph
enol
B
Bis
ph
eno
l B is
com
pone
nt o
f Phe
nolic
Res
in w
hich
is th
erm
oset
ting
resi
n us
ed a
s A
dhes
ive
and
Rei
nfor
cem
ent.
Bis
phen
ol B
is u
sed
in m
any
indu
stria
l app
licat
ions
. Bis
phen
ol B
is a
ccor
ding
to th
e E
SIS
dat
abas
e pr
oduc
ed in
low
am
ount
and
is n
eith
er a
HP
V o
r LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 1
0 to
nes
per
year
has
bee
n us
ed. B
isph
enol
B is
not
rea
dily
bio
degr
adab
le a
nd h
as a
hig
h po
tent
ial t
o bi
oacc
umul
ate
in th
e en
vi-
ronm
ent (
log
kow
=4.
69).
Bis
phen
ol B
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
as
wel
l as
sedi
men
ts
and
agric
ultu
ral s
oils
. Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
Bis
phen
ol B
is e
xpec
ted
to b
e fo
und
in
fish
and
top
pred
ator
s in
min
or a
mou
nt. A
med
ium
hum
an e
xpos
ure
is e
xpec
ted.
Bis
phen
ol B
is c
onsi
dere
d as
bei
ng
of M
ediu
m C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
was
foun
d.
92-6
9-3
4-H
ydro
xybi
phen
yl =
4-
Phe
nylp
heno
l 4-
Ph
enyl
ph
eno
l in
an in
dust
rial i
nter
med
iate
. 4-P
heny
lphe
nol i
s ac
cord
ing
to th
e E
SIS
dat
abas
e a
LPV
sub
stan
ce.
For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 1
000
tone
s pe
r ye
ar h
as b
een
used
. 4-P
heny
lphe
nol i
s no
t rea
d-ily
bio
degr
adab
le a
nd h
as p
oten
tial t
o bi
oacc
umul
ate
in th
e en
viro
nmen
t (lo
g ko
w=3
.2).
4-P
heny
lphe
nol i
s in
the
en-
viro
nmen
t mai
nly
dist
ribut
ed to
sur
face
wat
er in
con
cent
ratio
ns u
p to
app
rox.
4 m
g/L.
Bas
ed o
n E
US
ES
est
imat
ions
fo
r se
cond
ary
pois
onin
g an
d hu
man
inta
ke 4
-Phe
nylp
heno
l is
expe
cted
to b
e fo
und
in fi
sh, p
reda
tors
and
hum
an
food
in m
inor
am
ount
s. 4
-Phe
nylp
heno
l is
cons
ider
ed a
s be
ing
of M
ediu
m C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
92
-88-
6 4,
4'-
Dih
ydro
xybi
phen
yl =
4,
4'-B
iphe
nol
4,4'
-Bip
hen
ol u
sed
as s
unsc
reen
s, p
rese
rvat
ives
, dis
infe
ctan
ts, a
ntio
xida
nts,
flav
orin
gs, o
r fo
r pe
rfum
ery.
4,4
'-B
iphe
nol i
s ac
cord
ing
to th
e E
SIS
dat
abas
e pr
oduc
ed in
am
ount
s <
10
tone
s/ye
ar a
nd is
thus
not
a L
PV
sub
stan
ce.
For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 1
0 to
nes
per
year
has
bee
n us
ed. 4
,4'-B
iphe
nol i
s no
t rea
dily
bi
odeg
rada
ble
and
has
a m
ediu
m p
oten
tial t
o bi
oacc
umul
ate
in th
e en
viro
nmen
t (lo
g ko
w=
2.8)
. 4,4
'-Bip
heno
l is
in th
e en
viro
nmen
t mai
nly
dist
ribut
ed to
sur
face
wat
er in
con
cent
ratio
ns u
p to
app
rox.
1 m
g/L.
Bas
ed o
n E
US
ES
est
ima-
tions
for
seco
ndar
y po
ison
ing
and
hum
an in
take
4,4
'-Bip
heno
l is
expe
cted
to b
e fo
und
in fi
sh, p
reda
tors
and
hum
an
food
in in
sign
ifica
nt a
mou
nts,
how
ever
, a h
igh
hum
an e
xpos
ure
is e
xpec
ted
due
to th
e de
fined
use
of t
he s
ubst
ance
. 4,
4'-B
iphe
nol i
s co
nsid
ered
as
bein
g of
Hig
h C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
w
as fo
und.
94
-13-
3 n-
prop
yl p
-hy
drox
yben
zoat
e N
-pro
pyl
p-h
ydro
xyb
enzo
ate
is u
sed
as a
pre
serv
ativ
e in
food
, pha
rmac
eutic
al a
nd c
osm
etic
form
ulat
ions
. N-p
ropy
l p-
hydr
oxyb
enzo
ate
is p
rodu
ced
in a
mou
nts
up to
10
tone
s pe
r ye
ar a
nd th
us a
LP
V s
ubst
ance
. N-p
rop
yl p
-hy
drox
yben
zoat
e is
rea
dily
bio
degr
adab
le a
nd h
as p
oten
tial f
or b
ioac
cum
ulat
ion
(log
Kow
=3.
04).
Bas
ed E
US
ES
cal
-cu
latio
ns N
-pro
pyl p
-hyd
roxy
benz
oate
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
s in
con
cent
ratio
ns u
p to
app
rox.
10
mg/
L. N
-pro
pyl p
-hyd
roxy
benz
oate
is e
xpec
ted
to b
e fo
und
in fi
sh, p
reda
tors
and
hum
an fo
od in
insi
g-ni
fican
t am
ount
s. H
owev
er, a
s n-
prop
yl p
-hyd
roxy
benz
oate
is u
sed
as a
pre
serv
ativ
e in
food
and
cos
met
ics
a hi
gh
hum
an e
xpos
ure
is e
xpec
ted.
N-p
ropy
l p-h
ydro
xybe
nzoa
te is
thus
con
side
red
as b
eing
of M
ediu
m C
on
cern
. Non
e sp
ecifi
cally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
was
foun
d. It
is th
e op
iniu
m o
f the
Sci
entif
ic C
omm
itee
on
Con
sum
er P
rodu
cts
(SC
CP
) th
at, v
iew
ing
the
curr
ent k
now
ledg
e, th
ere
is n
o ev
iden
ce o
f dem
onst
rabl
e ris
k fo
r th
e de
velo
pmen
t of b
reas
t can
cer
caus
ed b
y th
e us
e of
und
erar
m c
osm
etic
s in
clud
ing
para
bens
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
13
CA
SN
R
NA
ME
C
oncl
usio
n 94
-26-
8 n-
But
yl p
-H
ydro
xybe
nzoa
te
n-B
uty
l p-H
ydro
xyb
enzo
ate
is u
sed
as a
pre
serv
ativ
e in
food
, pha
rmac
eutic
al a
nd c
osm
etic
form
ulat
ions
. N-B
utyl
p-
hydr
oxyb
enzo
ate
is a
ccor
ding
to th
e E
SIS
dat
abas
e pr
oduc
ed in
am
ount
s <
10
tone
s/ye
ar a
nd is
thus
not
a L
PV
su
bsta
nce.
For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 1
0 to
nes
per
year
has
bee
n us
ed. N
-But
yl p
-hy
drox
yben
zoat
e is
rea
dily
bio
degr
adab
le a
nd h
as a
rel
ativ
ely
high
pot
entia
l for
bio
accu
mul
atio
n (lo
g K
ow=
3.57
).
Bas
ed E
US
ES
cal
cula
tions
N-B
utyl
p-h
ydro
xybe
nzoa
te is
in th
e en
viro
nmen
t mai
nly
dist
ribut
ed to
sur
face
wat
ers
in
conc
entr
atio
ns u
p to
app
rox.
1 m
g/L.
N-B
utyl
p-h
ydro
xybe
nzoa
te is
exp
ecte
d to
be
foun
d in
fish
, pr
edat
ors
and
hu-
man
food
in in
sign
ifica
nt a
mou
nts.
How
ever
, as
n-B
utyl
p-h
ydro
xybe
nzoa
te is
use
d as
a p
rese
rvat
ive
in fo
od a
nd
cosm
etic
s a
high
dire
ct h
uman
exp
osur
e is
exp
ecte
d. N
-But
yl p
-hyd
roxy
benz
oate
is th
us c
onsi
dere
d as
bei
ng o
f M
e-d
ium
Co
nce
rn. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce w
as fo
und.
It is
the
opin
ium
of t
he S
ci-
entif
ic C
omm
itee
on C
onsu
mer
Pro
duct
s (S
CC
P)
that
, vie
win
g th
e cu
rren
t kno
wle
dge,
ther
e is
no
evid
ence
of d
e-m
onst
rabl
e ris
k fo
r th
e de
velo
pmen
t of b
reas
t can
cer
caus
ed b
y th
e us
e of
und
erar
m c
osm
etic
s in
clud
ing
para
bens
96
-12-
8 D
ibro
moc
hlor
opro
-pa
ne (
DB
CP
) D
ibro
mo
chlo
rop
rop
ane
(DB
CP
) is
use
d as
a p
estic
ide
as w
ell a
s an
indu
stria
l int
erm
edia
te. D
BC
P is
acc
ordi
ng to
th
e E
SIS
dat
abas
e pr
oduc
ed in
am
ount
s <
10
tone
s/ye
ar a
nd is
thus
not
a L
PV
sub
stan
ce. F
or th
e E
US
ES
cal
cula
-tio
ns a
pro
duct
ion
volu
me
of 1
0 to
nes
per
year
has
bee
n us
ed. D
BC
P is
not
rea
dily
bio
degr
adab
le a
nd h
as m
ediu
m
pote
ntia
l to
bioa
ccum
ulat
e in
the
envi
ronm
ent (
log
kow
=2.
96).
DB
CP
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
ur-
face
wat
er in
con
cent
ratio
ns u
p to
app
rox.
1 m
g/L.
Bas
ed o
n E
US
ES
est
imat
ions
for
seco
ndar
y po
ison
ing
and
hu-
man
inta
ke D
BC
P is
exp
ecte
d to
be
foun
d in
fish
, pre
dato
rs a
nd h
uman
food
in m
inor
am
ount
s. D
BC
P is
con
side
red
as b
eing
of M
ediu
m C
on
cern
. Cov
ered
by
Cou
ncil
Dire
ctiv
e 91
/414
/EE
C. N
o R
AR
has
bee
n pr
ovid
ed a
nd th
e su
b-st
ance
is n
ot in
clud
ed in
the
list f
or p
estic
ides
to b
e re
view
ed. C
lass
ifica
tion:
CA
RC
2;R
45 M
UT
2;R
46 R
EP
1;R
60
T;R
25 X
N;R
48/2
0/22
R52
/53
99-7
6-3
Met
hyl p
-H
ydro
xybe
nzoa
te
Met
hyl
p-H
ydro
xyb
enzo
ate
is u
sed
as a
pre
serv
ativ
e in
food
, pha
rmac
eutic
al a
nd c
osm
etic
form
ulat
ions
. Met
hyl p
-H
ydro
xybe
nzoa
te is
acc
ordi
ng to
the
ES
IS d
atab
ase
a LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
vol-
ume
of 5
00 to
nes
per
year
has
bee
n us
ed. M
ethy
l p-h
ydro
xybe
nzoa
te is
rea
dily
bio
degr
adab
le a
nd h
as a
low
pot
en-
tial f
or b
ioac
cum
ulat
ion
(log
Kow
=1.
96).
Bas
ed E
US
ES
cal
cula
tions
Met
hyl p
-hyd
roxy
benz
oate
is in
the
envi
ronm
ent
mai
nly
dist
ribut
ed to
sur
face
wat
er in
con
cent
ratio
ns u
p to
app
rox.
1 m
g/L.
Met
hyl p
-hyd
roxy
benz
oate
is e
xpec
ted
to
be fo
und
in fi
sh, p
reda
tors
and
hum
an fo
od in
insi
gnifi
cant
am
ount
s. H
owev
er, a
s M
ethy
l p-h
ydro
xybe
nzoa
te is
use
d as
a p
rese
rvat
ive
in fo
od a
nd c
osm
etic
s a
high
dire
ct h
uman
exp
osur
e is
exp
ecte
d. M
ethy
l p-h
ydro
xybe
nzoa
te is
th
us c
onsi
dere
d as
bei
ng o
f Med
ium
Co
nce
rn. N
one
spec
ifica
lly r
egul
ator
y or
lega
l sta
tus
for
this
sub
stan
ce w
as
foun
d. It
is th
e op
iniu
m o
f the
Sci
entif
ic C
omm
itee
on C
onsu
mer
Pro
duct
s (S
CC
P)
that
, vie
win
g th
e cu
rren
t kno
wl-
edge
, the
re is
no
evid
ence
of d
emon
stra
ble
risk
for
the
deve
lopm
ent o
f bre
ast c
ance
r ca
used
by
the
use
of u
nder
arm
co
smet
ics
incl
udin
g pa
rabe
ns
ERA/53559/Revised report/2007.06.04
DHI Water & Environment
14
CA
SN
R
NA
ME
C
oncl
usio
n 99
-96-
7 p-
Hyd
roxy
benz
oic
acid
p
-Hyd
roxy
ben
zoic
aci
d is
the
com
mon
met
abol
ite o
f all
para
bens
and
thus
use
d as
a p
rese
rvat
ive
in fo
od, p
harm
a-ce
utic
al a
nd c
osm
etic
form
ulat
ions
. p-H
ydro
xybe
nzoa
te is
acc
ordi
ng to
the
ES
IS d
atab
ase
a LP
V s
ubst
ance
. For
the
EU
SE
S c
alcu
latio
ns a
pro
duct
ion
volu
me
of 1
000
tonn
es p
er y
ear
has
been
use
d. P
-hyd
roxy
benz
oic
acid
is r
eadi
ly
biod
egra
dabl
e an
d ha
s a
low
pot
entia
l for
bio
accu
mul
atio
n (lo
g K
ow=
1.58
). B
ased
EU
SE
S c
alcu
latio
ns p
-H
ydro
xybe
nzoi
c ac
id is
dis
trib
uted
to th
e en
viro
nmen
t at l
ow c
once
ntra
tions
. P-h
ydro
xybe
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, pre
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sign
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mou
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ever
, as
P-h
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xybe
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use
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pres
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cern
. Non
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cally
reg
ulat
ory
or le
gal s
tatu
s fo
r th
is s
ubst
ance
was
foun
d. It
is
the
opin
ium
of t
he S
cien
tific
Com
mite
e on
Con
sum
er P
rodu
cts
(SC
CP
) th
at, v
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ing
the
curr
ent k
now
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ere
is
no e
vide
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of d
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stra
ble
risk
for
the
deve
lopm
ent o
f bre
ast c
ance
r ca
used
by
the
use
of u
nder
arm
cos
met
ics
incl
udin
g pa
rabe
ns
96-4
5-7
Eth
ylen
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hiou
rea
(ET
U)
Eth
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eth
iou
rea
(ET
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is o
ne o
f the
deg
rada
tion
prod
ucts
of e
thyl
eneb
is-d
ithio
carb
amat
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ngic
ides
, suc
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m
aneb
and
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hav
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idel
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n fo
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rops
. ET
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acc
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the
ES
IS d
atab
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a LP
V s
ub-
stan
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or th
e E
US
ES
cal
cula
tions
a p
rodu
ctio
n vo
lum
e of
100
0 to
nes
per
year
has
bee
n us
ed. E
TU
is n
ot r
eadi
ly
biod
egra
dabl
e an
d ha
s a
low
pot
entia
l for
bio
accu
mul
atio
n (lo
g K
ow=
-0.6
6). B
ased
EU
SE
S c
alcu
latio
ns E
TU
is in
the
envi
ronm
ent m
ainl
y di
strib
uted
to s
urfa
ce w
ater
in c
once
ntra
tions
up
to a
ppro
x. 0
.5 m
g/L.
ET
U is
exp
ecte
d to
be
foun
d in
fish
, pre
dato
rs a
nd h
uman
food
in in
sign
ifica
nt a
mou
nts.
ET
U is
thus
con
side
red
as b
eing
of L
ow
Co
nce
rn.
The
sub
stan
ce is
cov
ered
by
Cou
ncil
Dire
ctiv
e 91
/414
/EE
C. N
o R
AR
has
bee
n pr
ovid
ed a
nd th
e su
bsta
nce
is n
ot
incl
uded
in th
e lis
t for
pes
ticid
es to
be
revi
ewed
. Cla
ssifi
catio
n: R
EP
2;R
61 X
N;R
22
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 15
3 INTRODUCTION
3.1 Background
In both human beings and animals, endocrine disruption is a mechanism whose effects relate to the functioning of the endocrine system, which influences development, growth, reproduction and behaviour. According to accepted Weybridge definition (EU 1997) as supported by the Commission (COM(1999) 706), an endocrine disrupter is an exogenous substance or mixture that alters function(s) of the endocrine system and con-sequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations. In recent years, there has been growing concern over a range of sub-stances, which are suspected to interfere with the endocrine system, the so-called endo-crine disrupters. Endocrine disrupters may act by the following mechanisms: • Direct damage to an endocrine organ • Direct altering of the function of an endocrine organ • Interaction with receptors • Altering the hormone metabolism, either in endocrine organs or peripherally The observed adverse effects of endocrine disrupters in humans and animals include cancer, behavioural changes and reproductive abnormalities. However, the knowledge of endocrine disrupters and their effects is still characterised by many uncertainties and data gaps. In 1996, the European Commission implemented a policy as to the use and regulation of suspected endocrine disturbing substances, and, in December 1999, it adopted a Com-munity Strategy for Endocrine Disrupters. This strategy addresses the key elements of further research, international co-operation, public communication and appropriate pol-icy actions. The strategy contains actions on short-, medium- and long-term time scales. Short-term actions include gathering of scientific data, identification of substances for further evaluation with a view to prioritising testing, guidance of research and monitoring of ef-forts and to identifying exposure target groups. Medium-term actions focus on testing issues. Long-term actions include review and possible adaptation of policy and legisla-tion. A key short-term action is the establishment of a priority list of substances for further evaluation of their role in endocrine disruption. The first study carried out in 2000 on the behalf of the Commission (BKH 2000) identified a candidate list of 553 substances. Among these substances, 59 substances were identified as mixtures and/or polymers, and/or double inputs and/or group names and will not be evaluated further, while 118 were identified as High Production Volume substances and/or persistent man-made chemicals showing scientific evidence of endocrine disruption or potential for endocrine disruption. Most of these substances (109) were already subject to bans or restrictions or were being addressed under existing Community legislation although for reasons not
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necessarily related to endocrine disruption. In the short term, priority was thus given to nine substances, which are neither restricted nor currently being addressed under exist-ing Community legislation, and for which more in depth studies were necessary. In ad-dition, three natural and/or synthetic hormones, oestrone, ethinylestradiol and oestradiol were evaluated in order to gather up-to-date evidence of environmental exposure and ef-fects related to these substances. These substances were studied by WRc and reported in: “Study on the scientific evaluation of 12 substances in the context of Endocrine Dis-rupter priority list of actions”. WRc-NSF published November 2002. A second study was performed in 2002 (RPS-BKH, 2002), in which the remaining 435 substances in the 2000 report, for which there had been insufficient data to assess endo-crine disruption or potential for endocrine disruption, were evaluated. The aim of this study was to gather data/information on persistence, production volumes and legal status of these substances. The study primarily focused on industrial chemicals used in industry, agriculture and consumer goods. The substances were categorised according to different levels of available information for the following four selection criteria: • Production volume • Persistence in the environment • Evidence for endocrine disruption from literature data • Exposure considerations Among the 553 substances of the original candidate list, 173 substances had not been evaluated for endocrine or potential endocrine effects on humans and wildlife. In the IUCLID database, 7829 chemicals are registered as Low Production Volume Chemicals (LPVC) but no information regarding their potential endocrine disrupting ef-fects is registered. It was agreed that the present evaluation should include possible identification of additional substances among these, which may have endocrine disrupt-ing properties. For this purpose, stakeholders were consulted. The endocrine properties of 173 substances plus 22 substances identified by stakeholders were thus evaluated in the present study. Throughout the present report, the definitions of ‘Low Production Volume Chemicals’ and ‘High Production Volume Chemicals’ are based on the definitions given in ESIS (European chemical substances information system): HPVC (High Production Volume Chemical). A HPVC is a chemical which is defined as being produced or imported in quantity of at least 1000 tonnes per year in EU by at least one Industry. LPVC (Low Production Volume Chemical). A LPVC, is a chemical which has been produced or imported in EU with a tonnage >10 t/y but never more than 1000 t/y. By definition, a LPV Chemical is a chemical which is not a HPV Chemical.
3.2 Objectives and scope of the current project
The main objective with the present project was to improve the database developed in the RPS-BKH 2002 project and to include collected data on endocrine disrupting prop-erties of the remaining substances placed on the candidate list.
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The subject of this project belongs to the short-term priority actions of the European Commission. It entails a study to gather data and information on LPVC as well as on substances with a production volume < 10 tonnes/year and to enhance the Endocrine Disrupter priority list with a view to providing information on the priority list at the DG Environment Endocrine Disrupters Website and inform relevant EU policy areas. According to the Community Strategy for Endocrine Disrupters (1999), the present study is a short-term key action and a follow-up on the EC DG-ENV study (2002) “To-wards the establishment of a priority list of substances for further evaluation of their role in endocrine disruption – preparation of a candidate list of substances as a basis for priority setting”. The present study “Study on enhancing the Endocrine Disrupter priority list with a fo-cus on low production volume chemicals” is a follow-up study for the establishment of a priority list of substances for further in-depth evaluation of their role in endocrine dis-ruption. Two previous studies in this area were carried out by BKH in 2000 and by RPS BKH in 2002. The present study is thus the last of three evaluations going through the remaining candidate substances (173 substances) from the EU candidate list including 553 substances in total. For comparability reasons and as the present study is the last of three evaluations of the candidate substances, the same methodology as used in the pre-vious RPS-BKH 2002 project was applied. The compilation of the priority list is based on a screening of available literature and should therefore be regarded as a starting point for further hazard and risk assessments of the substances placed on the priority list. The evaluations shall be seen in line with the previous studies (BKH 2000 and RPS-BKH 2002) and shall NOT be seen as risk as-sessments. Future in-depth evaluations of the substances placed on the list need to be performed and a methodology must be developed to make the list iterative meaning that a substance can enter or be deleted from the list based on a weight of evidence ap-proach. The present evaluation included: 1. A written consultation with stakeholders, which, as far as possible, ensured that pos-
sible new candidates for the Endocrine Disrupter candidate list were identified among substances listed in the ESIS database
2. The identified substances were evaluated for endocrine disrupting effects and the following screening criteria have as far as possible been taken into account:
• Relevance of effect parameter • Test reliability • Dose-response relationship • Endocrine disruption potency • Comparison with systemic toxicity • Evaluation of exposure concern to humans and wildlife • Consumption/use patterns • Environmental concentration ranges
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In order to reach the objectives, the following four tasks were formulated:
• Identification of relevant stakeholders • Identification of new candidate LPVC for further evaluation of their endocrine
disrupting properties • Collection and evaluation of data/information on LPVC to establish priorities for
further evaluation of their role in endocrine disruption • Update of database, list and meetings
Below, the methodology used to fulfil the tasks is described.
3.3 Study approach
Below, the four tasks identified to fulfil the study objectives are described. Task 1 Identification of relevant stakeholders
• Relevant stakeholders were identified in consultation with the Commission • The same stakeholders were used as a written consultation group based on
a web-based response
Task 2 Identification of new candidate LPVC for further evaluation of their endocrine disrupting properties • The substances were identified by a written consultation with the stake-
holders identified in Task 1. Task 3 Collection and evaluation of data/information on LPVC to establish priorities
for further evaluation of their role in endocrine disruption The execution of this task was based on the following activities:
• Data search strategy, data collection and data evaluation • Evaluation of exposure of humans and wildlife
Task 4 Update of database, list and meetings
• The major objective of this task was to report the study in a way that en-ables the Commission to make the results available at the Commission’s Endocrine Disrupters Website.
• The progress of the study was placed at the web site: (http://projects.dhi.dk/Endocrine_Disrupter/testsite/) together with the ex-isting version of the database. A link to the DHI homepage was placed at the ECB homepage on endocrine disrupters (http://ec.europa.eu/environment/endocrine/strategy/substances_en.htmon) allowing third party to follow the progress in the project as well as provid-ing comments on the draft final report and the final outcome of the data-base.
• In order to ensure close co-operation with the Commission, four meetings took place during the project period
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4 METHODOLOGY
4.1 Identification of relevant stakeholders (Task 1)
The main objective of this task was to identify relevant contacts among stakeholders. Relevant stakeholders were contacted in the written consultation described under Task 2. Task 1.1 Identification of stakeholders for written consultation Relevant stakeholders were identified in consultation with the Commission taking a starting point in the following groups: • National focal points in EU Member States • ECETOC • Experts involved in international work regarding endocrine disrupters, e.g. OECD
Validation Management Groups for Ecotoxicity Tests (VMG-eco) and Mammalian toxicity test (VMG-mammal) of the Task Force on Endocrine Disrupters Testing and Assessment (EDTA)
• Members of the EU projects on endocrine disrupters e.g., CREDO, EDEN, FIRE • Environmental NGOs • Industrial branch organisations, e.g. CEFIC, EUROCHLOR and individual indus-
tries, Task 1.2 Identification of stakeholders for consultation group At the interim report meeting (29 June 2006) between DHI and DG ENV, it was de-cided that all contacted stakeholders were invited to go through the draft final report and the collected data on substances categorised as Category 1 substances (evidence for en-docrine disrupting effects) in the database. Due to cost limitations, it was decided not to have a physical meeting but instead have web-based stakeholder responses.
4.2 Identification of new candidate LPVC for further evaluation of their endocrine disrupting properties (Task 2)
The major objective of this task was to identify substances (preferably LPVC) with a potential for endocrine disruption, which have not been included in previous lists. The substances were identified by a written consultation with the stakeholders identified in Task 1.1. The request included a brief presentation of the background for the query with reference to the existing lists of potentially endocrine disrupting substances. Fur-thermore, a short questionnaire included questions regarding the knowledge of endo-crine disrupting properties of other chemicals, references regarding this knowledge and possible information relevant to exposure assessment, e.g. regarding production vol-umes and use of the chemicals.
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4.3 Collection and evaluation of data/information on LPVC to estab-lish priorities for further evaluation of their role in endocrine disruption (Task 3)
The major objective of this task was to gather data/information on LPVC specifically on their potential role in endocrine disruption. The study was based on the the remaining of the 553 substances placed on the candidate substance list, which were identified in the BKH Report of 2000, and on new candidate substances, which were identified in Task 2 as described above. Starting points were the methodology developed in the RPS-BKH report (2002) and the database containing the candidate substances identified in the BKH report of 2000, with data from background documents. The methodological approaches and evaluation of the selected substances with respect to endocrine disrupter potency towards humans and wildlife were elaborated by the project team and included the subtasks described below.
4.3.1 Data search strategy and data collection (Task 3.1) Literature was searched in different databases both free databases available on the inter-net and licensed databases purchased by DHI. For all substances, a general screening of the literature was performed. The following databases were searched (for the specific CAS number or name): • HSDB (Hazardous Substances Data Bank) • RTECS via Thomes (Thomson, Micromedex)
The following databases were searched for original peer-review scientific papers: • TOXCENTER (Toxicology Center) is a bibliographic database that covers the phar-
macological, biochemical, physiological and toxicological effects of drugs and other chemicals.
TOXCENTER is composed of the following file segments:
• ANEUPL - Aneuploidy File • BIOSIS - 1969 to the present • CAplus - 1907 to the present • CIS - CIS Abstracts • CRISP - Toxicology Research Projects • DART - Development and Reproductive Toxicology File • EMIC - Environmental Mutagen Information Center File • EPIDEM - Epidemiology Information System, • ETIC - Environmental Teratology Information Center File • FEDRIP - Federal Research in Progress • HAPAB - Health Aspects of Pesticides Abstract Bulletin • HMTC - Hazardous Materials Technical Center File • IPA - 1970 to the present • MEDLINE - 1950 to the present
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• PESTAB - Pesticides Abstracts • PPBIB - Poisonous Plants Bibliography • RISKLINE - Swedish National Chemicals Inspecorate • TSCATS - Toxic Substances Control Act Test Submissions
The records in the file contain bibliographic data, abstracts, indexing terms, chemical names and CAS Registry Numbers.
• EMBASE (Excerpta Medica) is a comprehensive bibliographic database that covers
the worldwide literature on biomedical and pharmaceutical fields. It is produced by Elsevier B.V., the world's largest publisher of scientific information.
• Science Citation Index (SciSearch®) contains all records published in Science Cita-
tion Index ExpandedTM. Records from January 1991 up to the present. It includes abstracts, author keywords, and KeyWords Plus®. Authors, bibliographic informa-tion cited references and KeyWords Plus are searchable.
The search strategy for the substances was: • Search on CAS No., chemical name and synonyms • The hits identified searching on CAS No. and names were combined with the fol-
lowing search terms: For substances with many hits, the following search terms were used: testes, undescended OR testis, undescended OR testic? feminization OR androgen in-sensitivity OR oestrus OR estrus OR cryptorchidism OR hypospadias OR uterotrophic OR Hershberger OR gonadal disorder# OR gonadal dysgenesis OR gonadal agenesis OR gonad? Inhibiting hormone# OR estrogen? receptor# OR oestrogen? receptor# OR estrogen? Effect# OR oestrogen? effect# OR anti-androgen? effect# OR androgen? re-ceptor# OR vitellogen? OR 11-ketotestosterone OR progesterone# receptor# OR testos-terone# receptor# OR endocrine disrupt? OR thyroid? hormone# For substances with few hits, the following search terms were used: testes OR testis OR testic? OR androgen? OR oestrus OR estrus OR cryptorchidism OR hypospadias OR uterotrophic OR Hershberger OR preputial OR vagina? OR sperm? OR gonad? OR estrogen? OR oestrogen? OR anti-androgen? OR vitellogen? OR 11-ketotestosterone OR pituitary OR progesterone# OR testosterone# OR endocrine dis-rupt? OR thyroid? If more than approx. 100-150 hits were identified by either of these search strategies, a further limitation was performed. In few cases, the exclusion of in-vitro studies was used as a limitation criterion but this only resulted in a small limitation of hits. Limita-tion on year of publication was mostly used by starting with excluding literature pub-lished before 1980 and then excluding literature with 5-10 years intervals until approx. 100 hits were reached.
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The identified hits were screened for relevant/valuable titles. For selected titles, ab-stracts were downloaded. Due to cost limitations (the database search and downloading of abstracts turned out to be very costly), evaluations were mainly based on the downloaded abstracts.
4.3.2 Evaluation of endocrine potential (Task 3.2) The evaluation of endocrine disrupting-related effects on humans and wildlife has re-sulted in categorisation of the substances based on the following screening criteria: • Relevance of test parameter (with aspects such as endocrine specific effects in con-
trast to general toxicity (teratogenic effects)) • Test reliability (validated protocols; experimental design; suitability, health and life
stage of test species; statistics). Ranked indication of Data Quality (DQ 1-4). DQ: Good Data Quality, fulfilling all (important) criteria; DQ2: Sufficient Data Quality, study fulfilling most of the (important) criteria; DQ3: Insufficient Data Quality, study cannot be used for identification; and DQ4: Not evaluated .
• Dose-response relationship or indications of effect thresholds • Endocrine disruption potency (including a categorisation of the chemicals into three
groups: 1. Evidence for endocrine disrupting (ED) effect; 2. Potential ED effect; 3. No evidence for ED effect)
• Endocrine disruption structure-activity relationship • Comparison with systemic toxicity (Standard toxicity data –NOECs/LOECs,
E(E)C50s, NOALs/LOAELs from RTECS, ECOTOX (AQUIRE), DOSE and Ver-shuren databases)
Based on the above screening, the substances have been divided into the following four Categories:
CAT 1 At least one in-vivo study providing clear evidence for endocrine disruption in an intact organism. Not a formal weight of evidence approach.
CAT 2 Potential for endocrine disruption. In-vitro data indicating potential for endocrine disruption in intact organisms. May also include in-vivo effects, however, then with insufficient convincing character.
CAT 3a No scientific basis for inclusion in list (ED studies available but no indications of ED effects)
CAT 3b. Substances with no or insufficient data gathered.
4.3.3 Evaluation of exposure of humans and wildlife (Task 3.3) For substances categorised as CAT 1 and CAT 2, evaluation of exposure of humans and wildlife have been based on the following methodology: 1. Data on production and import quantity (ECB, IUCLID database). Also consump-
tion/use patterns have been obtained from the ECB, IUCLID database on existing substances manufactured or imported in quantities of more than 10 tonnes per year. For substances manufactured or imported in quantities less than 10 tonnes per year a
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default value of 10 tonnes per year was used. The information includes quantity and use pattern (Main Category, Industrial Category) data.
2. Environmental concentration ranges (COMMPS, European Environment Agency (EEA)).
3. Evaluation of exposure of humans and environment by use of the PC program EUSES.
1) Data on production, import and use quantities (IUCLID) Data concerning quantity of chemicals manufactured in or imported to the EU, and the use within the EU is based on information provided by the European Chemical Bureau (September 2004) as extracts of the IUCLID database. These data reflects the use re-ported to the ECB during the years 1999-2004. The IUCLID database contains informa-tion, which has been submitted by manufacturers and importers of existing chemicals in quantities exceeding 10 tonnes per year. The following data were obtained for each entry: • CAS numbers (several entries per CAS) • DSN number coding for the registrant (one or more registrants per CAS) • Quantities manufactured or imported per year (per entry) • Industry Category (IC) • Use Category (UC) • Main Categories (MC) The IUCLID extract contains separate entries defined by the substance CAS number, the registrant DSN and the year for which the quantity pertains. For example, if one substance is registered by 3 registrants and each of them registers the quantity for 3 years, there will be 9 separate entries for the CAS number. Each registration dossier from a manufacturer or importer of a chemical contains the to-tal quantity of the chemical produced or imported per year. It also contains information on the Main Categories (MC) used to characterise the general release scenarios of the chemical as well as information on the more specific Industrial Categories (IC) and Use Categories (UC) describing the production and use of the chemical in more detail. Chemicals may have different use within different industries according to different products and processes. In agreement to this, one chemical may have several codes for Industrial Categories and Use Categories (UC). In our case, EUSES calculation is based on maximum quantities manufactured or imported per year by one or several manufac-turer and the most likely use pattern. 2) Environmental concentration ranges (COMMPS) Environmental concentration ranges for CAT 1 and CAT 2 substances were searched in COMMPS database/EEA. COMMPS includes water and sediment monitoring data from all EEC Member States. 3) EUSES The PC program EUSES is designed to be a decision-support system for the evaluation of the exposure of chemicals to man and the environment. The system is fully described in the EUSES documentation (http://ecb.jrc.it/euses/) and is based on the EU Technical
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 24
Guidance Documents (TGDs; EC-TGD, 2003) for risk assessment of new and existing substances and biocides. Input to the EUSES calculations are data on volume produced, imported or used, the use pattern and physico-chemical properties of the chemical con-cerned. The EUSES summary reports include among other things information concerning: • Volume produced, imported or used in EU (IUCLID, ECB data (1999-2004) • Codes for use pattern (IUCLID, ECB data) • Physico-chemical properties of the substance (complied and evaluated data) • Release to environment on local, regional and continental scale • Concentration in water, soil, sediment on local scale (highest concentration) • Concentration in water and sediment local, regional and continental • Concentration in fish for secondary poisoning (fresh water) • Concentration in top predators • Concentration in earthworms from agricultural soil • Human daily intake doses due the environment on local and regional scale
4.3.3.1 Using EUSES For many chemicals, information on actual exposure doses or concentrations is limited or even absent and concentrations generally vary significantly in time and space. There-fore, doses and environmental concentrations of a chemical are predicted in a two-step procedure: • First, releases to environmental compartments or the indoor environment are pre-
dicted on the basis of the volume produced, imported or used, the use pattern and physico-chemical properties of the chemical concerned.
• Next, environmental concentrations and human daily intake doses are calculated us-ing models, which take into account the transport and fate of the substance.
The main structure of EUSES is presented in Figure 4.1. In the present project, only the release estimation, the environmental distribution and the exposure assessment are in-cluded. If effect data are entered EUSES also gives the possibility to calculate the envi-ronmental risk, risk for human health as well as calculations of exposure via working places. These calculations are not included in the present evaluations.
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ERA/53559/Revised report/2007.06.04 25
Figure 4.1 The main modules of EUSES
INPUT The following physico-chemical input data are needed: • Melting point (Mp) • Boiling point (Bp) • Vapour pressure (Psat) • Henry’s Law constant (KH) • Water solubility (Ws) • Octanol-water partition coeffients (Kow) • Organic carbon-water partition coefficient (Koc) • Bioconcentration factor (BCF) • Abiotic degradation (OH radical oxidation) in air (t½(air)) • Abiotic degradation in surface waters by hydrolysis (t½(hydro)) • Biodegradation – ready/inherent biodegradability The input data were compiled from the following free data sources: • IUCLID • RAR (ORATS)
RELEASE ESTIMATION Use data
Local and regional emissions
ENVIRONMENTAL DISTRIBUTION Sewage treatment plant model
Local dedicated models Regional model
EXPOSURE ASSESSMENT Bioconcentration factors
Secondary poisoning Human exposure through the environment
Consumer exposure Non-professional user esposure (biocides)
INPUT Substance identification
Physico-chemical properties Partition coefficients Degradation rates
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ERA/53559/Revised report/2007.06.04 26
• CHRIP NITE Biodegradation and bio-concentration • SYRACUSE-CHEMFATE • MST-database • EPI-Suite IUCLID The International Uniform ChemicaL Information Database (IUCLID database) con-tains various measured and estimated physico-chemical parameters and fate properties on 2,465 high production volume chemicals reported by European Industry in the frame of the European existing chemicals risk assessment programme. RAR (ORATS) Provides on-line access to the 141 complete and draft European risk assessment reports (RARs). The reports contain evaluated risk assessment data. Chemical Risk Information Platform (CHRIP) - CHRIP NITE Biodegradation and Bioconcentration Formerly Biodegradation and Bio Accumulation of Existing Chemicals (Chemical Evaluation and Research Institute, Japan) The database on Biodegradation and Bioconcentration of the Existing Chemical Sub-stances under the Chemical Substances Control Law (Japan) contains information on biodegradation and bioconcentration of existing chemical substances and on their test-ing conditions (i.e. measured data), which have been published in the Official Bulletin of Economy, Trade and Industry. The Biodegradation and Bioconcentration of the Ex-isting Chemical Substances under the Chemical Substances Control Law system con-tains data on 1,294 chemical compounds. Syracuse-Chemfate The Syracuse Chemfate contains 25 categories of measured environmental fate and physico-chemical property information on 1,728 chemical compounds. All in all, Chem-fate contains 17,260 records. MST-database (not public available) This database has been developed by the QSAR team of the Danish Environmental Pro-tection Agency (DEPA). It contains QSAR estimates on various physico-chemical, fate and ecotoxicological endpoints on 45,453 EINECs chemicals. The physico-chemical data and fate parameters have been estimated by application of EPI-Suite (see below). The database is not an online facility but a stand-alone database. EPI-Suite -The EPI SuiteTM (previously EPIWIN) This database has been developed by the USEPA Office of Pollution Prevention Toxics and the Syracuse Research Corporation (SRC). EPI SuiteTM uses a single input such as structure (i.e. SMILES notation), CAS No. or name to run the following physico-chemical and fate property estimation models: KOWWINTM, HENRYWINTM, MPBPWINTM, WSKOWWINTM and STPWINTM. The EPI Suite also contains the Syracuse PhysProp database, which includes measured physico-chemical properties on 25,000 chemical compounds.
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Prioritization and selection of data In the present project all compiled data were evaluated in relation to their quality ac-cording to the approach shown in Figure 4.2 and assigned a quality index(QI) between 1 (low quality) and 4 (high quality).
Figure 4.2 General data prioritization approach
The data are assigned a quality index primarily based on origin (estimation/measure-ment) and secondly on a general uncertainty assessment. For the measured data, the un-certainty is estimated from the method of measurement (standard/non-standard meas-urement) and for the estimated data, the uncertainty is estimated from the estimation al-gorithm input (property/structure). (QI= Quality Index, QSAR = Quantitative Structure-Activity Relationship, QPPR= Quantitative Property-Property Relationship, info.=information). It is, however, clear that in some cases only data having the same quality index (for in-stance only QSAR data) are available for a given property of a specific chemical com-pound. In such cases, it is necessary to perform an expert assessment of the data origin and evaluate the credibility and uncertainty of the data origin. Complementary to the quality index data, the credibility of the database/sources was used in the selection procedures of data. Databases and data sources were ranked ac-cording to credibility.
Table 4.1 Credibility of database/data sources. Values from 1-6 indicate credibility from high to low.
1 IUCLID 2 RAR (ORATS) 3 CHRIP NITE Biodegradation and bio-concentration 4 SYRACUSE-CHEMFATE 5 MST-database 6 EPI-Suite
Data for the EUSES evaluation of the exposure of chemicals to man and the environ-ment were selected by use of the following procedure:
QI=3QI=2
Have the data been measured or estimated?
QI=1
Have the data been estimated using QSAR or
QPPR?
QI=4
Have the data been measured according to a
standard method?
Estimated/no info. Measured
QPPR QSAR/no info.According to standard
No/no info.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 28
• Data with the highest QI is selected. • If the QI values are equal, firstly, data obtained at 25ºC and neutral pH 7 and, sec-
ondly, data from database/sources with the highest credibility are selected. • Possible comments attached to the data may affect the selection of data The following general criteria were applied in selection of data: • Tests conducted at > 25-30ºC are not included • Only boiling points obtained at ≈ 1013 hPa are included • Biodegradation: Only tests performed under aerobic conditions are included and
where many data are available, primarily OECD 301 tests are considered • IUCLID database: Where method is described as “other”, the origin is assumed to
be EXP (experimental). A note about the origin is made in “Comments” • EPISUITE database: Biodegradation from this reference is evaluated on the basis of
data from EPISUITE algorithms RELEASE ESTIMATION Based on the known properties, uses and functions of a substance, emission factors for various life-cycle stages are chosen from a database with default values. Daily emission rates are subsequently calculated using either again default values or specific emission models. EUSES operates with 16 different Industry Categories (IC) and 56 different Use Cate-gories (UC) with reference to use pattern. The different categories determine the magni-tude and pattern of release, distribution and exposure to humans and the environment. For every use pattern, the emission input data must be specified, consisting of Industrial Category, Use Category and (if appropriate) extra details on Use Category, and the frac-tion of tonnage for each application. Furthermore, it needs to be indicated here which stages of the life cycle are relevant for the current use pattern in the assessment. If rele-vant for the following stages of the life cycle, i.e. production, formulation and process-ing, the Main Category may be specified (otherwise a default value is used). Releases to the environment can take place at any stage of the life cycle of a chemical substance. The life cycle is split up in six stages: 1. Production is the stage in which the substance is manufactured, i.e. formed by
chemical reaction(s), isolated, purified, drummed or bagged, etc. 2. Formulation is the stage in which chemicals are combined in a process of blending
and mixing to obtain a product or a preparation. 3. Industrial use. The processing stage consists of all kinds of processes whereby the
substance as such, as a formulation or as an article containing the substance assessed is applied or used. The substance may be used as a processing aid or be incorporated in a product.
4. Private use. This stage considers the use and application of substances (as such or in
formulations) on the scale of households.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 29
5. Service life. A substance might be released during the life span of an article in
which it is present. Release may be caused by diffusion, leaching or abrasion 6. Waste treatment (disposal). At the stage of disposal, the substance (or the products
containing the substance) is disposed of with waste or waste water. Waste water may be treated in a sewage treatment plant. Waste materials may be incinerated or dumped. At the stage of disposal, recovery to the environment may take place. For some Industrial Categories, recovery was considered.
ENVIRONMENTAL DISTRIBUTION This module contains all the models necessary to estimate the distribution of a sub-stance in the environment at the appropriate spatial scale. End-points are concentrations in the relevant environmental compartments (air, surface water, marine water, sediment, soil and groundwater). EXPOSURE ASSESSMENT Based on estimated environmental concentrations, this module calculates the exposure levels for predating birds and mammals (through fish and earthworms) and humans. For humans, exposure through the environment can be estimated as well as exposure through consumer products, including biocides, and exposure at the workplace.
4.4 Update of database and list (Task 4)
The major objective of this task was to report the study in a way that enables the Com-mission to make the results available at the Commission’s Endocrine Disrupters Web-site. The reporting included written reports and revision of the database and list of the sub-stances categorized in the BKH 2000 and RPS-BKH 2002 reports, to include those categorized in the present study and make the information and list available in Access, Excel and PDF formats. Furthermore, a DHI homepage was prepared (http://projects.dhi.dk/Endocrine_Disrupter/testsite/). in which the work progress was presented together with the possibility get access to the existing version of the database. A link to the DHI homepage was placed on the ECB homepage (http://ec.europa.eu/environment/endocrine/strategy/substances_en.htmon) allowing third party to follow the progress in the project. Meetings In order to ensure close co-operation with the Commission, four meetings were planned with the following issues: 1. Kick-off meeting. 17 November 2005. Minutes from the meeting are presented in
Appendix A 2. Discussion of list of substances to be evaluated. 15 March 2006. Minutes from the
meeting are presented in Appendix B 3. Discussion of interim report. 29 June 2006. Minutes from the meeting are presented
in Appendix C
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 30
4. Discussion of draft final deliverables, i.e. report, database and list. 8 December 2006. Minutes from the meeting are presented in Appendix D
5 RESULTS
5.1 Identification of relevant stakeholders (Task 1)
The questionnaire was sent to 160 potential stakeholders both by mail and by e-mail in December 2005. Two letters and 5 e-mails were returned with a message on delivery failure. Thus, in total, the request was sent to approx. 155 people and organisations. Although the deadline for response was 1 February 2006, quite many did not respond before late February/early March. A total of 34 stakeholders responded to the question-naire. This means that the answer percentage was approx. 22%, which is considered ac-ceptable. Most of the responses received were kind replies that the questionnaire was received but that no further data could be provided (65%). However, among the replies, in which new information and data were provided, a total of 22 new substances has been suggested for addition to the list and thus to be evaluated in the present project. Due to financial issues in connection with accommodations and travel expenses, it was decided at the interim report meeting (29 June 2006) not to have a physical meeting in connection with the draft final deliverables but instead have web-based responses from stakeholders to the draft final report and database. The stakeholders and experts con-tacted for written consultation were thus invited to go through the draft final report and the collected data on the selected CAT 1 substances evaluated in the present study. The list of stakeholders and experts contacted are presented in Appendix E. The group of stakeholders for consultation at meeting are indicated as shaded names in Appendix A.
5.2 Identification of new candidate LPVC for further evaluation of their endocrine disrupting properties (Task 2)
The questionnaire for identification of new candidate LPVC with potential endocrine disrupting effects is presented in Appendix F. As the amount of information, which followed the suggested new substances, was quite diverse (from just a CAS No. to detailed information about the substances including at-tached references about EDC effects), it was decided to include all suggested chemicals in the present study and perform the evaluation on these as on the rest of the priority substances. The suggested substances to be added to the list are shown in Table 5.1.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 31
Table 5.1 New candidate substances identified by stakeholders
556-67-2 Cyclotetrasiloxane HPV 81-14-1 1-tert-Butyl-3,5-dimethyl-2,6-dinitro-4-
acetylbenzene LPV
1222-05-5 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyrane
HPV
13171-00-1 4-Acetyl-1,1-dimethyl-6-tert.-butylindane LPV 5466-77-3 2-Ethyl-hexyl-4-methoxycinnamate HPV 118-56-9 3,3,5-Trimethyl-cyclohexyl salicilate LPV 21245-02-3 2-Ethyl-hexyl-4-dimethyl-aminobenzoate LPV 36861-47-9 3-(4-Methylbenzylidene)camphor LPV 131-57-7 2-Hydroxy-4-methoxy-benzophenone LPV 99-96-7 p-Hydroxybenzoic acid LPV 99-76-3 Methyl p-Hydroxybenzoate LPV 120-47-8 Ethyl 4-hydroxybenzoate LPV 94-13-3 n-Propyl p-hydroxybenzoate LPV 15087-24-8 3-Benzylidene camphor (3-BC) LPV 131-55-5 Benzophenone-2 (Bp-2), 2,2',4,4'-
tetrahydroxybenzophenone LPV
10043-35-3 Boric acid HPV 1582-09-8 Trifluralin HPV 100-02-7 4-Nitrophenol HPV 106-44-5 4-Nitro-3-phenylphenol HPV 33704-61-9 6,7-Dihydro-1,1,2,3,3-pentamethyl-4(5H)indanone Neither LPV nor HPV 94-26-8 n-Butyl p-Hydroxybenzoate Neither LPV nor HPV 2581-34-2 3-Methyl-4-nitrophenol Neither LPV nor HPV
During a thorough evaluation of the candidate list to be evaluated in the present study (173 substances from the ordinary list + 22 new candidate substances) it was found that several substances were not included in the ECB-ESIS database and thus not considered as relevant for evaluation of their endocrine disrupting effects as they probaply are not in use any longer. It was also found that a few of the substances were HPVC and that the majority of the substances were neither HPVC nor LPVC. They are existing sub-stances but produced or imported in amounts ≤10 tons per year. Based on this information, it was decided that the present work should only include HPVC and LPVC plus existing substances registered in the ECB-ESIS database al-though they were produced or imported in amounts ≤10 tons per year. Based on a close evaluation of the candidate substances list including the 22 new substances added by the written stakeholders (195 substances), the substances were divided into the following subgroups: 1. Current LPVC (26 substances) and HPVC (10 substances) according to ECB-ESIS 2. Substances found on ECB-ESIS list but neither LPVC nor HPVC (production vol-
ume < 10 ton/year) (73 substances) 3. Substances not found on ECB-ESIS list and therefore excluded from the evaluation
(73 substances) 4. Substances with no CAS number and therefore excluded from the evaluation (15
substances) For substances in Categories 3 and 4, it was decided to contact CEFIC to ask if they had any knowledge whether the substances are still produced and if yes in which amounts.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 32
The request to CEFIC is presented in Appendix G. No answer from CEFIC was ob-tained on either this specific request or the request for identification of new candidate substances. No cooperation with the industry, e.g. identification of new ED substances, availability of ED data on substances placed on the candidate list or information about substances without CAS numbers, was thus obtained. The revised list of priority substances is presented in Appendix I.
5.3 Collection and evaluation of data/information on LPVC to estab-lish priorities for further evaluation of their role in endocrine disruption (Task 3)
5.3.1 Evaluation of endocrine potential (Task 3.2) The tender from the Commission and the proposal submitted by DHI clearly stated the data evaluation to be performed was given. I.e., “Starting points are the methodology used in the RPS-BKH report (2002) and the database including the candidate substances which were identified in the BKH report of 2000, with data from background docu-ments. The methodological approaches and evaluation of the selected substances with respect to endocrine disrupter potency towards humans and wildlife will be elaborated by the project team.” The evaluation of endocrine disrupting potential was based on the following screening criteria: 1. Relevance of test parameter (with aspects such as endocrine specific effects in con-
trast to general toxicity (teratogenic effects)) 2. Test reliability (validated protocols; experimental design; suitability, health and life
stage of test species; statistics. Ranked indication of Data Quality (DQ 1-4). DQ: Good Data Quality, fulfilling all (important) criteria; DQ2: Sufficient Data Quality, study fulfilling most of the (important) criteria; DQ3: Insufficient Data Quality, study cannot be used for identification; and DQ4: Not evaluated
3. Dose-response relationship or indications of effect thresholds 4. Endocrine disruption potency (including a categorization of the chemicals into three
groups: 1. Evidence for endocrine disrupting (ED) effect; 2. Potential ED effect; 3. No evidence for ED effect)
5. Comparison with systemic toxicity (Standard toxicity data – NOECs/LOECs, E(L)C50s, NOALs/LOAELs from RTECS and HSDB.
As indicated in Section 4.3.1, literature was searched in different databases to obtain in-formation on endocrine disruption effects and systemic toxicity. Additionally, informa-tion was provided by stakeholders on 22 substances. All information from these sources was evaluated and incorporated in the EDS database. A thorough literature search was thus performed but mainly the abstracts were evaluated. In cases, in which the informa-tion obtained from the abstracts was not sufficient for categorisation of the individual substance, a primary reference check was performed (the original article was pur-chased). In the database, the abstracts are found in the remark field. The abstracts were evaluated according to the screening criteria described and an evaluated extract of the effects obtained are reflected in the ‘effect field’.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 33
As the outcome from the present study shall be comparable to the outcome from the 2002 work and end up with a priority list of CAT 1 candidates the same methodology as the one one developed in the previous work performed by RPS-BKH 2002 was used. The categorisation of the substances was performed according to the following evalua-tion criteria:
CAT 1 At least one in-vivo study providing clear evidence for endocrine disruption in an intact organism.
CAT 2 Potential for endocrine disruption. In-vitro data indicating potential for endocrine disruption in intact organisms. Also includes effects in-vivo that may, or may not, be ED-mediated.
CAT 3a No scientific basis for inclusion in list (ED studies available but no indications of ED effects)
CAT 3b Substances with no or insufficient data gathered
In the database, several studies are included and evaluated according to the screening criteria but only one study was selected as the key study and the categorisation of the substance was thus mainly based on the key study. It shall however, be emphasized that the amount of evidence provided by other studies not selected as key studies has influ-enced the conclusions for categorisation as well. The choice of categories was made solely by the consultant, and apart from the clear evaluation criteria for the categories given above, it may thus be regarded as subjective. As the present study is based on a screening of available data on the substances on the priority list (a total of 107 substances) and as the quality of the available data is not standardised but quite diverse, a description of a more standardised procedure than the one given above is not possible. When it comes to a future, in-depth evaluation of the selected CAT 1 candidates, the methodology for characterising the substances as having endocrine disrupting properties shall be well defined and fully transparent. Furthermore, it shall be clearly stated how the priority list can be developed as an iterative list. It shall thus be possible to enter chemicals as well as take out chemicals from the priority list based on sufficient weight of evidence evaluated case by case. As a starting point, a total of 195 substances were evaluated. An overview of the evalua-tion and the final categorisation is presented in Table 5.2.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 34
Table 5.2 Overview of the evaluation and the final categorisation
Category Substance identification Number of substances Remaining substances on the Candidate list 173 Stakeholder-identified substances 22 Total 195
LPVC 26 HPVC 10 Neither LPVC nor HPVC 73 Substances not in ESIS database 73 Substances with no CAS No. 15 Substances included in the present evaluation 107
CAT 1 At least one study providing evidence for endo-
crine disruption in an intact organism 34
CAT 2 Potential for endocrine disruption. In-vitro data indicating potential for endocrine disruption in intact organisms.
21
CAT 3a No scientific basis for inclusion in list (ED studies available but no indications of ED effects)
4
CAT 3b Substances with no or insufficient data gathered 48 The human health effects resulting in CAT 1 substances were selected on a wide range of endocrine disrupting effects as presented in Table 5.3. The main effects were effects on uterus-, testes- or other sex organ weight, effect on sperm development, effects on progeny and effects on sex hormone and levels. Information on wildlife ED effects is relatively scarce and when wildlife effects were used as decisive for a CAT 1 conclu-sions, these effects were mainly ED-effects on fish, e.g. an in-vivo Vitellogenin re-sponse. The effects resulting in CAT 2 substances are as CAT 1 substances based on a wide range of endocrine disrupting effects but solely based on in-vitro data as presented in Table 5.4.
35ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Tab
le 5
.3
ED
effe
cts
obse
rved
in C
ateg
ory
1 su
bsta
nces
. Hum
an [H
H] a
nd w
ildlif
e [W
L] r
elat
ed d
ata
CA
SN
R
NA
ME
Q
ualif
ying
rem
arks
_HH
Q
ualif
ying
rem
arks
_WL
1004
3-35
-3
Bor
ic a
cid
Rat
in v
ivo
stud
y: A
fter
a 4-
wk
adm
inis
trat
ion
by g
avag
e, te
stis
an
d ep
idid
ymis
wts
. wer
e de
crea
sed
in th
e 30
0 an
d 50
0 m
g/kg
gr
oups
Am
phib
ian
in v
ivo
stud
y: B
oric
aci
d ex
erte
d re
prod
uctiv
e to
xici
ty in
Xen
opus
laev
is +
tra
nsge
nera
tiona
l tox
icity
to th
e de
velo
ping
pro
geny
. 10
4-40
-5
4-N
onyl
phen
ol (
4-N
P)
Rat
in v
ivo
stud
y: U
terin
e w
eigh
t, ut
erin
e/bo
dy w
eigh
t sig
nifi-
cant
ly in
crea
sed
in 9
0 m
g/kg
and
120
mg/
kg g
roup
s an
d a
dose
-res
pons
e re
latio
nshi
p w
as o
bser
ved.
Fis
h in
viv
o st
udy:
Indu
ctio
n of
VT
G. L
OE
C=
24.
8 ug
/l
1113
-02-
6 O
met
hoat
e M
ice
in v
ivo
stud
y: In
crea
se in
bod
y w
t. an
d de
crea
sed
test
icle
w
t. T
he a
ctiv
ities
of A
KP
, AC
P, L
DH
in m
ouse
test
icle
s si
gnifi
-ca
ntly
incr
ease
d co
mpa
red
with
the
cont
rol.
No
or in
suff
icie
nt d
ata
gath
ered
1131
-60-
8 4- C
yclo
hexy
lphe
nol
Rat
in v
ivo
stud
y: U
tero
trop
hic
assa
y. In
crea
sed
uter
ine
wei
ght.
LOA
EL=
200
mg/
kg
No
or in
suff
icie
nt d
ata
gath
ered
120-
47-8
et
hyl
4-
hydr
oxyb
enzo
ate
Rat
and
mic
e in
viv
o st
udy:
Incr
ease
d ut
erin
e w
eigh
t in
imm
a-tu
re a
nd o
varie
ctom
ized
ani
mal
s. E
D50
18-
74 µ
mol
/ kg
body
w
eigh
t
Fis
h in
viv
o st
udy.
VT
G in
duct
ion
in r
ainb
ow tr
outs
. LO
AE
L=10
0 m
g/kg
131-
18-0
D
i-n-
pent
ylph
thal
ate
(DP
P)
=
Dip
enty
lpht
hala
te
Mic
e in
viv
o st
udy:
A c
ontin
uous
bre
edin
g pr
otoc
ol w
as u
tiliz
ed
to e
xam
ine
the
repr
oduc
tive
toxi
city
of d
i-n-p
enty
l pht
hala
te
(DP
P).
DP
P w
as to
xic
to th
e re
prod
uctiv
e sy
stem
as
evid
ence
d by
a c
ompl
ete
inhi
bitio
n of
fert
ility
at 1
.25
and
2.5%
DP
P a
nd
redu
ced
fert
ility
(lit
ter
size
)
No
or in
suff
icie
nt d
ata
gath
ered
131-
55-5
B
enzo
phen
one-
2 (B
p-2)
, 2,2
',4,4
'-te
trah
ydro
xybe
n-zo
phen
one
Rat
in v
ivo
stud
y: In
crea
sed
rat u
terin
e w
eigh
ts. E
D10
=54
4.6
mg/
kg b
ody
wei
ght/d
ay
Fis
h in
viv
o st
udy:
Dos
e re
spon
se r
elat
ed V
TG
indu
ctio
n.
LOE
C =
878
3 m
g/L
131-
56-6
2,
4-D
ihyd
roxy
benz
o-ph
enon
= R
es-
benz
ophe
none
Rat
in v
ivo
stud
y: B
enzo
phen
one
(Bp)
-1 in
crea
sed
uter
ine
wt.
in im
mat
ure
rats
. Fur
ther
mor
e, b
enzo
phen
one-
1 (B
p-1)
was
in
a pr
evio
us in
vitr
o ex
perim
ent (
MC
F-7
cel
ls)
show
n to
hav
e cl
ear
estr
ogen
ic a
ctiv
ity (
EC
-50:
2.0
8 uM
)
Fis
h in
viv
o st
udy:
Aqu
atiic
exp
osur
e of
fath
ead
min
now
w
ith B
P1
indu
ced
vite
lloge
nin
sign
ifica
ntly
at 4
919
mg/
l
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at in
viv
o st
udy:
Dec
reas
ed m
ale
anog
enita
l dis
tanc
e an
d in
crea
sed
inci
denc
e of
fetu
ses
with
und
esce
nded
test
es.
LOA
EL=
250
mg/
kg b
ody
wei
ght/d
ay
No
or in
suff
icie
nt d
ata
gath
ered
1359
3-03
-8
Qui
nalp
hos
=
Chi
nalp
hos
In v
ivo
rat s
tudy
: Sub
leth
al c
hron
ic a
dmin
istr
atio
n of
qui
nalp
hos
resu
lted
in: d
ecre
ased
test
icul
ar m
ass
and
AC
hE a
ctiv
ity in
ce
ntra
l as
wel
l as
perip
hera
l org
ans;
incr
ease
d se
rum
LH
, F
SH
, pro
lact
in, a
nd te
stos
tero
ne c
oncn
s.; d
ecre
ased
pitu
itary
or
incr
ease
d te
stic
ular
AC
E. E
d 7-
14 m
g/kg
/da
y.
Fis
h in
viv
o st
udy:
Impa
irmen
t of
test
is fu
nctio
n du
e to
the
inhi
bitio
n of
ste
roid
ogen
ic e
nzym
es a
ctiv
ities
. EC
=0.
025
mg/
L
36ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
Q
ualif
ying
rem
arks
_HH
Q
ualif
ying
rem
arks
_WL
1508
7-24
-8
3-B
enzy
liden
e ca
mph
or (
3-B
C)
Rat
in v
ivo
stud
y: In
crea
se in
ute
rus
wei
ght.
LOE
D =
2 m
g/kg
bo
dy w
eigh
t.day
F
ish
in v
ivo
stud
y: V
itello
geni
n in
duct
ion.
ED
10, E
D50
and
E
D90
of 3
-ben
zylid
ene
cam
phor
afte
r 6
days
(2
inje
ctio
ns)
wer
e 6.
4, 1
6 an
d 26
mg/
kg/in
ject
ion,
res
p 15
82-0
9-8
Trif
lura
lin
In v
ivo
ewe
stud
y. C
once
ntra
tions
of e
stra
diol
wer
e si
gnifi
-ca
ntly
incr
ease
d in
ew
es g
iven
trifl
ural
in. N
o ef
fect
on
thyr
oxin
e co
ncen
trat
ion.
Mea
n se
rum
con
cent
ratio
ns o
f LH
wer
e m
ark-
edly
dec
reas
ed b
y tr
iflur
alin
, and
bas
al L
H c
once
ntra
tions
wer
e si
gnifi
cant
ly d
ecre
ased
. Onl
y on
e do
sis
(17.
5 m
g/kg
2 ti
mes
pe
r w
eek)
was
inve
stig
ated
Fis
h in
viv
o st
udy:
Pitu
itary
effe
cts
- po
ssib
ly in
dire
ct e
ffect
of
exp
osur
e.
1634
-04-
4 m
ethy
l ter
tiary
bu
tyl e
ther
(M
TB
E)
Rat
in v
io s
tudy
: Inc
reas
e of
test
is w
eigh
t. In
ters
titia
l flu
id a
nd
seru
m te
stos
tero
ne le
vels
as
wel
l as
seru
m p
rola
ctin
leve
ls
wer
e de
crea
sed
only
in a
nim
als
trea
ted
with
150
0 m
g M
TB
E/k
g/da
y fo
r 15
day
s.
Am
phib
ian
in v
ivo
stud
y: A
ccel
arat
ed d
evel
opm
ent a
nd e
ar-
lier
met
amor
phos
is. L
OE
C<
2500
mg/
L
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
ni-
sole
(B
HA
)
In v
ivo
rat s
tudy
. In
one-
gene
ratio
n ra
ts, s
ex r
atio
of m
ale
was
de
crea
sed
and
the
anog
enita
l dis
tanc
es w
ere
shor
tene
d an
d va
gina
l pat
ency
and
pre
putia
l sep
arat
ion
wer
e ob
serv
ed la
ter
than
con
trol
gro
up. A
lso,
BH
A d
ecre
ased
spe
rm m
otili
ty a
nd
num
ber
and
the
wid
th a
nd le
ngth
. LO
EL=
10 m
g/kg
bod
y w
eigh
t/day
Fis
h in
viv
o st
udy:
Incr
ease
d vi
tello
geni
n sy
nthe
sis.
E
C50
=14
.14
ug/L
2719
3-28
-8
Phe
nol,
(1,1
,3,3
-te
tram
ethy
lbut
yl)-
=
Oct
ylph
enol
Rat
in v
ivo
stud
y. R
educ
ed s
perm
cou
nts
resu
lting
from
low
-er
ed p
lasm
a te
stos
tero
ne in
mal
e ra
ts ju
st a
fter
pube
rty.
ED
=3
mg/
kg b
ody
wei
ght.d
ay
Fis
h in
viv
o st
udy.
VT
G in
duct
ion
+ in
ters
ex g
onad
s.
LOE
C=
11.4
ug/
L
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
ame-
thyl
cycl
otet
rasi
-lo
xane
- 2
,6-c
is-
[(P
hMe-
SiO
)2(M
e2S
iO)2
][
In v
ivo
rat s
tudy
. Inh
ibite
d fe
rtili
ty a
nd a
ltera
tions
in m
easu
red
char
acte
ristic
s of
the
ejac
ulat
e. L
OA
EL=
0.5
mg/
kg/d
ay
No
or in
suff
icie
nt d
ata
gath
ered
3686
1-47
-9
3-(4
-M
ethy
lben
-zy
liden
e)ca
mph
or
Rat
in v
ivo
stud
y. D
elay
ed m
ale
pube
rty,
and
dos
e-de
pend
ently
affe
cted
rep
rodu
ctiv
e or
gan
wts
. of a
dult
mal
e an
d fe
mal
e F
1 of
fspr
ing,
with
par
tly d
iffer
ent e
ffect
pat
tern
s. T
hy-
roid
wt.
was
incr
ease
d by
hig
her
4-M
BC
dos
es. L
OA
EL=
7 m
g/kg
/day
Am
phib
ian
in v
ivo
stud
y.T
he r
ate
of m
etam
orph
osis
was
not
af
fect
ed, a
nd n
o ob
viou
s di
ffere
nces
in b
ody
and
tail
leng
th
com
pare
d to
con
trol
s w
ere
obse
rved
.
4376
-20-
9 M
ono
2 et
hyl
hex
-yl
phth
alat
e (M
EH
P)
Rat
in v
ivo
stud
y. S
igni
fican
tly d
ecre
ased
bod
y w
eigh
ts a
nd
mot
ile s
perm
s. L
OA
EL=
250
mg/
kg b
ody
wei
ght/d
ay
No
or in
suff
icie
nt d
ata
gath
ered
37ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
Q
ualif
ying
rem
arks
_HH
Q
ualif
ying
rem
arks
_WL
50-1
8-0
Cyc
loph
os-
pham
ide
Rat
in v
ivo
assa
y: D
ecre
ased
ova
rian
and
uter
in w
eigh
t and
re
duct
ion
seru
m e
stra
diol
and
pro
gest
eron
e. L
OA
EL=
50 m
g/kg
bo
dy w
eigh
t
No
or in
suff
icie
nt d
ata
gath
ered
5466
-77-
3 2-
ethy
l-hex
yl-4
-m
etho
xyci
nna-
mat
e
Rat
in v
ivo
assa
y. U
terin
e w
t. w
as d
ose-
depe
nden
tly in
crea
sed
by O
MC
(E
D50
935
mg/
kg/d
ay)
Fis
h in
viv
o as
say.
Incr
ease
in p
lasm
a V
TG
+ a
nd in
-cr
ease
d m
RN
A e
xpre
ssio
n le
vels
of e
stro
gen
rece
ptor
(E
R)
alph
a, a
mon
g se
x ho
rmon
e re
cept
ors
in th
e liv
er.
556-
67-2
C
yclo
tetr
asilo
x-an
e R
at in
viv
o as
say.
Ute
rotr
ophi
c as
say
with
two
spec
ies:
Rel
a-tiv
e ut
erin
e w
ts. a
nd u
terin
e ep
ithel
ial c
ell h
eigh
t wer
e st
atis
ti-ca
lly s
igni
fican
tly in
crea
sed
in b
oth
stra
ins
of r
ats
at d
oses
ab
ove
100
mg/
kg/d
ay. L
OA
EL=
250
mg/
kg/d
ay
No
or in
suff
icie
nt d
ata
gath
ered
611-
99-4
4,
4'-
Dih
ydro
xybe
nzo-
phen
on
rat i
n vi
vo a
ssay
: Ind
uced
ute
rotr
ophy
and
exe
rted
bot
h es
tro-
gen
agon
istic
effe
ct a
nd r
educ
ed th
e es
trog
enic
effe
ct o
f eth
y-ny
lest
radi
ol
Fis
h in
viv
o as
say:
VT
G r
espo
nse.
In v
itro:
Ful
l dos
e-re
spon
se c
urve
s in
in v
itro
assa
y (r
ecom
bina
nt y
east
car
ry-
ing
the
estr
ogen
rec
epto
r of
rai
nbow
trou
t (rt
ER
a)).
In v
ivo:
V
TG
res
pons
e 61
64-9
8-3
Chl
ordi
mef
orm
In
viv
o ra
t stu
dy. D
elay
in b
reed
ing
and
a si
gnifi
cant
red
n. in
lit
ter
size
. ED
=50
mg/
kg.
No
or in
suff
icie
nt d
ata
gath
ered
7400
-08-
0 p-
Cou
mar
ic a
cid
(PC
A)
Rat
in v
ivo
assa
y: 1
89 a
nd 2
01%
thyr
oid
wts
incr
ease
com
-pa
red
to c
ontr
ol v
alue
. hyr
oid
lesi
ons
in p
-cou
mar
ic a
cid
grou
p w
ere
asso
cd. w
ith s
igni
fican
t inc
reas
es in
cel
lula
r pr
olife
ratio
n as
indi
cate
d b
y [3
H]th
ymid
ine
inco
rpor
atio
n. In
add
n., t
he g
oi-
trog
enic
effe
ct o
f p-c
oum
aric
aci
d w
as fu
rthe
r co
nfirm
ed b
y si
gnifi
cant
dec
reas
es (
50%
) in
ser
um tr
iiodo
thyr
onin
e (T
3) a
nd
thyr
oxin
e (T
4), a
nd a
par
alle
l inc
reas
e (9
0%)
in s
erum
TS
H
com
pare
d to
con
trol
gro
up. E
D=
0.25
mm
ol/k
g/da
y
No
or in
suff
icie
nt d
ata
gath
ered
77-0
9-8
3,3'
-Bis
(4-
hydr
oxy-
phen
yl)p
htha
lid =
P
heno
lpht
hale
ine
Rat
and
mic
e in
viv
o st
udy.
Exp
osur
e of
mic
e to
phe
nolp
htha
l-ei
n in
feed
for
2 ye
ars
resu
lted
in in
crea
sed
inci
denc
es o
f at
ypic
al h
yper
plas
ia o
f the
thym
us in
mal
es a
nd fe
mal
es, d
e-ge
nera
tion
of th
e ge
rmin
al e
pith
eliu
m o
f the
test
is in
mal
es,
and
ovar
ian
hype
rpla
sia
in fe
mal
es. L
OA
EL=
300
mg/
kg
No
or in
suff
icie
nt d
ata
gath
ered
77-4
0-7
2,2-
Bis
(4-
hydr
oxyp
heny
l)-n-
buta
n =
Bis
phen
ol
B
In v
ivo
imm
atur
e ra
t ute
rotr
ophi
c as
say:
Pos
itive
res
pons
e in
th
e ut
erot
roph
ic a
ssay
. Dos
e re
pons
e re
latio
nshi
p (0
, 2, 2
0 an
d 20
0 m
g/kg
)
No
or in
suff
icie
nt d
ata
gath
ered
92-6
9-3
4- Hyd
roxy
biph
enyl
=
4-P
heny
lphe
nol
Rat
in v
ivo
assa
y: U
tero
trop
hic
assa
y an
d C
albi
ndin
-D9k
(C
aBP
-9K
) m
RN
A e
xpre
ssio
n w
ere
exam
d. in
ova
riect
omiz
ed
Spr
ague
-Daw
ley
fem
ale
rats
. 4-
phen
ylph
enol
pro
duce
d do
se-
depe
nden
t (10
, 50,
200
, and
400
mg/
kg/d
ay(
incr
ease
s in
the
uter
ine
wts
. of o
varie
ctom
ized
rat
s). L
OA
EL=
200
mg/
kg/d
ay
No
or in
suff
icie
nt d
ata
gath
ered
38ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
Q
ualif
ying
rem
arks
_HH
Q
ualif
ying
rem
arks
_WL
92-8
8-6
4,4'
-D
ihyd
roxy
bi-
phen
yl =
4,4
'-B
iphe
nol
Rat
in v
ivo
stud
y. R
at u
tero
trop
hic
assa
y. U
terin
e w
eigh
t in-
crea
se. L
OA
EL=
60 m
g/kg
bod
y w
eigh
t/day
. In
vitr
o st
udy.
Rec
ombi
nant
yea
st a
ssay
for
trou
t ER
and
tr
out h
epat
ocyt
e cu
lture
s. C
ompe
titiv
e bi
ndin
g to
ER
94-1
3-3
n-pr
opyl
p-
hydr
oxyb
enzo
ate
In v
ivo
rat a
ssay
: The
epi
didy
mal
spe
rm r
eser
ves
and
conc
en-
trat
ions
dec
reas
ed d
ose
depe
nden
tly a
nd th
e di
ffere
nce
was
si
gnifi
cant
at d
oses
of 0
.1%
and
abo
ve. L
OA
EL=
0.1%
Fis
h in
viv
o as
say:
Cle
ar d
ose
resp
onse
incr
ease
in V
TG
re
spon
se. E
D50
= 2
2 m
g kg
-1 2
-d. N
OE
C =
225
mg/
L
94-2
6-8
n-B
utyl
p-
Hyd
roxy
benz
oate
In
viv
o m
ice
stud
y. A
dos
e-de
pend
ent d
ecre
ase
of b
oth
roun
d an
d el
onga
ted
sper
mat
id o
unts
in s
tage
s V
II-V
III s
emin
ifero
us
tubu
les
was
obs
erve
d, a
nd th
e el
onga
ted
sper
mat
id c
ount
s w
ere
sign
ifica
ntly
low
er in
all
of th
e tr
eate
d gr
oups
. The
ser
um
test
oste
rone
con
cent
ratio
n de
crea
sed
in a
dos
e-de
pend
ent
fash
ion
and
was
sig
nific
ant a
t 1.0
0%. L
OA
EL=
1504
mg/
kg
body
wei
ght.
Day
Rai
nbow
trou
t in
vivo
stu
dy. V
itello
geni
n re
spon
se. L
OE
D:
oral
exp
osur
e to
9 m
g bu
tylp
arab
en k
g-1
2d-1
96-1
2-8
Dib
rom
ochl
oro-
prop
ane
(DB
CP
) E
xpos
ed h
uman
wor
kers
. Azo
ospe
rmia
olig
ospe
rmia
and
do
se-d
epen
dent
cha
nge
in F
SH
, LH
and
test
icle
siz
e N
o or
insu
ffic
ient
dat
a ga
ther
ed
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
In v
ivo
rat a
ssay
: Alte
ratio
n in
thyr
oid
func
tion
and
a si
gnifi
cant
ch
ange
in th
yroi
d m
orph
ol (
125
and
625
ppm
) .
NO
EC
= 2
5 pp
m
Am
phib
ian
in v
ivo
assa
y: In
a s
tand
ardi
sed
ringt
este
d te
st
prop
osal
(X
enop
us m
etam
orph
osis
ass
ay)
and
five
diffe
rent
E
TU
con
cns.
(5,
10,
25,
50,
and
100
mg/
L) a
con
cn.-
depe
nden
t inh
ibiti
on o
f met
amor
phos
is w
as o
bsd.
99
-76-
3 M
ethy
l p-
Hyd
roxy
benz
oate
In
viv
o m
ice
assa
y: T
he h
ighe
st M
ePbe
n do
se (
165
mg/
kg)
was
abl
e to
pro
duce
ute
rotr
ophi
c ef
fect
s (3
8 to
76%
) co
mpa
red
to E
-2 e
fect
s (1
00%
). L
OA
EL=
165
mg/
kg
No
or in
suff
icie
nt d
ata
gath
ered
99-9
6-7
p-H
ydro
xybe
nzoi
c ac
id
Rat
in v
ivo
assa
y: D
ose-
depe
nden
t res
pons
e (0
.5, 5
, 50,
and
50
0 g/
kg)
on v
agin
al c
orni
ficat
ion
and
uter
otro
phic
act
ivity
in
both
imm
atur
e an
d ad
ult o
varie
ctom
ized
mic
e.
No
or in
suff
icie
nt d
ata
gath
ered
39ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Tab
le 5
.4
ED
effe
cts
obse
rved
in C
ateg
ory
2 su
bsta
nces
. Hum
an [H
H] a
nd w
ildlif
e [W
L] r
elat
ed d
ata
CA
SN
R
NA
ME
Q
ualif
ying
rem
arks
_HH
Q
ualif
ying
rem
arks
_WL
100-
02-7
4-
nitr
ophe
nol
In v
itro
assa
y: A
nti-a
ndro
geni
city
in a
ll fo
ur n
itrop
heno
ls in
clud
-in
g 4-
nitr
ophe
nol.
No
or in
suff
icie
nt d
ata
gath
ered
106-
44-5
p-
cres
ol
in v
itro
assa
y: A
nti-a
ndro
geni
city
in a
ll fo
ur n
itrop
heno
ls in
clud
-in
g 4-
nitr
ophe
nol i
nclu
ding
4-n
itro-
3-ph
enyl
phen
ol (
P-c
reso
l).
No
or in
suff
icie
nt d
ata
gath
ered
121-
29-9
P
yret
hrin
In
viv
o m
ice
assa
y: S
igni
fican
t per
cent
age
of s
perm
abn
orm
ali-
ties.
LO
AE
L=45
mg/
kg b
ody
wei
ght.
Wea
k en
docr
ine
effe
ct.
No
or in
suff
icie
nt d
ata
gath
ered
131-
16-8
D
i-n-
prop
ylph
thal
ate
(Dpr
P)
=
Dip
ropy
lpht
hala
te
In v
itro
mic
e st
udy.
Rep
rodu
ctio
n/te
rato
geni
c ef
fect
s. 4
4% r
e-du
ctio
n in
the
num
ber
of li
ve p
ups
per
litte
r. H
ighe
st d
ose
grou
p (8
.63
g/kg
) st
erile
No
or in
suff
icie
nt d
ata
gath
ered
131-
54-4
2,
2'-D
ihyd
roxy
-4,
4'-
dim
etho
xybe
nzo-
phen
on
In v
itro
assa
y: C
ompa
red
with
the
vehi
cle
cont
rol 2
,2’-
Dih
ydro
xy-
4,4’
-dim
etho
xybe
nzop
heno
ne s
how
ed p
ositi
ve e
f-fe
ct in
theM
CF
-7 c
ell p
rolif
erat
ion
assa
y.
No
or in
suff
icie
nt d
ata
gath
ered
131-
57-7
2-
hydr
oxy-
4-m
etho
xy-
benz
ophe
none
In v
itro
test
.: H
MB
at a
low
-tox
ic le
vel (
0.25
mM
) in
the
hepa
to-
cyte
sus
pens
ions
was
con
vert
ed e
nzym
atic
ally
to 2
,4-
dihy
drox
yben
zoph
enon
e (D
HB
). D
HB
at c
once
ntra
tions
from
10
-8 to
10-
6 M
cau
sed
a co
ncen
trat
ion-
depe
nden
t pro
lifer
atio
n of
MC
F-7
cel
ls. H
ydro
xyla
ted
inte
rmed
iate
s su
ch a
s D
HB
ra
ther
than
the
pare
nt c
ompo
und
act a
s a
xeno
estr
ogen
via
bi
otra
nsfo
rmat
ion.
Rec
ombi
nant
yea
st c
arry
ing
the
estr
ogen
rec
epto
r of
rai
n-bo
w tr
out (
rtE
Ra)
was
use
d. R
elat
ivel
y lo
w a
ctiv
ity o
f ben
-zo
phen
one-
3 w
as d
etec
ted
1400
7-30
-8
2,2-
Bis
(4-
hydr
oxyp
heny
l)-n-
hexa
ne
Rat
in v
ivo
assa
y: C
orni
ficat
ion
of v
agin
al e
pith
eliu
m. L
O-
AE
L=25
mg/
anim
al. V
ery
old
refe
renc
e N
o or
insu
ffic
ient
dat
a ga
ther
ed
1806
-29-
7 2,
2'-
Dih
ydro
xybi
-ph
enyl
= 2
,2'-
Bip
heno
l
in v
ivo
rat a
ssay
: Inc
reas
e ut
erus
gly
coge
n. L
OA
EL=
40 m
g/kg
2,
2'-B
iphe
nol s
how
ed a
ver
y w
eak
estr
ogen
ic a
ctiv
ity, r
e-qu
ring
> 1
0.00
0 fo
ld e
xces
s co
ncen
trat
ion
to in
hibi
t 50%
bi
ndin
g of
E2.
2042
7-84
-3
4- Non
ylph
enol
di-
etho
xyla
te
(NP
2EO
)
In v
itro
assa
y: 4
-non
ylph
enol
diet
hoxy
late
sho
wed
onl
y ve
ry
wea
k or
no
com
petit
ion
(rel
ativ
e bi
ndin
g af
finiti
es <
< 0
.1%
c.f.
es
trad
iol)
Fis
h in
viv
o as
say.
Slig
ht in
crea
se in
vite
lloge
nin
synt
hesi
s (E
C=
38uL
)
2051
-60-
7 P
CB
1 (
2-C
hlor
obip
heny
l) In
vitr
o su
dy. I
nduc
tion
of M
CF
-7 F
oci.
LOE
L=5x
10-6
M
No
or in
suff
icie
nt d
ata
gath
ered
2051
-61-
8 P
CB
2 (
3-C
hlor
obip
heny
l) R
at in
viv
o st
udy.
Incr
ease
d ut
erus
wei
ght.
LOA
EL=
160
mg/
kg.
Old
ref
eren
ce -
nee
ds to
be
conf
irmed
. N
o or
insu
ffic
ient
dat
a ga
ther
ed
40ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
Q
ualif
ying
rem
arks
_HH
Q
ualif
ying
rem
arks
_WL
2051
-62-
9 P
CB
3 (
4-C
hlor
obip
heny
l) In
vitr
o as
say.
Indu
ctio
n of
MC
F-7
foci
N
o or
insu
ffici
ent d
ata
gath
ered
2581
-34-
2 3-
met
hyl-4
-ni
trop
heno
l In
vitr
o as
say:
Pos
itive
est
roge
nic
and
anti-
andr
ogen
ic a
ctiv
ity
No
or in
suff
icie
nt d
ata
gath
ered
3115
-49-
9 4-
nony
lphe
noxy
ac
etic
aci
d In
vitr
o as
say:
For
[3H
]est
radi
ol b
indi
ng to
AF
P, 4
-no
nylp
heno
xyac
etic
aci
d sh
owed
sig
nific
ant c
ompe
titio
n at
co
ncns
. abo
ut 1
00-f
old
grea
ter
than
est
radi
ol
Fis
h in
viv
o as
say:
Incr
ease
d pl
asm
a vi
tello
geni
n le
vel
491-
80-5
B
ioch
anin
A
In v
itro
stud
y. A
ctiv
atio
n of
ER
and
est
roge
nic
effe
ct o
n se
nsi-
tive
bioc
hem
ical
par
amet
ers
in m
ouse
ute
rus
No
or in
suff
icie
nt d
ata
gath
ered
6807
-17-
6 2,
2-B
is(4
-hy
drox
yphe
nyl)-
4-m
ethy
l-n-p
enta
ne
In v
ivo
+ in
vitr
o as
say.
Pos
itive
effe
ct in
ute
rotr
ophi
c as
say
+
posi
tive
in th
e re
port
er g
ene
assa
y fo
r E
R-a
lpha
ago
nist
s N
o or
insu
ffic
ient
dat
a ga
ther
ed
81-9
2-5
2-[B
is(4
-hy
drox
y-ph
enyl
)met
hyl]b
enz
ylal
koho
l =
Phe
nolp
htha
lol
In v
ivo
assa
y: In
crea
sed
uter
us w
eigh
t. LO
AE
L=4
mg/
kg. O
ld
refe
renc
e N
o or
insu
ffic
ient
dat
a ga
ther
ed
83-0
5-6
p,p'
-DD
A
In v
itro
assa
y: in
hibi
tion
of p
roge
ster
one-
indu
ced
repo
rter
gen
e ac
tivity
in a
dos
e-de
pend
ent m
anne
r Ja
pane
se q
uail
- T
hyro
id g
land
: dec
reas
e in
folli
cula
r re
-so
rptio
n va
cuol
es, a
nd a
n in
crea
se in
folli
cula
r si
ze. O
ld
refe
renc
e 84
-69-
5 D
iisob
utyl
phth
a-la
te
The
stu
dy d
emon
stra
tes
a de
velo
pmet
al to
xici
ty o
f DIB
P a
d-m
inis
tere
d to
rat
s by
gav
age,
thro
ugho
ut th
e em
bryo
nic
and
feta
l per
iod.
Fur
ther
exp
erim
ents
are
nee
ded
to c
hara
cter
ize
the
full
scal
e of
DIB
P d
evel
opm
enta
l tox
icity
.
No
or in
suff
icie
nt d
ata
gath
ered
84-7
5-3
Di-n
-hex
yl p
htha
-la
te (
DnH
P)
=
Dih
exyl
phth
alat
e (D
HP
)
Rev
iew
: The
dat
a ar
e su
ffici
ent t
o in
dica
te th
at D
nHP
is a
re-
prod
uctiv
e to
xica
nt in
bot
h se
xes
of tw
o ro
dent
spe
cies
follo
w-
ing
oral
exp
osur
e +
indi
catio
n of
thyr
oid
effe
cts.
No
or in
suff
icie
nt d
ata
gath
ered
99-7
1-8
4-se
c-B
utyl
phen
ol
= 4
-(1-
Met
hylp
ro-
pyl)p
heno
l
In v
itro
assa
y. S
timul
atio
n of
cel
l pro
lifer
atio
n. L
OE
L=10
uM
In v
itro
assa
y. o
-t-b
utyl
phen
ol e
xhib
ited
TR
-bin
ding
act
ivi-
ties
with
RE
C10
val
ues
of 4
.8 ×
10-
5 M
2597
-03-
7'
Els
an =
Di-
mep
hent
hoat
e N
o or
insu
ffici
ent d
ata
gath
ered
in
viv
o fis
h as
say:
Sig
nific
ant r
edn.
in th
e ov
aria
n w
eigh
t. LO
EC
=21
1ppb
41ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Tab
le 5
.5
Ove
rvie
w o
f the
hum
an h
ealth
rel
evan
t sys
tem
ic to
xici
ty d
ata
of C
ateg
ory
1 su
bsta
nces
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 10
043-
35-3
B
oric
aci
d ra
bbits
D
ecre
ased
food
inta
ke a
nd v
agin
al
blee
ding
ass
ocd.
with
pre
gnan
cy lo
ss
wer
e th
e on
ly c
lear
man
ifest
atio
ns o
f to
xici
ty
LOE
D
250
mg/
kg b
ody
wei
ght.
day
1004
3-35
-3
Bor
ic a
cid
Spr
ague
-D
awle
y m
ale
rats
Effe
ct le
vel n
ot g
iven
1004
3-35
-3
Bor
ic a
cid
rats
S
igni
fican
t dec
reas
e in
HD
L3-
chol
este
rol.
No
chan
ge in
bod
y or
tes-
ticul
ar w
eigh
t bet
wee
n th
e co
ntro
l and
tr
eatm
ent g
roup
s
ED
2
mg/
day
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
End
ocrin
e -
Est
roge
nic
Mat
erna
l Ef-
fect
s -
Ute
rus,
cer
vix,
vag
ina
Oth
ers
- C
hang
es in
ute
rine
wei
ght
TD
Lo
270
mg/
kg/3
D in
-te
rmitt
ent
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Mat
erna
l Effe
cts
- O
varie
s, fa
llopi
an
tube
s M
ater
nal E
ffect
s -
Ute
rus,
cer
vix,
va
gina
TD
Lo
300
mg/
kg /3
D in
-te
rmitt
ent
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
W
eigh
t los
s or
dec
reas
ed w
eigh
t gai
n
TD
Lo
600
mg/
kg /3
D in
-te
rmitt
ent
10
4-40
-5
4-N
onyl
phen
ol (
4-N
P)
Rat
E
ndoc
rine
- E
vide
nce
of th
yroi
d hy
po-
func
tion
End
ocrin
e -
Cha
nges
in p
itui-
tary
wei
ght N
utrit
iona
l and
Gro
ss
Met
abol
ic -
Wei
ght l
oss
or d
ecre
ased
w
eigh
t gai
n
TD
Lo
2000
m
g/kg
/20D
in
term
itten
t
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Kid
ney,
Ure
ter,
and
Bla
dder
- C
hang
es
in k
idne
y w
eigh
t Mat
erna
l Effe
cts
- O
varie
s, fa
llopi
an tu
bes
Mat
erna
l Ef-
fect
s -
Ute
rus,
cer
vix,
vag
ina
TD
Lo
2000
m
g/kg
/20D
in
term
itten
t
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Oth
ers
- C
hang
es in
ute
rine
wei
ght
T
DLo
15
0 m
g/kg
/3D
in-
term
itten
t
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Oth
ers
- C
hang
es in
ute
rine
wei
ght
T
DLo
60
0 m
g/kg
/3D
in-
term
itten
t
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Mat
erna
l Effe
cts
- O
ther
effe
cts
Effe
cts
on N
ewbo
rn -
Gro
wth
sta
tistic
s (e
.g.,
redu
ced
wei
ght g
ain)
Effe
cts
on N
ew-
born
- B
ehav
iora
l
TD
Lo
1.25
m
g/kg
42ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 10
4-40
-5
4-N
onyl
phen
ol (
4-N
P)
Rat
M
ater
nal E
ffect
s -
Men
stru
al c
ycle
ch
ange
s or
dis
orde
rs
TD
Lo
2500
m
g/kg
/25D
in-
term
itten
t
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Mat
erna
l Effe
cts
- M
enst
rual
cyc
le
chan
ges
or d
isor
ders
T
DLo
20
00
mg/
kg /2
0D
inte
rmitt
ent
10
4-40
-5
4-N
onyl
phen
ol (
4-N
P)
Rat
M
ater
nal E
ffect
s -
Oth
er e
ffect
s
TD
Lo
4625
ug
/kg
10
4-40
-5
4-N
onyl
phen
ol (
4-N
P)
Rat
LD50
16
20
mg/
kg
10
4-40
-5
4-N
onyl
phen
ol (
4-N
P)
Rat
E
ndoc
rine
- E
stro
geni
c O
ther
s -
Cha
nges
in u
terin
e w
eigh
t
TD
Lo
600
mg/
kg/3
D in
-te
rmitt
ent
10
4-40
-5
4-N
onyl
phen
ol (
4-N
P)
Rat
M
ater
nal E
ffect
s -
Ute
rus,
cer
vix,
va-
gina
T
DLo
70
0 m
g/kg
/14D
in-
term
itten
t
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
W
eigh
t los
s or
dec
reas
ed w
eigh
t gai
n
TD
Lo
200
mg/
kg
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Mat
erna
l Effe
cts
- U
teru
s, c
ervi
x, v
a-gi
na
TD
Lo
1000
m
g/kg
/20D
in
term
itten
t
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Mat
erna
l Effe
cts
- M
enst
rual
cyc
le
chan
ges
or d
isor
ders
T
DLo
30
0 m
g/kg
/3D
in-
term
itten
t
104-
40-5
4-
Non
ylph
enol
(4-
NP
) R
at
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Hep
atob
iliar
y sy
stem
Spe
cific
Dev
el-
opm
enta
l Abn
orm
aliti
es -
Uro
geni
tal
syst
em
TD
Lo
120
mg/
kg
1113
-02-
6 O
met
hoat
e C
hick
en
LD
50
125
mg/
kg
11
13-0
2-6
Om
etho
ate
Cat
LD50
50
m
g/kg
1113
-02-
6 O
met
hoat
e G
uine
a P
ig
LD
50
100
mg/
kg
11
13-0
2-6
Om
etho
ate
Rab
bit
LD
50
50
mg/
kg
11
13-0
2-6
Om
etho
ate
Mou
se
Bio
chem
ical
- T
rue
chol
ines
tera
se
LD50
19
m
g/kg
1113
-02-
6 O
met
hoat
e M
ouse
LD50
13
m
g/kg
1113
-02-
6 O
met
hoat
e M
ouse
B
ioch
emic
al -
Tru
e ch
olin
este
rase
LD
50
140
mg/
m3/
4H
11
13-0
2-6
Om
etho
ate
Rat
LD50
30
m
g/kg
1113
-02-
6 O
met
hoat
e R
at
LC
50
>15
00
mg/
m3/
1H
11
13-0
2-6
Om
etho
ate
Rat
LD50
70
0 m
g/kg
1113
-02-
6 O
met
hoat
e R
at
LD
50
55
mg/
kg
11
13-0
2-6
Om
etho
ate
Rat
B
lood
- O
ther
cha
nges
Bio
chem
ical
-
Tru
e ch
olin
este
rase
T
DLo
45
500
ug/k
g/13
W in
-te
rmitt
ent
11
13-0
2-6
Om
etho
ate
Hum
an
90
mg/
L
1113
-02-
6 O
met
hoat
e B
acte
ria -
E
Col
i
63
85
ug/p
late
(-S
9)
43ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 11
13-0
2-6
Om
etho
ate
Qua
il (L
abo-
rato
ry)
LD
50
50
mg/
kg
1113
-02-
6 O
met
hoat
e C
hick
en
Pat
erna
l Effe
cts
- O
ther
effe
cts
on m
ale
LD
50
75
mg/
kg
11
13-0
2-6
Om
etho
ate
Rat
B
ioch
emic
al -
Tru
e ch
olin
este
rase
LD
50
1440
0 ug
/kg
11
13-0
2-6
Om
etho
ate
Mou
se
Blo
od -
Cha
nges
in b
one
mar
row
not
in
clud
ed a
bove
T
DLo
45
00
ug/k
g/5D
in-
term
itten
t
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
P
ater
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, sp
erm
duc
t
TD
Lo
440
mg/
kg
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
K
idne
y, U
rete
r, a
nd B
ladd
er -
Oth
er
chan
ges
in u
rine
com
posi
tion
T
DLo
22
0 m
g/kg
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Mou
se
Effe
cts
on N
ewbo
rn -
Liv
e bi
rth
inde
x (s
imila
r to
T26
, exc
ept m
easu
red
afte
r bi
rth)
TD
Lo
504
gm/k
g
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Mou
se
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct
T
DLo
50
4 gm
/kg/
15W
co
ntin
uous
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Mou
se
Live
r -
Cha
nges
in li
ver
wei
ght K
idne
y,
Ure
ter,
and
Bla
dder
- C
hang
es in
kid
-ne
y w
eigh
t Nut
ritio
nal a
nd G
ross
Met
a-bo
lic -
Wei
ght l
oss
or d
ecre
ased
wei
ght
gain
TD
Lo
504
gm/k
g/15
W
cont
inuo
us
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
E
ndoc
rine
- E
stro
geni
c B
lood
-
Cha
nges
in s
erum
com
posi
tion
(e.g
., T
P, b
iliru
bin,
cho
lest
erol
)
TD
Lo
9000
m
g/kg
/9D
in-
term
itten
t
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
P
ater
nal E
ffect
s -
Spe
rmat
ogen
esis
(in
clud
ing
gene
tic m
ater
ial,
sper
m
mor
phol
ogy,
mot
ility
, and
cou
nt)
TD
Lo
1100
m
g/kg
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Mou
se
Effe
cts
on N
ewbo
rn -
Liv
e bi
rth
inde
x (s
imila
r to
T26
, exc
ept m
easu
red
afte
r bi
rth)
TD
Lo
504
gm/k
g
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
O
ther
s -
Cha
nges
in te
stic
ular
wei
ght
T
DLo
22
00
mg/
kg
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Mou
se
Effe
cts
on F
ertil
ity -
Fem
ale
fert
ility
in-
dex
(e.g
., #
fem
ales
pre
gnan
t pe
r #
sper
m p
ositi
ve f
emal
es #
fem
ales
pr
egna
nt p
er #
fem
ales
mat
ed)
Effe
cts
on N
ewbo
rn -
Liv
e bi
rth
inde
x (s
imila
r to
T26
, exc
ept m
easu
red
afte
r bi
rth)
TD
Lo
26.6
gm
/kg
44ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 13
1-18
-0
Di-n
-pen
tylp
htha
late
(D
PP
) =
D
ipen
tylp
htha
late
M
ouse
E
ffect
s on
Fer
tility
- F
emal
e fe
rtili
ty in
-de
x (e
.g.,
# fe
mal
es p
regn
ant
per
# sp
erm
pos
itive
fem
ales
# fe
mal
es
preg
nant
per
# fe
mal
es m
ated
) E
ffect
s on
Fer
tility
- M
ale
fert
ility
inde
x (e
.g.,
# m
ales
impr
egna
ting
fem
ales
per
#
mal
es e
xpos
ed to
fert
ile n
TD
Lo
316
gm/k
g
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
P
ater
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, sp
erm
duc
t
TD
Lo
6600
m
g/kg
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
P
ater
nal E
ffect
s -
Oth
er e
ffect
s on
mal
e
TD
Lo
2206
m
g/kg
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
P
ater
nal E
ffect
s -
Spe
rmat
ogen
esis
(in
clud
ing
gene
tic m
ater
ial,
sper
m
mor
phol
ogy,
mot
ility
, and
cou
nt)
Pat
er-
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, spe
rm
duct
Effe
cts
on F
ertil
ity -
Mal
e fe
rtili
ty
inde
x (e
.g.,
# m
ales
impr
egna
ting
fe-
mal
es p
er #
mal
es e
xpos
ed
TD
Lo
2 gm
/kg
131-
18-0
D
i-n-p
enty
lpht
hala
te (
DP
P)
=
Dip
enty
lpht
hala
te
Rat
P
ater
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, sp
erm
duc
t Pat
erna
l Effe
cts
- P
rost
ate,
se
min
al v
essi
cle,
Cow
per's
gla
nd, a
c-ce
ssor
y g
land
s
TD
Lo
2800
0 m
g/kg
/10D
in-
term
itten
t
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
R
at
Gas
troi
ntes
tinal
- O
ther
cha
nges
Kid
-ne
y, U
rete
r, a
nd B
ladd
er -
Cha
nges
in
tubu
les
(incl
udin
g ac
ute
rena
l fa
ilure
, ac
ute
tubu
lar
necr
osis
)
LD50
86
00
mg/
kg
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
M
amm
al -
U
nspe
cifie
d S
peci
es
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
W
eigh
t los
s or
dec
reas
ed w
eigh
t gai
n
TD
Lo
1020
0 m
g/kg
/85D
in-
term
itten
t
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
M
ouse
N
utrit
iona
l and
Gro
ss M
etab
olic
-
Wei
ght l
oss
or d
ecre
ased
wei
ght g
ain
T
DLo
99
00
mg/
kg/3
5D in
-te
rmitt
ent
13
1-56
-6
2,4-
Dih
ydro
xybe
nzop
heno
n =
R
esbe
nzop
heno
ne
Rat
Li
ver
- C
hang
es in
live
r w
eigh
t Blo
od -
P
igm
ente
d or
nuc
leat
ed r
ed b
lood
cel
ls
Blo
od -
Cha
nges
in e
ryth
rocy
te (
RB
C)
coun
t
TD
Lo
5460
0 m
g/kg
/91D
in-
term
itten
t
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
R
abbi
t M
ild
DR
AIZ
E
reac
tion
100
mg/
24H
45ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 13
1-56
-6
2,4-
Dih
ydro
xybe
nzop
heno
n =
R
esbe
nzop
heno
ne
Mou
se
Gas
troi
ntes
tinal
- O
ther
cha
nges
Kid
-ne
y, U
rete
r, a
nd B
ladd
er -
Cha
nges
in
tubu
les
(incl
udin
g ac
ute
rena
l fa
ilure
, ac
ute
tubu
lar
necr
osis
)
LD50
25
00
mg/
kg
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
M
ouse
LD50
10
0 m
g/kg
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
R
at
End
ocrin
e -
Est
roge
nic
T
DLo
47
.5
mg/
kg
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
R
at
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
W
eigh
t los
s or
dec
reas
ed w
eigh
t gai
n
TD
Lo
1000
m
g/kg
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
R
at
Beh
avio
ral -
Som
nole
nce
(gen
eral
de-
pres
sed
activ
ity)
Beh
avio
ral -
Foo
d in
-ta
ke (
anim
al)
Gas
troi
ntes
tinal
- H
yper
-m
otili
ty, d
iarr
hea
LD50
86
00
mg/
kg
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
=
Res
benz
ophe
none
M
ouse
LD50
85
m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Beh
avio
ral -
Foo
d in
take
(an
imal
) N
utri-
tiona
l and
Gro
ss M
etab
olic
- W
eigh
t lo
ss o
r de
crea
sed
wei
ght g
ain
TD
Lo
1500
m
g/kg
/3D
in-
term
itten
t
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Live
r -
Cha
nges
in li
ver
wei
ght B
lood
-
Cha
nges
in s
erum
com
posi
tion
(e.g
., T
P, b
iliru
bin,
cho
lest
erol
) B
ioch
emic
al -
Li
pids
incl
udin
g tr
ansp
ort
TD
Lo
8400
m
g/kg
/1W
con
-tin
uous
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Cra
niof
acia
l (in
clud
ing
nose
and
to
ngue
) S
peci
fic D
evel
opm
enta
l Ab-
norm
aliti
es -
Oth
er d
evel
opm
enta
l ab-
norm
aliti
es
TD
Lo
4500
m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Beh
avio
ral -
Foo
d in
take
(an
imal
) N
utri-
tiona
l and
Gro
ss M
etab
olic
- W
eigh
t lo
ss o
r de
crea
sed
wei
ght g
ain
TD
Lo
4500
m
g/kg
/9D
con
-tin
uous
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Effe
cts
on E
mbr
yo o
r F
etus
- O
ther
ef-
fect
s to
em
bryo
T
DLo
40
0 m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Effe
cts
on F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
per
tota
l num
ber
of im
plan
ts)
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Uro
geni
tal s
yste
m
TD
Lo
1500
m
g/kg
46ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 13
1-70
-4
Mon
o-n-
buty
lpht
hala
te
Rat
E
ffect
s on
Fer
tility
- P
ost-
impl
anta
tion
mor
talit
y (e
.g.,
dead
and
or
res
orbe
d im
plan
ts p
er to
tal n
umbe
r of
impl
ants
) E
ffect
s on
Em
bryo
or
Fet
us -
Fet
otox
ic-
ity (
exce
pt d
eath
, e.g
., st
unte
d fe
tus)
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
U
roge
nita
l sys
tem
TD
Lo
2250
m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Uro
geni
tal s
yste
m
TD
Lo
750
mg/
kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Beh
avio
ral -
Foo
d in
take
(an
imal
) N
utri-
tiona
l and
Gro
ss M
etab
olic
- W
eigh
t lo
ss o
r de
crea
sed
wei
ght g
ain
Oth
ers
- C
hang
es in
ute
rine
wei
ght
TD
Lo
9000
m
g/kg
/9D
con
-tin
uous
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Effe
cts
on F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
per
tota
l num
ber
of im
plan
ts)
TD
Lo
1200
m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Beh
avio
ral -
Str
aub
Tai
l
TD
Lo
4500
m
g/kg
13
1-70
-4
Mon
o-n-
buty
lpht
hala
te
Rat
E
ffect
s on
Fer
tility
- P
ost-
impl
anta
tion
mor
talit
y (e
.g.,
dead
and
or
res
orbe
d im
plan
ts p
er to
tal n
umbe
r of
impl
ants
) S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
M
uscu
losk
elet
al s
yste
m S
peci
fic D
e-ve
lopm
enta
l Abn
orm
aliti
es -
Oth
er d
e-ve
lopm
enta
l abn
orm
aliti
es
TD
Lo
1875
m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Effe
cts
on F
ertil
ity -
Pre
-impl
anta
tion
mor
talit
y (e
.g.,
redu
ctio
n in
num
ber
of
impl
ants
per
fem
ale
tota
l num
ber
of
impl
ants
per
cor
pora
lute
a) E
ffect
s on
F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
pe
r to
tal n
umbe
r of
i
TD
Lo
2250
m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct
T
DLo
32
00
mg/
kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
M
ouse
E
ffect
s on
Fer
tility
- P
ost-
impl
anta
tion
mor
talit
y (e
.g.,
dead
and
or
res
orbe
d im
plan
ts p
er to
tal n
umbe
r of
impl
ants
) E
ffect
s on
Em
bryo
or
Fet
us -
Fet
al
deat
h
TD
Lo
400
mg/
kg
47ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 13
1-70
-4
Mon
o-n-
buty
lpht
hala
te
Mou
se
Effe
cts
on E
mbr
yo o
r F
etus
- F
etot
oxic
-ity
(ex
cept
dea
th, e
.g.,
stun
ted
fetu
s)
TD
Lo
1200
m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
M
ouse
P
ater
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, sp
erm
duc
t
TD
Lo
1680
0 m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Effe
cts
on F
ertil
ity -
Pre
-impl
anta
tion
mor
talit
y (e
.g.,
redu
ctio
n in
num
ber
of
impl
ants
per
fem
ale
tota
l num
ber
of
impl
ants
per
cor
pora
lute
a) E
ffect
s on
F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
pe
r to
tal n
umbe
r of
i
TD
Lo
6750
m
g/kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
M
ouse
1.
6 gm
/kg
13
1-70
-4
Mon
o-n-
buty
lpht
hala
te
Mou
se
LD
50
1 gm
/kg
13
1-70
-4
Mon
o-n-
buty
lpht
hala
te
Mou
se
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
W
eigh
t los
s or
dec
reas
ed w
eigh
t gai
n
TD
Lo
400
mg/
kg
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Uro
geni
tal s
yste
m
TD
Lo
40
gm/k
g
131-
70-4
M
ono-
n-bu
tylp
htha
late
R
at
Effe
cts
on F
ertil
ity -
Pre
-impl
anta
tion
mor
talit
y (e
.g.,
redu
ctio
n in
num
ber
of
impl
ants
per
fem
ale
tota
l num
ber
of
impl
ants
per
cor
pora
lute
a) E
ffect
s on
F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
pe
r to
tal n
umbe
r of
i
TD
Lo
9000
m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
abbi
t S
ense
Org
ans
and
Spe
cial
Sen
ses
(Nos
e, E
ye, E
ar, a
nd T
aste
) -
Chr
o-m
odac
ryor
rhea
Beh
avio
ral -
Mus
cle
cont
ract
ion
or s
past
icity
Bio
chem
ical
-
Tru
e ch
olin
este
rase
LD50
50
m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Pat
erna
l Effe
cts
- O
ther
eff
ects
on
mal
e E
ndoc
rine
- C
hang
e in
GH
End
ocrin
e -
And
roge
nic
TD
Lo
6500
ug
/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
abbi
t S
ever
e D
RA
IZE
re
actio
n 10
0 uL
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s P
igeo
n B
ehav
iora
l - A
ltere
d sl
eep
time
(incl
ud-
ing
chan
ge in
rig
htin
g re
flex)
Lun
g,
Tho
rax,
or
Res
pira
tion
- D
yspn
ea G
as-
troi
ntes
tinal
- H
yper
mot
ility
, dia
rrhe
a
LD50
10
500
ug/k
g
48ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Chi
cken
B
ehav
iora
l - A
ltere
d sl
eep
time
(incl
ud-
ing
chan
ge in
rig
htin
g re
flex)
Lun
g,
Tho
rax,
or
Res
pira
tion
- D
yspn
ea G
as-
troi
ntes
tinal
- H
yper
mot
ility
, dia
rrhe
a
LD50
10
250
ug/k
g
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s C
hick
en
LD
50
20
mg/
kg
13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Chi
cken
LD50
25
m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s D
og
LD
50
100
mg/
kg ['
Pre
hled
P
rum
yslo
ve
Tox
ikol
ogie
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s G
erbi
l B
ehav
iora
l - C
onvu
lsio
ns o
r ef
fect
on
seiz
ure
thre
shol
d Lu
ng, T
hora
x, o
r R
espi
ratio
n -
Bro
nchi
olar
con
stric
tion
Gas
troi
ntes
tinal
- H
yper
mot
ility
, dia
r-rh
ea
LD50
11
910
ug/k
g
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct P
ater
nal E
ffect
s -
Pro
stat
e,
sem
inal
ves
sicl
e, C
owpe
r's g
land
, ac-
cess
ory
gla
nds
Pat
erna
l Effe
cts
- O
ther
effe
cts
on m
ale
TD
Lo
6500
ug
/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s G
uine
a P
ig
Sen
se O
rgan
s an
d S
peci
al S
ense
s (N
ose,
Eye
, Ear
, and
Tas
te)
- C
hro-
mod
acry
orrh
ea B
ehav
iora
l - M
uscl
e co
ntra
ctio
n or
spa
stic
ity B
ioch
emic
al -
T
rue
chol
ines
tera
se
LD50
25
0 m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s C
at
Sen
se O
rgan
s an
d S
peci
al S
ense
s (N
ose,
Eye
, Ear
, and
Tas
te)
- C
hro-
mod
acry
orrh
ea B
ehav
iora
l - M
uscl
e co
ntra
ctio
n or
spa
stic
ity B
ioch
emic
al -
T
rue
chol
ines
tera
se
LD50
75
m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s M
ouse
LD50
56
m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s M
ouse
S
ense
Org
ans
and
Spe
cial
Sen
ses
(Nos
e, E
ye, E
ar, a
nd T
aste
) -
Chr
o-m
odac
ryor
rhea
Beh
avio
ral -
Mus
cle
cont
ract
ion
or s
past
icity
Bio
chem
ical
-
Tru
e ch
olin
este
rase
LD50
74
500
ug/k
g
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s M
ouse
LD50
34
m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s M
ouse
LC50
33
0 m
g/m
3/4H
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
LD
50
300
mg/
kg
49ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Rat
LD50
55
m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
LD
50
26
mg/
kg
13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Rat
LD50
39
m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
LC
50
175
mg/
m3
13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Dom
estic
A
nim
als
- G
oat,
She
ep
Per
iphe
ral N
erve
and
Sen
satio
n -
Spa
stic
par
alys
is w
ith o
r w
ithou
t sen
-so
ry c
hang
e B
ehav
iora
l - S
omno
lenc
e (g
ener
al d
epre
ssed
act
ivity
) G
astr
oin-
test
inal
- C
hang
es in
str
uctu
re o
r fu
nc-
tion
of s
aliv
ary
glan
ds
LDLo
85
00
ug/k
g
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s H
amst
er
LC
50
600
mg/
m3/
4H
13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Mou
se
Tum
orig
enic
- N
eopl
astic
by
RT
EC
S
crite
ria L
ung,
Tho
rax,
or
Res
pira
tion
- O
ther
cha
nges
TD
Lo
30
mg/
kg/3
W
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
End
ocrin
e -
Est
roge
nic
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is, s
perm
duc
t Bio
-ch
emic
al -
Mul
tiple
enz
yme
effe
cts
TD
Lo
3.75
m
g/kg
/15D
in-
term
itten
t
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Oth
ers
- D
eath
T
DLo
55
7 m
g/kg
/60D
in-
term
itten
t
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Bio
chem
ical
- T
rue
chol
ines
tera
se
TD
Lo
1080
0 m
g/kg
/90D
co
ntin
uous
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Pat
erna
l Effe
cts
- S
perm
atog
enes
is
(incl
udin
g ge
netic
mat
eria
l, sp
erm
m
orph
olog
y, m
otili
ty, a
nd c
ount
) B
io-
chem
ical
- T
rue
chol
ines
tera
se
TD
Lo
105
mg/
kg/1
5D in
-te
rmitt
ent
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Pat
erna
l Effe
cts
- S
perm
atog
enes
is
(incl
udin
g ge
netic
mat
eria
l, sp
erm
m
orph
olog
y, m
otili
ty, a
nd c
ount
) B
io-
chem
ical
- T
rue
chol
ines
tera
se O
ther
s -
Cha
nges
in te
stic
ular
wei
ght
TD
Lo
150
mg/
kg/1
5D in
-te
rmitt
ent
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct O
ther
s -
Cha
nges
in te
s-tic
ular
wei
ght
TD
Lo
750
ug/k
g/3D
in-
term
itten
t
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Beh
avio
ral -
Tre
mor
Pat
erna
l Effe
cts
- S
perm
atog
enes
is (
incl
udin
g ge
netic
m
ater
ial,
sper
m m
orph
olog
y, m
otili
ty,
and
coun
t) O
ther
s -
Cha
nges
in te
stic
u-la
r w
eigh
t
TD
Lo
210
mg/
kg/1
5D in
-te
rmitt
ent
50ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Gui
nea
Pig
B
rain
and
Cov
erin
gs -
Cha
nges
in b
rain
w
eigh
t Kid
ney,
Ure
ter,
and
Bla
dder
-
Cha
nges
in b
ladd
er w
eigh
t Oth
ers
- C
hang
es in
ova
rian
wei
ght
TD
Lo
60
mg/
kg/3
0D
cont
inuo
us
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s D
omes
tic
Ani
mal
s -
Goa
t, S
heep
Blo
od -
Oth
er c
hang
es B
ioch
emic
al -
T
rue
chol
ines
tera
se B
ioch
emic
al -
O
ther
est
eras
es
TD
Lo
1050
0 ug
/kg/
21D
con
-tin
uous
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s M
ouse
5
mg/
kg
13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Mou
se
5 m
g/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Effe
cts
on E
mbr
yo o
r F
etus
- F
etot
oxic
-ity
(ex
cept
dea
th, e
.g.,
stun
ted
fetu
s)
TD
Lo
2250
0 ug
/kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s R
at
Mat
erna
l Effe
cts
- O
ther
effe
cts
T
DLo
75
00
ug/k
g
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s G
erbi
l P
ater
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, sp
erm
duc
t
TD
Lo
15
mg/
kg
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s M
ouse
5
mg/
kg
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
at
Kid
ney,
Ure
ter,
and
Bla
dder
- C
hang
es
in b
ladd
er w
eigh
t Blo
od -
Cha
nges
in
seru
m c
ompo
sitio
n (e
.g.,
TP
, bili
rubi
n,
chol
este
rol)
Nut
ritio
nal a
nd G
ross
M
etab
olic
- C
a
TD
Lo
27
gm/k
g/90
D in
-te
rmitt
ent
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
LC
50
2800
0 m
g/m
3/2H
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct
T
DLo
6
gm/k
g
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
Effe
cts
on F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
per
tota
l num
ber
of im
plan
ts)
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Cra
niof
acia
l (in
clud
ing
nose
and
to
ngue
) S
peci
fic D
evel
opm
enta
l Ab-
norm
aliti
es -
Mus
culo
skel
etal
TC
Lo
8000
pp
m/6
H
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
Effe
cts
on E
mbr
yo o
r F
etus
- F
etot
oxic
-ity
(ex
cept
dea
th, e
.g.,
stun
ted
fetu
s)
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Mus
culo
skel
etal
sys
tem
TC
Lo
4000
pp
m/6
H
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
E
ffect
s on
New
born
- V
iabi
lity
inde
x (e
.g.,
# al
ive
at d
ay 4
per
# b
orn
aliv
e)
Effe
cts
on N
ewbo
rn -
Gro
wth
sta
tistic
s (e
.g.,
redu
ced
wei
ght g
ain)
TC
Lo
8000
pp
m/6
H
51ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
at
>14
8 m
g/kg
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
incr
ease
d se
rum
cor
ticos
tero
ne le
vels
LO
EL
8000
pp
m
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Bac
teria
- S
T
yphi
mur
ium
15
00
ug/p
late
(+
S9)
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
N
utrit
iona
l and
Gro
ss M
etab
olic
-
Wei
ght l
oss
or d
ecre
ased
wei
ght g
ain
T
DLo
4.
2 gm
/kg/
2W c
on-
tinuo
us
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) M
ouse
LD50
59
60
uL/k
g
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
Beh
avio
ral -
Gen
eral
ane
sthe
tic
LC50
14
1 gm
/m3/
15M
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
LD50
4
gm/k
g
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
LC50
41
000
mg/
m3/
4H
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
at
LC
50
2357
6 pp
m/4
H
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
at
LD
Lo
148
mg/
kg
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
at
End
ocrin
e -
And
roge
nic
T
DLo
10
00
mg/
kg
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) M
ouse
LD50
17
00
uL/k
g
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
N
utrit
iona
l and
Gro
ss M
etab
olic
-
Wei
ght l
oss
or d
ecre
ased
wei
ght g
ain
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
De-
hydr
atio
n O
ther
s -
Cha
nges
in te
stic
u-la
r w
eigh
t
TD
Lo
4200
0 m
g/kg
/28D
in-
term
itten
t
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
K
idne
y, U
rete
r, a
nd B
ladd
er -
Cha
nges
in
tubu
les
(incl
udin
g ac
ute
rena
l fa
il-ur
e, a
cute
tubu
lar
necr
osis
)
TC
Lo
1516
pp
m/6
H/1
0D
inte
rmitt
ent
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
End
ocrin
e -
Cha
nges
in p
ituita
ry w
eigh
t M
ater
nal E
ffect
s -
Ute
rus,
cer
vix,
va-
gina
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
W
eigh
t los
s or
dec
reas
ed w
eigh
t gai
n
TC
Lo
8000
pp
m/1
6W c
on-
tinuo
us
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
Mat
erna
l Effe
cts
- U
teru
s, c
ervi
x, v
a-gi
na M
ater
nal E
ffect
s -
Men
stru
al c
ycle
ch
ange
s or
dis
orde
rs O
ther
s -
Cha
nges
in
ute
rine
wei
ght
TC
Lo
8000
pp
m/3
2W c
on-
tinuo
us
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mam
mal
-
Uns
peci
fied
Spe
cies
Kid
ney,
Ure
ter,
and
Bla
dder
- O
ther
ch
ange
s B
ioch
emic
al -
Cyt
ochr
ome
oxid
ases
(in
clud
ing
oxid
ativ
e ph
os-
phor
ylat
ion)
Bio
chem
ical
- T
rans
ami-
nase
s
TC
Lo
180
mg/
m3/
6H/1
5W
inte
rmitt
ent
52ERA/53559/Revised report/2007.06.04
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ME
S
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FE
CT
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IUM
DO
SE
_CO
NC
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NIT
_DO
SE
_ 16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) M
ouse
E
ndoc
rine
- C
hang
es in
pitu
itary
wei
ght
Mat
erna
l Effe
cts
- U
teru
s, c
ervi
x, v
a-gi
na O
ther
s -
Cha
nges
in u
terin
e w
eigh
t
TC
Lo
8000
pp
m/2
1D c
on-
tinuo
us
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
B
rain
and
Cov
erin
gs -
Rec
ordi
ngs
from
sp
ecifi
c ar
c-as
of C
NS
Bio
chem
ical
-
Cat
alas
es B
ioch
emic
al -
Oth
er e
n-zy
mes
TD
Lo
210
mg/
kg/1
4D
cont
inuo
us
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Mou
se
Mat
erna
l Effe
cts
- U
teru
s, c
ervi
x, v
a-gi
na
TC
Lo
8000
pp
m/3
D c
on-
tinuo
us
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
at
End
ocrin
e -
Cha
nges
in a
dren
al w
eigh
t N
utrit
iona
l and
Gro
ss M
etab
olic
-
Wei
ght l
oss
or d
ecre
ased
wei
ght g
ain
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
De-
hydr
atio
n
TD
Lo
2250
0 m
g/kg
/15D
in-
term
itten
t
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
E
ndoc
rine
- E
vide
nce
of th
yroi
d hy
per-
func
tion
T
DLo
15
000
mg/
kg/1
5D in
-te
rmitt
ent
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
at
End
ocrin
e -
And
roge
nic
Oth
ers
- D
eath
T
DLo
75
00
mg/
kg/1
1D in
-te
rmitt
ent
16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
at
Live
r -
Cha
nges
in li
ver
wei
ght E
ndo-
crin
e -
And
roge
nic
Nut
ritio
nal a
nd
Gro
ss M
etab
olic
- W
eigh
t los
s or
de-
crea
sed
wei
ght g
ain
TD
Lo
1120
0 m
g/kg
/28D
in-
term
itten
t
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
Li
ver
- C
hang
es in
live
r w
eigh
t Kid
ney,
U
rete
r, a
nd B
ladd
er -
Cha
nges
in b
lad-
der
wei
ght B
lood
- C
hang
es in
ser
um
com
posi
tion
(e.g
., T
P, b
iliru
bin,
cho
les-
tero
l)
TD
Lo
49
gm/k
g/28
D in
-te
rmitt
ent
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Rat
K
idne
y, U
rete
r, a
nd B
ladd
er -
Cha
nges
in
bla
dder
wei
ght B
lood
- C
hang
es in
er
ythr
ocyt
e (R
BC
) co
unt N
utrit
iona
l and
G
ross
Met
abol
ic -
Wei
ght l
oss
or d
e-cr
ease
d w
eigh
t gai
n
TD
Lo
20
gm/k
g/14
D in
-te
rmitt
ent
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
T
umor
igen
ic -
Neo
plas
tic b
y R
TE
CS
cr
iteria
Lun
g, T
hora
x, o
r R
espi
ratio
n -
Tum
ors
42
00
mg/
kg/1
0W
cont
inuo
us
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria G
astr
oint
estin
al -
Tum
ors
728
gm/k
g/2Y
con
-tin
uous
53ERA/53559/Revised report/2007.06.04
DHI Water & Environment
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PE
CIE
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FE
CT
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IUM
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_CO
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.U
NIT
_DO
SE
_ 25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Tum
orig
enic
- C
arci
noge
nic
by R
TE
CS
cr
iteria
Gas
troi
ntes
tinal
- T
umor
s
87
4 gm
/kg/
1Y c
on-
tinuo
us
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Lung
, Tho
rax,
or
Res
pira
tion
- C
hang
es in
Lun
g W
eigh
t Blo
od -
Oth
er
hem
olys
is w
ith o
r w
ithou
t ane
mia
Nut
ri-tio
nal a
nd G
ross
Met
abol
ic -
Wei
ght
loss
or
decr
ease
d w
eigh
t gai
n
TD
Lo
2688
m
g/kg
/7D
in-
term
itten
t
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria G
astr
oint
estin
al -
Tum
ors
En-
docr
ine
- T
umor
s
87
4 gm
/kg/
2Y c
on-
tinuo
us
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria K
idne
y, U
rete
r, a
nd B
ladd
er -
T
umor
s T
umor
igen
ic -
Cel
ls (
cultu
red)
tr
ansf
orm
ed
26
9 gm
/kg/
32W
co
ntin
uous
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Ham
ster
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria G
astr
oint
estin
al -
Tum
ors
T
DLo
43
7 gm
/kg/
1Y c
on-
tinuo
us
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) H
amst
er
100
umol
/L
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) O
ther
Mic
ro-
orga
nism
s
12
500
ug/L
(-S
9)
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria G
astr
oint
estin
al -
Tum
ors
T
DLo
72
8 gm
/kg/
2Y c
on-
tinuo
us
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Tum
orig
enic
- E
quiv
ocal
tum
orig
enic
ag
ent b
y R
TE
CS
crit
eria
Gas
troi
ntes
ti-na
l - T
umor
s
18
2 gm
/kg/
2Y c
on-
tinuo
us
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
Li
ver
- C
hang
es in
live
r w
eigh
t
TD
Lo
182
mg/
kg/2
Y c
on-
tinuo
us
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Live
r -
Oth
er c
hang
es N
utrit
iona
l and
G
ross
Met
abol
ic -
Oth
er c
hang
es B
io-
chem
ical
- H
epat
ic m
icro
som
al m
ixed
ox
idas
e (d
ealk
ylat
ion,
hyd
roxy
latio
n,
etc.
)
TD
Lo
3300
m
g/kg
/12D
in-
term
itten
t
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Mon
key
Live
r -
Oth
er c
hang
es L
iver
- C
hang
es
in li
ver
wei
ght B
ioch
emic
al -
Pho
s-ph
atas
es
TD
Lo
14
gm/k
g/4W
in-
term
itten
t
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Mon
key
Gas
troi
ntes
tinal
- O
ther
cha
nges
Liv
er -
C
hang
es in
live
r w
eigh
t Bio
chem
ical
-
Oth
er e
nzym
es
TD
Lo
15
gm/k
g/84
D in
-te
rmitt
ent
54ERA/53559/Revised report/2007.06.04
DHI Water & Environment
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CT
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ER
IUM
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SE
_CO
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NIT
_DO
SE
_ 25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Tum
orig
enic
- N
eopl
astic
by
RT
EC
S
crite
ria G
astr
oint
estin
al -
Tum
ors
202
gm/k
g/24
W
cont
inuo
us
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) H
amst
er
Tum
orig
enic
- N
eopl
astic
by
RT
EC
S
crite
ria G
astr
oint
estin
al -
Tum
ors
202
gm/k
g/24
W
cont
inuo
us
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) M
ouse
T
umor
igen
ic -
Equ
ivoc
al tu
mor
igen
ic
agen
t by
RT
EC
S c
riter
ia G
astr
oint
esti-
nal -
Tum
ors
TD
Lo
874
gm/k
g/1Y
con
-tin
uous
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
Li
ver
- C
hang
es in
live
r w
eigh
t Bio
-ch
emic
al -
Pho
spha
tase
s
TD
Lo
700
mg/
kg/7
D in
-te
rmitt
ent
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Live
r -
Oth
er c
hang
es L
iver
- C
hang
es
in li
ver
wei
ght B
ioch
emic
al -
Hep
atic
m
icro
som
al m
ixed
oxi
dase
(de
alky
la-
tion,
hyd
roxy
latio
n, e
tc.)
TD
Lo
4676
m
g/kg
/28D
co
ntin
uous
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Mou
se
Lung
, Tho
rax,
or
Res
pira
tion
- T
umor
s T
umor
igen
ic -
Pro
tect
s ag
ains
t ind
uc-
tion
of e
xper
imen
tal t
umor
s T
umor
i-ge
nic
- A
ctiv
e as
ant
i-can
cer
agen
t
TD
Lo
1154
gm
/kg/
8W in
-te
rmitt
ent
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Mou
se
Live
r -
Oth
er c
hang
es L
iver
- C
hang
es
in li
ver
wei
ght B
ioch
emic
al -
Hep
atic
m
icro
som
al m
ixed
oxi
dase
(de
alky
la-
tion,
hyd
roxy
latio
n, e
tc.)
TD
Lo
1090
0 ng
/kg/
12D
in-
term
itten
t
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
Li
ver
- T
umor
s T
umor
igen
ic -
Pro
tect
s ag
ains
t ind
uctio
n of
exp
erim
enta
l tu-
mor
s T
umor
igen
ic -
Act
ive
as a
nti-
canc
er a
gent
TD
Lo
6300
m
g/kg
/6W
con
-tin
uous
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Hum
an
400
umol
/L
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Bio
chem
ical
- O
ther
tran
sfer
ases
T
DLo
96
0 m
g/kg
/2D
in-
term
itten
t
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
25
0 um
ol/L
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Mou
se
Beh
avio
ral -
Alte
red
slee
p tim
e (in
clud
-in
g ch
ange
in r
ight
ing
refle
x) B
ehav
-io
ral -
Ata
xia
Lung
, Tho
rax,
or
Res
pira
-tio
n -
Res
pira
tory
stim
ulat
ion
LD50
11
00
mg/
kg
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Mou
se
Effe
cts
on N
ewbo
rn -
Beh
avio
ral
T
DLo
12
600
mg/
kg
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rab
bit
LD
50
2100
m
g/kg
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
E
ffect
s on
New
born
- G
row
th s
tatis
tics
(e.g
., re
duce
d w
eigh
t gai
n)
TD
Lo
30
gm/k
g
55ERA/53559/Revised report/2007.06.04
DHI Water & Environment
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R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Blo
od -
Hem
orrh
age
LD
50
881
mg/
kg
25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) R
at
Bio
chem
ical
- H
epat
ic m
icro
som
al
mix
ed o
xida
se (
deal
kyla
tion,
hyd
roxy
-la
tion,
etc
.)
TD
Lo
480
mg/
kg
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
E
ffect
s on
New
born
- W
eani
ng o
r la
cta-
tion
inde
x (e
.g.,
# al
ive
at w
eani
ng p
er
# al
ive
at d
ay
4)
TD
Lo
36
gm/k
g
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
17
6 gm
/kg/
21W
co
ntin
uous
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Rat
B
ehav
iora
l - A
ltere
d sl
eep
time
(incl
ud-
ing
chan
ge in
rig
htin
g re
flex)
Beh
av-
iora
l - A
taxi
a Lu
ng, T
hora
x, o
r R
espi
ra-
tion
- R
espi
rato
ry s
timul
atio
n
LD50
2
gm/k
g
2719
3-28
-8
Phe
nol,
(1,1
,3,3
-tet
ram
ethy
lbut
yl)-
=
Oct
ylph
enol
R
at
Oth
ers
- C
hang
es in
ute
rine
wei
ght
T
DLo
90
0 m
g/kg
/3D
in-
term
itten
t
2719
3-28
-8
Phe
nol,
(1,1
,3,3
-tet
ram
ethy
lbut
yl)-
=
Oct
ylph
enol
M
ouse
LD50
25
m
g/kg
2719
3-28
-8
Phe
nol,
(1,1
,3,3
-tet
ram
ethy
lbut
yl)-
=
Oct
ylph
enol
D
omes
tic
Ani
mal
s -
Goa
t, S
heep
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
End
ocrin
e sy
stem
T
DLo
6
mg/
kg
2719
3-28
-8
Phe
nol,
(1,1
,3,3
-tet
ram
ethy
lbut
yl)-
=
Oct
ylph
enol
R
at
Oth
ers
- C
hang
es in
ute
rine
wei
ght
T
DLo
24
00
mg/
kg/3
D in
-te
rmitt
ent
33
204-
76-1
2,
6-ci
s-D
iphe
nylh
exam
ethy
lcyc
lote
tras
i-lo
xane
- 2
,6-c
is-
[(P
hMeS
iO)2
(Me2
SiO
)2][
Rab
bit
Pat
erna
l Effe
cts
- S
perm
atog
enes
is
(incl
udin
g ge
netic
mat
eria
l, sp
erm
m
orph
olog
y, m
otili
ty, a
nd c
ount
)
TD
Lo
1800
ug
/kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Mon
key
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct
T
DLo
28
0 m
g/kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Mon
key
Pat
erna
l Effe
cts
- S
perm
atog
enes
is
(incl
udin
g ge
netic
mat
eria
l, sp
erm
m
orph
olog
y, m
otili
ty, a
nd c
ount
)
TD
Lo
28
mg/
kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Dog
P
ater
nal E
ffect
s -
Pro
stat
e, s
emin
al
vess
icle
, Cow
per's
gla
nd, a
cces
sory
gl
ands
TD
Lo
400
mg/
kg
56ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 33
204-
76-1
2,
6-ci
s-D
iphe
nylh
exam
ethy
lcyc
lote
tras
i-lo
xane
- 2
,6-c
is-
[(P
hMeS
iO)2
(Me2
SiO
)2][
Dog
P
ater
nal E
ffect
s -
Spe
rmat
ogen
esis
(in
clud
ing
gene
tic m
ater
ial,
sper
m
mor
phol
ogy,
mot
ility
, and
cou
nt)
Pat
er-
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, spe
rm
duct
TD
Lo
400
mg/
kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Rab
bit
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct
T
DLo
4
mg/
kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Mou
se
Pat
erna
l Effe
cts
- P
rost
ate,
sem
inal
ve
ssic
le, C
owpe
r's g
land
, acc
esso
ry
glan
ds
TD
Lo
210
mg/
kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Rat
M
ater
nal E
ffect
s -
Ute
rus,
cer
vix,
va-
gina
T
DLo
3
mg/
kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Rat
E
ffect
s on
Fer
tility
- F
emal
e fe
rtili
ty in
-de
x (e
.g.,
# fe
mal
es p
regn
ant
per
# sp
erm
pos
itive
fem
ales
# fe
mal
es
preg
nant
per
# fe
mal
es m
ated
)
TD
Lo
1 m
g/kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Dog
P
ater
nal E
ffect
s -
Pro
stat
e, s
emin
al
vess
icle
, Cow
per's
gla
nd, a
cces
sory
gl
ands
Pat
erna
l Effe
cts
- O
ther
effe
cts
on m
ale
TD
Lo
10
gm/k
g
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Mou
se
LD
50
>5
gm/k
g
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Rat
M
ater
nal E
ffect
s -
Ute
rus,
cer
vix,
va-
gina
T
DLo
30
0 ug
/kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Rat
E
ffect
s on
Fer
tility
- O
ther
mea
sure
s of
fe
rtili
ty
TD
Lo
3 m
g/kg
57ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
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NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
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IUM
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SE
_CO
NC
.U
NIT
_DO
SE
_ 33
204-
76-1
2,
6-ci
s-D
iphe
nylh
exam
ethy
lcyc
lote
tras
i-lo
xane
- 2
,6-c
is-
[(P
hMeS
iO)2
(Me2
SiO
)2][
Rat
E
ffect
s on
Fer
tility
- P
ost-
impl
anta
tion
mor
talit
y (e
.g.,
dead
and
or
res
orbe
d im
plan
ts p
er to
tal n
umbe
r of
impl
ants
)
TD
Lo
10
mg/
kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Rat
P
ater
nal E
ffect
s -
Pro
stat
e, s
emin
al
vess
icle
, Cow
per's
gla
nd, a
cces
sory
gl
ands
TD
Lo
7 m
g/kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Rat
P
ater
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, sp
erm
duc
t Pat
erna
l Effe
cts
- P
rost
ate,
se
min
al v
essi
cle,
Cow
per's
gla
nd, a
c-ce
ssor
y g
land
s
TD
Lo
231
mg/
kg
3320
4-76
-1
2,6-
cis-
Dip
heny
lhex
amet
hylc
yclo
tetr
asi-
loxa
ne -
2,6
-cis
-[(
PhM
eSiO
)2(M
e2S
iO)2
][
Rat
LD50
>
5 gm
/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Bio
chem
ical
- D
ehyd
roge
nase
s
TD
Lo
675
mg/
kg/9
0D
cont
inuo
us
43
76-2
0-9
Mon
o 2
eth
yl h
exyl
phth
alat
e (M
EH
P)
Ham
ster
P
ater
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, sp
erm
duc
t
TD
Lo
9 gm
/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
E
ffect
s on
Fer
tility
- P
re-im
plan
tatio
n m
orta
lity
(e.g
., re
duct
ion
in n
umbe
r of
im
plan
ts p
er fe
mal
e to
tal n
umbe
r of
im
plan
ts p
er c
orpo
ra lu
tea)
TD
Lo
350
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) B
acte
ria -
B
Sub
tilis
40
0 ug
/dis
c
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
200
umol
/L/2
4H
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) H
amst
er
750
mg/
L (+
S9)
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
N
utrit
iona
l and
Gro
ss M
etab
olic
-
Wei
ght l
oss
or d
ecre
ased
wei
ght g
ain
T
DLo
51
11
mg/
kg/1
9D
cont
inuo
us
43
76-2
0-9
Mon
o 2
eth
yl h
exyl
phth
alat
e (M
EH
P)
Rat
Li
ver
- C
hang
es in
live
r w
eigh
t Bio
-ch
emic
al -
Deh
ydro
gena
ses
Bio
chem
i-ca
l - O
ther
tran
sfer
ases
TD
Lo
7 gm
/kg/
14D
in-
term
itten
t
58ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
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R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 43
76-2
0-9
Mon
o 2
eth
yl h
exyl
phth
alat
e (M
EH
P)
Rat
Li
ver
- C
hang
es in
live
r w
eigh
t Blo
od -
C
hang
es in
ser
um c
ompo
sitio
n (e
.g.,
TP
, bili
rubi
n, c
hole
ster
ol)
Bio
chem
ical
-
Lipi
ds in
clud
ing
tran
spor
t
TD
Lo
8400
m
g/kg
/1W
con
-tin
uous
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Live
r -
Cha
nges
in li
ver
wei
ght
T
DLo
68
25
mg/
kg/2
6W
cont
inuo
us
43
76-2
0-9
Mon
o 2
eth
yl h
exyl
phth
alat
e (M
EH
P)
Ham
ster
Li
ver
- C
hang
es in
live
r w
eigh
t Bio
-ch
emic
al -
Hep
atic
mic
roso
mal
mix
ed
oxid
ase
(dea
lkyl
atio
n, h
ydro
xyla
tion,
et
c.)
Bio
chem
ical
- O
ther
tran
sfer
ases
TD
Lo
7 gm
/kg/
14D
in-
term
itten
t
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
LD
50
415
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) H
amst
er
750
mg/
L
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Blo
od -
Pig
men
ted
or n
ucle
ated
red
bl
ood
cells
Blo
od -
Cha
nges
in le
uko-
cyte
(W
BC
) co
unt
TD
Lo
168
mg/
kg/2
8D
cont
inuo
us
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) H
amst
er
375
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
25
m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
LD
50
150
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
LD
50
1340
m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) H
amst
er
25
mg/
L
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
2 m
mol
/L
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
LD50
24
0 m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
LD50
20
8 m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct
T
DLo
40
0 m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Not
rep
orte
d D
RA
IZE
re
actio
n 10
0 m
g
59ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
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NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 43
76-2
0-9
Mon
o 2
eth
yl h
exyl
phth
alat
e (M
EH
P)
Mou
se
Effe
cts
on F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
per
tota
l num
ber
of im
plan
ts)
Effe
cts
on E
mbr
yo o
r F
etus
- O
ther
ef-
fect
s to
em
bryo
TD
Lo
1241
m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
E
ffect
s on
Fer
tility
- P
ost-
impl
anta
tion
mor
talit
y (e
.g.,
dead
and
or
res
orbe
d im
plan
ts p
er to
tal n
umbe
r of
impl
ants
) E
ffect
s on
Em
bryo
or
Fet
us -
Fet
al
deat
h
TD
Lo
665
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) H
uman
5
mm
ol/L
/1H
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
M
uscu
losk
elet
al s
yste
m
TD
Lo
100
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
E
ffect
s on
Fer
tility
- P
ost-
impl
anta
tion
mor
talit
y (e
.g.,
dead
and
or
res
orbe
d im
plan
ts p
er to
tal n
umbe
r of
impl
ants
) E
ffect
s on
Fer
tility
- L
itter
siz
e (e
.g.,
# fe
tuse
s pe
r lit
ter,
mea
sure
d b
efor
e bi
rth)
TD
Lo
596.
7 m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Effe
cts
on N
ewbo
rn -
Oth
er n
eona
tal
mea
sure
s or
effe
cts
T
DLo
45
00
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
E
ffect
s on
Em
bryo
or
Fet
us -
Fet
otox
ic-
ity (
exce
pt d
eath
, e.g
., st
unte
d fe
tus)
T
DLo
10
0 m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Pat
erna
l Effe
cts
- S
perm
atog
enes
is
(incl
udin
g ge
netic
mat
eria
l, sp
erm
m
orph
olog
y, m
otili
ty, a
nd c
ount
)
TD
Lo
3750
m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
E
ffect
s on
Em
bryo
or
Fet
us -
Fet
otox
ic-
ity (
exce
pt d
eath
, e.g
., st
unte
d fe
tus)
T
DLo
25
46
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Pat
erna
l Effe
cts
- S
perm
atog
enes
is
(incl
udin
g ge
netic
mat
eria
l, sp
erm
m
orph
olog
y, m
otili
ty, a
nd c
ount
)
TD
Lo
2 gm
/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Pat
erna
l Effe
cts
- T
este
s, e
pidi
dym
is,
sper
m d
uct
T
DLo
63
20
ug/k
g
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) R
at
Pat
erna
l Effe
cts
- O
ther
effe
cts
on m
ale
T
DLo
50
0 m
g/kg
60ERA/53559/Revised report/2007.06.04
DHI Water & Environment
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NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 43
76-2
0-9
Mon
o 2
eth
yl h
exyl
phth
alat
e (M
EH
P)
Rat
P
ater
nal E
ffect
s -
Pro
stat
e, s
emin
al
vess
icle
, Cow
per's
gla
nd, a
cces
sory
gl
ands
TD
Lo
1 gm
/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
E
ffect
s on
Fer
tility
- L
itter
siz
e (e
.g.,
# fe
tuse
s pe
r lit
ter,
mea
sure
d b
efor
e bi
rth)
TD
Lo
4360
m
g/kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
E
ffect
s on
Fer
tility
- P
ost-
impl
anta
tion
mor
talit
y (e
.g.,
dead
and
or
res
orbe
d im
plan
ts p
er to
tal n
umbe
r of
impl
ants
) E
ffect
s on
Fer
tility
- L
itter
siz
e (e
.g.,
# fe
tuse
s pe
r lit
ter,
mea
sure
d b
efor
e bi
rth)
Effe
cts
on E
mbr
yo o
r F
etus
- F
e-to
toxi
city
(ex
cep
TD
Lo
1193
.4
mg/
kg
4376
-20-
9 M
ono
2 et
hyl
hex
ylph
thal
ate
(ME
HP
) M
ouse
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
C
ardi
ovas
cula
r (c
ircul
ator
y) s
yste
m
TD
Lo
1387
m
g/kg
611-
99-4
4,
4'-D
ihyd
roxy
benz
ophe
non
Rat
E
ndoc
rine
- E
stro
geni
c
TD
Lo
47.5
m
g/kg
611-
99-4
4,
4'-D
ihyd
roxy
benz
ophe
non
Mou
se
>50
0 m
g/kg
611-
99-4
4,
4'-D
ihyd
roxy
benz
ophe
non
Ham
ster
20
0 um
ol/L
611-
99-4
4,
4'-D
ihyd
roxy
benz
ophe
non
Rat
O
ther
s -
Cha
nges
in u
terin
e w
eigh
t
TD
Lo
600
mg/
kg/3
D in
-te
rmitt
ent
61
64-9
8-3
Chl
ordi
mef
orm
R
at
End
ocrin
e -
Oth
er c
hang
es
TD
Lo
40
mg/
kg
61
64-9
8-3
Chl
ordi
mef
orm
M
ouse
LD50
71
m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Mou
se
Blo
od -
Tum
ors
T
DLo
21
84
mg/
kg/1
04W
co
ntin
uous
6164
-98-
3 C
hlor
dim
efor
m
Rat
E
ndoc
rine
- C
hang
e in
gon
adot
ropi
ns
End
ocrin
e -
Evi
denc
e of
thyr
oid
hypo
-fu
nctio
n E
ndoc
rine
- A
ndro
geni
c
TD
Lo
100
mg/
kg
6164
-98-
3 C
hlor
dim
efor
m
Ham
ster
E
ndoc
rine
- E
ffect
on
men
stru
al c
ycle
LD
50
200
mg/
kg
61
64-9
8-3
Chl
ordi
mef
orm
R
at
LD
50
160
mg/
kg
61
64-9
8-3
Chl
ordi
mef
orm
m
ice
decr
ease
in Ig
M a
ntib
ody-
form
ing
cells
LO
EL
20
mg/
kg b
ody-
wei
ght.d
ay
6164
-98-
3 C
hlor
dim
efor
m
Mam
mal
-
Uns
peci
fied
Spe
cies
LC
50
>58
00
mg/
m3/
1H
6164
-98-
3 C
hlor
dim
efor
m
Rab
bit
LD
50
625
mg/
kg
61
64-9
8-3
Chl
ordi
mef
orm
R
abbi
t S
ever
e D
RA
IZE
re
actio
n 10
0 m
g
61ERA/53559/Revised report/2007.06.04
DHI Water & Environment
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ME
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PE
CIE
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EF
FE
CT
C
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IUM
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SE
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NIT
_DO
SE
_ 61
64-9
8-3
Chl
ordi
mef
orm
R
abbi
t
LD50
64
0 m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Rat
E
ffect
s on
New
born
- B
ehav
iora
l
TD
Lo
1800
ug
/kg
61
64-9
8-3
Chl
ordi
mef
orm
R
at
Beh
avio
ral -
Alte
ratio
n if
oper
ant c
ondi
-tio
ning
T
DLo
60
m
g/kg
/3D
in-
term
itten
t
6164
-98-
3 C
hlor
dim
efor
m
Mou
se
Tum
orig
enic
- C
arci
noge
nic
by R
TE
CS
cr
iteria
Vas
cula
r -
Tum
ors
Lung
, Tho
-ra
x, o
r R
espi
ratio
n -
Tum
ors
TD
Lo
6552
m
g/kg
/78W
co
ntin
uous
6164
-98-
3 C
hlor
dim
efor
m
Hum
an
1 m
mol
/L
61
64-9
8-3
Chl
ordi
mef
orm
In
sect
s -
D
Mel
anog
aste
r
10
pp
b
6164
-98-
3 C
hlor
dim
efor
m
Bac
teria
- S
T
yphi
mur
ium
2
umol
/pla
te (
-S
9)
61
64-9
8-3
Chl
ordi
mef
orm
R
at
60
mg/
kg
61
64-9
8-3
Chl
ordi
mef
orm
H
amst
er
End
ocrin
e -
Oth
er c
hang
es
TD
Lo
75
mg/
kg
61
64-9
8-3
Chl
ordi
mef
orm
R
at
Bio
chem
ical
- E
ffect
on
infla
mm
atio
n or
m
edia
tion
of in
flam
mat
ion
T
DLo
40
m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Rat
C
ardi
ac -
Cha
nge
in r
ate
Vas
cula
r -
BP
lo
wer
ing
not c
hara
cter
ized
in a
uto-
nom
ic s
ectio
n
TD
Lo
5 m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Rat
E
ndoc
rine
- A
ndro
geni
c P
ater
nal E
f-fe
cts
- S
perm
atog
enes
is (
incl
udin
g ge
-ne
tic m
ater
ial,
sper
m m
orph
olog
y, m
o-til
ity, a
nd c
ount
) N
utrit
iona
l and
Gro
ss
Met
abol
ic -
Wei
ght l
oss
or d
ecre
ased
w
eigh
t gai
n
TD
Lo
200
mg/
kg
6164
-98-
3 C
hlor
dim
efor
m
Rat
E
ndoc
rine
- C
hang
e in
gon
adot
ropi
ns
Blo
od -
Oth
er c
hang
es
TD
Lo
50
mg/
kg
6164
-98-
3 C
hlor
dim
efor
m
rat
incr
ease
in A
CT
H, C
OR
T a
nd P
L LO
EL
20
mg/
kg b
ody
wei
ght
6164
-98-
3 C
hlor
dim
efor
m
Rat
E
ndoc
rine
- A
dren
al c
orte
x hy
perp
lasi
a
TD
Lo
20
mg/
kg
61
64-9
8-3
Chl
ordi
mef
orm
R
at
Blo
od -
U28
T
DLo
20
m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Ham
ster
E
ndoc
rine
- C
hang
e in
gon
adot
ropi
ns
Mat
erna
l Effe
cts
- O
ogen
esis
Mat
erna
l E
ffect
s -
Ova
ries,
fallo
pian
tube
s
TD
Lo
150
mg/
kg
6164
-98-
3 C
hlor
dim
efor
m
Mou
se
Bra
in a
nd C
over
ings
- O
ther
deg
ener
a-tiv
e ch
ange
s
TD
Lo
35
mg/
kg
62ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 61
64-9
8-3
Chl
ordi
mef
orm
H
amst
er
End
ocrin
e -
Cha
nge
in G
H E
ndoc
rine
- E
stro
geni
c
TD
Lo
37.5
m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Rat
LD50
90
m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Rat
LD50
26
3 m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Hum
an
1 m
mol
/L
61
64-9
8-3
Chl
ordi
mef
orm
M
ouse
LD50
16
0 m
g/kg
6164
-98-
3 C
hlor
dim
efor
m
Mou
se
LD
50
225
mg/
kg
74
00-0
8-0
p-C
oum
aric
aci
d (P
CA
) M
ouse
E
ffect
s on
Fer
tility
- A
bort
ion
T
DLo
50
m
g/kg
74
00-0
8-0
p-C
oum
aric
aci
d (P
CA
) M
ouse
LD50
65
7 m
g/kg
7400
-08-
0 p-
Cou
mar
ic a
cid
(PC
A)
Mou
se
Effe
cts
on F
ertil
ity -
Oth
er m
easu
res
of
fert
ility
T
DLo
35
m
g/kg
7400
-08-
0 p-
Cou
mar
ic a
cid
(PC
A)
Rat
P
ater
nal E
ffect
s -
Tes
tes,
epi
didy
mis
, sp
erm
duc
t Pat
erna
l Effe
cts
- P
rost
ate,
se
min
al v
essi
cle,
Cow
per's
gla
nd, a
c-ce
ssor
y g
land
s E
ffect
s on
Fer
tility
-
Mat
ing
perf
orm
ance
(e.
g., #
spe
rm
posi
tive
fem
ales
per
# fe
mal
es m
ated
#
copu
latio
ns p
er #
est
rus
cy
TD
Lo
2800
m
g/kg
7400
-08-
0 p-
Cou
mar
ic a
cid
(PC
A)
Mam
mal
-
Uns
peci
fied
Spe
cies
Mat
erna
l Effe
cts
- U
teru
s, c
ervi
x, v
a-gi
na
TD
Lo
9600
m
g/kg
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e R
at
End
ocrin
e -
Est
roge
nic
T
DLo
95
m
g/kg
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
ouse
16
80
mg/
kg/1
4D
cont
inuo
us
77
-09-
8 3,
3'-B
is(4
-hyd
roxy
phen
yl)p
htha
lid
= P
heno
lpht
hale
ine
Mou
se
Tum
orig
enic
- C
arci
noge
nic
by R
TE
CS
cr
iteria
Blo
od -
Lym
phom
as in
clud
ing
Hod
gkin
's d
isea
se
TD
Lo
4326
00
mg/
kg/1
03W
co
ntin
uous
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e R
at
Tum
orig
enic
- N
eopl
astic
by
RT
EC
S
crite
ria E
ndoc
rine
- A
dren
al c
orte
x tu
-m
ors
TD
Lo
3605
00
mg/
kg/1
03W
co
ntin
uous
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e R
at
LD
Lo
500
mg/
kg
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
ouse
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
U
roge
nita
l sys
tem
T
DLo
84
0 m
g/kg
63ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
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NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 77
-09-
8 3,
3'-B
is(4
-hyd
roxy
phen
yl)p
htha
lid
= P
heno
lpht
hale
ine
Mou
se
Effe
cts
on N
ewbo
rn -
Liv
e bi
rth
inde
x (s
imila
r to
T26
, exc
ept m
easu
red
afte
r bi
rth)
TD
Lo
840
mg/
kg
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e R
at
Live
r -
Cha
nges
in li
ver
wei
ght B
lood
-
Cha
nges
in s
erum
com
posi
tion
(e.g
., T
P, b
iliru
bin,
cho
lest
erol
) N
utrit
iona
l an
d G
ross
Met
abol
ic -
Wei
ght l
oss
or
decr
ease
d w
eigh
t gai
n
TD
Lo
324
gm/k
g/13
W
cont
inuo
us
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
ouse
Li
ver
- C
hang
es in
live
r w
eigh
t Blo
od -
C
hang
es in
ery
thro
cyte
(R
BC
) co
unt
Oth
ers
- C
hang
es in
test
icul
ar w
eigh
t
TD
Lo
106
gm/k
g/13
W
cont
inuo
us
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
ouse
Li
ver
- T
umor
s T
umor
igen
ic -
Act
ive
as
anti-
canc
er a
gent
T
DLo
28
8400
m
g/kg
/103
W
cont
inuo
us
77
-09-
8 3,
3'-B
is(4
-hyd
roxy
phen
yl)p
htha
lid
= P
heno
lpht
hale
ine
Rat
T
umor
igen
ic -
Equ
ivoc
al tu
mor
igen
ic
agen
t by
RT
EC
S c
riter
ia K
idne
y, U
re-
ter,
and
Bla
dder
- K
idne
y tu
mor
s
TD
Lo
1442
000
mg/
kg/1
03W
co
ntin
uous
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e H
uman
23
.2
mg/
L/22
H
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
ouse
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria E
ndoc
rine
- T
umor
s S
kin
and
App
enda
ges
- T
umor
s
TD
Lo
281
gm/k
g/2Y
con
-tin
uous
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
ouse
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria B
lood
- L
ymph
omas
incl
udin
g H
odgk
in's
dis
ease
TD
Lo
2884
00
mg/
kg/1
03W
co
ntin
uous
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e R
at
Tum
orig
enic
- C
arci
noge
nic
by R
TE
CS
cr
iteria
Kid
ney,
Ure
ter,
and
Bla
dder
-
Tum
ors
End
ocrin
e -
Adr
enal
cor
tex
tu-
mor
s
TD
Lo
364
gm/k
g/2Y
con
-tin
uous
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e R
at
Tum
orig
enic
- E
quiv
ocal
tum
orig
enic
ag
ent b
y R
TE
CS
crit
eria
End
ocrin
e -
Adr
enal
cor
tex
tum
ors
TD
Lo
3605
00
mg/
kg/1
03W
co
ntin
uous
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e R
at
>1
gm/k
g
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
ouse
K
idne
y, U
rete
r, a
nd B
ladd
er -
Cha
nges
in
kid
ney
wei
ght P
ater
nal E
ffect
s -
Tes
-te
s, e
pidi
dym
is, s
perm
duc
t
TD
Lo
123.
48
gm/k
g/21
W
cont
inuo
us
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
ouse
M
ater
nal E
ffect
s -
Par
turit
ion
Effe
cts
on
Fer
tility
- O
ther
mea
sure
s of
fert
ility
T
DLo
29
.4
gm/k
g
64ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
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NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
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NC
.U
NIT
_DO
SE
_ 77
-09-
8 3,
3'-B
is(4
-hyd
roxy
phen
yl)p
htha
lid
= P
heno
lpht
hale
ine
Mou
se
Effe
cts
on N
ewbo
rn -
Liv
e bi
rth
inde
x (s
imila
r to
T26
, exc
ept m
easu
red
afte
r bi
rth)
TD
Lo
123.
48
gm/k
g
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e R
at
End
ocrin
e -
Est
roge
nic
End
ocrin
e -
Cha
nges
in e
ndoc
rine
wei
ght (
unsp
eci-
fied)
Bio
chem
ical
- O
ther
car
bohy
-dr
ates
TD
Lo
160
mg/
kg/1
8H
77-0
9-8
3,3'
-Bis
(4-h
ydro
xyph
enyl
)pht
halid
=
Phe
nolp
htha
lein
e M
an
Gas
troi
ntes
tinal
- G
astr
itis
Gas
troi
ntes
-tin
al -
Nau
sea
or v
omiti
ng K
idne
y,
Ure
ter,
and
Bla
dder
- O
ther
cha
nges
in
urin
e co
mpo
sitio
n
TD
Lo
29
mg/
kg
77-4
0-7
2,2-
Bis
(4-h
ydro
xyph
enyl
)-n-
buta
n =
Bis
phen
ol B
R
at
Mat
erna
l Effe
cts
- U
teru
s, c
ervi
x, v
a-gi
na M
ater
nal E
ffect
s -
Oth
er e
ffect
s
TD
Lo
600
mg/
kg/3
D in
-te
rmitt
ent
92
-69-
3 4-
Hyd
roxy
biph
enyl
= 4
-P
heny
lphe
nol
Mou
se
LD
50
150
mg/
kg
92-6
9-3
4-H
ydro
xybi
phen
yl =
4-
Phe
nylp
heno
l M
ouse
Li
ver
- O
ther
cha
nges
LD
50
150
mg/
kg
92-6
9-3
4-H
ydro
xybi
phen
yl =
4-
Phe
nylp
heno
l M
ouse
T
umor
igen
ic -
Equ
ivoc
al tu
mor
igen
ic
agen
t by
RT
EC
S c
riter
ia L
ung,
Tho
rax,
or
Res
pira
tion
- T
umor
s B
lood
- L
eu-
kem
ia
TD
Lo
153
gm/k
g/78
W
inte
rmitt
ent
92-6
9-3
4-H
ydro
xybi
phen
yl =
4-
Phe
nylp
heno
l M
ouse
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria B
lood
- T
umor
s
TD
Lo
1000
m
g/kg
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-B
iphe
nol
Mou
se
Blo
od -
Cha
nges
in b
one
mar
row
not
in
clud
ed a
bove
T
DLo
40
m
g/kg
/12H
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-B
iphe
nol
Hum
an
100
nmol
/L
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-B
iphe
nol
Mou
se
40
mg/
kg
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-B
iphe
nol
Hum
an
5 um
ol/L
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-B
iphe
nol
Rab
bit
LD
50
1780
m
g/kg
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-B
iphe
nol
Rat
Lu
ng, T
hora
x, o
r R
espi
ratio
n -
Oth
er
chan
ges
Live
r -
Oth
er c
hang
es K
idne
y,
Ure
ter,
and
Bla
dder
- O
ther
cha
nges
LD50
49
20
mg/
kg
65ERA/53559/Revised report/2007.06.04
DHI Water & Environment
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PE
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FE
CT
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.U
NIT
_DO
SE
_ 92
-88-
6 4,
4'-D
ihyd
roxy
biph
enyl
= 4
,4'-
Bip
heno
l R
at
End
ocrin
e -
Est
roge
nic
T
DLo
19
0 m
g/kg
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-B
iphe
nol
Mou
se
LD
50
100
mg/
kg
94-1
3-3
Phe
nol,
2-oc
tyl-
Rat
LD50
28
00
mg/
kg
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Tum
orig
enic
- C
arci
noge
nic
by R
TE
CS
cr
iteria
End
ocrin
e -
Thy
roid
tum
ors
T
DLo
10
815
mg/
kg/1
03W
co
ntin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
N
utrit
iona
l and
Gro
ss M
etab
olic
-
Wei
ght l
oss
or d
ecre
ased
wei
ght g
ain
T
DLo
75
m
g/kg
/8W
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria E
ndoc
rine
- T
hyro
id tu
mor
s
TD
Lo
5475
m
g/kg
/1Y
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
Li
ver
- C
hang
es in
live
r w
eigh
t End
o-cr
ine
- C
hang
es in
thyr
oid
wei
ght
T
DLo
37
5 m
g/kg
/8W
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria L
ung,
Tho
rax,
or
Res
pira
tion
- T
umor
s E
ndoc
rine
- T
hyro
id tu
mor
s
TD
Lo
5306
m
g/kg
/77W
co
ntin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
C
ardi
ac -
Cha
nges
in h
eart
wei
ght
T
DLo
22
81
mg/
kg/2
6W
cont
inuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Tum
orig
enic
- C
arci
noge
nic
by R
TE
CS
cr
iteria
End
ocrin
e -
Thy
roid
tum
ors
T
DLo
90
12.5
m
g/kg
/103
W
cont
inuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Kid
ney,
Ure
ter,
and
Bla
dder
- C
hang
es
in k
idne
y w
eigh
t End
ocrin
e -
Cha
nges
in
Spl
een
wei
ght
TD
Lo
1500
m
g/kg
/8W
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ndoc
rine
- E
vide
nce
of th
yroi
d hy
po-
func
tion
T
DLo
11
40.6
m
g/kg
/26W
co
ntin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ndoc
rine
- E
vide
nce
of th
yroi
d hy
per-
func
tion
T
DLo
22
81
mg/
kg/1
Y c
on-
tinuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
End
ocrin
e -
Oth
er c
hang
es E
ndoc
rine
- C
hang
es in
thyr
oid
wei
ght B
lood
-
Cha
nges
in s
erum
com
posi
tion
(e.g
., T
P, b
iliru
bin,
cho
lest
erol
)
TD
Lo
764
mg/
kg/9
0D
cont
inuo
us
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria E
ndoc
rine
- T
hyro
id tu
mor
s
TD
Lo
9125
m
g/kg
/1Y
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
Tum
orig
enic
- C
arci
noge
nic
by R
TE
CS
cr
iteria
Liv
er -
Tum
ors
End
ocrin
e -
Thy
-ro
id tu
mor
s
TD
Lo
8652
0 m
g/kg
/103
W
cont
inuo
us
66ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
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NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) M
ouse
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria L
iver
- T
umor
s E
ndoc
rine
- T
hy-
roid
tum
ors
TD
Lo
8736
0 m
g/kg
/2Y
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Man
E
ndoc
rine
- E
vide
nce
of th
yroi
d hy
po-
func
tion
T
CLo
10
ug
/m3/
10Y
in-
term
itten
t
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ndoc
rine
- O
ther
cha
nges
Blo
od -
C
hang
es in
ser
um c
ompo
sitio
n (e
.g.,
TP
, bili
rubi
n, c
hole
ster
ol)
TD
Lo
297
mg/
kg/2
8D
cont
inuo
us
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ndoc
rine
- O
ther
cha
nges
End
ocrin
e -
Cha
nges
in th
yroi
d w
eigh
t Nut
ritio
nal
and
Gro
ss M
etab
olic
- W
eigh
t los
s or
de
crea
sed
wei
ght g
ain
TD
Lo
3600
m
g/kg
/17W
co
ntin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ndoc
rine
- E
vide
nce
of th
yroi
d hy
po-
func
tion
End
ocrin
e -
Cha
nges
in th
yroi
d w
eigh
t
TD
Lo
34.8
6 m
g/kg
/7D
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ndoc
rine
- E
vide
nce
of th
yroi
d hy
po-
func
tion
T
DLo
29
.05
mg/
kg/7
D c
on-
tinuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
End
ocrin
e -
Cha
nges
in S
plee
n w
eigh
t T
DLo
54
75
mg/
kg/2
6W
cont
inuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) M
ouse
Li
ver
- C
hang
es in
live
r w
eigh
t End
o-cr
ine
- E
vide
nce
of th
yroi
d hy
pofu
nctio
n B
ioch
emic
al -
Cyt
ochr
ome
oxid
ases
(in
clud
ing
oxid
ativ
e ph
osph
oryl
atio
n)
TD
Lo
840
mg/
kg/7
D c
on-
tinuo
us
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ndoc
rine
- E
vide
nce
of th
yroi
d hy
po-
func
tion
T
DLo
10
950
mg/
kg/1
Y c
on-
tinuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) M
ouse
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria L
iver
- T
umor
s B
lood
- L
ym-
phom
as in
clud
ing
Hod
gkin
's d
isea
se
TD
Lo
77
gm/k
g/82
W
cont
inuo
us
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
Live
r -
Cha
nges
in li
ver
wei
ght E
ndo-
crin
e -
Evi
denc
e of
thyr
oid
hypo
func
tion
T
DLo
27
7.2
mg/
kg/7
D c
on-
tinuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Beh
avio
ral -
Foo
d in
take
(an
imal
) E
n-do
crin
e -
Cha
nges
in th
yroi
d w
eigh
t N
utrit
iona
l and
Gro
ss M
etab
olic
-
Wei
ght l
oss
or d
ecre
ased
wei
ght g
ain
TD
Lo
220
mg/
kg/7
W c
on-
tinuo
us
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ndoc
rine
- C
hang
es in
thyr
oid
wei
ght
Nut
ritio
nal a
nd G
ross
Met
abol
ic -
W
eigh
t los
s or
dec
reas
ed w
eigh
t gai
n
TD
Lo
900
mg/
kg/8
W c
on-
tinuo
us
67ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Kid
ney,
Ure
ter,
and
Bla
dder
- C
hang
es
in k
idne
y w
eigh
t
TD
Lo
1800
m
g/kg
/8W
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria E
ndoc
rine
- T
hyro
id tu
mor
s
TD
Lo
1092
0 m
g/kg
/2Y
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
Li
ver
- C
hang
es in
live
r w
eigh
t
TD
Lo
450
mg/
kg/8
W c
on-
tinuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Cen
tral
ner
vous
sys
tem
Effe
cts
on
New
born
- W
eani
ng o
r la
ctat
ion
inde
x (e
.g.,
# al
ive
at w
eani
ng p
er #
aliv
e at
da
y 4)
TD
Lo
30
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
Effe
cts
on F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
per
tota
l num
ber
of im
plan
ts)
Effe
cts
on E
mbr
yo o
r F
etus
- F
etal
de
ath
Spe
cific
Dev
elop
men
tal A
bnor
-m
aliti
es -
Mus
culo
skel
etal
sys
tem
TD
Lo
2 gm
/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Cra
niof
acia
l (in
clud
ing
nose
and
to
ngue
)
TD
Lo
2 gm
/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Mus
culo
skel
etal
sys
tem
T
DLo
2
gm/k
g
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
T
umor
igen
ic -
Neo
plas
tic b
y R
TE
CS
cr
iteria
End
ocrin
e -
Thy
roid
tum
ors
T
DLo
27
37.5
m
g/kg
/1Y
con
-tin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
C
entr
al n
ervo
us s
yste
m S
peci
fic D
e-ve
lopm
enta
l Abn
orm
aliti
es -
Cra
niof
a-ci
al (
incl
udin
g no
se a
nd t
ongu
e) S
pe-
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Mus
culo
skel
etal
sys
tem
TD
Lo
300
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
2 gm
/kg
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Cen
tral
ner
vous
sys
tem
Spe
cific
De-
velo
pmen
tal A
bnor
mal
ities
- C
rani
ofa-
cial
(in
clud
ing
nose
and
ton
gue)
Spe
-ci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
M
uscu
losk
elet
al s
yste
m
TD
Lo
100
mg/
kg
68ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Mus
culo
skel
etal
sys
tem
Spe
cific
De-
velo
pmen
tal A
bnor
mal
ities
- H
omeo
-st
asis
TD
Lo
80
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ffect
s on
Em
bryo
or
Fet
us -
Fet
otox
ic-
ity (
exce
pt d
eath
, e.g
., st
unte
d fe
tus)
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
C
entr
al n
ervo
us s
yste
m S
peci
fic D
e-ve
lopm
enta
l Abn
orm
aliti
es -
Cra
niof
a-ci
al (
incl
udin
g no
se a
nd t
ongu
e)
TD
Lo
80
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ffect
s on
New
born
- V
iabi
lity
inde
x (e
.g.,
# al
ive
at d
ay 4
per
# b
orn
aliv
e)
Effe
cts
on N
ewbo
rn -
Wea
ning
or
lact
a-tio
n in
dex
(e.g
., #
aliv
e at
wea
ning
per
#
aliv
e at
da
y 4)
TD
Lo
10
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
G
astr
oint
estin
al s
yste
m
TD
Lo
100
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ffect
s on
Em
bryo
or
Fet
us -
Fet
otox
ic-
ity (
exce
pt d
eath
, e.g
., st
unte
d fe
tus)
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
M
uscu
losk
elet
al s
yste
m
TD
Lo
50
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
Effe
cts
on E
mbr
yo o
r F
etus
- F
etot
oxic
-ity
(ex
cept
dea
th, e
.g.,
stun
ted
fetu
s)
TD
Lo
2400
m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
C
rani
ofac
ial (
incl
udin
g no
se a
nd
tong
ue)
TD
Lo
60
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
Effe
cts
on N
ewbo
rn -
Sex
rat
io
TD
Lo
1600
m
g/kg
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Uro
geni
tal s
yste
m
TD
Lo
60
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ffect
s on
New
born
- V
iabi
lity
inde
x (e
.g.,
# al
ive
at d
ay 4
per
# b
orn
aliv
e)
TD
Lo
30
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
C
entr
al n
ervo
us s
yste
m E
ffect
s on
N
ewbo
rn -
Wea
ning
or
lact
atio
n in
dex
(e.g
., #
aliv
e at
wea
ning
per
# a
live
at
day
4)
TD
Lo
30
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ffect
s on
New
born
- G
row
th s
tatis
tics
(e.g
., re
duce
d w
eigh
t gai
n)
TD
Lo
30
mg/
kg
69ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Effe
cts
on F
ertil
ity -
Litt
er s
ize
(e.g
., #
fetu
ses
per
litte
r, m
easu
red
bef
ore
birt
h) S
peci
fic D
evel
opm
enta
l Abn
or-
mal
ities
- C
entr
al n
ervo
us s
yste
m E
f-fe
cts
on N
ewbo
rn -
Via
bilit
y in
dex
(e.g
., #
aliv
e at
da
y 4
per
# bo
rn a
live)
TD
Lo
30
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
M
uscu
losk
elet
al s
yste
m
TC
Lo
2720
0 ug
/m3/
3H
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ffect
s on
Em
bryo
or
Fet
us -
Fet
otox
ic-
ity (
exce
pt d
eath
, e.g
., st
unte
d fe
tus)
E
ffect
s on
Em
bryo
or
Fet
us -
Fet
al
deat
h
TC
Lo
120
mg/
m3/
3H
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rab
bit
Mild
D
RA
IZE
re
actio
n 50
0 m
g/24
H
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
LD
50
7800
m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
LD
50
3 gm
/kg
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) M
ouse
LD50
20
0 m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
LD50
18
32
mg/
kg
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
End
ocrin
e -
Oth
er c
hang
es
TD
Lo
1000
m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
E
ffect
s on
Em
bryo
or
Fet
us -
Fet
otox
ic-
ity (
exce
pt d
eath
, e.g
., st
unte
d fe
tus)
T
DLo
84
m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Yea
st -
S
Cer
evis
iae
50
mg/
L
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria E
ndoc
rine
- T
hyro
id tu
mor
s
11
466
mg/
kg/7
8W
cont
inuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Tum
orig
enic
- E
quiv
ocal
tum
orig
enic
ag
ent b
y R
TE
CS
crit
eria
Liv
er -
Tum
ors
5470
m
g/kg
/26W
co
ntin
uous
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria E
ndoc
rine
- T
umor
s E
ndoc
rine
- T
hyro
id tu
mor
s
91
25
mg/
kg/2
Y c
on-
tinuo
us
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
T
umor
igen
ic -
Car
cino
geni
c by
RT
EC
S
crite
ria E
ndoc
rine
- T
hyro
id tu
mor
s
14
6 gm
/kg/
2Y c
on-
tinuo
us
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
Tum
orig
enic
- C
arci
noge
nic
by R
TE
CS
cr
iteria
End
ocrin
e -
Thy
roid
tum
ors
Tum
orig
enic
Effe
cts
- T
estic
ular
tum
ors
44
gm
/kg/
2Y c
on-
tinuo
us
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Bac
teria
- E
C
oli
10
gm/L
70ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) H
amst
er
80
ug/L
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rat
M
ater
nal E
ffect
s -
Par
turit
ion
Effe
cts
on
New
born
- S
tillb
irth
Effe
cts
on N
ewbo
rn
- G
row
th s
tatis
tics
(e.g
., re
duce
d w
eigh
t gai
n)
TD
Lo
2800
m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mol
d -
A
Nid
ulan
s
39
200
umol
/L
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rab
bit
Effe
cts
on F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
per
tota
l num
ber
of im
plan
ts)
TD
Lo
1120
m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Inse
cts
- D
M
elan
ogas
ter
500
umol
/L
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
6 gm
/kg
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) R
at
200
mg/
kg
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) H
amst
er
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Cen
tral
ner
vous
sys
tem
Spe
cific
De-
velo
pmen
tal A
bnor
mal
ities
- C
rani
ofa-
cial
(in
clud
ing
nose
and
ton
gue)
TD
Lo
1200
m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mou
se
1800
m
g/L
(+S
9)
96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) B
acte
ria -
E
Col
i
50
0 m
g/L
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Rab
bit
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Cen
tral
ner
vous
sys
tem
T
DLo
14
0 m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Ham
ster
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
M
uscu
losk
elet
al s
yste
m
TD
Lo
600
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Cat
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
E
ye, e
ar S
peci
fic D
evel
opm
enta
l Ab-
norm
aliti
es -
Bod
y w
all S
peci
fic D
evel
-op
men
tal A
bnor
mal
ities
- C
rani
ofac
ial
(incl
udin
g no
se a
nd t
ongu
e)
TD
Lo
600
mg/
kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Ham
ster
S
peci
fic D
evel
opm
enta
l Abn
orm
aliti
es -
C
rani
ofac
ial (
incl
udin
g no
se a
nd
tong
ue)
Spe
cific
Dev
elop
men
tal A
b-no
rmal
ities
- M
uscu
losk
elet
al s
yste
m
Spe
cific
Dev
elop
men
tal A
bnor
mal
ities
-
Gas
troi
ntes
tinal
sys
tem
TD
Lo
6480
m
g/kg
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Ham
ster
E
ffect
s on
Em
bryo
or
Fet
us -
Fet
otox
ic-
ity (
exce
pt d
eath
, e.g
., st
unte
d fe
tus)
T
DLo
21
60
mg/
kg
71ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
PE
CIE
S
EF
FE
CT
C
RIT
ER
IUM
DO
SE
_CO
NC
.U
NIT
_DO
SE
_ 96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) H
amst
er
Effe
cts
on F
ertil
ity -
Pos
t-im
plan
tatio
n m
orta
lity
(e.g
., de
ad a
nd o
r r
esor
bed
impl
ants
per
tota
l num
ber
of im
plan
ts)
Effe
cts
on E
mbr
yo o
r F
etus
- F
etal
de
ath
TD
Lo
2400
m
g/kg
72ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Tab
le 5
.6
Ove
rvie
w o
f wild
life
rele
vant
sys
tem
ic to
xici
ty d
ata
of c
ateg
ory
1 su
bsta
nces
CA
SN
R
NA
ME
S
peci
es N
ame
EF
FE
CT
C
RIT
ER
IUM
CO
NC
EN
TR
AT
UN
IT_O
F_C
O92
-69-
3 4-
Hyd
roxy
biph
enyl
= 4
-Phe
nylp
heno
l D
aphn
ia m
agna
M
orta
lity
LC50
3.
66
mg/
l 92
-69-
3 4-
Hyd
roxy
biph
enyl
= 4
-Phe
nylp
heno
l T
etra
hym
ena
pyrif
orm
is
Pop
ulat
ion
Cha
nges
, Gen
eral
; D
ecre
ase
EC
50
7.05
m
g/l
92-6
9-3
4-H
ydro
xybi
phen
yl =
4-P
heny
lphe
nol
Dap
hnia
mag
na
Mor
talit
y LC
50
3.66
m
g/l
92-6
9-3
4-H
ydro
xybi
phen
yl =
4-P
heny
lphe
nol
Dap
hnia
mag
na
Imm
obile
E
C50
3.
66
mg/
l 16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) R
ana
tem
pora
ria
Mor
talit
y; In
crea
se
LC50
25
00
mg/
l 16
34-0
4-4
met
hyl t
ertia
ry b
utyl
eth
er (
MT
BE
) A
lbur
nus
albu
r-nu
s M
orta
lity
LC50
10
00
mg/
l
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Pim
epha
les
prom
elas
M
orta
lity
LC50
67
2 m
g/l
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Nito
cra
spin
ipes
M
orta
lity
LC50
10
00
mg/
l 11
13-0
2-6
Om
etho
ate
Dap
hnia
mag
na
Imm
obile
E
C50
0.
021
mg/
l 11
13-0
2-6
Om
etho
ate
Aph
aniu
s fa
scia
-tu
s M
orta
lity
LC50
* 2.
69
mg/
l
1113
-02-
6 O
met
hoat
e A
rtem
ia s
p.
Mor
talit
y; In
crea
se
EC
50
25
mg/
l 11
13-0
2-6
Om
etho
ate
Dap
hnia
mag
na
Mor
talit
y LC
25
0.00
38
mg/
l 11
13-0
2-6
Om
etho
ate
Dap
hnia
mag
na
Mor
talit
y LC
50
0.00
42
mg/
l 11
13-0
2-6
Om
etho
ate
Aph
aniu
s fa
scia
-tu
s M
orta
lity
LC50
* 1.
61
mg/
l
1113
-02-
6 O
met
hoat
e A
phan
ius
fasc
ia-
tus
Mor
talit
y LC
50*
1.51
m
g/l
314-
40-9
B
rom
acil
Sce
nede
smus
su
bspi
catu
s P
opul
atio
n C
hang
es, G
ener
al;
Dec
reas
e N
OE
C
0.04
5 m
g/l
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s P
enae
us m
ono-
don
Mor
talit
y LC
50
0.00
0327
m
g/l
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s P
enae
us m
ono-
don
Mor
talit
y LC
50
0.00
064
mg/
l
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s P
enae
us m
ono-
don
Mor
talit
y LC
50
0.00
0768
m
g/l
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s P
enae
us m
ono-
don
Mor
talit
y LC
50
0.00
0514
m
g/l
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s B
ella
mya
ben
-ga
lens
is
Mor
talit
y LC
50
0.00
19
mg/
l
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s P
enae
us m
ono-
don
Mor
talit
y LC
50
0.00
0313
m
g/l
73ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
peci
es N
ame
EF
FE
CT
C
RIT
ER
IUM
CO
NC
EN
TR
AT
UN
IT_O
F_C
O13
593-
03-8
Q
uina
lpho
s =
Chi
nalp
hos
Tila
pia
mos
-sa
mbi
ca
Mor
talit
y; In
crea
se
LC50
0.
003
mg/
l
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s P
enae
us m
ono-
don
Mor
talit
y LC
50
0.00
0124
m
g/l
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Poe
cilia
ret
icu-
lata
M
orta
lity;
Incr
ease
LC
50
7500
m
g/l
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Chl
orel
la p
yre-
noid
osa
Gro
wth
, Gen
eral
E
C50
66
00
mg/
l
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Onc
orhy
nchu
s m
ykis
s M
ultip
le E
ffect
s R
epor
ted
as
One
Res
ult
LOE
C
100
mg/
l
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Dap
hnia
mag
na
Mor
talit
y LC
50
18
mg/
l 96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) D
aphn
ia m
agna
M
orta
lity
LC50
26
.4
mg/
l 96
-45-
7 E
thyl
ene
Thi
oure
a (E
TU
) O
ncor
hync
hus
myk
iss
Gro
wth
, Gen
eral
LO
EC
10
0 m
g/l
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Mic
rohy
la o
rnat
a M
orta
lity
NO
LC
5 m
g/l
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Onc
orhy
nchu
s m
ykis
s M
ultip
le E
ffect
s R
epor
ted
as
One
Res
ult
EC
50
1000
m
g/l
1582
-09-
8 T
riflu
ralin
M
ugil
ceph
alus
A
bnor
mal
; Inc
reas
e N
OE
C
0.00
3 m
g/l
1582
-09-
8 T
riflu
ralin
C
yprin
odon
va
riega
tus
Mor
talit
y LC
50-F
T
190
ug/l
1582
-09-
8 T
riflu
ralin
m
alla
rd d
uck
embr
yoni
c de
ath,
red
uced
gr
owth
, inc
reas
ed r
ate
of b
ile
form
atio
n an
d of
stu
nted
ness
of
the
embr
yos
1582
-09-
8 T
riflu
ralin
M
ugil
ceph
alus
A
bnor
mal
; Inc
reas
e LO
EC
0.
005
mg/
l 15
82-0
9-8
Trif
lura
lin
Onc
orhy
nchu
s m
ykis
s M
orta
lity;
Incr
ease
LC
50
0.01
35
mg/
l
1582
-09-
8 T
riflu
ralin
R
asbo
ra h
et-
erom
orph
a M
orta
lity
LC50
0.
0034
7 m
g/l
1582
-09-
8 T
riflu
ralin
Le
pom
is m
acro
-ch
irus
Mor
talit
y; In
crea
se
LC50
0.
01
mg/
l
1582
-09-
8 T
riflu
ralin
O
ncor
hync
hus
myk
iss
Mor
talit
y LC
50
0.00
025
mg/
l
1582
-09-
8 T
riflu
ralin
D
aphn
ia m
agna
M
orta
lity
NO
LC
0.00
72
mg/
l 15
82-0
9-8
Trif
lura
lin
Pim
epha
les
prom
elas
M
orta
lity
NO
LC
0.01
65
mg/
l
74ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
peci
es N
ame
EF
FE
CT
C
RIT
ER
IUM
CO
NC
EN
TR
AT
UN
IT_O
F_C
O92
-88-
6 4,
4'-D
ihyd
roxy
biph
enyl
= 4
,4'-B
iphe
nol
Tet
rahy
men
a th
erm
ophi
la
Pop
ulat
ion
Cha
nges
, Gen
eral
E
C50
11
.5
mg/
l
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-Bip
heno
l T
etra
hym
ena
ther
mop
hila
C
hem
ical
Avo
idan
ce; I
n-cr
ease
E
C10
9
mg/
l
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-Bip
heno
l T
etra
hym
ena
ther
mop
hila
P
opul
atio
n C
hang
es, G
ener
al
NO
EC
1
mg/
l
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-Bip
heno
l T
etra
hym
ena
ther
mop
hila
C
hem
ical
Avo
idan
ce; N
EF
E
C0
7.5
mg/
l
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,4
'-Bip
heno
l T
etra
hym
ena
ther
mop
hila
B
iom
ass;
Incl
udes
Har
vest
Y
ield
, Fru
it or
See
d Y
ield
, M
ass
of O
rgan
ism
, Mas
s of
P
opul
atio
n.
EC
20
6.9
mg/
l
104-
40-5
4-
Non
ylph
enol
(4-
NP
) S
alm
o sa
lar
Mor
talit
y LC
50
0.19
m
g/l
104-
40-5
4-
Non
ylph
enol
(4-
NP
) P
imep
hale
s pr
omel
as
Mor
talit
y LC
50
0.14
m
g/l
104-
40-5
4-
Non
ylph
enol
(4-
NP
) S
alm
o sa
lar
Mor
talit
y LC
50
0.13
m
g/l
104-
40-5
4-
Non
ylph
enol
(4-
NP
) C
hiro
nom
us te
n-ta
ns
Mor
talit
y; In
crea
se
NO
EC
0.
042
mg/
l
104-
40-5
4-
Non
ylph
enol
(4-
NP
) D
aphn
ia m
agna
M
orta
lity
NO
LC
0.00
62
mg/
l 10
4-40
-5
4-N
onyl
phen
ol (
4-N
P)
Pim
epha
les
prom
elas
Le
sion
s; In
crea
se
LOE
C
0.00
19
mg/
l
104-
40-5
4-
Non
ylph
enol
(4-
NP
) S
alm
o sa
lar
Mor
talit
y LC
50
0.16
m
g/l
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Dre
isse
na p
oly-
mor
pha
Abi
lity
to D
etac
h fr
om S
ub-
stra
te; I
ncre
ase
EC
50
3.4
mg/
l
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Ory
zias
latip
es
Mor
talit
y LC
50
2.5
mg/
l 25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) Ic
talu
rus
punc
-ta
tus
Mor
talit
y; In
crea
se
LC50
1.
5 m
g/l
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Onc
orhy
nchu
s m
ykis
s M
orta
lity;
Incr
ease
LC
50
1 m
g/l
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Ory
zias
latip
es
Mor
talit
y LC
50
5.6
mg/
l 25
013-
16-5
te
rt.-
But
ylhy
drox
yani
sole
(B
HA
) O
ryzi
as la
tipes
M
orta
lity
LC50
2.
5 m
g/l
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le (
BH
A)
Ory
zias
latip
es
Mor
talit
y LC
50
5.5
mg/
l 43
76-2
0-9
Mon
o 2
ethy
l hex
ylph
thal
ate
(ME
HP
) C
hiro
nom
us
plum
osus
Im
mob
ile
EC
50
72
mg/
l
4376
-20-
9 M
ono
2 et
hyl h
exyl
phth
alat
e (M
EH
P)
Chi
rono
mus
pl
umos
us
Mor
talit
y; In
crea
se
LC50
72
m
g/l
75ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
SN
R
NA
ME
S
peci
es N
ame
EF
FE
CT
C
RIT
ER
IUM
CO
NC
EN
TR
AT
UN
IT_O
F_C
O43
76-2
0-9
Mon
o 2
ethy
l hex
ylph
thal
ate
(ME
HP
) C
hiro
nom
us
plum
osus
Im
mob
ile; I
ncre
ase
EC
50
72
mg/
l
7400
-08-
0 p-
Cou
mar
ic a
cid
(PC
A)
Sel
enas
trum
ca
pric
ornu
tum
P
opul
atio
n C
hang
es, G
ener
al;
Dec
reas
e LO
EC
16
4.16
m
g/l
6164
-98-
3 C
hlor
dim
efor
m
Onc
orhy
nchu
s m
ykis
s M
orta
lity;
Incr
ease
LC
50
29
mg/
l
6164
-98-
3 C
hlor
dim
efor
m
Icta
luru
s pu
nc-
tatu
s M
orta
lity;
Incr
ease
LC
50
20.2
m
g/l
6164
-98-
3 C
hlor
dim
efor
m
Onc
orhy
nchu
s m
ykis
s M
orta
lity;
Incr
ease
LC
50
29
mg/
l
6164
-98-
3 C
hlor
dim
efor
m
Onc
orhy
nchu
s m
ykis
s M
orta
lity;
Incr
ease
LC
50
13.2
m
g/l
6164
-98-
3 C
hlor
dim
efor
m
Icta
luru
s pu
nc-
tatu
s M
orta
lity;
Incr
ease
LC
50
20.7
m
g/l
6164
-98-
3 C
hlor
dim
efor
m
Onc
orhy
nchu
s m
ykis
s M
orta
lity;
Incr
ease
LC
50
13.2
m
g/l
6164
-98-
3 C
hlor
dim
efor
m
Onc
orhy
nchu
s m
ykis
s M
orta
lity
LC50
13
.2
mg/
l
96-1
2-8
Dib
rom
ochl
orop
ropa
ne (
DB
CP
) In
dopl
anor
bis
exus
tus
Mor
talit
y LC
50
57
mg/
l
96-1
2-8
Dib
rom
ochl
orop
ropa
ne (
DB
CP
) C
ipan
gopa
ludi
na
mal
leat
a M
orta
lity
LC50
53
m
g/l
96-1
2-8
Dib
rom
ochl
orop
ropa
ne (
DB
CP
) S
emis
ulco
spira
lib
ertin
a M
orta
lity
LC50
50
m
g/l
96-1
2-8
Dib
rom
ochl
orop
ropa
ne (
DB
CP
) P
hyse
lla a
cuta
M
orta
lity
LC50
24
m
g/l
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 76
5.3.2 Evaluation of exposure of humans and wildlife (Task 3.3) Monitoring data for CAT 1 and CAT 2 substance has been searched in the COMMPS database/EEA. However, since COMMPS included monitoring data for only a few CAT 1 and CAT 2 substances (5 substances) it has been decided not to include these in the present project. Evaluation of the exposure of the environment has thus in the present project been based on the PC program EUSES. EUSES summary report for CAT 1 and CAT 2 substance are now included in the EDC database. Selected EUSES data (release to the environment, distribution and concentra-tion in water, sediment and soil, second poising in fish and top predators, and human in-take) are included in datasheet of the CAT 1 substances and based on an evaluation of the results of the EUSES calculations together with an evaluation of the use category (e.g. cosmetic, pesticide etc.) a subjective evaluation of exposure concern (high, me-dium, low) was performed. E.g. if a substance turned out to be ready biodegradable, but used in cosmetics a relative high human exposure can be foreseen and the substance is rated as ‘high concern’. It shall be clearly emphasised that the exposure evaluation is not a risk assessment and that the choices for the categorisation (high, medium, low concern) has solely been made by the consultant. An overview of selected EUSES data for CAT 1 substances is presented in Table 5.5 and Figures 5.1-5.6 below.
77ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Tab
le 5
.5
Ove
rvie
w o
f sel
ecte
d E
US
ES
dat
a fo
r C
AT
1 s
ubst
ance
s
CA
S N
o.
Che
mic
al n
ame
Ton
nage
of
subs
tanc
e us
ed in
E
US
ES
cal
-cu
latio
ns
Tot
al r
e-le
ase
to
envi
ron-
men
t (%
of u
se)
Rel
ease
to
air
Rel
ease
to
was
te w
a-te
r
Loca
l PE
C
in s
urfa
ce
wat
er d
urin
g em
issi
on
epis
ode
(dis
solv
ed)
Loca
l PE
C in
fr
esh
wat
er
sedi
men
t du
ring
em
is-
sion
epi
sode
Con
cent
ra-
tion
in fi
sh fo
r se
cond
ary
pois
onin
g (f
resh
wat
er)
Con
cent
ra-
tion
in fi
sh-
eatin
g m
arin
e to
p-pr
edat
ors
Loca
l tot
al
daily
inta
ke
for
hum
ans
Reg
iona
l tot
al
daily
inta
ke
for
hum
ans
[tonn
es.y
r-1]
(%
) [k
g.ye
ar-1
][k
g.ye
ar-1
][m
g.l-
1]
[mg.
kgw
wt-
1]
[mg.
kgw
wt-
1][m
g.kg
ww
t-1]
[mg.
kg-1
.d-1
][m
g.kg
-1.d
-1]
1004
3-35
-3
Bor
ic a
cid
5000
0 0.
2 37
5.0
1125
00
2.4
2.1
1.4
0.2
6.7E
-02
1.6E
-05
104-
40-5
P
heno
l, 4-
nony
l- 10
2.
0 0.
1 20
0 4.
3 97
9.0
933.
0 42
4.0
2.5E
+02
1.
6E-0
4
1113
-02-
6 O
met
hoat
e 50
0 1.
5 3.
8 75
00
2.5
2.2
0.7
0.0
3.6E
-02
1.0E
-05
1131
-60-
8 P
heno
l, 4-
cycl
ohex
yl-
10
2.0
0.1
200
8.3
302.
0 8.
8 0.
2 1.
7E+
01
9.6E
-06
120-
47-8
B
enzo
ic a
cid,
4-
hydr
oxy-
, et
hyl e
ster
50
2.0
0.5
999
0.0
0.1
0.2
0.0
1.8E
-03
2.3E
-07
131-
18-0
1,
2-B
enze
nedi
-ca
rbox
ylic
aci
d,
dipe
ntyl
50
1.6
0.4
799
0.4
66.9
15
50.0
12
90.0
1.
5E+
01
7.7E
-05
131-
55-5
M
etha
none
, bi
s(2,
4-di
-hy
drox
y-ph
enyl
)-
50
2.0
0.5
1000
9.
6 68
.8
3.0
0.1
4.1E
+00
4.
1E-0
6
131-
56-6
M
etha
none
, (2
,4-
dihy
drox
y-ph
enyl
)phe
nyl-
50
5.9
1.1
2970
5.
2 45
.4
12.7
0.
3 2.
3E+
00
1.1E
-05
131-
70-4
1,
2-B
enze
nedi
-ca
rbox
ylic
aci
d,
mon
obut
yl
10
2.0
0.1
200
1.2
9.4
0.1
0.0
6.3E
-02
7.5E
-08
1359
3-03
-8
Die
thqu
inal
-ph
ion
500
1.5
3.8
7500
2.
0 93
.1
482.
0 12
.2
8.0E
+00
8.
2E-0
4
1508
7-24
-8
Bic
yclo
[2.2
.1]
hept
an-2
-one
, 1,
7,7-
trim
e
50
2.0
0.5
1000
7.
2 44
5.0
183.
0 10
.2
3.8E
+01
7.
0E-0
5
1582
-09-
8 B
enzo
ic a
cid,
4-
hydr
oxy-
, et
hyl e
ster
1000
0 0.
2 80
.1
2400
0 2.
0 27
0.0
5600
0.0
2250
0.0
6.4E
+01
8.
0E-0
3
78ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
S N
o.
Che
mic
al n
ame
Ton
nage
of
subs
tanc
e us
ed in
E
US
ES
cal
-cu
latio
ns
Tot
al r
e-le
ase
to
envi
ron-
men
t (%
of u
se)
Rel
ease
to
air
Rel
ease
to
was
te w
a-te
r
Loca
l PE
C
in s
urfa
ce
wat
er d
urin
g em
issi
on
epis
ode
(dis
solv
ed)
Loca
l PE
C in
fr
esh
wat
er
sedi
men
t du
ring
em
is-
sion
epi
sode
Con
cent
ra-
tion
in fi
sh fo
r se
cond
ary
pois
onin
g (f
resh
wat
er)
Con
cent
ra-
tion
in fi
sh-
eatin
g m
arin
e to
p-pr
edat
ors
Loca
l tot
al
daily
inta
ke
for
hum
ans
Reg
iona
l tot
al
daily
inta
ke
for
hum
ans
[tonn
es.y
r-1]
(%
) [k
g.ye
ar-1
][k
g.ye
ar-1
][m
g.l-
1]
[mg.
kgw
wt-
1]
[mg.
kgw
wt-
1][m
g.kg
ww
t-1]
[mg.
kg-1
.d-1
][m
g.kg
-1.d
-1]
1634
-04-
4 P
ropa
ne, 2
-m
etho
xy-2
-m
ethy
l-
5000
0 2.
7 12
5100
0.0
7500
0 4.
7 7.
5 3.
1 0.
2 4.
0E-0
1 4.
1E-0
5
2501
3-16
-5
Phe
nol,
(1,1
-di
met
hyle
thyl
)-4-
met
hoxy
-
500
1.5
3.8
7500
2.
3 29
.1
59.8
1.
3 8.
3E-0
1 6.
3E-0
5
2719
3-28
-8
Phe
nol,
(1,1
,3,3
-te
tram
eth
ylbu
-ty
l)-
10
2.0
0.1
200
5.2
860.
0 67
2.0
256.
0 1.
7E+
02
1.1E
-04
3320
4-76
-1
Cyc
lote
tras
i-lo
xane
, 2,
2,4,
6,6,
8-he
xam
et
10
2.0
0.1
200
0.4
727.
0 20
2.0
913.
0 2.
7E+
02
1.1E
-03
3686
1-47
-9
Rig
tig
50
1.6
0.4
799
0.9
102.
0 17
30.0
59
4.0
1.6E
+01
2.
4E-0
4 43
76-2
0-9
Mon
o(2-
ethy
l-he
xyl)p
htha
late
10
2.
0 0.
1 20
0 7.
3 48
3.0
41.8
2.
3 4.
4E+
01
2.9E
-05
50-1
8-0
Cyc
loph
os-
pham
ide
10
1.8
0.1
180
1.0
1.3
0.0
0.0
4.4E
-02
2.1E
-07
5466
-77-
3 2-
Pro
peno
ic
acid
, 3-(
4-m
etho
xy-
phen
yl)-
,
5000
0.
0 5.
0 15
000
1.1
251.
0 73
900.
0 34
400.
0 8.
9E+
01
1.3E
-02
556-
67-2
O
ctam
ethy
ltet-
rasi
loxa
ne
5000
0 0.
8 30
0000
.090
000
0.7
31.4
32
8.0
149.
0 1.
2E+
00
3.8E
-04
611-
99-4
U
nkno
wn
10
1.8
0.1
180
1.0
3.9
0.2
0.0
3.4E
-01
4.4E
-07
6164
-98-
3 C
hlor
dim
efor
m
10
1.8
0.1
180
1.0
7.7
0.7
0.0
1.3E
-01
7.5E
-07
7400
-08-
0 2-
Pro
peno
ic
acid
, 3-(
4-hy
drox
y-ph
enyl
)-
10
2.0
0.1
200
1.3
3.4
0.0
0.0
1.3E
-01
2.9E
-08
79ERA/53559/Revised report/2007.06.04
DHI Water & Environment
CA
S N
o.
Che
mic
al n
ame
Ton
nage
of
subs
tanc
e us
ed in
E
US
ES
cal
-cu
latio
ns
Tot
al r
e-le
ase
to
envi
ron-
men
t (%
of u
se)
Rel
ease
to
air
Rel
ease
to
was
te w
a-te
r
Loca
l PE
C
in s
urfa
ce
wat
er d
urin
g em
issi
on
epis
ode
(dis
solv
ed)
Loca
l PE
C in
fr
esh
wat
er
sedi
men
t du
ring
em
is-
sion
epi
sode
Con
cent
ra-
tion
in fi
sh fo
r se
cond
ary
pois
onin
g (f
resh
wat
er)
Con
cent
ra-
tion
in fi
sh-
eatin
g m
arin
e to
p-pr
edat
ors
Loca
l tot
al
daily
inta
ke
for
hum
ans
Reg
iona
l tot
al
daily
inta
ke
for
hum
ans
[tonn
es.y
r-1]
(%
) [k
g.ye
ar-1
][k
g.ye
ar-1
][m
g.l-
1]
[mg.
kgw
wt-
1]
[mg.
kgw
wt-
1][m
g.kg
ww
t-1]
[mg.
kg-1
.d-1
][m
g.kg
-1.d
-1]
77-0
9-8
1(3H
)-Is
oben
zo-
fura
none
, 3,3
-bi
s(4-
hydr
o
10
2.0
0.1
200
9.5
91.9
1.
0 0.
0 4.
3E+
00
1.2E
-06
77-4
0-7
2,2-
bis(
4-hy
drox
y-ph
enyl
)but
ane
10
1.8
0.09
18
0 0.
738
46.7
35
.2
1.9
4.2E
+00
2.
9E-0
5
92-6
9-3
1,1'
-Bip
hen
yl -
4-ol
10
00
2.4
30.0
24
000
3.8
42.5
16
2.0
3.4
2.2E
+00
7.
5E-0
5
92-8
8-6
1,1'
-Bip
hen
yl -
4,4'
-dio
l 10
1.
8 0.
1 18
0 1.
0 7.
0 0.
6 0.
0 4.
1E-0
1 8.
5E-0
7
94-1
3-3
Ben
zoic
aci
d,
4-hy
drox
y-,
prop
yl e
ster
10
2.0
0.1
200
9.5
90.0
1.
0 0.
0 2.
1E+
00
1.1E
-06
94-2
6-8
Ben
zoic
aci
d,
4-hy
drox
y-,
buty
l est
er
10
2.0
0.1
200
1.2
20.4
0.
4 0.
1 1.
1E-0
1 2.
5E-0
7
96-1
2-8
Pro
pane
, 1,2
-di
brom
o-3-
chlo
ro-
10
1.9
9.0
180
0.8
6.6
0.6
0.0
4.1E
-02
1.8E
-07
96-4
5-7
2-Im
ida-
zolid
inet
hion
e 10
00
0.3
10.0
30
00
0.5
0.4
0.3
0.0
1.4E
-02
3.1E
-06
99-7
6-3
50
0 2.
0 5.
0 10
000
1.3
4.0
0.8
0.1
2.8E
-02
1.5E
-06
99-9
6-7
Ben
zoic
aci
d,
4-hy
drox
y-
1000
0.
3 10
.0
3000
0.
1 0.
1 0.
1 0.
0 8.
6E-0
3 4.
2E-0
7
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 80
Release to air and wastewater - CAT 1 substances
0
20000
40000
60000
80000
100000
120000
140000
1004
3-35
-3
104-
40-5
1113
-02-
6
1131
-60-
8
120-
47-8
131-
18-0
131-
55-5
131-
56-6
131-
70-4
1359
3-03
-8
1508
7-24
-8
1582
-09-
8
1634
-04-
4
2501
3-16
-5
2719
3-28
-8
3320
4-76
-1
3686
1-47
-9
4376
-20-
9
50-1
8-0
5466
-77-
3
556-
67-2
611-
99-4
6164
-98-
3
7400
-08-
0
77-0
9-8
77-4
0-7
92-6
9-3
92-8
8-6
94-1
3-3
94-2
6-8
96-1
2-8
96-4
5-7
99-7
6-3
99-9
6-7
kg.y
ear-
1
Release to air [kg.year-1] Release to wastewater [kg.year-1]
Figure 5.1 Release to the environment by air and wastewater. The magnitude of release is dependent on the production tonnage, the use pattern, and the physico-chemical properties of the substances.
Local concentrations in soils and sediment - CAT 1 substances
0
500
1000
1500
2000
2500
3000
3500
4000
1004
3-35
-3
104-
40-5
1113
-02-
6
1131
-60-
8
120-
47-8
131-
18-0
131-
55-5
131-
56-6
131-
70-4
1359
3-03
-8
1508
7-24
-8
1582
-09-
8
1634
-04-
4
2501
3-16
-5
2719
3-28
-8
3320
4-76
-1
3686
1-47
-9
4376
-20-
9
50-1
8-0
5466
-77-
3
556-
67-2
611-
99-4
6164
-98-
3
7400
-08-
0
77-0
9-8
77-4
0-7
92-6
9-3
92-8
8-6
94-1
3-3
94-2
6-8
96-1
2-8
96-4
5-7
99-7
6-3
99-9
6-7
mg
kg w
wt
-1
Local PEC in fresh-water sediment during emission episode [mg.kgwwt-1] Local PEC in agric. soil (total) averaged over 180 days [mg.kgwwt-1]
Local PEC in grassland (total) averaged over 180 days [mg.kgwwt-1]
Figure 5.2 Local concentration in soils (agricultural soil and grassland) and sediments
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 81
Local PEC in surface water during release episode (dissolved) - CAT 1 substances
0
2
4
6
8
10
12
1004
3-35
-3
104-
40-5
1113
-02-
6
1131
-60-
8
120-
47-8
131-
18-0
131-
55-5
131-
56-6
131-
70-4
1359
3-03
-8
1508
7-24
-8
1582
-09-
8
1634
-04-
4
2501
3-16
-5
2719
3-28
-8
3320
4-76
-1
3686
1-47
-9
4376
-20-
9
50-1
8-0
5466
-77-
3
556-
67-2
611-
99-4
6164
-98-
3
7400
-08-
0
77-0
9-8
77-4
0-7
92-6
9-3
92-8
8-6
94-1
3-3
94-2
6-8
96-1
2-8
96-4
5-7
99-7
6-3
99-9
6-7
mg
l-1
Figure 5.3 Local concentration in surface water
Secondary poisoning and concentrations in top predators - CAT 1 substances
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
1004
3-35
-310
4-40
-511
13-0
2-6
1131
-60-
812
0-47
-813
1-18
-013
1-55
-513
1-56
-613
1-70
-413
593-
03-8
1508
7-24
-815
82-0
9-8
1634
-04-
425
013-
16-5
2719
3-28
-833
204-
76-1
3686
1-47
-943
76-2
0-9
50-1
8-0
5466
-77-
355
6-67
-261
1-99
-461
64-9
8-3
7400
-08-
077
-09-
877
-40-
792
-69-
392
-88-
694
-13-
394
-26-
896
-12-
896
-45-
799
-76-
399
-96-
7
mg
kg w
wt -
1
Concentration in fish for secondary poisoning (fresh water) [mg.kgwwt-1] Concentration in top-predators [mg.kgwwt-1]
Figure 5.4 Secondary poisoning and concentration in top predators. Furthermore, consider-able concentrations are found for 5-6 more substances.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 82
Local total daily intake for humans - CAT 1 substancs
0
50
100
150
200
250
300
1004
3-35
-3
104-
40-5
1113
-02-
6
1131
-60-
8
120-
47-8
131-
18-0
131-
55-5
131-
56-6
131-
70-4
1359
3-03
-8
1508
7-24
-8
1582
-09-
8
1634
-04-
4
2501
3-16
-5
2719
3-28
-8
3320
4-76
-1
3686
1-47
-9
4376
-20-
9
50-1
8-0
5466
-77-
3
556-
67-2
611-
99-4
6164
-98-
3
7400
-08-
0
77-0
9-8
77-4
0-7
92-6
9-3
92-8
8-6
94-1
3-3
94-2
6-8
96-1
2-8
96-4
5-7
99-7
6-3
99-9
6-7
mg
kg
-1 d
ay-1
Figure 5.5 Estimated values for local total daily intake for humans
Regional total daily intake for humans - CAT 1 substances
0
0,002
0,004
0,006
0,008
0,01
0,012
0,014
1004
3-35
-3
104-
40-5
1113
-02-
6
1131
-60-
8
120-
47-8
131-
18-0
131-
55-5
131-
56-6
131-
70-4
1359
3-03
-8
1508
7-24
-8
1582
-09-
8
1634
-04-
4
2501
3-16
-5
2719
3-28
-8
3320
4-76
-1
3686
1-47
-9
4376
-20-
9
50-1
8-0
5466
-77-
3
556-
67-2
611-
99-4
6164
-98-
3
7400
-08-
0
77-0
9-8
77-4
0-7
92-6
9-3
92-8
8-6
94-1
3-3
94-2
6-8
96-1
2-8
96-4
5-7
99-7
6-3
99-9
6-7
mg
kg
-1 d
ay-1
Figure 5.6 Estimated values for regional total daily intake for humans
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 83
The magnitude of release is dependent on the tonnage, the use pattern, and the physico-chemical properties of the substances. As indicated in the figures, large differences are seen in release of CAT 1 substances, from less than 1 kg/year and up to more than 1,300,000 kg/year. In average, 1.8% of the tonnage used is estimated to be released to the environment with a variability between 0-6% of the tonnage used. The EUSES estimations indicated an accumulation of substances in sediments and soils for about half of the CAT 1 substances. The concentration of CAT 1 substances in sur-face waters may be up to 10 mg/l although, for about half of the substances, a concen-tration of ≤ 1 mg/L was found. For secondary poisoning and concentration in top predators, EUSES estimations indi-cated very high concentration, up to 7,400 mg/kg wwt for two substances (CAS Nos. 1582-09-8 and 5466-77-3). Furthermore, considerable concentrations were found for 5-6 other substances. Estimations for human intake of substances via the environment depict considerable in-take of about one third of the CAT 1 substance (local human intake). In Table 5.8, an overview of the human health relevant effect data for Category 1 sub-stances in comparison with EUSES estimated local and regional intake via the environ-ment is presented. In Table 5.9, an overview of wildlife relevant effect data for Cate-gory 1 substances in comparison with EUSES estimated local surface water concentra-tions is presented.
84
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
Tab
le 5
.8
Out
put f
rom
dat
abas
e: O
verv
iew
of t
he h
uman
hea
lth r
elev
ant E
D e
ffect
dat
a of
Cat
egor
y 1
subs
tanc
es. P
lus
EU
SE
S e
stim
ated
dat
a on
hu
man
inta
ke (
for
abre
vias
ions
see
Ann
ex 1
)
CA
S N
O
NA
ME
S
PE
CIE
S
Qua
lifyi
ng r
emar
ks_H
H
CR
ITE
RIO
N
DO
SE
C
ON
C.
UN
IT_D
OS
R
EC
NO
Loca
l tot
al d
aily
in
take
for
hu-
man
s (m
g/kg
/day
)
Reg
iona
l tot
al
daily
inta
ke fo
r hu
man
s (m
g/kg
/day
) 10
043-
35-3
B
oric
aci
d W
ista
r ra
ts
Rat
in v
ivo
stud
y: A
fter
a 4-
wk
adm
ini-
stra
tion
by g
avag
e, te
stis
and
epi
di-
dym
is w
ts. w
ere
decr
ease
d in
the
300
and
500
mg/
kg g
roup
s.
LOA
EL
300
mg/
kg b
ody
wei
ght.
day
GP
h131
yr06
0.06
7000
002
1.63
E-0
5
104-
40-5
4-
Non
ylph
enol
(4
-NP
) ra
ts.
uter
otro
-ph
ic a
s-sa
y
Rat
in v
ivo
stud
y: U
terin
e w
eigh
t, ut
er-
ine/
bod
y w
eigh
t sig
nific
antly
incr
ease
d in
90
mg/
kg a
nd 1
20 m
g/kg
gro
ups
and
a do
se-r
espo
nse
rela
tions
hip
was
ob-
serv
ed.
LOA
EL
90
mg/
kg
GP
h144
yr06
245
0.00
0157
1113
-02-
6 O
met
hoat
e K
unm
ing
mal
e m
ice
Mic
e in
viv
o st
udy:
Incr
ease
in b
ody
wt.
and
decr
ease
d te
stic
le w
t. T
he a
ctiv
i-tie
s of
AK
P, A
CP
, LD
H in
mou
se te
sti-
cles
sig
nific
antly
incr
ease
d co
mpa
red
with
the
cont
rol.
ED
1,
2
and
4 m
g/kg
G
Ph0
43yr
060.
0359
9999
8 1.
02E
-05
1131
-60-
8 4- C
yclo
hexy
l-ph
enol
Rat
R
at in
viv
o st
udy:
Ute
rotr
ophi
c as
say.
In
crea
sed
uter
ine
wei
ght.
LOA
EL=
200
mg/
kg.
LOE
L 20
0 m
g/kg
T
Th0
31yr
0616
.700
0007
6 9.
63E
-06
120-
47-8
et
hyl 4
-hy
drox
yben
-zo
ate
CD
1 m
ice
and
Wis
-ta
r ra
ts
Rat
and
mic
e in
viv
o st
udy:
Incr
ease
d ut
erin
e w
eigh
t in
imm
atur
e an
d ov
arie
c-to
miz
ed a
nim
als.
ED
50 1
8-74
µm
ol/ k
g bo
dy
wei
ght.
ED
50
18 to
74
µ
mol
/ kg
body
wei
ght
GP
h110
yr06
0.00
177
2.33
E-0
7
131-
18-0
D
i-n-
pent
ylph
thal
ate
(DP
P)
=
Dip
enty
lpht
hal
ate
Mic
e M
ice
in v
ivo
stud
y: A
con
tinuo
us b
reed
-in
g pr
otoc
ol w
as u
tiliz
ed to
exa
min
e th
e re
prod
uctiv
e to
xici
ty o
f di-n
-pen
tyl
phth
alat
e (D
PP
). D
PP
was
toxi
c to
the
repr
oduc
tive
syst
em a
s ev
iden
ced
by a
co
mpl
ete
inhi
bitio
n of
fert
ility
at 1
.25
and
2.5%
DP
P a
nd r
educ
ed fe
rtili
ty.
LOA
EL
1.25
%
G
Ph0
12yr
0614
.699
9998
1 7.
74E
-05
85
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
CA
S N
O
NA
ME
S
PE
CIE
S
Qua
lifyi
ng r
emar
ks_H
H
CR
ITE
RIO
N
DO
SE
C
ON
C.
UN
IT_D
OS
R
EC
NO
Loca
l tot
al d
aily
in
take
for
hu-
man
s (m
g/kg
/day
)
Reg
iona
l tot
al
daily
inta
ke fo
r hu
man
s (m
g/kg
/day
) 13
1-55
-5
Ben
zoph
e-no
ne-2
(B
p-2)
, 2,
2',4
,4'-
tetr
ahyd
roxy
-be
nzop
he-
none
rat
Rat
in v
ivo
stud
y: In
crea
sed
rat u
terin
e w
eigh
ts. E
D10
=54
4.6
mg/
kg b
ody
wei
ght/d
ay.
ED
10
544.
6 m
g/kg
bod
y w
eigh
t. da
y G
Ph1
23yr
064.
0700
0017
2 4.
13E
-06
131-
56-6
2,
4-D
ihyd
roxy
-be
nzop
heno
n =
Res
benz
o-ph
enon
e
Long
Ev-
ans
rats
R
at in
viv
o st
udy:
Ben
zoph
enon
e (B
p)-
1 in
crea
sed
uter
ine
wt.
in im
mat
ure
rats
. Fur
ther
mor
e, b
enzo
phen
one-
1 (B
p-1)
was
in a
pre
viou
s in
vitr
o ex
-pe
rimen
t (M
CF
-7 c
ells
) sh
own
to h
ave
clea
r es
trog
enic
act
ivity
(E
C-5
0: 2
.08
uM)
ED
50
2-12
00
mg/
kg b
ody
wei
ght
GP
h026
yr06
2.31
9999
933
1.05
E-0
5
131-
70-4
M
ono-
n-bu
tylp
htha
late
W
ista
r ra
ts
Rat
in v
ivo
stud
y: D
ecre
ased
mal
e an
ogen
ital d
ista
nce
and
incr
ease
d in
ci-
denc
e of
fetu
ses
with
und
esce
nded
te
stes
. LO
AE
L=25
0 m
g/kg
bod
y w
eigh
t/day
LOA
EL
250
mg/
kg b
ody
wei
ght.
day
GP
h206
yr06
0.06
3100
003
7.52
E-0
8
1359
3-03
-8
Qui
nalp
hos
=
Chi
nalp
hos
Adu
lt m
ale
rats
In
viv
o ra
t stu
dy: S
uble
thal
chr
onic
ad-
min
istr
atio
n of
qui
nalp
hos
resu
lted
in:
decr
ease
d te
stic
ular
mas
s an
d A
ChE
ac
tivity
in c
entr
al a
s w
ell a
s pe
riphe
ral
orga
ns; i
ncre
ased
ser
um L
H, F
SH
, pr
olac
tin, a
nd te
stos
tero
ne c
oncn
s.;
decr
ease
d pi
tuita
ry o
r in
crea
sed
tes-
ticul
ar A
CE
. Ed
7-14
mg/
kg/d
ay.
ED
7-
14
mg/
kg/d
ay
GP
h050
yr06
7.96
9999
79
0.00
0822
1508
7-24
-8
3-B
enzy
liden
e ca
mph
or (
3-B
C)
Rat
ute
ro-
trop
hic
assa
y
Rat
in v
ivo
stud
y: In
crea
se in
ute
rus
wei
ght.
LOE
D =
2 m
g/kg
bod
y w
eigh
t.day
LOE
D
2 m
g/kg
bod
y w
eigh
t.day
G
Ph1
20yr
0638
6.
95E
-05
86
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
CA
S N
O
NA
ME
S
PE
CIE
S
Qua
lifyi
ng r
emar
ks_H
H
CR
ITE
RIO
N
DO
SE
C
ON
C.
UN
IT_D
OS
R
EC
NO
Loca
l tot
al d
aily
in
take
for
hu-
man
s (m
g/kg
/day
)
Reg
iona
l tot
al
daily
inta
ke fo
r hu
man
s (m
g/kg
/day
) 15
82-0
9-8
Trif
lura
lin
Ew
es
In v
ivo
ewe
stud
y. C
once
ntra
tions
of
estr
adio
l wer
e si
gnifi
cant
ly in
crea
sed
in
ewes
giv
en tr
iflur
alin
. No
effe
ct o
n th
y-ro
xine
con
cent
ratio
n. M
ean
seru
m c
on-
cent
ratio
ns o
f LH
wer
e m
arke
dly
de-
crea
sed
by tr
iflur
alin
, and
bas
al L
H
conc
entr
atio
ns w
ere
sign
ifica
ntly
de-
crea
sed.
Onl
y on
e do
sis
(17.
5 m
g/kg
2
times
per
wee
k) w
as in
vest
igat
ed
LOE
C
17.5
m
g/kg
bod
y w
eigh
t G
Ph1
36yr
0663
.900
0015
3 0.
0079
8
1634
-04-
4 m
ethy
l ter
tiary
bu
tyl e
ther
(M
TB
E)
Spr
ague
-D
awle
y ra
ts
Rat
in v
io s
tudy
: Inc
reas
e of
test
is
wei
ght.
Inte
rstit
ial f
luid
and
ser
um te
s-to
ster
one
leve
ls a
s w
ell a
s se
rum
pro
-la
ctin
leve
ls w
ere
decr
ease
d on
ly in
an
imal
s tr
eate
d w
ith 1
500
mg
MT
BE
/kg/
day
for
15 d
ays.
LOE
C
1500
m
g/kg
/day
G
Ph0
32yr
060.
3950
0001
1 4.
1E-0
5
2501
3-16
-5
tert
.-B
utyl
hy-
drox
yani
sole
(B
HA
)
rats
(on
e-ge
nera
-tio
n re
-pr
oduc
tion
stud
y)
In v
ivo
rat s
tudy
. In
one-
gene
ratio
n ra
ts,
sex
ratio
of m
ale
was
dec
reas
ed a
nd
the
anog
enita
l dis
tanc
es w
ere
shor
t-en
ed a
nd v
agin
al p
aten
cy a
nd p
repu
tial
sepa
ratio
n w
ere
obse
rved
late
r th
an c
ontr
ol g
roup
. Als
o, B
HA
de-
crea
sed
sper
m m
otili
ty a
nd n
umbe
r an
d th
e w
idth
and
leng
th. L
OE
L=10
mg/
kg
bod
y w
eigh
t/day
LOA
EL
10
mg/
kg b
ody
wei
ght.
day
GP
h190
yr06
0.83
3999
991
6.33
E-0
5
2719
3-28
-8
Phe
nol,
(1,1
,3,3
-te
tram
ethy
lbu-
tyl)-
= O
ctyl
-ph
enol
mal
e W
is-
tar
rats
R
at in
viv
o st
udy.
Red
uced
spe
rm
coun
ts r
esul
ting
from
low
ered
pla
sma
test
oste
rone
in m
ale
rats
just
afte
r pu
-be
rty.
ED
=3
mg/
kg b
ody
wei
ght.d
ay
ED
3
mg/
kg b
ody
wei
ght.d
ay
GP
h171
yr06
167
0.00
0107
87
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
CA
S N
O
NA
ME
S
PE
CIE
S
Qua
lifyi
ng r
emar
ks_H
H
CR
ITE
RIO
N
DO
SE
C
ON
C.
UN
IT_D
OS
R
EC
NO
Loca
l tot
al d
aily
in
take
for
hu-
man
s (m
g/kg
/day
)
Reg
iona
l tot
al
daily
inta
ke fo
r hu
man
s (m
g/kg
/day
) 33
204-
76-1
2,
6-ci
s-D
iphe
nyl-
hexa
met
hyl-
cycl
otet
rasi
-lo
xane
- 2
,6-
cis-
[(P
hMe-
SiO
)2(M
e2S
iO
)2][
Rat
In
viv
o ra
t stu
dy. I
nhib
ited
fert
ility
and
al
tera
tions
in m
easu
red
char
acte
ristic
s of
the
ejac
ulat
e. L
OA
EL=
0.5
mg/
kg/d
ay
LOA
EL
0.5
mg/
kg/d
ay
GP
h210
yr06
273
0.00
112
3686
1-47
-9
3-(4
-M
ethy
lben
-zy
liden
e)ca
mp
hor
Lon
g E
v-an
s (L
E)
rats
.
Rat
in v
ivo
stud
y. D
elay
ed m
ale
pu-
bert
y, a
nd d
ose-
depe
nden
tly a
ffect
ed
repr
oduc
tive
orga
n w
ts. o
f adu
lt m
ale
and
fem
ale
F1
offs
prin
g, w
ith p
artly
dif-
fere
nt e
ffect
pat
tern
s. T
hyro
id w
t. w
as
incr
ease
d by
hig
her
4-M
BC
dos
es.
LOA
EL=
7 m
g/kg
/day
LOA
EL
7 m
g/kg
.day
G
Ph0
91yr
0615
.699
9998
1 0.
0002
37
4376
-20-
9 M
ono
2 et
hyl
hexy
lpht
hala
te
(ME
HP
)
5-w
eek
old
mal
e ra
ts
Spr
ague
-D
awle
y ra
ts
Rat
in v
ivo
stud
y. S
igni
fican
tly d
e-cr
ease
d bo
dy w
eigh
ts a
nd m
otile
sp
erm
s. L
OA
EL=
250
mg/
kg b
ody
wei
ght/d
ay
LOA
EL
250
mg/
kg b
ody
wei
ght.
day
GP
h202
yr06
44.2
9999
924
2.94
E-0
5
50-1
8-0
Cyc
loph
os-
pham
ide
Rat
R
at in
viv
o as
say:
Dec
reas
ed o
varia
n an
d ut
erin
wei
ght a
nd r
educ
tion
seru
m
estr
adio
l and
pro
gest
eron
e. L
OA
EL=
50
mg/
kg b
ody
wei
ght
LOE
L 50
m
g/kg
bod
y w
eigh
t C
Gh5
14
0.04
3499
999
2.12
E-0
7
5466
-77-
3 2-
eth
yl-h
exyl
-4- m
etho
xyci
n-na
mat
e
imm
atur
e Lo
ng-
Eva
ns
rats
Rat
in v
ivo
assa
y. U
terin
e w
t. w
as
dose
-dep
ende
ntly
incr
ease
d by
OM
C
(ED
50 9
35 m
g/kg
/day
)
ED
50
935
mg/
kg b
ody-
wei
ght.d
ay
GP
h084
yr06
89.1
9999
695
0.01
31
88
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
CA
S N
O
NA
ME
S
PE
CIE
S
Qua
lifyi
ng r
emar
ks_H
H
CR
ITE
RIO
N
DO
SE
C
ON
C.
UN
IT_D
OS
R
EC
NO
Loca
l tot
al d
aily
in
take
for
hu-
man
s (m
g/kg
/day
)
Reg
iona
l tot
al
daily
inta
ke fo
r hu
man
s (m
g/kg
/day
) 55
6-67
-2
Cyc
lote
tras
i-lo
xane
S
prag
ue-
Daw
ley
(SD
) an
d F
isch
er
344
(F-
344)
rat
s
Rat
in v
ivo
assa
y. U
tero
trop
hic
assa
y w
ith tw
o sp
ecie
s: R
elat
ive
uter
ine
wts
. an
d ut
erin
e ep
ithel
ial c
ell h
eigh
t wer
e st
atis
tical
ly s
igni
fican
tly in
crea
sed
in
both
str
ains
of r
ats
at d
oses
abo
ve 1
00
mg/
kg/d
ay. L
OA
EL=
250
mg/
kg/d
ay
LOA
EL
250
mg/
kg/d
ay
GP
h063
yr06
1.14
9999
976
0.00
0384
611-
99-4
4,
4'-
Dih
ydro
xy-
benz
ophe
non
imm
atur
e ra
t ute
ro-
trop
hic
assa
y +
H
ersh
ber-
ger
assa
y
rat i
n vi
vo a
ssay
: Ind
uced
ute
rotr
ophy
an
d ex
erte
d bo
th e
stro
gen
agon
istic
ef
fect
and
red
uced
the
estr
ogen
ic e
ffect
of
eth
ynyl
estr
adio
l
S
ee
re-
mar
ks
G
Ph2
27yr
060.
3440
0001
2 4.
36E
-07
6164
-98-
3 C
hlor
dim
e-fo
rm
fem
ale
rat
In v
ivo
rat s
tudy
. Del
ay in
bre
edin
g an
d a
sign
ifica
nt r
edn.
in li
tter
size
. ED
=50
m
g/kg
.
ED
50
m
g/kg
G
Ph2
53yr
060.
1340
0000
3 7.
53E
-07
7400
-08-
0 p-
Cou
mar
ic
acid
(P
CA
) W
ista
r al
bino
rat
s R
at in
viv
o as
say:
189
and
201
% th
y-ro
id w
ts in
crea
se c
ompa
red
to c
ontr
ol
valu
e. h
yroi
d le
sion
s in
p-c
oum
aric
aci
d gr
oup
wer
e as
socd
. with
sig
nific
ant i
n-cr
ease
s in
cel
lula
r pr
olife
ratio
n as
indi
-ca
ted
by
[3H
]thym
idin
e in
corp
orat
ion.
In
addn
., th
e go
itrog
enic
effe
ct o
f p-
coum
aric
aci
d w
as fu
rthe
r co
nfirm
ed b
y si
gnifi
cant
dec
reas
es (
50%
) in
ser
um
triio
doth
yron
ine
(T3)
and
thyr
oxin
e (T
4),
and
a pa
ralle
l inc
reas
e (9
0%)
in s
erum
T
SH
com
pare
d to
con
trol
gro
up.
ED
=0.
25 m
mol
/kg/
day
ED
0.
25
mm
ol/k
g/da
yG
Ph2
38yr
060.
1309
9999
7 2.
91E
-08
77-0
9-8
3,3'
-Bis
(4-
hydr
oxy-
phen
yl)p
htha
lid
= P
heno
l-ph
thal
eine
F34
4/N
ra
ts a
nd
B6C
3F
mic
e
Rat
and
mic
e in
viv
o st
udy.
Exp
osur
e of
m
ice
to p
heno
lpht
hale
in in
fee
d fo
r 2
year
s re
sulte
d in
incr
ease
d in
cide
nces
of
aty
pica
l hyp
erpl
asia
of t
he th
ymus
in
mal
es a
nd fe
mal
es, d
egen
erat
ion
of th
e ge
rmin
al e
pith
eliu
m o
f the
test
is in
m
ales
, and
ova
rian
hype
rpla
sia
in fe
-m
ales
. LO
AE
L=30
0 m
g/kg
LOA
EL
300
mg/
kg
GP
h229
yr06
4.26
9999
981
1.22
E-0
6
89
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
CA
S N
O
NA
ME
S
PE
CIE
S
Qua
lifyi
ng r
emar
ks_H
H
CR
ITE
RIO
N
DO
SE
C
ON
C.
UN
IT_D
OS
R
EC
NO
Loca
l tot
al d
aily
in
take
for
hu-
man
s (m
g/kg
/day
)
Reg
iona
l tot
al
daily
inta
ke fo
r hu
man
s (m
g/kg
/day
) 77
-40-
7 2,
2-B
is(4
-hy
drox
y-ph
enyl
)-n-
buta
n =
B
isph
enol
B
imm
atur
e ra
t ute
ro-
trop
hic
assa
y
In v
ivo
imm
atur
e ra
t ute
rotr
ophi
c as
say:
P
ositi
ve r
espo
nse
in th
e ut
erot
roph
ic
assa
y. D
ose
repo
nse
rela
tions
hip
(0, 2
, 20
and
200
mg/
kg)
See
rem
arks
0, 2
, 20
and
200
mg/
kg
GP
h223
yr06
4.17
9999
828
2.94
E-0
5
92-6
9-3
4- Hyd
roxy
bi-
phen
yl =
4-
Phe
nylp
heno
l
Spr
ague
-D
awle
y fe
mal
e ra
ts
Rat
in v
ivo
assa
y: U
tero
trop
hic
assa
y an
d C
albi
ndin
-D9k
(C
aBP
-9K
) m
RN
A
expr
essi
on w
ere
exam
d. in
ova
riec-
tom
ized
Spr
ague
-Daw
ley
fem
ale
rats
. 4-
phen
ylph
enol
pro
duce
d do
se-
depe
nden
t (10
, 50,
200
, and
400
m
g/kg
/day
( in
crea
ses
in th
e ut
erin
e w
ts.
of o
varie
ctom
ized
rat
s). L
OA
EL=
200
mg/
kg/d
ay
LOA
EL
200
mg/
kg/d
ay
GP
002h
yr06
2.16
0000
086
7.51
E-0
5
92-8
8-6
4,4'
-D
ihyd
roxy
bi-
phen
yl =
4,4
'-B
iphe
nol
Rat
R
at in
viv
o st
udy.
Rat
ute
rotr
ophi
c as
-sa
y. U
terin
e w
eigh
t inc
reas
e. L
O-
AE
L=60
mg/
kg b
ody
wei
ght/d
ay.
LOE
L 60
m
g/kg
bod
y w
eigh
t. da
y T
Th0
28yr
060.
4090
0000
9 8.
48E
-07
94-1
3-3
n-pr
opyl
p-
hydr
oxyb
en-
zoat
e
3.w
eek-
old
rats
In
viv
o ra
t ass
ay: T
he e
pidi
dym
al s
perm
re
serv
es a
nd c
once
ntra
tions
dec
reas
ed
dose
dep
ende
ntly
and
the
diffe
renc
e w
as s
igni
fican
t at d
oses
of 0
.1%
and
ab
ove.
LO
AE
L=0.
1%
LOE
C
0.1
%
GP
h114
yr06
2.07
9999
924
1.06
E-0
6
94-2
6-8
n-B
utyl
p-
Hyd
roxy
ben-
zoat
e
Mic
e In
viv
o m
ice
stud
y. A
dos
e-de
pend
ent
decr
ease
of b
oth
roun
d an
d el
onga
ted
sper
mat
id o
unts
in s
tage
s V
II-V
III
sem
inife
rous
tubu
les
was
obs
erve
d,
and
the
elon
gate
d sp
erm
atid
cou
nts
wer
e si
gnifi
cant
ly lo
wer
in a
ll of
the
trea
ted
grou
ps. T
he s
erum
test
oste
rone
co
ncen
trat
ion
decr
ease
d in
a d
ose-
depe
nden
t fas
hion
and
was
sig
nific
ant
at 1
.00%
. LO
AE
L=15
04 m
g/kg
bod
y w
eigh
t. D
ay
LOA
EL
1504
m
g/kg
bod
y w
eigh
t. da
y G
Ph2
72yr
060.
1049
9999
7 2.
46E
-07
90
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
CA
S N
O
NA
ME
S
PE
CIE
S
Qua
lifyi
ng r
emar
ks_H
H
CR
ITE
RIO
N
DO
SE
C
ON
C.
UN
IT_D
OS
R
EC
NO
Loca
l tot
al d
aily
in
take
for
hu-
man
s (m
g/kg
/day
)
Reg
iona
l tot
al
daily
inta
ke fo
r hu
man
s (m
g/kg
/day
) 96
-12-
8 D
ibro
mo-
chlo
ropr
opan
e (D
BC
P)
Hum
an
Exp
osed
hum
an w
orke
rs. A
zoos
perm
ia
olig
ospe
rmia
and
dos
e-de
pend
ent
chan
ge in
FS
H, L
H a
nd te
stic
le s
ize
G
Fh0
09
0.04
1299
999
1.77
E-0
7
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
rat
In v
ivo
rat a
ssay
: Alte
ratio
n in
thyr
oid
func
tion
and
a si
gnifi
cant
cha
nge
in
thyr
oid
mor
phol
(12
5 an
d 62
5 pp
m)
. N
OE
C =
25
ppm
NO
EC
0,
1,
58,
125,
or
625
ppm
G
Ph0
55yr
060.
0143
3.
12E
-06
99-7
6-3
Met
hyl p
-H
ydro
xybe
n-zo
ate
adul
t ova
-rie
c-to
miz
ed
(Ovx
) C
D1
mic
e
In v
ivo
mic
e as
say:
The
hig
hest
MeP
-be
n do
se (
165
mg/
kg)
was
abl
e to
pro
-du
ce u
tero
trop
hic
effe
cts
(38
to 7
6%)
com
pare
d to
E-2
efe
cts
(100
%).
LO
-A
EL=
165
mg/
kg
LOA
EL
165
mg/
kg
GP
h103
yr06
0.02
76
1.45
E-0
6
99-9
6-7
p- Hyd
roxy
ben-
zoic
aci
d
Imm
atur
e an
d ad
ult
ovar
iec-
tom
ized
fe
mal
e m
ice
(CD
1)
Rat
in v
ivo
assa
y: D
ose-
depe
nden
t re-
spon
se (
0.5,
5, 5
0, a
nd 5
00 g
/kg)
on
vagi
nal c
orni
ficat
ion
and
uter
otro
phic
ac
tivity
in b
oth
imm
atur
e an
d ad
ult o
va-
riect
omiz
ed m
ice.
ED
0.
5, 5
, 50
, and
50
0
g/kg
G
Ph1
02yr
060.
0086
3 4.
17E
-07
91
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
Tab
le 5
.9
Out
put f
rom
dat
abas
e: O
verv
iew
of t
he w
ildlif
e re
leva
nt E
D e
ffect
dat
a of
Cat
egor
y 1
subs
tanc
es. P
lus
EU
SE
S e
stim
ated
dat
a on
loca
l su
rfac
e w
ater
con
cent
ratio
ns
CA
S N
O
NA
ME
S
peci
eNam
e C
ON
C.
UN
IT
Qua
lifyi
ng r
emar
ks_W
L
Loca
l PE
C in
su
rfac
e w
ater
du
ring
em
is-
sion
epi
sode
(d
isso
lved
) (m
g/L)
15
82-0
9-8
Trif
lura
lin
Cyp
rinod
on
varie
gatu
s (s
heep
shea
d m
1-5
ug/l
Fis
h in
viv
o st
udy:
Pitu
itary
effe
cts
- po
ssib
ly in
di-
rect
effe
ct o
f exp
osur
e.
1.97
2501
3-16
-5
tert
.-B
utyl
hydr
oxya
niso
le
(BH
A)
Sal
mo
gaird
neri
14.1
4 ug
/l F
ish
in v
ivo
stud
y: In
crea
sed
vite
lloge
nin
synt
he-
sis.
EC
50=
14.1
4 ug
/L
2.33
1634
-04-
4 m
ethy
l ter
tiary
but
yl e
ther
(M
TB
E)
Ran
a te
mpo
raria
<
2500
m
g/l
Am
phib
ian
in v
ivo
stud
y: A
ccel
arat
ed d
evel
op-
men
t and
ear
lier
met
amor
phos
is. L
OE
C<
2500
m
g/L
4.73
131-
56-6
2,
4-D
ihyd
roxy
benz
ophe
non
= R
esbe
nzop
heno
ne
Pim
epha
les
pro-
mel
as
4919
µg
/l F
ish
in v
ivo
stud
y: A
quat
iic e
xpos
ure
of fa
thea
d m
inno
w w
ith B
P1
indu
ced
vite
lloge
nin
sign
ifica
ntly
at
491
9 m
g/l
5.24
1359
3-03
-8
Qui
nalp
hos
= C
hina
lpho
s C
laria
s ba
trac
hus
0.02
5 m
g/l
Fis
h in
viv
o st
udy:
Impa
irmen
t of
test
is fu
nctio
n du
e to
the
inhi
bitio
n of
ste
roid
ogen
ic e
nzym
es
activ
ities
. EC
=0.
025
mg/
L
1.98
96-4
5-7
Eth
ylen
e T
hiou
rea
(ET
U)
Not
spe
cifie
d 5,
10,
25,
50
, and
10
0
mg/
l A
mph
ibia
n in
viv
o as
say:
In a
sta
ndar
dise
d rin
g-te
sted
test
pro
posa
l (X
enop
us m
etam
orph
osis
as
say)
and
five
diff
eren
t ET
U c
oncn
s. (
5, 1
0, 2
5,
50, a
nd 1
00 m
g/L)
a c
oncn
.-de
pend
ent i
nhib
ition
of
met
amor
phos
is w
as o
bsd.
0.5
5466
-77-
3 2-
eth
yl-h
exyl
-4-
met
hoxy
cinn
amat
e O
ryzi
as la
tipes
.
. F
ish
in v
ivo
assa
y. In
crea
se in
pla
sma
VT
G +
and
in
crea
sed
mR
NA
exp
ress
ion
leve
ls o
f est
roge
n re
cept
or (
ER
) al
pha,
am
ong
sex
horm
one
rece
p-to
rs in
the
liver
.
1.06
3686
1-47
-9
3-(4
-M
ethy
lben
zylid
ene)
cam
phor
X
enop
us la
evis
1,
5 a
nd
50
µg/l
Am
phib
ian
in v
ivo
stud
y.T
he r
ate
of m
etam
orph
o-si
s w
as n
ot a
ffect
ed, a
nd n
o ob
viou
s di
ffere
nces
in
bod
y an
d ta
il le
ngth
com
pare
d to
con
trol
s w
ere
obse
rved
.
0.85
9
120-
47-8
et
hyl 4
-hyd
roxy
benz
oate
R
ainb
ow tr
out
100
mg/
kg
Fis
h in
viv
o st
udy.
VT
G in
duct
ion
in r
ainb
ow
trou
ts. L
OA
EL=
100
mgk
g 0.
0207
94-1
3-3
n-pr
opyl
p-h
ydro
xybe
nzoa
te
Onc
orch
ynch
us
myk
iss
22
mg/
kg b
ody
wei
ght.d
ay
Fis
h in
viv
o as
say:
Cle
ar d
ose
resp
onse
incr
ease
in
VT
G r
espo
nse.
ED
50 =
22
mg
kg-1
2-d
. NO
EC
9.
52
92
DHI Water & Environment
ERA/53559/Revised report/2007.06.04
CA
S N
O
NA
ME
S
peci
eNam
e C
ON
C.
UN
IT
Qua
lifyi
ng r
emar
ks_W
L
Loca
l PE
C in
su
rfac
e w
ater
du
ring
em
is-
sion
epi
sode
(d
isso
lved
) (m
g/L)
=
225
mg/
L 15
087-
24-8
3-
Ben
zylid
ene
cam
phor
(3-
BC
) O
ncor
chyn
chus
m
ykis
s 6.
4 m
g/kg
/inje
ctio
nF
ish
in v
ivo
stud
y: V
itello
geni
n in
duct
ion.
ED
10,
ED
50 a
nd E
D90
of 3
-ben
zylid
ene
cam
phor
afte
r 6
days
(2
inje
ctio
ns)
wer
e 6.
4, 1
6 an
d 26
m
g/kg
/inje
ctio
n, r
esp
7.2
131-
55-5
B
enzo
phen
one-
2 (B
p-2)
, 2,
2',4
,4'-
tetr
ahyd
roxy
benz
ophe
none
Pim
epha
les
pro-
mel
as
8783
m
g/l
Fis
h in
viv
o st
udy:
Dos
e re
spon
se r
elat
ed V
TG
in
duct
ion.
LO
EC
= 8
783
mg/
L 9.
64
1004
3-35
-3
Bor
ic a
cid
Xen
opus
laev
is
.
Am
phib
ian
in v
ivo
stud
y: B
oric
aci
d ex
erte
d re
pro-
duct
ive
toxi
city
in X
enop
us la
evis
+ t
rans
gene
ra-
tiona
l tox
icity
to th
e de
velo
ping
pro
geny
.
2.37
92-8
8-6
4,4'
-Dih
ydro
xybi
phen
yl =
4,
4'-B
iphe
nol
Onc
orch
ynch
us
myk
iss
10-8
- 1
0-4
mg
In v
itro
stud
y. R
ecom
bina
nt y
east
ass
ay fo
r tr
out
ER
and
trou
t hep
atoc
yte
cultu
res.
Com
petit
ive
bind
ing
to E
R
0.96
4
104-
40-5
4-
Non
ylph
enol
(4-
NP
) O
ryzi
as la
tipes
24
.8
µg/l
Fis
h in
viv
o st
udy:
Indu
ctio
n of
VT
G. L
OE
C=
24.
8 ug
/l 4.
34
2719
3-28
-8
Phe
nol,
(1,1
,3,3
-te
tram
ethy
lbut
yl)-
= O
ctyl
-ph
enol
Ory
zias
latip
es
11.4
µg
/l F
ish
in v
ivo
stud
y. V
TG
indu
ctio
n +
inte
rsex
go-
nads
. LO
EC
=11
.4 u
g/L
5.19
611-
99-4
4,
4'-D
ihyd
roxy
benz
ophe
non
Pim
epha
les
pro-
mel
as
. .
Fis
h in
viv
o as
say:
VT
G r
espo
nse.
In v
itro:
Ful
l do
se-r
espo
nse
curv
es in
in v
itro
assa
y (r
ecom
bi-
nant
yea
st c
arry
ing
the
estr
ogen
rec
epto
r of
rai
n-bo
w tr
out (
rtE
Ra)
). In
viv
o: V
TG
res
pons
e
0.98
2
94-2
6-8
n-B
utyl
p-H
ydro
xybe
nzoa
te
Onc
orch
ynch
us
myk
iss
35
mg/
l R
ainb
ow tr
out i
n vi
vo s
tudy
. Vite
lloge
nin
re-
spon
se. L
OE
D: o
ral e
xpos
ure
to 9
mg
buty
lpar
a-be
n kg
-1 2
d-1
1.19
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 93
5.4 Update of database and list (Task 4)
The database, which was already available for the substances categorized in the BKH 2000 and the RPS-BKH 2002 studies, was revised to include the information gathered and conclusions drawn in the present study. Likewise, the existing Endocrine Disrupter priority list was revised. The database and the Priority List were delivered in formats applicable for publication on the Commission’s Endocrine Disrupters Website (Access, Excel and PDF). The revision included the addition of the new substances (identified under Task 2 and evaluated under Task 3). The ranked priority list contains the following information on all substances: • CAS No. and substance name • Endocrine Disrupter category (1, 2, 3a or 3b). • Indication of High Production Volume or Low Production Volume substance • If the substance is assigned a R53 phrase The updated priority list is given in Appendix L as well as in the database. A short manual to supplement the manual for the former version of the database (RPS-BKH 2002) is prepared and both the former manual and the supplementary manual is available from the internet: http://projects.dhi.dk/Endocrine_Disrupter/testsite/)) as well as given in Appendix K. In total, the database now includes 428 substances. The distribution (CAT 1, 2 and 3) between the evaluated substances is given in Table 5.10. Table 5.10 Distribution of CAT 1, 2 and 3 substances now included in the database
Total number of substances evaluated 575 CAT 1 At least one study providing evidence for endocrine
disruption in an intact organism 194
CAT 2 Potential for endocrine disruption. In-vitro data indicat-ing potential for endocrine disruption in intact organ-isms.
125
CAT 3 No scientific basis for inclusion in list or no data 109 Not evaluated Not in ESIS; Mixtures; no CAS; group name etc. 147
Below, the summary profiles of the 34 category 1 substances identified in the present study are presented. The summary profiles give an overview of human and wildlife re-lated endocrine effects, physical and chemical properties, selected EUSES estimations on bioaccumulation, biodegradability in the environment, an overview of the use, pro-duction volumes, emissions, estimated environmental concentration ranges and human daily intake, the present regulatory and legal status and finally a conclusion of the level of concern (High, Medium or Low concern).
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 94
Tert.-Butylhydroxyanisole (BHA) (CAS No.: 25013-16-5) 2(3)-tert-Butyl-4-hydroxyanisole; antioxyne b; BHA; BOA; Butylated hydroxyanisole; Butyl Hydroxyani-sole; tert-butyl-4-hydroxyanisole; tert-butyl-4-methoxyphenol; tert-butylhydroxyanisole; Vertac; Human related effects In vivo rat study. In one-generation rats, sex ratio of male was decreased and the anogenital distances were shortened and vaginal patency and preputial separation were observed later than control group. Also, BHA decreased sperm motility and number and the width and length. LOEL=10 mg/kg body weight/day Wildlife related effect Fish in vivo study: Increased vitellogenin synthesis. EC50=14.14 ug/L Chemical characteristics: Molecular formula: C11 H16 O2
Table 1: Physical/chemical properties of tert.-Butylhydroxyanisole (BHA) Parameter Value Unit Reference Molecular weight 180.25 g/mol Melting point 51 ºC EPISUITE Boiling point 268 ºC EPISUITE Vapour pressure at 25 [oC] 0.312 Pa EPISUITE Water solubility at 25 [oC] 212.8 mg/L EPISUITE Octanol-water partition coefficient 3.29 - MST Koc 1390 L/kg EPISUITE BCF 11.5 - EPISUITE Henry's law constant 0.00868 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - CHRIP NITE
t½(hydrolysis) Year t½(air) 3.56 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 500 Tonnes/year Release to air 3.75 kg/year Release to wastewater 7500 kg/year Local PEC in surface water during emission episode (dissolved) 2.3299999 mg/l Local PEC in fresh-water sediment during emission episode 29.1 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 43.599998 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 13.5 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 59.799999 mg/(kg wet weight) Concentration in fish-eating marine top-predators 1.29 mg/(kg wet weight) Local total daily intake for humans 0.83399999 mg/(kg⋅d) Regional total daily intake for humans 6.3300002E-5 mg/(kg wet weight) Conclusion Tert.-Butylhydroxyanisole (BHA) is used as an antioxidant to preserve and stabilize the freshness of food and feed and is according to the ESIS database a LPV substance. BHA is not readily biodegradable and has a high potential to bioaccumulate in the environment (log kow=3.29). BHA is in the environment
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 95
mainly distributed to surface water. Based on EUSES estimations for secondary poisoning BHA is not expected to be of significant concern. A relatively low daily human intake is expected. However, as BHA is added directly to food items to preserve and stabilize the freshness of food and feed a direct human exposure is obvious. BHA is thus considered as being of High Concern. None specifically regulatory or legal status for this substance was found.
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 96
Di-n-pentylphthalate (DPP) = Dipentylphthalate (CAS No.: 131-18-0) Amoil; Di-N-pentyl phthalate; Dipentyl 1,2-benzenedicarboxylate; dipentyl ester phthalic acid; dipentyl phthalate; DPP; amyl phthalate; Phthalic acid di-n-amyl ester; phthalic acid dipentyl ester; Human related effects Mice in vivo study: A continuous breeding protocol was utilized to examine the reproductive toxicity of di-n-pentyl phthalate (DPP). DPP was toxic to the reproductive system as evidenced by a complete inhibi-tion of fertility at 1.25 and 2.5% DPP and reduced fertility (litte Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C18 H26 O4
Table 1: Physical/chemical properties of Di-n-pentylphthalate (DPP) = Dipentylphthalate Parameter Value Unit Reference Molecular weight 306.41 g/mol Melting point ºC Boiling point 342 ºC EPISUITE Vapour pressure at 25 [oC] 0.026131112 Pa EPISUITE Water solubility at 25 [oC] 100 mg/L EPISUITE Octanol-water partition coefficient 5.62 - EPISUITE Koc 4966 L/kg EPISUITE BCF 29.17 - EPISUITE Henry's law constant 0.219 Pa·m3/mole EPISUITE Biodegradation Inherent biode-
gradable - MST
t½(hydrolysis) 3.427 Year EPISUITE t½(air) 10.605 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50 Tonnes/year Release to air 0.3996 kg/year Release to wastewater 799.20001 kg/year Local PEC in surface water during emission episode (dissolved) 0.34999999 mg/l Local PEC in fresh-water sediment during emission episode 66.900002 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 128 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 41.099998 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 1550 mg/(kg wet weight) Concentration in fish-eating marine top-predators 1290 mg/(kg wet weight) Local total daily intake for humans 14.7 mg/(kg⋅d) Regional total daily intake for humans 0.0000774 mg/(kg wet weight) Conclusion Consumer and industrial applications for phthalates are numerous and range from making nail polish flexible and screwdriver handles less brittle to helping make the time-release coatings on numerous pharmaceutical products. Dipentylphthalate is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 50 tones per year has been used. Dipentylphthalate is inher-ently biodegradable and has a high potential to bioaccumulate (log Kow=5.62). Based on EUSES calcula-tions dipentylphthalate is not expected to be found in significant amounts in the environment (surface wa-ters and sediments). However as Dipentylphthalate is of medium concern in relation to secondary poison-ing. Dipentylphthalate is thus considered as being of Medium Concern. None specifically regulatory or legal status for this substance was found.
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2,6-cis-Diphenylhexamethylcyclotetrasiloxane - 2,6-cis-[(PhMeSiO)2(Me2SiO)2][ (CAS No.: 33204-76-1) Quadrosilan; Human related effects In vivo rat study. Inhibited fertility and alterations in measured characteristics of the ejaculate. LOAEL=0.5 mg/kg/day Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C18 H28 O4 Si4
Table 1: Physical/chemical properties of 2,6-cis-Diphenylhexamethylcyclotetrasiloxane - 2,6-cis-[(PhMeSiO)2(Me2SiO)2][ Parameter Value Unit Reference Molecular weight 420.76001 g/mol Melting point 120.13 ºC EPISUITE Boiling point 360.69 ºC EPISUITE Vapour pressure at 25 [oC] 0.001116 Pa EPISUITE Water solubility at 25 [oC] 8.301e-005 mg/L EPISUITE Octanol-water partition coefficient 7.52 - EPISUITE Koc 10580000 L/kg EPISUITE BCF 7224 - EPISUITE Henry's law constant 33.5 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - EPISUITE
t½(hydrolysis) Year t½(air) 26.755 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 0.39199999 mg/l Local PEC in fresh-water sediment during emission episode 727 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 376 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 87.099998 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 202 mg/(kg wet weight) Concentration in fish-eating marine top-predators 913 mg/(kg wet weight) Local total daily intake for humans 273 mg/(kg⋅d) Regional total daily intake for humans 0.00112 mg/(kg wet weight)
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Conclusion Diphenylhexamethylcyclotetrasiloxane is used for various purposes as e.g. breast implants and bear-ing grease. Diphenylhexamethylcyclotetrasiloxane is according to the ESIS database not a LPV sub-stance. For the EUSES calculations a production volume of 10 tones per year has been used. Diphenyl-hexamethylcyclotetrasiloxane is not readily biodegradable and has a high potential to bioaccumulate in the environment (log kow=7.52). Diphenylhexamethylcyclotetrasiloxane is in the environment distributed to surface water as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning Diphenylhexamethylcyclotetrasiloxane is expected to be of medium concern. A high local daily human intake is expected (up to approx. 275 mg/kg/day). Diphenylhexamethylcyclotetrasiloxane is con-sidered as being of High Concern. None specifically regulatory or legal status for this substance was found.
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Ethylene Thiourea (ETU) (CAS No.: 96-45-7) 1,3-ethylene-2-thiourea; 1,3-Ethylenethiourea; Sanceller 22; sodium-22 neoprene accelerator; tetrahydro-2H-imidazole-2-thione; Vulkacit NPV/C; vulkacit npv/C2; warecure c; 2-Imidazolidimethione; 2-Imidazolidinethione; 2-mercapto-4,5-dihydroimidazole; 2-Mercaptoimidazoline; 2-thiol-dihydroglyoxaline; 4,5-dihydro-2-mercaptoimidazole; 4,5-dihydroimidazole-2(3H)-thione; Akrochem ETU-22; Ethylenethio-urea; Ethylene Thiourea; Ethylene thiourea ; ETHYLENE THIOUREA (2-IMIDAZOLIDINETHIONE); ETU; imidizolidenethione; Imidazolidinethione; Imidazoline-2-thiol; Mercaptoimidazoline; Mercozen; NA-22; NA-22-D; N,N'-ethylenethiourea; pennac cra; rhodanin s 62; Robac 22; Human related effects In vivo rat assay: Alteration in thyroid function and a significant change in thyroid morphol (125 and 625 ppm) . NOEC = 25 ppm Wildlife related effect Amphibian in vivo assay: In a standardised ringtested test proposal (Xenopus metamorphosis assay) and five different ETU concns. (5, 10, 25, 50, and 100 mg/L) a concn.-dependent inhibition of metamorphosis was obsd. Chemical characteristics: Molecular formula: C3 H6 N2 S1
Table 1: Physical/chemical properties of Ethylene Thiourea (ETU) Parameter Value Unit Reference Molecular weight 102.15 g/mol Melting point 203 ºC Boiling point 347.18 ºC Vapour pressure at 25 [oC] 0.01866508 Pa Water solubility at 25 [oC] 20000 mg/L Octanol-water partition coefficient -0.66 - Koc 6.511 L/kg BCF 25 - Henry's law constant Pa·m3/mole Biodegradation Not readily bio-
degradable -
t½(hydrolysis) Year t½(air) hr
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 1000 Tonnes/year Release to air 9.9899998 kg/year Release to wastewater 3000 kg/year Local PEC in surface water during emission episode (dissolved) 0.5 mg/l Local PEC in fresh-water sediment during emission episode 0.44299999 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 0.00679 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 0.00162 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.28999999 mg/(kg wet weight) Concentration in fish-eating marine top-predators 5.8200001E-3 mg/(kg wet weight) Local total daily intake for humans 0.0143 mg/(kg⋅d) Regional total daily intake for humans 0.00000312 mg/(kg wet weight) Conclusion Ethylenethiourea (ETU) is one of the degradation products of ethylenebis-dithiocarbamate fungicides, such as maneb and zineb, which have been widely used on food crops. ETU is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 1000 tones per year has been used. ETU is not readily biodegradable and has a low potential for bioaccumulation (log Kow=-0.66). Based EUSES calculations ETU is in the environment mainly distributed to surface water in con-centrations up to approx. 0.5 mg/L. ETU is expected to be found in fish, predators and human food in in-significant amounts. ETU is thus considered as being of Low Concern. The substance is covered by Council Directive 91/414/EEC. No RAR has been provided and the substance is not included in the list for pesticides to be reviewed. Classification: REP2;R61 XN;R22
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Trifluralin (CAS No.: 1582-09-8) 2,6-Dinitro-N,N-dipropyl-4-(trifluoromethyl)-benzamine; 2,6-Dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine; 2,6-dinitro-N,N-dipropyl-4-trifluoromethyl-aniline; 2,6-dinitro-N,N-dipropyl-alpha,alpha,alpha-trifluoro-p-toluidine; 4-(di-n-propylamino)-3,5-dinitro-1-trifluoromethylbenzene; al-pha,alpha,alpha-Trifluoro-2,6-Dinitro-N,N-Dipropyl-p-Toluidine; Agreflan; agriflan 24; Benezeneamine, 2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)-; digermin; Commence; crisalin; Elancolan; elanocolan; L-36352; lilly 36,352; nitran; N,N-di-n-propyl-2,6-dinitro-4-trifluoromethylaniline; N,N-dipropyl-2,6-dinitro-4-trifluoromethylaniline; N,N-dipropyl-4-trifluoromethyl-2,6-dinitroaniline; olitref; Scotts Stop Weeds Before They Start; su seguro carpidor; TR-10; trefanocide; treficon; Treflam; Treflan; Treflan 10G; Treflan 4EC; Treflan 5G; Treflan EC; Treflan MTF; treflanocide elancolan; Treflan TR-10; Trifluralin; Trifluralin ; trifurex; trikepin; Trilin 4EC; Trim; Human related effects In vivo ewe study. Concentrations of estradiol were significantly increased in ewes given trifluralin. No effect on thyroxine concentration. Mean serum concentrations of LH were markedly decreased by triflu-ralin, and basal LH concentrations were significantly decreased. Only one dosis (17.5 mg/kg 2 times per week) was investigated Wildlife related effect Fish in vivo study: Pituitary effects - possibly indirect effect of exposure. Chemical characteristics: Molecular formula: C13 H16 F3 N3 O4
Table 1: Physical/chemical properties of Trifluralin Parameter Value Unit Reference Molecular weight 335.29001 g/mol Melting point 49 ºC EPISUITE Boiling point 139.5 ºC EPISUITE Vapour pressure at 25 [oC] 0.0061061476 Pa EPISUITE Water solubility at 25 [oC] 0.184 mg/L EPISUITE Octanol-water partition coefficient 5.34 - EPISUITE Koc 9682 L/kg EPISUITE BCF 1.5 - EPISUITE Henry's law constant 10.43648 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - CHRIP NITE
t½(hydrolysis) Year t½(air) 5.347 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10000 Tonnes/year Release to air 80.099998 kg/year Release to wastewater 24000 kg/year Local PEC in surface water during emission episode (dissolved) 1.97 mg/l Local PEC in fresh-water sediment during emission episode 270 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 540 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 192 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 56000 mg/(kg wet weight) Concentration in fish-eating marine top-predators 22500 mg/(kg wet weight) Local total daily intake for humans 63.900002 mg/(kg⋅d) Regional total daily intake for humans 7.9800002E-3 mg/(kg wet weight) Conclusion Trifluralin is used as a pesticide and is according to the ESIS database a HPV substance. For the EUSES calculations a production volume of 10000 tones per year has been used. Trifluralin is not readily biodegradable and has a high potential to bioaccumulate in the environment (log kow=5.34). Trifluralin is in the environment mainly distributed to surface water as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning 2,4- Trifluralin is expected to be found in fish and top predators in extremely high amounts. A high human exposure up to 70 mg/kg/day is expected. Trifluralin is in the present evaluation considered as being of High Concern. Trifluralin is covered by Council Direc-tive 91/414/EEC. No RAR has been provided and the substance is not included in the list for pesticides to be reviewed. Classification: XI;R36 R43 N;R50/53. Finalised assessments review by EFSA. Agreement that there is only limited evidence for endocrine effects and that this was recorded at high dose levels and was hard to distinguish from systemic toxicity. Trifluralin is considered as a POP candidate
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Quinalphos = Chinalphos (CAS No.: 13593-03-8) O,O-diethyl O-2-quinoxalinyl phosphorothioate; Bayrusil; Diethquinalphion; Diethyl O-2-quinoxalinyl phosphorothioate; Diethyl O-(2-quinoxalyl) phosphorothioate; Diethyl O-quinoxalin-2-yl thionophosphate; Diethyl O-(quinoxalin-2-yl) thiophosphate; Ekalux; Quinalphos; Quinalphos ; QUINALPHOS [O,O-DIETHYL-O-2-QUINOXALYLTHIOPHOSPHATE]; SRA 7312; Wie oben; Human related effects In vivo rat study: Sublethal chronic administration of quinalphos resulted in: decreased testicular mass and AChE activity in central as well as peripheral organs; increased serum LH, FSH, prolactin, and tes-tosterone concns.; decreased pituitary or increased testicular ACE. Ed 7-14 mg/kg/day. Wildlife related effect Fish in vivo study: Impairment of testis function due to the inhibition of steroidogenic enzymes activities. EC=0.025 mg/L Chemical characteristics: Molecular formula: C12 H15 N2 O3 P1 S1
Table 1: Physical/chemical properties of Quinalphos = Chinalphos Parameter Value Unit Reference Molecular weight 298.29999 g/mol Melting point 31.5 ºC EPISUITE Boiling point 142 ºC EPISUITE Vapour pressure at 25 [oC] 0.0003466372 Pa EPISUITE Water solubility at 25 [oC] 22 mg/L EPISUITE Octanol-water partition coefficient 4.44 - EPISUITE Koc 1857 L/kg EPISUITE BCF 4631 - EPISUITE Henry's law constant 0.005806 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) Year t½(air) 1.346 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 500 Tonnes/year Release to air 3.75 kg/year Release to wastewater 7500 kg/year Local PEC in surface water during emission episode (dissolved) 1.98 mg/l Local PEC in fresh-water sediment during emission episode 93.099998 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 180 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 67.199997 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 482 mg/(kg wet weight) Concentration in fish-eating marine top-predators 12.2 mg/(kg wet weight) Local total daily intake for humans 7.9699998 mg/(kg⋅d) Regional total daily intake for humans 8.2199997E-4 mg/(kg wet weight) Conclusion Quinalphos is used as a insecticide. Quinalphos is according to the ESIS database a LPV substance. Quinalphos is not readily biodegradable and has a high potential to bioaccumulate (log Kow=4.44). Based on EUSES estimations Quinalphos expected to be found in local surface water in concentrations up to 2 mg/L. Due to the persistency of the substance and the high potential bioaccumulation Quinalphos is of medium concern in relation to secondary poisoning and daily human intake. Quinalphos is considered as being of Medium Concern. Quinalphos is covered by Council Directive 91/414/EEC. No RAR has been provided and the substance is not included in the list for pesticides to be reviewed. Classification: XN;R21 T;R25 N;R50/53.
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Dibromochloropropane (DBCP) (CAS No.: 96-12-8) 1,2-Dibromo-3-Chloropropane; 1,3-Dibromo-3-chloropropane; os 1897; oxy dbcp; sd 1897; 1-chloro-2,3-dibromopropane; 3-chloro-1,2-dibromopropane; BBC 12; Dibromo-3-chloropropane, 1,2- (DBCP) ; dibro-mochloropropane; CBCP; DBCP; fumagon; Fumazone; fumazone 86; nemabrom; Nemafume; Nemagon; nemagon 20; nemagon 206; nemagon 20g; nemagon 90; nemagon soil fumigant; Nemanax; nemapaz; Nemaset; Nematocide; nematox; nemazon; Human related effects Exposed human workers. Azoospermia oligospermia and dose-dependent change in FSH, LH and testi-cle size Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C3 H5 Br2 CL1
Table 1: Physical/chemical properties of Dibromochloropropane (DBCP) Parameter Value Unit Reference Molecular weight 236.33 g/mol Melting point 6 ºC EPISUITE Boiling point 196 ºC EPISUITE Vapour pressure at 25 [oC] 77.32676 Pa EPISUITE Water solubility at 25 [oC] 1230 mg/L SYRACUSE
CHEMFATE Octanol-water partition coefficient 2.96 - EPISUITE Koc 130.8 L/kg EPISUITE BCF 1.8 - SYRACUSE
CHEMFATE Henry's law constant 14.89478 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) 36.124 Year EPISUITE t½(air) 28.636 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 9 kg/year Release to wastewater 180 kg/year Local PEC in surface water during emission episode (dissolved) 0.76200002 mg/l Local PEC in fresh-water sediment during emission episode 6.5999999 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 3.02 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 0.68099999 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.61500001 mg/(kg wet weight) Concentration in fish-eating marine top-predators 1.6100001E-2 mg/(kg wet weight) Local total daily intake for humans 4.1299999E-2 mg/(kg⋅d) Regional total daily intake for humans 1.77E-7 mg/(kg wet weight)
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Conclusion Dibromochloropropane (DBCP) is used as a pesticide as well as an industrial intermediate. DBCP is according to the ESIS database produced in amounts < 10 tones/year and is thus not a LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. DBCP is not read-ily biodegradable and has medium potential to bioaccumulate in the environment (log kow=2.96). DBCP is in the environment mainly distributed to surface water in concentrations up to approx. 1 mg/L. Based on EUSES estimations for secondary poisoning and human intake DBCP is expected to be found in fish, predators and human food in minor amounts. DBCP is considered as being of Medium Concern. Cov-ered by Council Directive 91/414/EEC. No RAR has been provided and the substance is not included in the list for pesticides to be reviewed. Classification: CARC2;R45 MUT2;R46 REP1;R60 T;R25 XN;R48/20/22 R52/53.
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4-Nonylphenol (4-NP) (CAS No.: 104-40-5) 4-Nonylphenol; 4-Nonylphenol, mixture of isomers; Human related effects Rat in vivo study: Uterine weight, uterine/body weight significantly increased in 90 mg/kg and 120 mg/kg groups and a dose-response relationship was observed. Wildlife related effect Fish in vivo study: Induction of VTG. LOEC= 24.8 ug/l Chemical characteristics: Molecular formula: C15 H24 O1
Table 1: Physical/chemical properties of 4-Nonylphenol (4-NP) Parameter Value Unit Reference Molecular weight 220.36 g/mol Melting point 42 ºC EPISUITE Boiling point 324.47 ºC MST Vapour pressure at 25 [oC] 0.109057396 Pa EPISUITE Water solubility at 25 [oC] 7 mg/L EPISUITE Octanol-water partition coefficient 5.76 - EPISUITE Koc 60890 L/kg EPISUITE BCF 6.22 - EPISUITE Henry's law constant 3.44505 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) Year t½(air) 2.483 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 4.3400002 mg/l Local PEC in fresh-water sediment during emission episode 979 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 1920 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 743 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 933 mg/(kg wet weight) Concentration in fish-eating marine top-predators 424 mg/(kg wet weight) Local total daily intake for humans 245 mg/(kg⋅d) Regional total daily intake for humans 0.000157 mg/(kg wet weight) Conclusion Nonylphenol (NP) is widely used as a component of detergents, paints, pesticides, and many other for-mulated products. 4-Nonylphenol is produced is low amount and is according to the ESIS database nei-ther a HPV or LPV substance. 4-Nonylphenol is not readily biodegradable and has a high potential to bio-accumulate (log Kow=5.76). 4-Nonylphenol is in the environment mainly distributed to surface water as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning 4-Nonylphenol is expected to be found both in fish and top predators in concentrations up to 1000 mg/kg wet weight. Local daily human intake is estimated to be up to 250 mg/kg body weight per day. Due to an
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expected close human contact to 4-Nonylphenol via detergents and paints, 4-Nonylphenol is considered as being of High Concern. In the EU there is a restriction on the use of nonylphenol and its ethoxylates (Annex I of Directive 76/769/EEC) limiting the inclusion of these substances in a variety of products to no more than 0.1%. Proposed classification: Rep.3;R62 Rep.3;R63 Xn;R22 C;R34 N;R50/53
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4-Cyclohexylphenol (CAS No.: 1131-60-8) p-Cyclohexylphenol; Human related effects Rat in vivo study: Uterotrophic assay. Increased uterine weight. LOAEL=200 mg/kg Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C12 H16 O1
Table 1: Physical/chemical properties of 4-Cyclohexylphenol Parameter Value Unit Reference Molecular weight 176.25999 g/mol Melting point 133 ºC EPISUITE Boiling point 294 ºC EPISUITE Vapour pressure at 25 [oC] 0.01016 Pa EPISUITE Water solubility at 25 [oC] 60 mg/L EPISUITE Octanol-water partition coefficient 4.22 - EPISUITE Koc 10120 L/kg EPISUITE BCF 15.92 - EPISUITE Henry's law constant 0.114 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) Year t½(air) 36.832 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 8.3000002 mg/l Local PEC in fresh-water sediment during emission episode 302 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 569 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 208 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 8.7700005 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.211 mg/(kg wet weight) Local total daily intake for humans 16.700001 mg/(kg⋅d) Regional total daily intake for humans 0.00000963 mg/(kg wet weight) Conclusion 4-Cyclohexylphenol is used in the formation of resin. Resin is widely used product. 4-Cyclohexylphenol is according to the ESIS database produced in low amount and is neither a HPV or LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. 4-Cyclohexylphenol is not readily biodegradable and has a high potential to bioaccumulate in the environment (log kow=4.22). 4-Cyclohexylphenol is in the environment mainly distributed to surface water as well as sediments and
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agricultural soils. Based on EUSES estimations for secondary poisoning 4-Cyclohexylphenol is expected to be found in fish and top predators in minor amount. A medium human exposure is expected. 4-Cyclohexylphenol is considered as being of Medium Concern. None specifically regulatory or legal status for this substance was found, however the substance is related to nonylphenol.
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2,4-Dihydroxybenzophenon = Resbenzophenone (CAS No.: 131-56-6) 2,4-Dihydroxybenzophenone; Benzoresorcinol; Methanone, (2,4-dihydroxyphenyl)phenyl-; Human related effects Rat in vivo study: Benzophenone (Bp)-1 increased uterine wt. in immature rats. Furthermore, benzophe-none-1 (Bp-1) was in a previous in vitro experiment (MCF-7 cells) shown to have clear estrogenic activity (EC-50: 2.08 uM) Wildlife related effect Fish in vivo study: Aquatiic exposure of fathead minnow with BP1 induced vitellogenin significantly at 4919 mg/l Chemical characteristics: Molecular formula: C13 H10 O3
Table 1: Physical/chemical properties of 2,4-Dihydroxybenzophenon = Resbenzophenone Parameter Value Unit Reference Molecular weight 214.22 g/mol Melting point 144 ºC EPISUITE Boiling point 374.59 ºC MST Vapour pressure at 25 [oC] 1.88e-005 Pa EPISUITE Water solubility at 25 [oC] 412.4 mg/L EPISUITE Octanol-water partition coefficient 2.96 - MST Koc 2885 L/kg EPISUITE BCF 94.5 - EPISUITE Henry's law constant 2.68e-006 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - CHRIP NITE
t½(hydrolysis) Year t½(air) 0.641 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50 Tonnes/year Release to air 1.08 kg/year Release to wastewater 2970 kg/year Local PEC in surface water during emission episode (dissolved) 5.2399998 mg/l Local PEC in fresh-water sediment during emission episode 45.400002 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 62.099998 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 18.4 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 12.7 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.266 mg/(kg wet weight) Local total daily intake for humans 2.3199999 mg/(kg⋅d) Regional total daily intake for humans 0.0000105 mg/(kg wet weight)
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Conclusion 2,4-Dihydroxybenzophenon is used as a UV sunscreen in cosmetics. 2,4-Dihydroxybenzophenon is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 50 tones per year has been used. 2,4-Dihydroxybenzophenon is not readily biodegradable and has a poten-tial to bioaccumulate in the environment (log kow=2.96). 2,4-Dihydroxybenzophenon is in the environ-ment mainly distributed to surface water as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning 2,4-Dihydroxybenzophenon is not expected to be found in fish and top predators. A high human exposure is expected mainly due to the fact that the substance is used as a UV screen in cosmetics. 2,4-Dihydroxybenzophenon is therefore considered as being of High Concern. None specifically regulatory or legal status for this substance was found..
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4,4'-Dihydroxybenzophenon (CAS No.: 611-99-4) 4,4'-Dihydroxybenzophenone; DHBP; Human related effects rat in vivo assay: Induced uterotrophy and exerted both estrogen agonistic effect and reduced the estro-genic effect of ethynylestradiol Wildlife related effect Fish in vivo assay: VTG response. In vitro: Full dose-response curves in in vitro assay (recombinant yeast carrying the estrogen receptor of rainbow trout (rtERa)). In vivo: VTG response Chemical characteristics: Molecular formula: C13 H10 O3
Table 1: Physical/chemical properties of 4,4'-Dihydroxybenzophenon Parameter Value Unit Reference Molecular weight 214.22 g/mol Melting point 210 ºC EPISUITE Boiling point 374.59 ºC MST Vapour pressure at 25 [oC] 3.28e-006 Pa EPISUITE Water solubility at 25 [oC] 1905 mg/L EPISUITE Octanol-water partition coefficient 2.19 - MST Koc 2826 L/kg EPISUITE BCF 33.52 - EPISUITE Henry's law constant 2.13e-009 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) Year t½(air) 2.103 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 9.0000004E-2 kg/year Release to wastewater 180 kg/year Local PEC in surface water during emission episode (dissolved) 0.98199999 mg/l Local PEC in fresh-water sediment during emission episode 3.8499999 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 3.05 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 0.73199999 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.176 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.00358 mg/(kg wet weight) Local total daily intake for humans 0.34400001 mg/(kg⋅d) Regional total daily intake for humans 4.3599999E-7 mg/(kg wet weight)
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Conclusion 4,4'-Dihydroxybenzophenon is used as a UV sunscreen in cosmetics. 4,4'-Dihydroxybenzophenon is according to the ESIS database produced in amounts < 10 tones/year and thus not a LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. 4,4'-Dihydroxybenzophenon is not readily biodegradable and has a medium potential to bioaccumulate in the environment (log kow=2.19). 4,4'-Dihydroxybenzophenon is in the environment mainly distributed to sur-face water. Based on EUSES estimations for secondary poisoning 4,4-Dihydroxybenzophenon is ex-pected to be found in fish and top predators in minor amounts. A high human exposure is expected mainly due to the fact that the substance is used as a UV screen in cosmetics. 4,4-Dihydroxybenzophenon is therefore considered as being of Medium Concern. None specifically regula-tory or legal status for this substance was found.
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Methyl tertiary butyl ether (MTBE) (CAS No.: 1634-04-4) 2-methoxy-2-methylpropane; methyl t-butyl ether; Methyl Tertiary Butyl Ether; Methyl Tertiary Butyl Ether (MTBE) ; MTBE; Tert-butyl methyl ether; Human related effects Rat in vio study: Increase of testis weight. Interstitial fluid and serum testosterone levels as well as serum prolactin levels were decreased only in animals treated with 1500 mg MTBE/kg/day for 15 days. Wildlife related effect Amphibian in vivo study: Accelarated development and earlier metamorphosis. LOEC<2500 mg/L Chemical characteristics: Molecular formula: C5 H12 O1
Table 1: Physical/chemical properties of methyl tertiary butyl ether (MTBE) Parameter Value Unit Reference Molecular weight 88.150002 g/mol Melting point -108.6 ºC IUCLID Boiling point 55.3 ºC IUCLID Vapour pressure at 25 [oC] 26800 Pa IUCLID Water solubility at 25 [oC] 26000 mg/L IUCLID Octanol-water partition coefficient 1.06 - IUCLID Koc 5.258 L/kg EPISUITE BCF 28.4 - IUCLID Henry's law constant 59.47778 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - IUCLID
t½(hydrolysis) Year t½(air) 2.6 hr IUCLID Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50000 Tonnes/year Release to air 1251000 kg/year Release to wastewater 75000 kg/year Local PEC in surface water during emission episode (dissolved) 4.73 mg/l Local PEC in fresh-water sediment during emission episode 7.54 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 0.199 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 8.6900003E-2 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 3.0899999 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.163 mg/(kg wet weight) Local total daily intake for humans 0.39500001 mg/(kg⋅d) Regional total daily intake for humans 4.0999999E-5 mg/(kg wet weight) Conclusion Methyl tertiary butyl ether is used as a petrol additive and is according to the ESIS database a HPV substance. For the EUSES calculations a production volume of 50000 tones per year has been used. Methyl tertiary butyl ether is not readily biodegradable and has a low potential to bioaccumulate in the environment (log kow=1.06). Methyl tertiary butyl ether is in the environment mainly distributed to surface
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waters. Based on EUSES estimations for secondary poisoning 2,4- Methyl tertiary butyl ether is expected to be found in fish and top predators in minor amount. A relatively low daily human intake is expected. Due to the fact that Methyl tertiary butyl ether is a high volume substance and not readily biodegradable relatively high concentrations in surface waters can be expected and Methyl tertiary butyl ether is thus considered as being of Medium Concern. RAR from 2002 is available on ESIS. Classification: F;R11 XI;R38
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Cyclotetrasiloxane (CAS No.: 556-67-2) Octamethylcyclotetrasiloxane; Human related effects Rat in vivo assay. Uterotrophic assay with two species: Relative uterine wts. and uterine epithelial cell height were statistically significantly increased in both strains of rats at doses above 100 mg/kg/day. LO-AEL=250 mg/kg/day Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C8 H24 O4 Si4
Table 1: Physical/chemical properties of Cyclotetrasiloxane Parameter Value Unit Reference Molecular weight 296.62 g/mol Melting point 17.5 ºC EPISUITE Boiling point 175.8 ºC EPISUITE Vapour pressure at 25 [oC] 139.9881 Pa EPISUITE Water solubility at 25 [oC] 0.005 mg/L EPISUITE Octanol-water partition coefficient 4.45 - SYRACUSE
CHEMFATE Koc 17960 L/kg EPISUITE BCF 1.392 - EPISUITE Henry's law constant 11855.03 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - EPISUITE
t½(hydrolysis) Year t½(air) 107.246 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50000 Tonnes/year Release to air 300000 kg/year Release to wastewater 90000 kg/year Local PEC in surface water during emission episode (dissolved) 0.65899998 mg/l Local PEC in fresh-water sediment during emission episode 31.4 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 4.3299999E-2 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 8.7299999E-3 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 328 mg/(kg wet weight) Concentration in fish-eating marine top-predators 149 mg/(kg wet weight) Local total daily intake for humans 1.15 mg/(kg⋅d) Regional total daily intake for humans 3.8400001E-4 mg/(kg wet weight)
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Conclusion Cyclotetrasiloxane has numerous industrial and consumer applications and is according to the ESIS database a HPV substance. For the EUSES calculations a production volume of 50000 tones per year has been used. Cyclotetrasiloxane is not readily biodegradable and has a high potential to bioaccumulate in the environment (log kow=5.45). Cyclotetrasiloxane is in the environment mainly distributed to surface water. Based on EUSES estimations for secondary poisoning Cyclotetrasiloxane is expected to be found in fish and top predators in minor amounts. Cyclotetrasiloxane has a potential for human exposure as it is used in numerous industrial and consumer. Applications. Cyclotetrasiloxane is considered as being of High Concern. None specifically regulatory or legal status for this substance was found. Classification: REP3;R62 R53
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2-ethyl-hexyl-4-methoxycinnamate (CAS No.: 5466-77-3) 2-Ethylhexyl 4-methoxycinnamate; 2-Ethylhexyl cinnamate; 3-(4-Methoxyphenyl)-2-propenoic acid 2-ethylhexyl ester; Escalol 557; Neo Heliopan AV.; Octyl 4-methoxycinnamate; Octyl methoxycinnamate; Parsol MCX; Parsol MOX; Human related effects Rat in vivo assay. Uterine wt. was dose-dependently increased by OMC (ED50 935 mg/kg/day) Wildlife related effect Fish in vivo assay. Increase in plasma VTG + and increased mRNA expression levels of estrogen recep-tor (ER) alpha, among sex hormone receptors in the liver. Chemical characteristics: Molecular formula: C18 H26 O3
Table 1: Physical/chemical properties of 2-ethyl-hexyl-4-methoxycinnamate Parameter Value Unit Reference Molecular weight 290.41 g/mol Melting point 99.87 ºC EPISUITE Boiling point 360.54 ºC MST Vapour pressure at 25 [oC] 0.00184 Pa EPISUITE Water solubility at 25 [oC] 0.1548 mg/L EPISUITE Octanol-water partition coefficient 5.8 - MST Koc 12280 L/kg EPISUITE BCF 12400 - EPISUITE Henry's law constant 0.18 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - MST
t½(hydrolysis) 35.562 Year EPISUITE t½(air) 2.483 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value unit Tonnage of substance in Europe 5000 Tonnes/year Release to air 5.0100002 kg/year Release to wastewater 15000 kg/year Local PEC in surface water during emission episode (dissolved) 1.0599999 mg/l Local PEC in fresh-water sediment during emission episode 251 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 490 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 190 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 73900 mg/(kg wet weight) Concentration in fish-eating marine top-predators 34400 mg/(kg wet weight) Local total daily intake for humans 89.199997 mg/(kg⋅d) Regional total daily intake for humans 0.0131 mg/(kg wet weight) Conclusion 2-ethyl-hexyl-4-methoxycinnamate is used as a UV sunscreen in cosmetics. 2-ethyl-hexyl-4-methoxycinnamate is according to the ESIS database a HPV substance. For the EUSES calculations a production volume of 5000 tones per year has been used. 2-ethyl-hexyl-4-methoxycinnamate is readily biodegradable and has a high potential to bioaccumulate in the environment (log kow=5.8). 2-ethyl-hexyl-4-methoxycinnamate is in the environment mainly distributed to surface water as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning 2-ethyl-hexyl-4-methoxycinnamate is expected to be found in fish and top predators in amounts up to approx. 70000 mg/kg ww. Furthermore a high regional human exposure is expected. Besides a high human exposure is expected mainly due to the fact that the substance is used as a UV screen in cosmetics. 2-ethyl-hexyl-4-methoxycinnamate is therefore considered as being of High Concern. None specifically regulatory or legal status for this substance was found.
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3-(4-Methylbenzylidene)camphor (CAS No.: 36861-47-9) 3-(4-Methylbenzyliden)camphor; Eusolex 6300; Human related effects Rat in vivo study. Delayed male puberty, and dose-dependently affected reproductive organ wts. of adult male and female F1 offspring, with partly different effect patterns. Thyroid wt. was increased by higher 4-MBC doses. LOAEL=7 mg/kg/day Wildlife related effect Amphibian in vivo study.The rate of metamorphosis was not affected, and no obvious differences in body and tail length compared to controls were observed. Chemical characteristics: Molecular formula: C18 H22 O1
Table 1: Physical/chemical properties of 3-(4-Methylbenzylidene)camphor Parameter Value Unit Reference Molecular weight 254.38 g/mol Melting point 121 ºC EPISUITE Boiling point 349.42 ºC MST Vapour pressure at 25 [oC] 0.002027 Pa EPISUITE Water solubility at 25 [oC] 0.1966 mg/L EPISUITE Octanol-water partition coefficient 5.22 - MST Koc 12210 L/kg EPISUITE BCF 3.162 - EPISUITE Henry's law constant 0.218 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - EPISUITE
t½(hydrolysis) Year t½(air) 1.443 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50 Tonnes/year Release to air 0.3996 kg/year Release to wastewater 799.20001 kg/year Local PEC in surface water during emission episode (dissolved) 0.85900003 mg/l Local PEC in fresh-water sediment during emission episode 102 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 202 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 76.599998 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 1730 mg/(kg wet weight) Concentration in fish-eating marine top-predators 594 mg/(kg wet weight) Local total daily intake for humans 15.7 mg/(kg⋅d) Regional total daily intake for humans 0.000237 mg/(kg wet weight)
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Conclusion 3-(4-Methylbenzylidene)camphor is used as a UV sunscreen in cosmetics. 3-(4-Methylbenzylidene)camphor is according to the ESIS database a LPV substance. For the EUSES calcu-lations a production volume of 50 tones per year has been used. 3-(4-Methylbenzylidene)camphor is not readily biodegradable and has a high potential to bioaccumulate in the environment (log kow=5.22). 3-(4-Methylbenzylidene)camphor is in the environment mainly distributed to surface water as well as sedi-ments and agricultural soils. Based on EUSES estimations for secondary poisoning 3-(4-Methylbenzylidene)camphor is expected to be found in fish and top predators in amounts up to approx. 2000 mg/kg ww. A high human exposure is expected mainly due to the fact that the substance is used as a UV screen in cosmetics. 3-(4-Methylbenzylidene)camphor is therefore considered as being of High Concern. None specifically regulatory or legal status for this substance was found.
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p-Hydroxybenzoic acid (CAS No.: 99-96-7) 4-Hydroxybenzenecarboxylic acid; 4-Hydroxybenzoic acid; Human related effects Rat in vivo assay: Dose-dependent response (0.5, 5, 50, and 500 g/kg) on vaginal cornification and utero-trophic activity in both immature and adult ovariectomized mice. Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C7 H6 O3
Table 1: Physical/chemical properties of p-Hydroxybenzoic acid Parameter Value Unit Reference Molecular weight 138.12 g/mol Melting point 214.5 ºC EPISUITE Boiling point 298.03 ºC MST Vapour pressure at 25 [oC] 2.6397756e-005 Pa EPISUITE Water solubility at 25 [oC] 5000 mg/L EPISUITE Octanol-water partition coefficient 1.58 - SYRACUSE
CHEMFATE Koc 23.47 L/kg EPISUITE BCF - EPISUITE Henry's law constant 1.14e-006 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - CHRIP NITE
t½(hydrolysis) Year t½(air) 9.873 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 1000 Tonnes/year Release to air 9.9899998 kg/year Release to wastewater 3000 kg/year Local PEC in surface water during emission episode (dissolved) 6.2899999E-2 mg/l Local PEC in fresh-water sediment during emission episode 0.14399999 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 0.0275 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 0.0106 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.114 mg/(kg wet weight) Concentration in fish-eating marine top-predators 1.8100001E-2 mg/(kg wet weight) Local total daily intake for humans 8.6300001E-3 mg/(kg⋅d) Regional total daily intake for humans 4.17E-7 mg/(kg wet weight) Conclusion p-Hydroxybenzoic acid is the common metabolite of all parabens and thus used as a preservative in food, pharmaceutical and cosmetic formulations. p-Hydroxybenzoate is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 1000 tonnes per year has been used. P-hydroxybenzoic acid is readily biodegradable and has a low potential for bioaccumulation (log Kow=1.58). Based EUSES calculations p-Hydroxybenzoic acid is distributed to the environment at low concentrations. P-hydroxybenzoic acid is expected to be found in fish, predators and human food in in-
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significant amounts. However, as P-hydroxybenzoic acid is used as a preservative in food and cosmetics a high direct human exposure is expected. P-hydroxybenzoic acid is thus considered as being of Medium Concern. None specifically regulatory or legal status for this substance was found. It is the opinium of the Scientific Commitee on Consumer Products (SCCP) that, viewing the current knowledge, there is no evi-dence of demonstrable risk for the development of breast cancer caused by the use of underarm cosmet-ics including parabens.
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Methyl p-hydroxybenzoate (CAS No.: 99-76-3) 4-Hydroxybenzoic acid methyl ester; 4-Hydroxy methyl benzoate; Aseptoform; Methyl paraben; Methyl 4-hydroxybenzoate; Methyl Parasept; Methyl Chemosept; Nipagin; Nipagin M; Tegosept M; Human related effects In vivo mice assay: The highest MePben dose (165 mg/kg) was able to produce uterotrophic effects (38 to 76%) compared to E-2 efects (100%). LOAEL=165 mg/kg Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C8 H8 O3
Table 1: Physical/chemical properties of Methyl p-Hydroxybenzoate Parameter Value Unit Reference Molecular weight 152.14999 g/mol Melting point 131 ºC EPISUITE Boiling point 275 ºC EPISUITE Vapour pressure at 25 [oC] 0.114 Pa EPISUITE Water solubility at 25 [oC] 2500 mg/L EPISUITE Octanol-water partition coefficient 1.96 - EPISUITE Koc 125.6 L/kg EPISUITE BCF 3.162 - EPISUITE Henry's law constant 0.000366 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - MST
t½(hydrolysis) 34.506 Year EPISUITE t½(air) 11.6 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 500 Tonnes/year Release to air 5 kg/year Release to wastewater 10000 kg/year Local PEC in surface water during emission episode (dissolved) 1.25 mg/l Local PEC in fresh-water sediment during emission episode 3.96 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 0.87199998 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 0.33899999 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.79500002 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.127 mg/(kg wet weight) Local total daily intake for humans 0.0276 mg/(kg⋅d) Regional total daily intake for humans 0.00000145 mg/(kg wet weight) Conclusion Methyl p-Hydroxybenzoate is used as a preservative in food, pharmaceutical and cosmetic formula-tions. Methyl p-Hydroxybenzoate is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 500 tones per year has been used. Methyl p-hydroxybenzoate is readily biodegradable and has a low potential for bioaccumulation (log Kow=1.96). Based EUSES calcu-
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lations Methyl p-hydroxybenzoate is in the environment mainly distributed to surface water in concentra-tions up to approx. 1 mg/L. Methyl p-hydroxybenzoate is expected to be found in fish, predators and hu-man food in insignificant amounts. However, as Methyl p-hydroxybenzoate is used as a preservative in food and cosmetics a high direct human exposure is expected. Methyl p-hydroxybenzoate is thus consid-ered as being of Medium Concern. None specifically regulatory or legal status for this substance was found. It is the opinium of the Scientific Commitee on Consumer Products (SCCP) that, viewing the cur-rent knowledge, there is no evidence of demonstrable risk for the development of breast cancer caused by the use of underarm cosmetics including parabens.
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Ethyl 4-hydroxybenzoate (CAS No.: 120-47-8) 4-Hydroxybenzoic acid ethyl ester; Ethyl paraben; Ethyl 4-hydroxybenzoate; Ethyl Parasept; Nipagin A; Solbrol A; Human related effects Rat and mice in vivo study: Increased uterine weight in immature and ovariectomized animals. ED50 18-74 µmol/ kg body weight Wildlife related effect Fish in vivo study. VTG induction in rainbow trouts. LOAEL=100 mgkg Chemical characteristics: Molecular formula: C9 H10 O3
Table 1: Physical/chemical properties of ethyl 4-hydroxybenzoate Parameter Value Unit Reference Molecular weight 254.38 g/mol Melting point 117 ºC EPISUITE Boiling point 297.5 ºC EPISUITE Vapour pressure at 25 [oC] 0.01239 Pa EPISUITE Water solubility at 25 [oC] 885 mg/L EPISUITE Octanol-water partition coefficient 2.47 - EPISUITE Koc 231.6 L/kg EPISUITE BCF 9.141 - EPISUITE Henry's law constant 0.000486 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - MST
t½(hydrolysis) Year t½(air) 10.207 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50 Tonnes/year Release to air 0.50099999 kg/year Release to wastewater 999 kg/year Local PEC in surface water during emission episode (dissolved) 0.0207 mg/l Local PEC in fresh-water sediment during emission episode 0.107 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 2.6799999E-2 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 0.0105 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.214 mg/(kg wet weight) Concentration in fish-eating marine top-predators 3.4400001E-2 mg/(kg wet weight) Local total daily intake for humans 0.00177 mg/(kg⋅d) Regional total daily intake for humans 2.3299999E-7 mg/(kg wet weight) Conclusion Ethyl 4-hydroxybenzoate is used as preservatives in food, pharmaceutical and cosmetic formulations. Ethyl 4-hydroxybenzoate is produced in amounts up to 50 tones per year and thus a LPV substance.
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Ethyl 4-hydroxybenzoate is readily biodegradable and has a medium potential for bioaccumulation. Based EUSES calculations Ethyl 4-hydroxybenzoate is expected to be released to the environment in insignifi-cant amounts and is not expected to give any problems in relation to secondary poisoning. However, as ethyl 4-hydroxybenzoate as a preservative in food and cosmetics a high human exposure is expected. Ethyl 4-hydroxybenzoate is thus considered as being of Medium Concern. None specifically regulatory or legal status for this substance was found.
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n-propyl p-hydroxybenzoate (CAS No.: 94-13-3) Parabens; 4-Hydroxybenzoic acid propyl ester; Propyl chemsept; protaben p; pulvis conservans; Solbrol P; tegosept p; 4-hydroxybenzoic propyl ester; p-hydroxy propyl benzoate; aseptoform p; betacide p; bo-nomold op; Chemacide PK; Chemocide PK; Chemoside PK; nipagin p; Nipasol; nipasol m; nipasol p; ni-pazol; n-Propyl paraben; n-propyl p-hydroxybenzoate; paseptol; preserval p; propagin; Propyl paraben; Propyl 4-hydroxybenzoate; Propyl Parasept; propyl aseptoform; propyl butex; Propyl Chemosept; Human related effects In vivo rat assay: The epididymal sperm reserves and concentrations decreased dose dependently and the difference was significant at doses of 0.1% and above. LOAEL=0.1% Wildlife related effect Fish in vivo assay: Clear dose response increase in VTG response. ED50 = 22 mg kg-1 2-d. NOEC = 225 mg/L Chemical characteristics: Molecular formula: C10 H12 O3
Table 1: Physical/chemical properties of n-propyl p-hydroxybenzoate Parameter Value Unit Reference Molecular weight 180.21001 g/mol Melting point 97 ºC EPISUITE Boiling point 285.14 ºC MST Vapour pressure at 25 [oC] 0.04093 Pa EPISUITE Water solubility at 25 [oC] 500 mg/L EPISUITE Octanol-water partition coefficient 3.04 - EPISUITE Koc 427.2 L/kg EPISUITE BCF 111.9 - EPISUITE Henry's law constant 0.000645 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - MST
t½(hydrolysis) 43.052 Year EPISUITE t½(air) 9.124 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 9.5200005 mg/l Local PEC in fresh-water sediment during emission episode 90 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 124 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 36.799999 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.99900001 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.021 mg/(kg wet weight) Local total daily intake for humans 2.0799999 mg/(kg⋅d) Regional total daily intake for humans 0.00000106 mg/(kg wet weight) Conclusion N-propyl p-hydroxybenzoate is used as a preservative in food, pharmaceutical and cosmetic formula-tions. N-propyl p-hydroxybenzoate is produced in amounts up to 10 tones per year and thus a LPV sub-stance. N-propyl p-hydroxybenzoate is readily biodegradable and has potential for bioaccumulation (log Kow=3.04). Based EUSES calculations N-propyl p-hydroxybenzoate is in the environment mainly distrib-uted to surface waters in concentrations up to approx. 10 mg/L. N-propyl p-hydroxybenzoate is expected to be found in fish, predators and human food in insignificant amounts. However, as n-propyl p-hydroxybenzoate is used as a preservative in food and cosmetics a high human exposure is expected. N-propyl p-hydroxybenzoate is thus considered as being of Medium Concern. None specifically regulatory or legal status for this substance was found. It is the opinium of the Scientific Commitee on Consumer Products (SCCP) that, viewing the current knowledge, there is no evidence of demonstrable risk for the development of breast cancer caused by the use of underarm cosmetics including parabens
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n-Butyl p-Hydroxybenzoate (CAS No.: 94-26-8) 4-(butoxycarbonyl)phenol; 4-Hydroxybenzoic acid butyl ester; p-hydroxybenzoic acid n-butyl ester; p-Hydroxy butyl benzoate; aseptoform butyl; Butoben; Butyl paraben; Butyl 4-hydroxybenzoate; Butyl Para-sept; butyl butex; Butyl Chemosept; butyl tegosept; n-Butyl paraben; n-Butyl p-Hydroxybenzoate; nipabu-tyl; preserval b; solbrol b; SPF; Tegosept B; tegosept butyl; Human related effects In vivo mice study. A dose-dependent decrease of both round and elongated spermatid ounts in stages VII-VIII seminiferous tubules was observed, and the elongated spermatid counts were significantly lower in all of the treated groups. The serum testosterone concentration decreased in a dose-dependent fash-ion and was significant at 1.00%. LOAEL=1504 mg/kg body weight. Day Wildlife related effect Rainbow trout in vivo study. Vitellogenin response. LOED: oral exposure to 9 mg butylparaben kg-1 2d-1 Chemical characteristics: Molecular formula: C11 H14 O3
Table 1: Physical/chemical properties of n-Butyl p-Hydroxybenzoate Parameter Value Unit Reference Molecular weight 194.23 g/mol Melting point 68.5 ºC EPISUITE Boiling point 300.26 ºC MST Vapour pressure at 25 [oC] 0.0334 Pa EPISUITE Water solubility at 25 [oC] 207 mg/L EPISUITE Octanol-water partition coefficient 3.57 - EPISUITE Koc 787.8 L/kg EPISUITE BCF 37.95 - EPISUITE Henry's law constant 0.000856 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - MST
t½(hydrolysis) 43.052 Year EPISUITE t½(air) 8.291 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 1.1900001 mg/l Local PEC in fresh-water sediment during emission episode 20.4 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 5.6700001 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 2.26 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.35299999 mg/(kg wet weight) Concentration in fish-eating marine top-predators 5.9099998E-2 mg/(kg wet weight) Local total daily intake for humans 0.105 mg/(kg⋅d) Regional total daily intake for humans 2.4600001E-7 mg/(kg wet weight) Conclusion n-Butyl p-Hydroxybenzoate is used as a preservative in food, pharmaceutical and cosmetic formula-tions. N-Butyl p-hydroxybenzoate is according to the ESIS database produced in amounts < 10 tones/year and is thus not a LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. n-Butyl p-hydroxybenzoate is readily biodegradable and has a relatively high potential for bioaccumulation (log Kow=3.57). Based EUSES calculations N-Butyl p-hydroxybenzoate is in the environment mainly distributed to surface waters in concentrations up to approx. 1 mg/L. N-Butyl p-hydroxybenzoate is expected to be found in fish, predators and human food in insignificant amounts. However, as n-Butyl p-hydroxybenzoate is used as a preservative in food and cosmetics a high direct human exposure is expected. N-Butyl p-hydroxybenzoate is thus considered as being of Medium Con-cern. None specifically regulatory or legal status for this substance was found. It is the opinium of the Scientific Commitee on Consumer Products (SCCP) that, viewing the current knowledge, there is no evi-dence of demonstrable risk for the development of breast cancer caused by the use of underarm cosmet-ics including parabens
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3-Benzylidene camphor (3-BC) (CAS No.: 15087-24-8) Human related effects Rat in vivo study: Increase in uterus weight. LOED = 2 mg/kg body weight.day Wildlife related effect Fish in vivo study: Vitellogenin induction. ED10, ED50 and ED90 of 3-benzylidene camphor after 6 days (2 injections) were 6.4, 16 and 26 mg/kg/injection, resp Chemical characteristics: Molecular formula: C17 H20 O1
Table 1: Physical/chemical properties of 3-Benzylidene camphor (3-BC) Parameter Value Unit Reference Molecular weight 240.35001 g/mol Melting point 109.87 ºC EPISUITE Boiling point 337.59 ºC MST Vapour pressure at 25 [oC] 0.005066 Pa EPISUITE Water solubility at 25 [oC] 0.6893 mg/L EPISUITE Octanol-water partition coefficient 4.67 - MST Koc 7540 L/kg EPISUITE BCF 385 - EPISUITE Henry's law constant 0.198 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - EPISUITE
t½(hydrolysis) Year t½(air) 2.015 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50 Tonnes/year Release to air 0.5 kg/year Release to wastewater 1000 kg/year Local PEC in surface water during emission episode (dissolved) 7.1999998 mg/l Local PEC in fresh-water sediment during emission episode 445 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 861 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 316 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 183 mg/(kg wet weight) Concentration in fish-eating marine top-predators 10.2 mg/(kg wet weight) Local total daily intake for humans 38 mg/(kg⋅d) Regional total daily intake for humans 6.9499998E-5 mg/(kg wet weight) Conclusion 3-Benzylidene camphor is used as a UV sunscreen in cosmetics. 3-Benzylidene camphor is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 50 tones per year has been used. 3-Benzylidene camphor is not readily biodegradable and has a high potential to bio-
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accumulate in the environment (log kow=4.67). 3-Benzylidene camphor is in the environment mainly dis-tributed to surface water as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning 3-Benzylidene camphor is expected to be found in fish and top predators in minor amount. A high human exposure is expected mainly due to the fact that the substance is used as a UV screen in cosmetics. 2,4-3-Benzylidene camphor is therefore considered as being of High Concern. None specifically regulatory or legal status for this substance was found.
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Benzophenone-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone (CAS No.: 131-55-5) 2,2',4,4'-Tetrahydroxybenzophenone; Benzophenone-2 (2,2',4,4'-tetrahydroxybenzophenone; Methanone, bis(2,4-dihydroxyphenyl)-; Human related effects Rat in vivo study: Increased rat uterine weights. ED10=544.6 mg/kg body weight/day Wildlife related effect Fish in vivo study: Dose response related VTG induction. LOEC = 8783 mg/L Chemical characteristics: Molecular formula: C13 H10 O5
Table 1: Physical/chemical properties of Benzophenone-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone Parameter Value Unit Reference Molecular weight 246.22 g/mol Melting point 186.56 ºC EPISUITE Boiling point 444.26 ºC MST Vapour pressure at 25 [oC] 6.586e-008 Pa EPISUITE Water solubility at 25 [oC] 398.5 mg/L EPISUITE Octanol-water partition coefficient 2.78 - MST Koc 7726 L/kg EPISUITE BCF 5.521 - EPISUITE Henry's law constant 3.66e-011 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) Year t½(air) 0.64 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50 Tonnes/year Release to air 0.5 kg/year Release to wastewater 1000 kg/year Local PEC in surface water during emission episode (dissolved) 9.6400003 mg/l Local PEC in fresh-water sediment during emission episode 68.800003 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 85.599998 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 24.1 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 3.04 mg/(kg wet weight) Concentration in fish-eating marine top-predators 6.3199997E-2 mg/(kg wet weight) Local total daily intake for humans 4.0700002 mg/(kg⋅d) Regional total daily intake for humans 0.00000413 mg/(kg wet weight) Conclusion Benzophenone-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone is used as a UV sunscreen in cosmet-ics. Benzophenone-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 50 tones per year has been used. Benzophenone-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone is not readily biodegradable and has a me-dium potential to bioaccumulate. Benzophenone-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone is in the environment mainly distributed to surface water as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning Benzophenone-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone is not expected to be found in fish and top predators. A high human exposure is expected mainly due to the fact that the substance is used as a UV screen in cosmetics. Benzophe-none-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone is therefore considered as being of High Concern. None specifically regulatory or legal status for this substance was found.
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Boric acid (CAS No.: 10043-35-3) Orthoboric acid; Orthoboric acid (H3BO3); Boracic acid; Borofax; Boron trihydroxide; hydrogen orthobo-rate; Kill-off; Kjel-sorb; three elephant; Trihydroxyborane; Human related effects Rat in vivo study: After a 4-wk administration by gavage, testis and epididymis wts. were decreased in the 300 and 500 mg/kg groups Wildlife related effect Amphibian in vivo study: Boric acid exerted reproductive toxicity in Xenopus laevis + transgenerational toxicity to the developing progeny. Chemical characteristics: Molecular formula: H3 O3 B1
Table 1: Physical/chemical properties of Boric acid Parameter Value Unit Reference Molecular weight 61.830002 g/mol Melting point 171 ºC IUCLID Boiling point 300 ºC IUCLID Vapour pressure at 25 [oC] 9.799e-015 Pa EPISUITE Water solubility at 25 [oC] 50000 mg/L EPISUITE Octanol-water partition coefficient -0.757 - IUCLID Koc 35.04 L/kg EPISUITE BCF 543.5 - EPISUITE Henry's law constant 0 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - EPISUITE
t½(hydrolysis) Year t½(air) 25.467 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 50000 Tonnes/year Release to air 375 kg/year Release to wastewater 112500 kg/year Local PEC in surface water during emission episode (dissolved) 2.3699999 mg/l Local PEC in fresh-water sediment during emission episode 2.0799999 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 0.0517 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 1.7999999E-2 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 1.38 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.21799999 mg/(kg wet weight) Local total daily intake for humans 6.7000002E-2 mg/(kg⋅d) Regional total daily intake for humans 0.0000163 mg/(kg wet weight) Conclusion Boric acid is used in consumer products as e.g. cosmetics and is according to the ESIS database a HPV substance. For the EUSES calculations a production volume of 50000 tones per year has been used. Bo-ric acid is not bioaccumulative and is readily biodegradable in the environment. EUSES calculations for secondary poisoning shows that the substance is not accumulated in significant amounts in fish and top predators. A relatively high human exposure is however expected due to the defined use of the sub-
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stance. Based on these evaluations Boric acid is considered as being of Medium Concern. Presently no EU classification is applied to Boric acid. A risk assessment on Boric acid is at the moment being per-formed by Austria. Proposed classification: R62; R63.
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2,2-Bis(4-hydroxyphenyl)-n-butan = Bisphenol B (CAS No.: 77-40-7) Human related effects In vivo immature rat uterotrophic assay: Positive response in the uterotrophic assay. Dose reponse rela-tionship (0, 2, 20 and 200 mg/kg) Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C16 H18 O2
Table 1: Physical/chemical properties of 2,2-Bis(4-hydroxyphenyl)-n-butan = Bisphenol B Parameter Value Unit Reference Molecular weight 242.32001 g/mol Melting point 102.5 ºC EPISUITE Boiling point 379.74 ºC MST Vapour pressure at 25 [oC] 3.293e-005 Pa EPISUITE Water solubility at 25 [oC] 29.23 mg/L EPISUITE Octanol-water partition coefficient 4.69 - MST Koc 149000 L/kg EPISUITE BCF 14.72 - EPISUITE Henry's law constant 1.23e-006 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) Year t½(air) 1.571 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 9.0000004E-2 kg/year Release to wastewater 180 kg/year Local PEC in surface water during emission episode (dissolved) 0.73799998 mg/l Local PEC in fresh-water sediment during emission episode 46.700001 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 91.699997 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 35 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 35.200001 mg/(kg wet weight) Concentration in fish-eating marine top-predators 1.9 mg/(kg wet weight) Local total daily intake for humans 4.1799998 mg/(kg⋅d) Regional total daily intake for humans 0.0000294 mg/(kg wet weight) Conclusion Bisphenol B is component of Phenolic Resin which is thermosetting resin used as Adhesive and Rein-forcement. Bisphenol B is used in many industrial applications. Bisphenol B is according to the ESIS da-tabase produced in low amount and is neither a HPV or LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. Bisphenol B is not readily biodegradable and has a high potential to bioaccumulate in the environment (log kow=4.69). Bisphenol B is in the environment mainly distributed to surface water as well as sediments and agricultural soils. Based on EUSES estima-tions for secondary poisoning Bisphenol B is expected to be found in fish and top predators in minor amount. A medium human exposure is expected. Bisphenol B is considered as being of Medium Con-cern. None specifically regulatory or legal status for this substance was found.
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3,3'-Bis(4-hydroxyphenyl)phthalid = Phenolphthaleine (CAS No.: 77-09-8) 2-[Bis (4-hydroxyphenyl)methyl]benzoic acid; 3,3-bis(4-hydroxyphenyl)-1(3H)-isobenzofuranone; 3,3-bis(p-hydroxyphenyl)phthalide; Alophen; Espotabs; Ex-Lax; Feen-a-mint; feen-a-mint gum; Figsen; Laxet-tes; Phenolax; Phenolphthalein; Human related effects Rat and mice in vivo study. Exposure of mice to phenolphthalein in feed for 2 years resulted in increased incidences of atypical hyperplasia of the thymus in males and females, degeneration of the germinal epi-thelium of the testis in males, and ovarian hyperplasia in females. LOAEL=300 mg/kg Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C20 H14 O4
Table 1: Physical/chemical properties of 3,3'-Bis(4-hydroxyphenyl)phthalid = Phenolphthaleine Parameter Value Unit Reference Molecular weight 318.32999 g/mol Melting point 262.5 ºC EPISUITE Boiling point 512.44 ºC MST Vapour pressure at 25 [oC] 8.373e-011 Pa EPISUITE Water solubility at 25 [oC] 400 mg/L EPISUITE Octanol-water partition coefficient 3.06 - MST Koc 307000 L/kg EPISUITE BCF 304.3 - EPISUITE Henry's law constant 9.1e-011 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - EPISUITE
t½(hydrolysis) Year t½(air) 1.525 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 9.5100002 mg/l Local PEC in fresh-water sediment during emission episode 91.900002 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 132 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 40.099998 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 1.04 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.0218 mg/(kg wet weight) Local total daily intake for humans 4.27 mg/(kg⋅d) Regional total daily intake for humans 1.2199999E-6 mg/(kg wet weight) Conclusion Phenolphthalein is used as a laboratory reagent and acid-base indicator and in over-the-counter laxative preparations. Phenolphthalein is according to the ESIS database produced in amounts < 10 tones/year and thus not a LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. Phenolphthalein is not readily biodegradable and has potential to bioaccumulate (log Kow=3.06). Based on EUSES estimations Phenolphthalein is expected to be found in local surface water in relatively high concentrations (approx. 10 mg/L) as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning and human intake Chlordimeform is expected to be found in fish, predators and human food in insignificant amounts. Based on the expected high concentrations in surface waters PCA is considered as being of Medium Concern. None specifically regulatory or legal status for this substance was found.
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4,4'-Dihydroxybiphenyl = 4,4'-Biphenol (CAS No.: 92-88-6) 4,4[-Dihydroxybiphenyl; 4,4'-Dihydroxybiphenyl; 4,4'-Biphenol; 4,4'-Biphenyldiol; PPDP; Human related effects Rat in vivo study. Rat uterotrophic assay. Uterine weight increase. LOAEL=60 mg/kg body weight/day. Wildlife related effect In vitro study. Recombinant yeast assay for trout ER and trout hepatocyte cultures. Competitive binding to ER Chemical characteristics: Molecular formula: C12 H10 O2
Table 1: Physical/chemical properties of 4,4'-Dihydroxybiphenyl = 4,4'-Biphenol Parameter Value Unit Reference Molecular weight 186.21001 g/mol Melting point 126.99 ºC EPISUITE Boiling point 354.41 ºC MST Vapour pressure at 25 [oC] 1.533e-006 Pa EPISUITE Water solubility at 25 [oC] 798.2 mg/L EPISUITE Octanol-water partition coefficient 2.8 - MST Koc 16400 L/kg EPISUITE BCF 43.73 - EPISUITE Henry's law constant 4.54e-007 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - CHRIP NITE
t½(hydrolysis) Year t½(air) 2.68 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 9.0000004E-2 kg/year Release to wastewater 180 kg/year Local PEC in surface water during emission episode (dissolved) 0.96399999 mg/l Local PEC in fresh-water sediment during emission episode 7.02 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 8.8299999 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 2.51 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.56900001 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.0118 mg/(kg wet weight) Local total daily intake for humans 0.40900001 mg/(kg⋅d) Regional total daily intake for humans 8.4800001E-7 mg/(kg wet weight) Conclusion 4,4'-Biphenol used as sunscreens, preservatives, disinfectants, antioxidants, flavorings, or for perfumery. 4,4'-Biphenol is according to the ESIS database produced in amounts < 10 tones/year and is thus not a LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. 4,4'-Biphenol is not readily biodegradable and has a medium potential to bioaccumulate in the environ-
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ment (log kow=2.8). 4,4'-Biphenol is in the environment mainly distributed to surface water in concentra-tions up to approx. 1 mg/L. Based on EUSES estimations for secondary poisoning and human intake 4,4'-Biphenol is expected to be found in fish, predators and human food in insignificant amounts, however, a high human exposure is expected due to the defined use of the substance. 4,4'-Biphenol is considered as being of High Concern. None specifically regulatory or legal status for this substance was found.
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4-Hydroxybiphenyl = 4-Phenylphenol (CAS No.: 92-69-3) [1,1'-Biphenyl]-4-ol; 4-Biphenylol; 4-hydroxybiphenyl; 4-Phenylphenol; Paraxenol; Biphenyl-4-ol; Human related effects Rat in vivo assay: Uterotrophic assay and Calbindin-D9k (CaBP-9K) mRNA expression were examd. in ovariectomized Sprague-Dawley female rats. 4-phenylphenol produced dose-dependent (10, 50, 200, and 400 mg/kg/day( increases in the uterine wts. of ovariectomized rats). LOAEL=200 mg/kg/day Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C12 H10 O1
Table 1: Physical/chemical properties of 4-Hydroxybiphenyl = 4-Phenylphenol Parameter Value Unit Reference Molecular weight 170.21001 g/mol Melting point 166 ºC EPISUITE Boiling point 305 ºC EPISUITE Vapour pressure at 25 [oC] 0.002306 Pa EPISUITE Water solubility at 25 [oC] 56.2 mg/L EPISUITE Octanol-water partition coefficient 3.2 - EPISUITE Koc 10120 L/kg EPISUITE BCF 25 - EPISUITE Henry's law constant 0.00436 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - CHRIP NITE
t½(hydrolysis) Year t½(air) 4.695 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 1000 Tonnes/year Release to air 30 kg/year Release to wastewater 24000 kg/year Local PEC in surface water during emission episode (dissolved) 3.77 mg/l Local PEC in fresh-water sediment during emission episode 42.5 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 63.900002 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 19.9 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 162 mg/(kg wet weight) Concentration in fish-eating marine top-predators 3.4400001 mg/(kg wet weight) Local total daily intake for humans 2.1600001 mg/(kg⋅d) Regional total daily intake for humans 7.5099997E-5 mg/(kg wet weight) Conclusion 4-Phenylphenol in an industrial intermediate. 4-Phenylphenol is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 1000 tones per year has been used. 4-Phenylphenol is not readily biodegradable and has potential to bioaccumulate in the environment (log
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kow=3.2). 4-Phenylphenol is in the environment mainly distributed to surface water in concentrations up to approx. 4 mg/L. Based on EUSES estimations for secondary poisoning and human intake 4-Phenylphenol is expected to be found in fish, predators and human food in minor amounts. 4-Phenylphenol is considered as being of Medium Concern. None specifically regulatory or legal status for this substance was found.
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p-Coumaric acid (PCA) (CAS No.: 7400-08-0) 3-(4-Hydroxyphenyl)propenoic acid; p-hydroxy-cinnamic acid; 4'-hydroxycinnamic acid; Human related effects Rat in vivo assay: 189 and 201% thyroid wts increase compared to control value. hyroid lesions in p-coumaric acid group were assocd. with significant increases in cellular proliferation as indicated by [3H]thymidine incorporation. In addn., the goitrogenic effect of p-coumaric acid was further confirmed by significant decreases (50%) in serum triiodothyronine (T3) and thyroxine (T4), and a parallel increase (90%) in serum TSH compared to control group. ED=0.25 mmol/kg/day Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C9 H8 O3
Table 1: Physical/chemical properties of p-Coumaric acid (PCA) Parameter Value Unit Reference Molecular weight 164.16 g/mol Melting point 211.5 ºC EPISUITE Boiling point 329.8 ºC MST Vapour pressure at 25 [oC] 0.0001613 Pa EPISUITE Water solubility at 25 [oC] 18300 mg/L EPISUITE Octanol-water partition coefficient 1.79 - EPISUITE Koc 78.21 L/kg EPISUITE BCF 45.18 - EPISUITE Henry's law constant 1.36e-007 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - MST
t½(hydrolysis) Year t½(air) 2.481 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 1.26 mg/l Local PEC in fresh-water sediment during emission episode 3.4200001 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 0.71100003 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 0.27500001 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.0114 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.00182 mg/(kg wet weight) Local total daily intake for humans 0.131 mg/(kg⋅d) Regional total daily intake for humans 2.9100001E-8 mg/(kg wet weight) Conclusion p-Coumaric acid (PCA) is a natural phenolic acid. PCA is according to the ESIS database produced in amounts < 10 tones/year and thus not a LPV substance. For the EUSES calculations a production vol-
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ume of 10 tones per year has been used. PCA is readily biodegradable and has a low potential to bioac-cumulate (log Kow=1.79). Based on EUSES estimations PCA is expected to be found in local surface water in concentrations up to approx. 1 mg/L. Based on EUSES estimations for secondary poisoning and human intake PCA is expected to be found in fish, predators and human food in insignificant amounts. PCA is considered as being of Low Concern. None specifically regulatory or legal status for this sub-stance was found.
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Phenol, (1,1,3,3-tetramethylbutyl)- = Octylphenol (CAS No.: 27193-28-8) (1,1,3,3-tetramethylbutyl)phenol; octyl phenol; OP; (Tetramethylbutyl)phenol; Human related effects Rat in vivo study. Reduced sperm counts resulting from lowered plasma testosterone in male rats just after puberty. ED=3 mg/kg body weight.day Wildlife related effect Fish in vivo study. VTG induction + intersex gonads. LOEC=11.4 ug/L Chemical characteristics: Molecular formula: C14 H22 O1
Table 1: Physical/chemical properties of Phenol, (1,1,3,3-tetramethylbutyl)- = Octylphenol Parameter Value Unit Reference Molecular weight 206.33 g/mol Melting point 82.77 ºC EPISUITE Boiling point 310.93 ºC MST Vapour pressure at 25 [oC] 0.01301 Pa EPISUITE Water solubility at 25 [oC] 3.114 mg/L EPISUITE Octanol-water partition coefficient 5.5 - MST Koc 33010 L/kg EPISUITE BCF 5.623 - EPISUITE Henry's law constant 0.456 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) Year t½(air) 2.553 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 5.1900001 mg/l Local PEC in fresh-water sediment during emission episode 860 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 1690 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 659 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 672 mg/(kg wet weight) Concentration in fish-eating marine top-predators 256 mg/(kg wet weight) Local total daily intake for humans 167 mg/(kg⋅d) Regional total daily intake for humans 0.000107 mg/(kg wet weight) Conclusion Octylphenol is used as a precursor to produce surfactants (ethoxylates) and in plastic products. Octyl-phenol is according to the ESIS database not a LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. Octylphenol is not readily biodegradable and has a high po-tential to bioaccumulate in the environment (log kow=5.5). Octylphenol is in the environment mainly dis-tributed to surface water as well as sediments and agricultural soils. Based on EUSES estimations for secondary poisoning Octylphenol is expected to be of medium concern. A high local daily human intake is
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expected (up to approx. 170 mg/kg/day). Octylphenol is considered as being of High Concern. The PBT properties have been assessed by the EU and it was concluded that Octylphenol does not fulfil the PBT criteria. The database for p-tert.-octylphenol is very comprehensive, including a high quality multi-generation study. The EU CMR group recently decided that Octylphenol should not be classified for re-protoxic effects.
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Chlordimeform (CAS No.: 6164-98-3) Acaron; Bermat; Dimethyl-N'-(2-methyl-4-chlorophenyl)formamidine; CDM; Chlordimeform; Chloro-phenamidine; Formamidine, N'-(4-chloro-o-tolyl)-N,N-dimethyl-; Fundal; Fundex; Galecon; Galecron; N'-(4-chloro-2-methylphenyl)-N,N-dimethylmethanimidamide; Ovatoxion; RS-141; Spanone; Human related effects In vivo rat study. Delay in breeding and a significant redn. in litter size. ED=50 mg/kg. Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C10 H13 CL1 N2
Table 1: Physical/chemical properties of Chlordimeform Parameter Value Unit Reference Molecular weight 196.67999 g/mol Melting point 35 ºC EPISUITE Boiling point 156.5 ºC EPISUITE Vapour pressure at 25 [oC] 0.123056206 Pa EPISUITE Water solubility at 25 [oC] 270 mg/L EPISUITE Octanol-water partition coefficient 2.89 - EPISUITE Koc 3090 L/kg EPISUITE BCF 1524 - EPISUITE Henry's law constant 0.034857 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - EPISUITE
t½(hydrolysis) Year t½(air) 1.416 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 9.0000004E-2 kg/year Release to wastewater 180 kg/year Local PEC in surface water during emission episode (dissolved) 0.958 mg/l Local PEC in fresh-water sediment during emission episode 7.6900001 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 9.71 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 2.74 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.67400002 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.0141 mg/(kg wet weight) Local total daily intake for humans 0.134 mg/(kg⋅d) Regional total daily intake for humans 7.5299999E-7 mg/(kg wet weight) Conclusion Chlordimeform is used as a insecticide. Chlordimeform is according to the ESIS database produced in amounts < 10 tones/year and thus not a LPV substance. For the EUSES calculations a production vol-ume of 10 tones per year has been used. Chlordimeform is not readily biodegradable and has a medium potential to bioaccumulate (log Kow=2.89). Based on EUSES estimations Chlordimeform is expected to
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be found in local surface waters in concentrations up to approx. 1 mg/L. Based on EUSES estimations for secondary poisoning and human intake Chlordimeform is expected to be found in fish, predators and hu-man food in minor amounts. Chlordimeform is considered as being of Low Concern. Covered by Council Directive 91/414/EEC. No RAR has been provided and the substance is not included in the list for pesti-cides to be reviewed.
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Cyclophosphamide (CAS No.: 50-18-0) Cyclophosphoramide; Cytophosphane; 2-(bis(2-Chloroethyl)-amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide; Cycloblastin; Cyclostin; Sendoxan; bis(2-Chloroethyl)phosphamide cyclic propanolamide ester; bis(2-Chloroethyl)phosphoramide cyclic propanolamide ester; N,N-bis(beta-Chloroethyl)-N',O-propylenephosphoric acid ester diamide; N-bis(beta-Chloroethyl)-N'O,trimethylenephosphoric acid ester diamide; N,N-Bis(beta-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide; N,N-Bis(2-chloroethyl)-N',O-propylenephosphoric acid ester diamide; N,N-Di(2-chloroethyl)-N,O-propylene-phosphoric acid ester diamide; Semdoxan; Senduxan; sk 20501; tatrahydro-2-(Bis(2-chloroethyl)amino)-2H-1,3,2-oxazaphosphorine 2-oxide; (-)-Cyclophosphamide; Asta B 518; Cla-fen; Claphene; Cyclophosphamidum; cb 4564; Endoxan R; Endoxan-Asta; Endoxana; Endoxanal; En-doxane; Enduxan; Genoxal; Mitoxan; Cyclophosphamides; Procytox; Cyclophosphamide; N,N-Bis(2-Chloroethyl)tetrahydro-2H-1,3,2-Oxazaphosphorin-2-Amine, 2-Oxide; Cytoxan; Cyclophosphane; B 518; Neosar; 1-(bis(2-chloroethyl)amino)-1-oxo-2-aza-5-oxaphosphoridine; 2-(di(2-chloroethyl)amino)-1-oxa-3-aza-2-phosphacyclohexane 2-oxide; ASTA; N,N-bis(2-chloroethyl)-N'-(3-hydroxypropyl)phosphorodiamidic acid intramol. ester; tetrahydro-N,N-bis(2-chloroethyl)-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide; Human related effects Rat in vivo assay: Decreased ovarian and uterin weight and reduction serum estradiol and progesterone. LOAEL=50 mg/kg body weight Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C7 H15 CL2 N2 O2 P1
Table 1: Physical/chemical properties of Cyclophosphamide Parameter Value Unit Reference Molecular weight 261.09 g/mol Melting point 51.5 ºC EPISUITE Boiling point 359.82 ºC MST Vapour pressure at 25 [oC] 0.005866 Pa EPISUITE Water solubility at 25 [oC] 40000 mg/L EPISUITE Octanol-water partition coefficient 0.63 - EPISUITE Koc 317.7 L/kg EPISUITE BCF 5856 - EPISUITE Henry's law constant 1.38e-006 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - EPISUITE
t½(hydrolysis) Year t½(air) 1.826 hr EPISUITE
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Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 9.0000004E-2 kg/year Release to wastewater 180 kg/year Local PEC in surface water during emission episode (dissolved) 0.99699998 mg/l Local PEC in fresh-water sediment during emission episode 1.26 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 0.12800001 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 3.0200001E-2 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.0174 mg/(kg wet weight) Concentration in fish-eating marine top-predators 3.4900001E-4 mg/(kg wet weight) Local total daily intake for humans 4.3499999E-2 mg/(kg⋅d) Regional total daily intake for humans 2.12E-7 mg/(kg wet weight) Conclusion Cyclophosphamide is used as a insecticide as well as in chemotherapy. Cyclophosphamide is accord-ing to the ESIS database produced in amounts < 10 tones/year and thus not a LPV substance. For the EUSES calculations a production volume of 10 tones per year has been used. Cyclophosphamide is not readily biodegradable and has a low potential to bioaccumulate (log Kow=0.63). Based on EUSES esti-mations Cyclophosphamide is expected to be found in local surface water in concentrations up to approx. 1 mg/L. Based on EUSES estimations for secondary poisoning and human intake Cyclophosphamide is expected to be found in fish, predators and human food in minor amounts. Chlordimeform is considered as being of Low Concern. The substance is covered by Council Directive 91/414/EEC. No RAR has been provided and the substance is not included in the list for pesticides to be reviewed.
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Mono-n-butylphthalate (CAS No.: 131-70-4) Butyl Hydrogen Phthalate; Monobutyl phthalate; Human related effects Rat in vivo study: Decreased male anogenital distance and increased incidence of fetuses with un-descended testes. LOAEL=250 mg/kg body weight/day Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C12 H14 O4
Table 1: Physical/chemical properties of Mono-n-butylphthalate Parameter Value Unit Reference Molecular weight 222.24001 g/mol Melting point 117.82 ºC EPISUITE Boiling point 353.12 ºC MST Vapour pressure at 25 [oC] 0.001787 Pa EPISUITE Water solubility at 25 [oC] 125.7 mg/L EPISUITE Octanol-water partition coefficient 2.84 - MST Koc 43.49 L/kg EPISUITE BCF 523.4 - EPISUITE Henry's law constant 0.000166 Pa·m3/mole EPISUITE Biodegradation Readily biode-
gradable - MST
t½(hydrolysis) 6.855 Year EPISUITE t½(air) 24.405 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 1.23 mg/l Local PEC in fresh-water sediment during emission episode 9.3800001 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 2.48 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 0.98199999 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 8.7499999E-2 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.0142 mg/(kg wet weight) Local total daily intake for humans 6.3100003E-2 mg/(kg⋅d) Regional total daily intake for humans 7.5199999E-8 mg/(kg wet weight)
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Conclusion Consumer and industrial applications for phthalates are numerous and range from making nail polish flexible and screwdriver handles less brittle to helping make the time-release coatings on numerous pharmaceutical products. Mono-n-butylphthalate is according to the ESIS database produced in amounts < 10 tones/year and thus not a LPV substance. For the EUSES calculations a production vol-ume of 10 tones per year has been used. Mono-n-butylphthalate is readily biodegradable and has a me-dium potential to bioaccumulate (log Kow=2.84). Based on EUSES calculations Mono-n-butylphthalate is not expected to be found in significant amounts in the environment (surface waters and sediments) and is not expected to give any problems in relation to secondary poisoning and human intake. Mono-n-butylphthalate is considered as being of Low Concern. None specifically regulatory or legal status for this substance was found. The related substance Dibutylphthalat is on the list of dangerous substances (An-nex I to Directive 67/548/EEC)
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Omethoate (CAS No.: 1113-02-6) O,O-dimethyl S-(2-methylamino)-2-oxoethyl phosphorothioate; BAY 45432; Dimethoate oxon; dimethoate oxygen analog; dimethoxon; Dimethyl S-((methylcarbamoyl)methyl) phosphorothioate; Folimat; Ometho-ate; Phosphorothioic acid, O,O-dimethyl ester, S-ester with 2-mercapto-N-methylacetamide; Human related effects Mice in vivo study: Increase in body wt. and decreased testicle wt. The activities of AKP, ACP, LDH in mouse testicles significantly increased compared with the control. Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C5 H12 N1 O4 P1 S1
Table 1: Physical/chemical properties of Omethoate Parameter Value Unit Reference Molecular weight 213.19 g/mol Melting point 87.02 ºC EPISUITE Boiling point 364.27 ºC MST Vapour pressure at 25 [oC] 0.0033063856 Pa EPISUITE Water solubility at 25 [oC] 1000000 mg/L EPISUITE Octanol-water partition coefficient -0.75 - EPISUITE Koc 77.67 L/kg EPISUITE BCF 707.5 - EPISUITE Henry's law constant 4.62e-009 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) Year t½(air) 4.938 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 500 Tonnes/year Release to air 3.75 kg/year Release to wastewater 7500 kg/year Local PEC in surface water during emission episode (dissolved) 2.5 mg/l Local PEC in fresh-water sediment during emission episode 2.1900001 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 0.0297 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 7.0400001E-3 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 0.72600001 mg/(kg wet weight) Concentration in fish-eating marine top-predators 0.0146 mg/(kg wet weight) Local total daily intake for humans 3.5999998E-2 mg/(kg⋅d) Regional total daily intake for humans 0.0000102 mg/(kg wet weight) Conclusion Omethoate is used as a pesticide. Omethoate is according to the ESIS database a LPV substance. For the EUSES calculations a production volume of 500 tones per year has been used. Omethoate is not readily biodegradable, but has a low potential to bioaccumulate (log Kow=-0.75). Based on EUSES esti-
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mations Omethoate expected to be found in local surface water in concentrations up to 4 mg/L. As Omethoate is not potential bioaccumulative the substance is not expected to give any problems in relation to secondary poisoning. Omethoate is considered as being of Low Concern. Covered by Council Direc-tive 91/414/EEC. No RAR has been provided and the substance is not included in the list for pesticides to be reviewed. Classification: XN;R21 T;R25 N;R50.
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Mono 2 ethyl hexylphthalate (MEHP) (CAS No.: 4376-20-9) 1,2-benzenedicarboxylic acid, mono-(2-ethylhexyl)ester; MEHP; mono(2-ethylhexyl) phthalate; Mono-ethylhexyl phthalate; PHTHALIC ACID MONO-2-ETHYLHEXYL ESTER; Human related effects Rat in vivo study. Significantly decreased body weights and motile sperms. LOAEL=250 mg/kg body weight/day Wildlife related effect No or insufficient data gathered Chemical characteristics: Molecular formula: C16 H22 O4
Table 1: Physical/chemical properties of Mono 2 ethyl hexylphthalate (MEHP) Parameter Value Unit Reference Molecular weight 278.35001 g/mol Melting point 142.61 ºC EPISUITE Boiling point 392.54 ºC MST Vapour pressure at 25 [oC] 0.0001087 Pa EPISUITE Water solubility at 25 [oC] 1.492 mg/L EPISUITE Octanol-water partition coefficient 4.73 - MST Koc 463 L/kg EPISUITE BCF 3.162 - EPISUITE Henry's law constant 0.000514 Pa·m3/mole EPISUITE Biodegradation Not readily bio-
degradable - MST
t½(hydrolysis) 10.671 Year EPISUITE t½(air) 11.066 hr EPISUITE Table 2: Use, exposure and emissions Parameter Value Unit Tonnage of substance in Europe 10 Tonnes/year Release to air 0.1 kg/year Release to wastewater 200 kg/year Local PEC in surface water during emission episode (dissolved) 7.2800002 mg/l Local PEC in fresh-water sediment during emission episode 483 mg/(kg wet weight) Local PEC in agric. soil (total) averaged over 180 days 948 mg/(kg wet weight) Local PEC in grassland (total) averaged over 180 days 361 mg/(kg wet weight) Concentration in fish for secondary poisoning (fresh water) 41.799999 mg/(kg wet weight) Concentration in fish-eating marine top-predators 2.29 mg/(kg wet weight) Local total daily intake for humans 44.299999 mg/(kg⋅d) Regional total daily intake for humans 0.0000294 mg/(kg wet weight)
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Conclusion Mono 2 ethyl hexylphthalate (MEHP) is the major DEHP metabolite. MEHP is according to the ESIS database produced in amounts < 10 tones/year and thus not a LPV substance. For the EUSES calcula-tions a production volume of 10 tones per year has been used. MEHP is not readily biodegradable and has a high potential to bioaccumulate (log Kow=4.73). MEHP is in the environment mainly distributed to surface water as well as sediments and agricultural soils. Based on EUSES calculations MEHP is ex-pected to give minor problems in relation to secondary poisoning and human intake. Due to the persis-tency and high bioaccumulation potential Mono-n-butylphthalate is considered as being of Medium Con-cern. None specifically regulatory or legal status for this substance was found.
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A P P E N D I X A
Minutes from kick off meeting (17 November 2006)
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Study on ED priority list with a focus on LPV chemicals – First meeting
Brussels 17 November 2005, Beaulieu 9 Salle D MINUTES
Attendants: Katharina Spens (KS) The Commission, D4, Gitte Petersen (GIP) and Lise Samsøe-Petersen (LSP) both DHI. 1. Practical information (K. Spens)
− Re: Organisational framework. ! The position of the person who described this project is vacant and will be
filled by February. Until the KS will manage this project.
− Re: Financial issues ! The project must be finalised in time for the invoice to be paid before De-
cember 31 2006. The implications of this were discussed and the attached time schedule was prepared.
− Re: Database related issues ! KS explained that the database for storage of raw data from the data col-
lection, which was developed during the RPS BKH 2002 project, was available in an Access format.
! This database will be used for reporting the data from the present project as well.
! The Access database is not suitable as an internet databases. For this, ORACLE or FULCRUM formats have been recommeded. It was agreed that DHI will make a proposal for the work needed for converting the Ac-cess database into an internet compatible database.
! .
2. Presentation of the work plan (DHI) and discussion, including identification of stakeholders − Identification of stakeholders- method. It was agreed that
! KS will identify the stakeholders, which were contacted during the RPS BKH 2002 project.
! KS will contact colleagues working with general chemicals (REACH), plant protection products, biocides and food.
! DHI will contact DK EPA expert on REACH, Members of the OECD VMG-eco and Mammalian, member of recent EU EDC projects, and sci-entific colleagues
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− Identification of stakeholders - timing. It was agreed that ! The list of stakeholders for written consultation must be ready before
Christmas.
! The stakeholders for the consultation group will be identified when the an-swers on the questionnaires have been received.
! The stakeholders for the consultation group need not to be established be-fore summer 2006
! Number of stakeholders should not be fixed
− Questionnaire for stakeholders - timing. It was agreed that ! A draft questionnaire must be forwarded to KS on December 10. ! The final questionnaire must be ready before Christmas. ! The questionnaire will be distributed to the stakeholders immediately after
New Year with a deadline for answers of 1 February 2006.
− Questionnaire for stakeholders - reporting. It was agreed that ! The procedure and questionnaire as well as a summary of the answers will
be described in the report. ! The original answers of the questionnaires will be stores in electronic for-
mat and attached to the final report as a CD-ROM.
− List of substances to be assessed - method. It was agreed that ! DHI needs the list of the 172 substances, which were not evaluated in the
RPS BKH 2002 project. If it is not available on the CD with the Access database, KS will try to find it.
! Otherwise, it must be constructed based on files containing the lists of the 553, the 435 and the 204 substances, described in the strategy. If relevant, DHI will request readable files with these lists.
− List of substances to be assessed - timing. It was agreed that ! The list must be forwarded to D4February 28, 2006. ! The discussion of the list will take place on a meeting between DHI and
D4 on March 15, 2006.
− Reporting and meetings - timing. It was agreed that ! Meeting (D4 + DHI): Discussion on list of substances to
be evaluated: March 15, 2006 ! Interim report: May 31, 2006 ! Meeting (D4 + DHI): Discussion of interim report: June29, 2006 ! Draft final report: September 15,
2006 ! Stakeholder meeting: October
12, 2006 ! Meeting on draft final deliverable (D4 + DHI): October 13, 2006 ! Informal “close-to-final” report: November 10,
2006
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! Comment from D4 on informal report November 17, 2006 ! Final report a.o. deliverables: November 20,
2006 ! Approval of final report a.o. deliverables: November 22,
2006
3. Conclusions and agreement of next steps. This is described above. 4. Any other business
− KS pointed out that there is a call for FP6, which is including the establishment of a database on EDCs. KS will contact the relevant colleagues in DG Research and inform them about this and previous projects.
2005.11.18 / Lise Samsøe-Petersen
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TIME SCHEDULE Study on enhancing the Endocrine Disrupter priority list with a focus on low production
volume chemicals Contractor: DHI Water & Environment, Agern Allé, DK-2970 Hørsholm, Denmark DG ENV contact: Katharina Spens, unit D.4, tel. 02-2990521, [email protected]
" 28 October 2005: Contract signed = starting date
" 17 November: kick-off meeting between contractor and D4 for discussing the tasks.
" 28 February 2006: Discussion on the list of substances to be evaluated between con-tractor and Commission.
" 31 May 2006: Interim report sent to Commission
" 29 June 2006: Discussion of interim report between contractor and Commission
" 15 September 2006: Submission of draft final report
" 12 October 2006: draft final report to be discussed in a stakeholder meeting in Brussels (Beaulieu), it is planned that contractor presents report, D4 should be present and report on the strategy)
" 13 October 2006: Discussion of draft final deliverables (report and database) between contractor and Commission (D4)
" 10 November 2006: Informal “close-to-final” report
" 17 November 2006: Comments on informal report from D4 to DHI
" 20 November 2006: Final report including database to be submitted to Commission
" Final payment has to be made before 31 December (22 December in practice). The re-port therefore has to be approved by 22 November at the latest.
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A P P E N D I X B
Minutes – List of substances (15 March 2006)
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Study on ED priority list with a focus on LPV chemicals – Second meeting
Brussels 15 March 2006, Beaulieu 9 Salle D MINUTES
Attendants: Katharina Spens (KS) The Commission, D4, Sylvain Bintein (SB) The Commission, C3 and Gitte Petersen (GIP) DHI. 1. Stakeholder response
GIP presented the aim of the project to SB and the outcome of the request to written stakeholders was briefly presented. The questionnaire was sent to 160 potential stakeholders both by normal mail and by e-mail in December 2005. Two letters were received in return and 5 e-mails were received in return with a message on deliv-ery failure. Thus in total the request was send to approximately 155 people. Although the deadline for response was February 1st, quite many did not respond before late Febru-ary/beginning of March. A total of 34 stakeholders responded to the questionnaire. This means that the answer percentage was approx. 22%, which is regarded as acceptable. Most of the response received was a kind reply that the questionnaire was received but that no further data could be provided (65%). How-ever, among the replies, in which new information and data were provided, a total of 27 new substances has been suggested for addition to the list and thus to be evaluated in the present project
As the amount of information which followed the suggested new substances were quite diverse (from just a CAS No. to thorough information about the substances including attached references about EDC ef-fects) it was decided to include all suggested chemicals in the present study and perform the evaluation on these as on the rest of the priority substances. The suggested substances to be added to the list are the fol-lowing: CAS No. Substance name 556-67-2 Cyclotetrasiloxane 125116-23-6 Metconazole 81-14-1 1-tert-Butyl-3,5-dimethyl-2,6-dinitro-4-acetylbenzene 81-14-1 4,6-Dinitro-1,1,3,3,5-pentamethylindane 1222-05-5 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyrane 13171-00-1 4-Acetyl-1,1-dimethyl-6-tert.-butylindane 33704-61-9 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)indanone 5466-77-3 2-ethyl-hexyl-4-methoxycinnamate 118-56-9 3,3,5-trimethyl-cyclohexyl salicilate 21245-02-3 2-ethyl-hexyl-4-dimethyl-aminobenzoate 36861-47-9 3-(4-Methylbenzylidene)camphor 131-57-7 2-hydroxy-4-methoxy-benzophenone No CAS Benzophenone derivatives 99-96-7 p-Hydroxybenzoic acid 99-76-3 Methyl p-Hydroxybenzoate 120-47-8 ethyl 4-hydroxybenzoate 94-13-3 n-propyl p-hydroxybenzoate 94-26-8 n-Butyl p-Hydroxybenzoate 15087-24-8 3-Benzylidene camphor (3-BC)
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CAS No. Substance name 131-55-5 Benzophenone-2 (Bp-2), 2,2',4,4'-tetrahydroxybenzophenone 10043-35-3 Boric acid 1303-96-4 Borax 1582-09-8 Trifluralin 13593-03-8 Chinalphos 100-02-7 4-nitrophenol 2581-34-2 3-methyl-4-nitrophenol No CAS 4-nitro-3-phenylphenol
It was agreed that GIP will prepare a list of approx. 20 potential stakeholders who will be invited to par-ticipate as a stakeholder group. The participating stakeholders should as far as possible represent NGO, governmental institutions and researchers furthermore it was emphasised that as many countries as possi-ble should be represented. Concerning the stakeholders meetings KS will find out the financial issues related to travel money and accommodation. 2. Definition of Low Production Volume Chemicals
The definition of Low Production Volume Chemicals has not been made clear neither in the invitation to tender nor in the proposal. A clear definition was thus necessary and it was decided to use the definitions given in ESIS: European chemical substances information system which is the following: HPVC (High Production Volume Chemical). A HPVC, is a chemical which is defined as being pro-duced or imported in quantity of at least 1000 tonnes per year in EU by at least one Industry. LPVC (Low Production Volume Chemical). A LPVC, is a chemical which has been produced or im-ported in EU with a tonnage >10 t/y but never more than 1000 t/y. By definition a LPV Chemical is a chemical which is not a HPV Chemical. 3. Priority list of substances to be evaluated
SB was invited by KS to attend the meeting for having his response on the stakeholder responses on new chemicals to be added to the list. Before the meeting SB reviewed the priority list and found that several substances were not included in the ECB-ESIS database and thus not in use any longer. He also found that few of the substances were HPVC and that the majority of the substances were neither HPVC nor LPVC substances. These are existing substances but produced or imported in amounts ≤10 tons per year. Based on this information it was decided that the priority list of substances should include HPVC and LPVC plus existing substances registered in the ECB-ESIS database although they were produced or im-ported in amounts ≤10 tons per year. It was agreed that GIP should make a close evaluation of the priority substances list including the 27 new substances added by the written stakeholders and classify the sub-stances into the following categories:
1 = Current LPVC and HPVC according to ECB-ESIS. 2 = Substance found on ECB-ESIS list, but neither LPV or HPV (production volume < 10 ton/year) 3 = Substances not found on ECB-ESIS list and therefore excluded from the evaluation 4 = Substances with no CAS number and therefore excluded from the evaluation
For substances in category 3 and 4 it was decided that GIP should contact CEFIC to ask if they have any knowledge if the substances are still produced and if yes in which amounts. GIP will prepare a draft request to CEFIC and send it to KS. Based on this KS will prepare an official supporting letter from ENV.D4. After the meeting GIP did categorise the priority list and based on this evaluation it was found that:
− Category 1 contains 10 HPVC and 26 LPVC.
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− Category 2 contains 74 substances registered in ECB-ESIS database
− Category 3 contains 73 substances not registered ECB-ESIS database and thus ex-cluded from the present study. Contact to CEFIC will be made for more information about these substances.
− Category 4 contains 17 substances without CAS No. and thus excluded from the pre-sent study. Contact to CEFIC will be made for more information about these sub-stances.
The revised categorised list of substances is attached as Annex 1 (in this document Appendix D) 4. Time schedule
As the official start of the project is 2005.10.28 it is for administrative reasons necessary to send a draft final report by October 28. 2006. It was agreed that this report should include the draft final report planned to be send September 15 plus minutes from the stakeholder meeting October 12 and the meeting on draft final deliverables October 13. 5. DHI web page
It was agreed that DHI web page prepared for the present project needs to be updated. The background and state of the art shall be clearer. It was also agreed that the revised priority list including the latest categorisation shall be made available. GIP will take action. 2006.03.17 / Gitte Petersen
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A P P E N D I X C
Minutes – List of substances (29 June 2006)
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Study on ED priority list with a focus on LPV chemicals – Interim meeting
Brussels 29 June 2006, Beaulieu 9 Salle BU 9 0/191, 12.00-17.00 MINUTES
Attendants: DHI: Gitte Petersen; DG ENV: Katharina Spens, Sylvain Bintain, Reinhild Puergy 1. DHI - Presentation of the work status – Preliminary Interim report and presentation of
the database It was specified that, in the final report, the main objective of the present project shall be made clear i.e., the development of a database including collected data on endocrine disrupting proper-ties of substances placed on the priority list/candidate list. The definition of ‘priority list’ was discussed under this agenda item: According to the Com-munity Strategy for Endocrine Disrupters (1999), a short-term key action is the establishment of a priority list of substances for further evaluation of their role in endocrine disruption. The first study carried out in 2000 on the behalf of the Commission (BKH 2000) identified a candidate list of 553 substances. This candidate list of substances has thus since the BKH project in 2000 been named as ‘The Priority List’. The meaning of this wording is that substances placed on ‘The Pri-ority List’ have higher priority at data collection on endocrine disrupting properties than other substance lists, e.g. PBT substances, CMR substances etc.
Due to limitations in time, the number of substances to be evaluated, amount of data available and cost limitations, the evaluation of data collected on each individual substance is only based on a screening exercise. The wording ‘priority list of substances’ is therefore to be regarded as a starting point for further in depth evaluation of the endocrine disrupting properties of the sub-stances placed on the priority list. Gitte briefly presented the work status and it was decided that for the draft final report the fol-lowing issues should be included and explained more thoroughly: Task 3.2 Evaluation of data on their endocrine disrupting properties
• The methodology used for the evaluation of data shall be more thoroughly explained and shall be fully transparent. E.g., the categories defined in the previous work (BKH 2002) shall be included:
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CAT1, 2, 3a or 3b CAT 1. CAT 2. CAT 3a. CAT 3b.
Category 1, 2, 3a or 3b At least one study providing evidence of endocrine disruption in an intact organism. Not a formal weight of evidence approach. Potential for endocrine disruption. In vitro data indicating potential for endocrine disruption in intact organisms. Also includes effects in-vivo that may, or may not, be ED-mediated. May include struc-tural analyses and metabolic considerations No scientific basis for inclusion in list (ED studies available but no indications on ED effects) Substances with no or insufficient data gathered.
• It shall be clear that the Categorisation of the substances is based on evaluation of data at
a screening level. E.g., a thorough literature research has been adopted, but mainly only the abstracts have been evaluated. In cases in which the information obtained from the abstracts were not sufficient for categorisation of the individual substance, a primarily reference check was performed (the original article was purchased). In the database, ab-stracts from the articles are copied and an evaluated extract of the effects obtained is re-flected in the ‘effect field’. It shall be clearly stated that the choices for the categorisation were made by the consultant, and apart from the definition on the categories given above, it may thus be regarded as subjective.
• According to the tender from the Commission and the proposal made by DHI, a clear statement on the data evaluation to be performed was given. Namely “Starting points are the methodology developed in the RPS-BKH report (2002) and the database including the candidate substances which were identified in the BKH report of 2000, with data from background documents. The methodological approaches and evaluation of the se-lected substances with respect to endocrine disrupter potency towards humans and wild-life will be elaborated by the project team.” As stated in the interim report, the evaluation of endocrine disrupting potential will be based on the following screening criteria:
1. Relevance of test parameter (with aspects such as relations between endocrine disrupting effects and mechanistic causes)
2. Test reliability (validated protocols; experimental design; suitability, health and life stage of test species; statistics. Ranked indication of Data Quality (DQ 1-4). DQ: good data quality, fulfilling all (important) criteria; DQ2: Sufficient Data Quality, study fulfilling most of the (important) criteria; DQ3: Insufficient Data Quality, study cannot be used for identification; and DQ4: Not evaluated
3. Dose-response relationship or indications of effects thresholds 4. Endocrine disruption potency (including a categorization of the chemicals into 3
groups: 1. Evidence for endocrine disrupting (ED) effect; 2. Potential ED effect; 3. No evidence for ED effect)
5. Comparison with systemic toxicity (Standard toxicity data –NOECs/LOECs, E(L)C50s, NOALs/LOAELs from RTECS, ECOTOX (AQUIRE), DOSE and Ver-shuren databases)
• As the present work is based on a screening of available data for the substances on the priority list (a total of 109 substances) and as the quality of the available data is not stan-dardised but quite diverse, a description of a more standardised procedure than the one
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given above can be difficult. It was agreed that, in future, in depth evaluations of the col-lected data the criteria and the methodology for evaluation of the substances as having endocrine disrupting properties shall be well defined and fully transparent. In the present work a preliminary description and set up of a standard operating procedure (SOP) for the update of the database and the inclusion and exclusion of substances on the working list shall as far as possible be included.
2. Financial status
• Interim report payment It was agreed that Reinhild will send the forwarded interim report for approval and, in 4 weeks time, it should be possible for DHI to forward an invoice for the interim payment (EUR 40,000.00) to the Commission.
• Amount of time until this date and final invoice Gitte presented the amount of time used until date and it was briefly discussed that as far the re-vised time schedule (see item 3) is not exceeded, there should be no problems in having the final invoice paid before 31.12.06. 1. Revised time schedule Gitte presented the revised time schedule forwarded for the meeting and the following dates were agreed:
• 01.10.2006: Draft final report shall be sent to Reinhild • 08.10.2006: Draft final report available on the web at the DHI-web page
(http://projects.dhi.dk/Endocrine_Disrupter/testsite/) for stakeholder response • 08.11.2006: Response back from stakeholders • 17.11.2006: DHI/DG ENV meeting: Discussion of final deliverables • 20.11.2006: Final report
It was agreed that at the 4th meeting (17.11.2006) Reinhild will invite colleagues specifically in-terested in endocrine disrupting chemicals to participate. According to the contract, a final report shall be available to the Commission by 28.10.2006. Reinhild will check up if the above time schedule will give any problems in this respect. 2. Stakeholder meeting
Due to accommodation and travel expenses in relation to a stakeholder meeting it was decided not to have a physical meeting but instead have web-based stakeholder responses. Thus stake-holders and experts from a list, based on the one used for the written consultation, will be invited to go through the draft final report and collected data on selected CAT 1 chemicals in the data-base. The list will be provided by Reinhild after discussion with Gitte. It will be available on 31. August latest. If there are more than 35 stakeholders are commenting, the potential revision work will be divided between DHI and DG ENV.
As stated above, the draft final report will be made available for selected stakeholders by 08.10.2006 and deadline for response will be 08.11.2006. Sylvain suggested that the substances evaluated in the present project are checked to ensure that they are not already regulated by other current community legislation (e.g. Dir 76/769/EEC or REG 793/93/EEC or DIR 91/414/EC).
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3. DHI EDS Website comments Reinhild will correct the link (http://projects.dhi.dk/Endocrine_Disrupter/testsite/) and make sure that it will be made more visible on the EEC web page than presently. The preliminary quotation for transformation of the Access database to either SQL or an Oracle database made by DHI was briefly discussed. According to Bjørn Hansen (who was contacted after the meeting), this work might be performed by ECB (Reinhild please correct me here) and until this has been clarified, DHI will not provide a final quotation. It was briefly discussed that due to the fact that the present evaluation of the available data and substances in the database is based on a screening level, there might be a second project aiming at update and maintenance of an iterative EDC priority list. However, as long as the Community Strategy for Endocrine Dis-rupting substances are not perfectly clear it was decided not to discuss this item further. 4. How to proceed further with substances lacking info on Category 3 and 4 substances.
Outcome of Bjorn Hansen’s contact to CEFIC There was still no response from CEFIC. Bjørn Hansen was contacted after the meeting and once more he will try to get a reply. The final cut for response from CEFIC is 15.07.2006. It was de-cided that if no reply was obtained, the categories 3 and 4 substances (substances presently not included in the ESIS database and substances without CAS number) will not be included in the present evaluation. 5. Discuss perspectives how to proceed with the elaborated knowledge about EDS Gitte presented the proposal “The EU dynamic priority list/candidate list of substances with potential endocrine disrupting effects – proposal for ensuring a dynamic process” for-warded to the Commission by the Danish Environmental Protection Agency, October 2003. The proposal was briefly discussed and it was decided that Reinhild will distribute the paper to rele-vant people at DG ENV and thereby try to make the EU strategy on EDCs more exposed in order to ensure a prioritisation of the EDC area. The proposal is attached as a pdf.file to the e-mail forwarded to Reinhild with the present minutes from the 3rd meeting.
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A P P E N D I X D
Minutes. Discussion on final deliverables. 8 December 2006
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 177
Study on ED priority list with a focus on LPV chemicals – Discussion of draft final deliverables, i.e.
report, database list
Brussels 8 December 2006, Beaulieu 9 Salle BU 9 0/191, 09.30-16.00
MINUTES
Attendants:; DG ENV: Sylvain Bintain and Reinhild Puergy DHI: Kim Gustavson and Gitte Petersen 1. Stakeholder response Stakeholders and experts from the list, based on the one used for the written consultation, were invited to go through the draft final report and collected data on selected CAT 1 chemicals in the database. An invi-tation to go through the report was forwarded to the stakeholders by November 3 2006 and as stated in the invitation the draft final report was made available on the web site: (http://projects.dhi.dk/Endocrine_Disrupter/testsite/) by November 15. Of the 141 stakeholders contacted 9 did respond by e-mail and approx 5 did respond by phone. The stakeholders that responded by phone did not have any comments to the report. Most of the comments received by e-mail were mainly minor. Major comments and criticism were received by the industry (CEFIC and European Crop Protection Association). Reinhild will have a meeting with CEFIC (Germot Klotz) before Christmas and comment the issues raised by CEFIC and European Crop Protection Asso-ciation. At the meeting all comments received were handled and discussed one by one and it was agreed that most of the comments received are appreciated very much and that they as far as possible will be taken into consideration in the final report. Beside taking the comments received into account in the final report the following specific corrections were agreed to be performed:
• A table with an overview of the systemic toxicity shall be included • In the summary a clear overview of the substances evaluated in the present study and previous
studies (BKH 2000 and RPS-BKH 2002) shall be given • In the summary a clear ‘break down’ of the 553 candidate substances shall be given • In the summary it shall be clearly described that the present evaluation is the last out of 3 evalua-
tions of substances placed on the EU candidate list and that the primary goal is the establishment of an EU priority-list on which further in depth evaluation of the endocrine properties shall be performed: 553 candidate substances => Evaluation at a screening level (BKH 2000 + RPS-BKH 2003 + DHI 2006)=> Priority list (CAT 1 substances) => Future in depth evaluation.
• The methodology was criticised by CEFIC. It shall therefore be clearly stated that due to the con-tinuation of the project (last out of 3 evaluations on the EU candidate list) the methodology used is comparable to the methodology used in the RPS-BKH 2002 project.
• In the summary and throughout the report it shall be clearly indicated that the present evaluation of the endocrine properties has been based on a screening level, that the evaluation shall be seen in line with previous studies and that the evaluations shall NOT be seen as risk assessments
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• In the presentation of the evaluated substances e.g., figures and tables the substances shall be or-dered by ascending CAS numbers.
• The use category of CAT 1 substances listed in table 5.3 shall be included in the table • The tonnage level used in the EUSES calculations shall be checked in relation to the tonnage
level (HPV/LPV) given in the ESIS database. • General editing (Headlines and wordings, annex with 2. stakeholder request)
2. Other issues Sylvain joined the meeting in the afternoon and the legal status of the evaluated CAT 1 substances were discussed. Among others Sylvain pointed out that Trifluralin was a POP candidate and that 4-nonylphenol has been restricted in the EU for some time. It was agreed that the legal status for all substances evaluated as CAT 1 substances in the present evalua-tion are checked carefully and that the legal status of the CAT 1 substances shall be described in the data-sheets of all 34 CAT 1 substances. 3. Discuss perspectives how to proceed with the elaborated knowledge about EDS Reinhild informed that ECB-Ispra are interested in taking the lead for the update of the Assess database to an ORACLE database. The hosting and future in depth evaluation of the priority substances will most probably be outsourced. 2006.12.11 Gitte Petersen
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A P P E N D I X E
List of stakeholders contacted
181ERA/53559/Revised report/2007.06.04
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182ERA/53559/Revised report/2007.06.04
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Firs
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Fed
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and
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entr
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D-4
2096
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logi
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+
39-0
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838
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503-
1486
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l-va
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si@
unim
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it A
nton
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errit
sen
Insi
tute
for
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ater
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-ag
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te W
ater
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IZA
)
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artm
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f Ind
ustr
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ontr
ol
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derw
agen
plei
n 2;
PO
Box
17
NL-
8200
AA
Le
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2982
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en@
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183ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Firs
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me
Las
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ame
Com
pan
y o
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D
epar
tmen
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ax
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ail
Dr.
Syl
via
Gim
eno,
Sen
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entis
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& G
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nova
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-375
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gium
+
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10
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3248
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Dep
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šlov
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+
420-
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3140
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0-2-
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3185
ja
na.h
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vsch
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ass;
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7538
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5669
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h@fd
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; jjl
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Bar
bara
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ich-
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ch
Fed
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for
heal
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of C
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ruxe
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03
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8852
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.eu
Pro
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phen
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Uni
vers
ity o
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nbur
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for
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dinb
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H16
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tland
, UK
+
44-1
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42-
2695
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-131
-242
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illie
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ock
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Le
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ür Z
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dem
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161-
7144
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m.d
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Pro
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. H
uhta
niem
i Im
peria
l Col
lege
facu
lty o
f M
edic
ine;
Ham
mer
smith
Hos
-pi
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Inst
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of R
epro
duct
ive
and
Dev
elop
men
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iol-
ogy
Du
Can
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oad
Lond
on W
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ON
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2104
+
44-2
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2184
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.ac
.uk
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stra
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-151
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tälje
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5029
1 +
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-552
-58
505
tom
.hut
chin
son@
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som
184ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Firs
t na
me
Las
t n
ame
Com
pan
y o
r in
stit
uti
on
D
epar
tmen
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ddr
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Cit
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ntr
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hon
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ax
Em
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Pro
f. F
aise
n Ig
uchi
N
atio
nal I
nstit
utes
of N
atur
al
Sci
ence
, Cen
tre
for
Inte
grat
ive
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scie
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zaki
Inst
itute
for
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-gr
ativ
e B
iosc
ienc
e, D
e-pa
rtm
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envi
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men
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44
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-645
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5236
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@ni
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In
tern
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-to
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nviro
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enev
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witz
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+41
-21-
802-
6553
+
41-2
1-80
2-65
54
pilli
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Toh
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Inou
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titut
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lth
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1-18
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8501
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okyo
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700-
1564
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81-3
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bioc
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g@ni
hs.g
o.jp
M
s. F
umi
Irie
, Chi
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nvi-
ronm
enta
l Hea
lth
Dep
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Min
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the
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ironm
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Env
ironm
enta
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lth a
nd
Saf
ety
Div
isio
n 1-
2-2
Kas
umi-
gase
ki, C
hiyo
da-
ku
100-
8975
T
okyo
Ja
pan
+81
-3-5
521-
8261
+
81-3
-358
0-35
96
fum
i_iri
e@en
v.go
.jp
Ric
hard
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ell (
Ass
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); P
rofe
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med
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ni-
vers
ity o
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laid
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Sch
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outh
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F
loor
F
rom
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laid
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A
5005
A
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alia
+
61-8
-83
0331
14
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d.iv
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adel
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.ed
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Mar
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ber
Wild
life
Ltd.
8598
Com
mer
ce
Driv
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ary-
land
216
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U.S
.A.
+1-
410-
822-
8600
+
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2-06
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-621
-605
-17
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P.O
. Box
63;
H
aart
man
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F
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358-
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1-25
040
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8-9-
191-
2504
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inki
.fi
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R.
Jean
not
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GM
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cien
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and
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3, a
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laud
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60
09
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5060
Or-
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EX
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Fra
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+33
-2-3
864-
3434
+
33-2
-386
4-35
18
r.je
anno
t@br
gm.fr
Ber
nard
JE
GO
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Uni
vers
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enne
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epro
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D
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men
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phys
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Cam
pus
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eau-
lieu,
Bât
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F-3
5042
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enne
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ranc
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33-2
-23
2369
11
+33
-2-
2323
5055
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r-na
rd.je
gou@
renn
es.in
serm
.fr
Pro
f. dr
. B
jørn
Mun
ro
Jens
sen
Nor
weg
ian
Uni
vers
ity o
f Sci
-en
ce a
nd T
echn
olog
y (N
TN
U),
D
epar
tmen
t of Z
oolo
gy
Dep
artm
ent o
f Bio
logy
, E
coph
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logy
and
Eco
-to
xico
logy
gro
up
Hog
skol
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gen
5 N
O-7
491
T
rond
heim
N
orw
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+47
-735
9626
7+
47-7
2591
309
bjor
n.m
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.jens
sen@
chem
bio.
ntnu
.no
Dr.
Sus
an
Jobl
ing
Bur
nel U
nive
rsity
In
stitu
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r th
e E
nviro
n-m
ent
U
xbrid
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Mid
dels
ex
UB
8 3P
H
Uni
ted
Kin
gdom
+
44-1
895-
2665
15
+44
-189
5-26
9761
su
-sa
n.jo
blin
g@br
unel
.ac
.uk
Dr.
Rod
ney
John
son
US
EP
A
OR
D-N
HE
ER
L, M
id C
on-
tinen
t Eco
logy
Div
isio
n 62
01 C
ongd
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Bui
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ulut
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N
5580
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.S.A
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9-51
17
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218-
529-
5003
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ley
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men
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D
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ted
Kin
gdom
“jo
hn-
son_
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rcpl
c.co
.uk
Ebb
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aran
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urop
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Com
mis
sion
; Re-
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ch D
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e-G
ener
al
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ctor
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E: B
iote
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gric
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ood;
U
nit E
2: F
ood
Qua
lity;
O
ffice
SD
ME
8/2
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are
de
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use
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-105
0 B
rus-
sels
B
elgi
um
+32
2 2
9 88
068
+32
-2-2
96
4322
eb
ba.b
aran
y@ec
.eur
opa.
eu
185ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Firs
t na
me
Las
t n
ame
Com
pan
y o
r in
stit
uti
on
D
epar
tmen
t A
ddr
ess
Cit
y C
ou
ntr
y P
hon
e F
ax
Em
ail
Pro
f. D
r.m
ed.
Die
ter
Klin
gmül
ler
Inst
. für
Klin
. Bio
chem
ie;
And
reas
Grig
ull
S
igm
und-
Fre
ud-
Str
. 25
D-5
3127
B
onn
Ger
man
y +
49-2
28-2
87-
6564
+
49-2
28-2
87-
6028
d.
klin
gmue
ller@
uni-
bonn
.de
Pro
f. W
erne
r K
loas
Le
ibni
z In
stitu
te o
f Fre
shw
ater
E
colo
gy a
nd In
land
Fis
herie
s
Müg
gels
eeda
mm
31
0 D
-128
57
Ber
lin
Ger
man
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49-3
0-64
-18
1-63
0 +
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0-64
-18
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berli
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GA
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-513
68
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5276
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ag.d
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rof.
Jose
f K
öhrle
H
umbo
lt U
nive
rsity
Ber
lin
repr
esen
ted
by C
harit
e U
ni-
vers
ity H
ospi
tal
Inst
itute
for
Exp
erim
enta
l E
ndoc
rinol
ogy;
Mol
ecul
ar
End
ocrin
olog
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Sch
uman
nstr
asse
20
-21
D-1
0098
B
erlin
G
erm
any
+49
-30-
450-
5240
21
+49
-30-
450-
5249
22
jose
f.koe
hrle
@ch
ari
te.d
e
Ann
eli
Koj
o, S
enio
r O
ffice
r N
atio
nal P
rodu
ct C
ontr
ol
Age
ncy
for W
elfa
re a
nd H
ealth
Che
mic
als
Dep
artm
ent
P.O
. Box
210
F
IN-0
0531
H
elsi
nki
Fin
land
+
358-
9-39
67-
2763
/+35
8-50
-51
44-2
21
+35
8-9-
3967
-27
97
anne
li.ko
jo@
sttv
.fi
And
reas
K
orte
nkam
p T
he S
choo
l of P
harm
acy
Cen
tre
for
Tox
icol
ogy
Uni
vers
ity o
f Lon
-do
n; B
runs
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k S
quar
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Lond
on W
C1N
1A
X
Uni
ted
Kin
gdom
+
44-2
0-77
5359
08
+44
-20-
7753
5908
A
n-dr
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. Ole
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U
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800
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ngby
D
enm
ark
+45
-452
5-15
69
ko
k@er
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.dk
Mat
thie
u LA
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M
inis
tère
de
l’Eco
logi
e et
de
Dév
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pem
ent D
urab
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/ SD
PD
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5302
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P
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4219
1542
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33-1
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68
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lass
us@
ecol
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D
r. H
ellm
uth
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l R
uhr
Uni
vers
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sens
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sittu
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tsm
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-447
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-234
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78
+49
-234
-302
-45
05
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Gw
ynne
Ly
ons,
Tox
ics
Sci
ence
and
P
olic
y A
dvis
er
WW
F-U
K
17
The
Ave
nues
N
orw
ich
NR
2 3P
H
Eng
land
, UK
+
44-1
603-
507-
363
+44
-160
3-50
7-36
3 Ly
onsw
wf@
aol.c
om
Dr.
Sar
i M
äkel
ä U
nive
rsity
of T
urku
; Ins
titut
e of
B
iom
edic
ine
Dep
artm
ent o
f Ana
tom
y K
iinam
ylly
nkat
u 10
FIN
-205
20
Tur
ku
Fin
land
+
358-
2-33
3-68
37
+35
8-2-
333-
7352
sa
rmak
@ut
u.fi
Pro
f. Lu
dwik
K
. M
alen
dow
icz
K. M
arci
nkow
ski U
nive
rsity
of
Med
ical
Sci
ence
s D
epar
tmen
t of H
isto
logy
an
d E
mbr
yolo
gy; L
abor
a-to
ry o
f Exp
erim
enta
l En-
docr
inol
ogy
6 S
wie
cick
i St.
PL-
60-7
81
Poz
nan
Pol
and
+48
-61-
854-
6444
+
48-6
1-86
4-64
40
lkm
@am
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nan.
pl
Alb
erto
M
anto
vani
Ita
lian
Nat
iona
l Hea
lth In
stitu
teD
ept.
of C
ompa
rativ
e T
oxic
olog
y V
iale
Rei
gna
Ele
na 2
99
I-00
161
Rom
a Ita
ly
+39
-06-
4990
-25
65
+39
-06-
4938
-71
39
albe
rto@
iss.
it
Erm
inio
M
araf
ante
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V
ia E
. Fer
mi 1
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2102
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pra
(VA
) Ita
ly
Er-
min
io.M
araf
ante
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c.it
Dr.
Sek
i M
asan
ori,
Re-
sear
cher
C
hem
ical
s E
valu
atio
n an
d R
esea
rch
Inst
itute
(C
ER
I)
Kur
ume
Labo
rato
ry, E
co-
toxi
city
Sec
tion
Kur
ume,
3-2
-7
Miy
anoj
in
839-
0801
F
ukuo
ka
Japa
n +
81-9
-423
4-15
00
+81
-9-4
239-
6139
se
ki-
mas
anor
i@ce
ri.jp
K
eith
D.
Mas
on
Per
man
ent D
eleg
atio
n S
cien
ce A
dvis
or fo
r E
nvi-
ronm
enta
l Affa
irs
12, a
venu
e R
apha
ël
F-7
5116
Par
is F
ranc
e +
33-1
-45
2474
25
+33
-1-
4524
7468
m
a-so
nkd@
stat
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rof.
Pet
er
Mat
thie
ssen
C
entr
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colo
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y-dr
olog
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anca
ster
Env
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men
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Env
ironm
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mis
try
and
Pol
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n Li
brar
y A
venu
e B
ailri
gg, L
an-
cast
er L
A1
4AP
Uni
ted
Kin
gdom
+
44-1
524-
5958
67
+44
-152
4-61
536
pmat
t@ce
h.ac
.uk
Ian
May
er
Uni
vers
ity o
f Ber
gen
Dep
artm
ent o
f Fis
herie
s an
d M
arin
e B
iolo
gy
PO
Box
780
0 N
-502
0 B
er-
gen
Nor
way
+
47-5
5-58
4444
2 +
47-5
5-58
4450
ia
n.m
ayer
@ifm
.uib
.no
186ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Firs
t na
me
Las
t n
ame
Com
pan
y o
r in
stit
uti
on
D
epar
tmen
t A
ddr
ess
Cit
y C
ou
ntr
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hon
e F
ax
Em
ail
John
-Dav
id
Met
thew
s, D
irec-
tor
Eur
opea
n A
ffairs
Rho
dia
R
ond
Poi
nt,
Sch
uman
6
B-1
040
Bru
x-el
les
Bel
gium
+
32-2
-234
-77
30/+
32-4
74-
481-
448
(mo-
bile
)
+32
-2-2
34-
7930
Jo
hn-
Dav
id.M
AT
TH
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S@
EU
.RH
OD
IA.C
OM
E
llen
Mih
aich
E
nviro
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egul
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esou
rces
6807
Lip
scom
D
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Dur
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27
712
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.A.
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919-
479-
6047
+
1-91
9-47
9-69
47
emih
a-ic
h@nc
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com
P
rof.
Jam
ie
A.
Mog
uile
vsky
U
nive
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ad d
e B
ueno
s A
ires;
F
acul
tad
de M
edic
ina
Dep
arta
men
to d
e F
isio
lo-
gia
D.P
. 112
1 B
ueno
s A
ires
Arg
entin
a
+54
-11-
4981
-99
12
mo-
fuile
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a.a
r M
s. R
io
Nak
agaw
a C
hem
ical
s E
valu
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n an
d R
esea
rch
Inst
itute
(C
ER
I)
Che
mic
als
Ass
essm
ent
Cen
tre,
Res
earc
h an
d P
lann
ing
Dep
artm
ent
Bun
kyou
-ku,
1-4
-25
, Kau
raku
11
2-00
04
Tok
yo
Japa
n +
81-3
-580
4-61
35
+81
-3-5
804-
6139
rio
-na
kaga
wa@
ceri.
jp
José
Mar
ía
Nav
as A
ntón
, S
cien
tific
Re-
sear
cher
Inst
itut N
atio
nal d
es
Rec
herc
hes
Agr
aire
s D
epar
tem
ent f
or th
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nvi-
ronm
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Ctr
a. d
e la
Cor
uña
Km
7.5
28
040
Mad
rid
Spa
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+34
-91-
347-
4155
+
34-9
1-35
7-22
93
jmna
vas@
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Pol
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opou
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Sta
mat
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edic
al S
choo
l, N
atio
nal a
nd
Kap
odis
tria
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nive
rsity
of
Ath
ens
Dep
t. of
Pat
holo
gy
Mic
ras
Asi
as 7
5 G
R-1
1527
A
then
s G
reec
e +
30-2
10-
7462
163
+30
-210
-68
4048
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-pi
s@at
h.fo
rthn
et.g
r
Pia
Juu
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iels
en
Dan
ish
Env
ironm
enta
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tec-
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Age
ncy
Bio
cide
s an
d C
hem
ical
s A
sses
smen
t (H
ealth
and
E
nvt G
roup
)
Str
andg
ade
29
DK
-140
1
Cop
enha
gen
K
Den
mar
k +
45-3
2660
418
+45
-326
6036
9pj
n@m
st.d
k
Leif
Nor
rgre
en
Sw
edis
h U
nive
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of A
gric
ul-
tura
l Sci
ence
s; F
acul
ty o
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-er
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edic
ine
and
Ani
mal
S
cien
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Dep
artm
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med
i-ci
ne a
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eter
inar
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ublic
H
ealth
; Div
isio
n of
Pat
hol-
ogy,
Pha
rmac
olog
y an
d T
oxic
olog
y
Box
708
2; T
rav-
väge
n 12
D
S-7
5007
U
ppsa
la
Sw
eden
+
46-1
8-67
1206
+
46-1
8-67
3532
le
if.no
rrgr
en@
pat.s
lu.
se
Pro
f. D
r.
Jörg
O
ehlm
ann
Joha
nn W
olfg
ang
Goe
the
Uni
vers
ity F
rank
furt
am
Mai
n;
Bio
logi
cal a
nd c
ompu
ter
Sci
-en
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Div
isio
n
Dep
artm
ent o
f Eco
logy
an
d E
volu
tion
- E
coto
xi-
colo
gy
Sie
smay
erst
rass
e 70
D
-600
54
Fra
nkfu
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Ger
man
y +
49-6
9-79
8-24
871
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man
n@zo
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y.un
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Agn
eta
Ohl
sson
, Ass
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prof
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nal C
hem
ical
s In
spec
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ate
(Kem
I)
B
ox 2
S
-172
13
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undb
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19-
4124
1 +
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-735
-76
98
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sson
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mi
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Mr.
Hiro
kazy
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kuda
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and
Dev
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ent T
est
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ioss
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esea
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Cen
-te
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ivis
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of E
xper
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Tox
icol
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2445
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saw
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7-00
15
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ano
Kan
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n +
81-4
63-8
2-39
11
+81
-463
-82-
3860
ho
kuda
@jis
ha.o
r.jp
Nic
olas
O
lea
Uni
vers
idad
de
Gra
nada
; Fa-
culta
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Med
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a D
ept.
Rad
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y M
edi-
cina
Fis
ica
G
rana
da
1807
1 S
pain
+
34-9
-58-
242-
864
+34
-9-5
8-24
9-95
3 no
lea@
ugr.
es
Pro
f. S
tina
Ore
dsso
n Lu
nd U
nive
rsity
D
epar
tmen
t of C
ell a
nd
Org
anis
m B
iolo
gy, A
nim
al
Phy
siol
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Bui
ldin
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Hel
gona
väge
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23 6
2 Lu
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+
46-4
6-22
2-94
97
+46
-46-
222-
4539
S
tina.
Ore
dsso
n@co
b.lu
.se
Will
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Ow
ens,
Prin
cipa
l S
cien
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Pro
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& G
ambl
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entr
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rodu
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afet
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810
Eas
t Mia
mi
Riv
er R
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Cin
cinn
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45
252
U.S
.A.
+1-
513-
627-
1385
+
1-51
3-62
7-12
08
owen
s.jw
@pg
.com
Joan
ne
Par
rott
Env
ironm
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anad
a N
atio
nal W
ater
Res
earc
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stitu
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867
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905-
336-
4451
+
1-90
5-33
6-64
30
jo-
anne
.par
rott@
ec.g
c.c
a D
r. J
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Par
sons
U
nive
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of A
mst
erda
m
Dep
t. E
nviro
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Tox
icol
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166
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L-10
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V
Am
ster
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T
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31-2
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80
+31
-20-
525-
6522
jp
ar-
sons
@ch
em.u
va.n
l
187ERA/53559/Revised report/2007.06.04
DHI Water & Environment
Firs
t na
me
Las
t n
ame
Com
pan
y o
r in
stit
uti
on
D
epar
tmen
t A
ddr
ess
Cit
y C
ou
ntr
y P
hon
e F
ax
Em
ail
Rag
nor
Ped
erse
n, S
cien
-tif
ic P
roje
ct M
an-
ager
Uni
vers
ity o
f Lon
don,
Sch
ool
of P
harm
acy
Clu
ster
of R
esea
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fran
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s.po
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gsi.
gov.
uk
Jean
-Mar
c P
OR
CH
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IN
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Uni
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+
33-3
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5567
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jean
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fr
Dr.
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ta
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400-
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+
34-9
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entr
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brar
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veny
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an-
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A1
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Uni
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Kin
gdom
+
44-1
524-
5958
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.uk
Juan
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go S
inte
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+
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31-
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Eng
land
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+
44-1
305-
2066
37
+44
-130
5-20
6601
a.
p.sc
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cefa
s.co
.uk
Hel
mut
S
egne
r U
nive
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of B
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Inst
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of A
nim
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5974
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DHI Water & Environment
Firs
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Com
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Man
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+
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Dep
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logi
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ton
Lane
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Mid
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UB
8 3P
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Eng
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+
44-1
895-
2740
00
+44
-189
5-20
3099
JP
S@
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Dr.
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Rev
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+
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E
nviro
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hem
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Eco
logi
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Che
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Sec
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81-2
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2851
ta
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jp
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Gar
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DHI Water & Environment
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A P P E N D I X F
Questionnaire for identification of new candidate LPVC
DHI Water & Environment
ERA/53559/Revised report/2007.06.04 191
<code>
Dear Study on enhancing the Endocrine Disrupter priority list with focus on low production volume chemicals
The European Commission DG Environment has contracted DHI Water and Environment to perform a study on enhancing the Endocrine Disrupter priority list with focus on Low Production Volume Chemicals (LPVC). The project includes two main tasks: • Identify new candidate substances that are LPVC and may have endocrine disrupting properties • Collect data on LPVC identified in this and previous studies in order to assess the potential of
endocrine disruption of each candidate substance For this, DHI needs the co-operation from academia, industry and governments. We have identified you, as a potential stakeholder because you belong to one or several of the following groups:
• National focal points in EU Member States • NGOs • Industrial branch organisations, e.g. CEFIC, EUROCHLOR, ECETOC and individual indus-
tries • Experts involved in international work regarding endocrine disrupters, e.g. OECD Validation
Management Groups for Ecotoxicity Tests (VMG-eco) and Mammalian toxicity test (VMG-mammal) of the Task Force on Endocrine Disrupters Testing and Assessment (EDTA)
• Participants in EU research projects on endocrine disrupters e.g., CREDO, EDEN, FIRE • Stakeholders consulted for previous studies to set up the ED priority list
As belonging to one of the above groups, we expect you to have access to specific knowledge on en-docrine disrupting chemicals and the effects related to these. Therefore, we would like to invite you to join this project as a stakeholder. Background In December 1999, the European Commission adopted the Communication Community Strategy for Endocrine Disrupters (COM(1999)706). One of the actions identified in the Strategy is the estab-lishment of a priority list of substances for further evaluation of their role in endocrine disruption.
Agern Allé 5 DK-2970 Hørsholm, Denmark Tel: +45 4516 9200 Fax: +45 4516 9292 Dept fax: +45 45169292 E-mail: [email protected] Web: www.dhigroup.com Ref: gip Init: gip Date: 2005.12.09
DHI Water & Environment
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In two previous studies (BKH-report 2000 and RPS-BKH report 20021) a preliminary candidate list of 553 substances was evaluated. The assessment exercise concentrated mainly on substances, which were either High Production Volume Chemicals and/or highly persistent in the environment. In their evaluation, the Scientific Committee on Toxicity, Eco-toxicity and Environment (CSTEE) concluded that the RPS-BKH report provided a significantly improved assessment methodology in comparison with the previous BKH report. The Committee was, however, of the opinion that LPVC of high endocrine potency or with high emission rates were not sufficiently covered in the evalua-tion2. Aims of this project and our request for information The overall objective of the present project is to enhance the Endocrine Disrupter priority list with special focus on LPVC. The study will be based on the candidate substance list, which was identified in the BKH-project and those of the candidate substances, which were not evaluated in the RPS-BKH-project. An overview of the chemicals in question is presented in Table 1 and from this it ap-pears that 173 substances will be evaluated in the present project. The candidate list including all 553 substances and their present status of evaluation is available on the web site: http://projects.dhi.dk/Endocrine_Disrupter. Table 1. Overview of candidate list substances Selection criteria No. sub-
stances No sub-stance
Original candidate list of substances with ED effects 565 565 Excluded at the ED expert meeting of 1999 11 Candidate list of substances with ED effects, 2000 553 553 HPV already restricted to bans (109) + in depth evaluation (9)
118
Remaining substances 435 435 HPV and/or persistent and/or high exposure (in depth evaluation RPS-BKH-2002)
204
Group names (not to be evaluated) 13 Mixtures or polymers (not to be evaluated) 41 Substances two times in list (not to be evaluated) 4 Remaining substances to be evaluated in the present project
173 173
In the IUCLID database, 7829 chemicals are registered as LPVC but no information regarding their potential endocrine disrupting effects is registered. One of the aims of this project is to identify addi-tional substances with endocrine disrupting properties among these 7829 chemicals. For this identifi-cation, we ask for your cooperation. Therefore, we kindly ask you as a stakeholder to assist us in:
6. Identifying new candidate substances, which are not included in the present list 7. Collecting data regarding endocrine disrupting effects on any of the chemicals to be evalu-
ated in the present project In order to facilitate your contribution to the project we have prepared a table (Appendix 1) for in-formation delivering. We kindly ask you to fill in your data and knowledge on chemicals, which you
1 http://europa.eu.int/comm/environment/endocrine/strategy/substances_en.htm#r 2 http://europa.eu.int/comm/health/ph_risk/committees/sct/documents/out208_en.pdf
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identify as new candidate substances, and/or regarding the 173 substances, which have already been identified for evaluation in the project. We need the following information on each chemical:
• Production volume • Persistence in the environment • Evidence of endocrine disruption from literature data (including reference) • Exposure considerations
We kindly ask you to provide answers (preferably by e-mail) to one of the below e-mail addresses. The deadline for the answers is 1 February, 2006. We thank you in advance for your cooperation and are looking forward hearing from you.
Yours sincerely DHI Water & Environment Gitte Petersen (Project manager) Lise Samsøe-Petersen Senior Biologist, Ph.D. Senior Biologist, Ph.D Phone: +45 4516 9312 (direct) Phone: +45 4516 9307 (direct) E-mail: [email protected] E-mail: [email protected]
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Appendix 1 Questionnaire scheme for Study on enhancing the Endocrine Disrupter priority list with focus on low production volume chemicals Name and contact details (for possible contact regarding clarification of answers) Substance name: CAS no. SMILE notation: Other information: Production volume Persistence in the
environment Evidence of endo-crine disruption from literature data (in-cluding reference)
Exposure consid-erations
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A P P E N D I X G
Request to CEFIC
DHI Water & Environment
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CEFIC Av.E. Van Nieuwenhuyse 4 B-1160 Bruxelles Belgium Att.: Simon Webb (I am not sure if he is the right person to contact) Dear Simon Webb?? Re.: Study on enhancing the Endocrine Disrupter priority list with focus on low production volume chemicals
The European Commission DG Environment has contracted DHI Water and Environment to perform a study on enhancing the Endocrine Disrupter priority list with focus on Low Production Volume Chemicals (LPVC). Background In December 1999, the European Commission adopted the Communication Community Strategy for Endocrine Disrupters (COM(1999)706). One of the actions identified in the Strategy is the estab-lishment of a priority list of substances for further evaluation of their role in endocrine disruption. In two previous studies (BKH-report 2000 and RPS-BKH report 20023) a preliminary candidate list of 553 substances was evaluated. The assessment exercise concentrated mainly on substances, which were either High Production Volume Chemicals and/or highly persistent in the environment. In their evaluation, the Scientific Committee on Toxicity, Eco-toxicity and Environment (CSTEE) concluded that the RPS-BKH report provided a significantly improved assessment methodology in comparison with the previous BKH report. The Committee was, however, of the opinion that LPVC of high endocrine potency or with high emission rates were not sufficiently covered in the evalua-tion4. Aims of this project and our request for information
3 http://europa.eu.int/comm/environment/endocrine/strategy/substances_en.htm#r 4 http://europa.eu.int/comm/health/ph_risk/committees/sct/documents/out208_en.pdf
Agern Allé 5 DK-2970 Hørsholm, Denmark Tel: +45 4516 9200 Fax: +45 4516 9292 Dept fax: +45 45169292 E-mail: [email protected] Web: www.dhigroup.com Ref: gip Init: gip Date: 2006.03.28
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The overall objective of the present project is to enhance the Endocrine Disrupter priority list with special focus on LPVC. The study will be based on the candidate substance list, which was identified in the BKH-project and those of the candidate substances, which were not evaluated in the RPS-BKH-project. The candidate list of substances to be evaluated in the present project consists of ap-prox. 200 substances. After a close evaluation of the priority list of substances it was found that 73 substances were not registered in the ECB-ESIS database (http://ecb.jrc.it/esis/) and thus regarded as chemicals not in use any longer and furthermore, that 17 substances were without CAS No. Please find these substances attached as Annex 1 and Annex 2. We kindly ask if CEFIC could assist us in identifying if the substances listed in Appendix 1 and 2 are still produced and if yes in which amounts. We kindly ask you to provide answers (preferably by e-mail) to the e-mail address below. We thank you for your kind cooperation and are looking forward hearing from you.
Yours sincerely DHI Water & Environment Gitte Petersen (Project manager) Senior Biologist, Ph.D Phone: +45 4516 9312 (direct) E-mail: [email protected]
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A P P E N D I X H
Request for comments to the draft final deliverables
DHI Water & Environment
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<code> Dear Re.: Study on enhancing the Endocrine Disrupter priority list with focus on low produc-tion volume chemicals As previously informed, the European Commission - DG Environment has contracted DHI Water & En-vironment to perform a study on enhancing the Endocrine Disrupter priority list with focus on Low Pro-duction Volume Chemicals (LPVC), which will be finalised at the end of this year Background In December 1999, the European Commission adopted the Communication Community Strategy for En-docrine Disrupters (COM(1999)706). One of the actions identified in the Strategy is the establishment of a priority list of substances for further evaluation of their role in endocrine disruption. In two previous studies (BKH-report 2000 and RPS-BKH report 20025), a preliminary candidate list of 553 substances was evaluated. The assessment exercise concentrated mainly on substances, which were either High Production Volume Chemicals and/or highly persistent in the environment. In their evaluation, the Scientific Committee on Toxicity, Eco-toxicity and Environment (CSTEE) con-cluded that the RPS-BKH report provided a significantly improved assessment methodology in compari-son with the previous BKH report. The Committee was, however, of the opinion that LPVC of high endo-crine potency or with high emission rates were not sufficiently covered in the evaluation6. Aims of this project and our request for information The overall objective of the present project is to enhance the Endocrine Disrupter priority list with special focus on LPVC. The study is based on the candidate substance list, which was identified in the BKH pro-ject and those of the candidate substances, which were not evaluated in the RPS-BKH project. The evalu-ated data are entered in the Access database developed in the RPS-BKH 2002 project. We are now close to finalising the study and would therefore kindly invite you to go through the draft final report and the collected data on selected CAT 1 chemicals in the database. Your comments would be highly appreciated.
5 http://europa.eu.int/comm/environment/endocrine/strategy/substances_en.htm#r 6 http://europa.eu.int/comm/health/ph_risk/committees/sct/documents/out208_en.pdf
Agern Allé 5 DK-2970 Hørsholm Denmark Tel: +45 4516 9200 Fax: +45 4516 9292 E-mail: [email protected] Web: www.dhigroup.com Ref: Init: GIP/TKH Date: 2006.11.03
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The draft final report and database will be made available for your evaluation on the web site: http://projects.dhi.dk/Endocrine_Disrupter/testsite/ on 15 November 2006. We kindly ask you to provide your response (preferably by e-mail) to the below e-mail address. The deadline for the answers is 1 December 2006. We thank you in advance for your cooperation and are looking forward to hearing from you. Yours sincerely DHI Water & Environment Gitte Petersen (Project manager) Senior Biologist, Ph.D. Phone: +45 4516 9312 (direct) E-mail: [email protected]
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A P P E N D I X I
Revised list of priority substances for evaluation in the present study
DHI Water & Environment
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According to ECB-ESIS database, current LPV and HPV substances. LPV: 10-<1000 ton/year; HPV >1000 ton/year Will be evaluated in the present study
No. CAS Name LPV/HPV Existing labeling (ESIS) 302 92-69-3 4-Hydroxybiphenyl = 4-
Phenylphenol LPV
244 3115-49-9 4-nonylphenoxy acetic acid LPV 271 131-18-0 Di-n-pentylphthalate (DPP) =
Dipentylphthalate LPV R60/61: May impair fertil-
ity / May cause harm to unborn child
291 131-54-4 2,2'-Dihydroxy-4,4'-dimethoxybenzophenon
LPV
293 131-56-6 2,4-Dihydroxybenzophenon = Res-benzophenone
LPV
295 620-92-8 Bis(4-hydroxyphenyl)methane LPV 320 90-15-3 1-Naphthol HPV 429 84-69-5 Diisobutylphthalate HPV 551 1634-04-4 methyl tertiary butyl ether (MTBE) HPV 158 79-44-7 Dimethyl carbamyl chloride LPV 182 2597-03-7 Elsan = Dimephenthoate LPV 184 2540-82-1 Formothion LPV 187 1113-02-6 Omethoate LPV 205 314-40-9 Bromacil LPV 190 13593-03-8 Quinalphos = Chinalphos LPV 169 96-45-7 Ethylene Thiourea (ETU) LPV R61: May cause harm to
unborn child New-4 556-67-2 Cyclotetrasiloxane HPV New-8 81-14-1 1-tert-Butyl-3,5-dimethyl-2,6-dinitro-
4-acetylbenzene LPV
New-8 1222-05-5 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyrane
HPV
New-8 13171-00-1 4-Acetyl-1,1-dimethyl-6-tert.-butylindane
LPV
New-8 5466-77-3 2-ethyl-hexyl-4-methoxycinnamate HPV New-8 118-56-9 3,3,5-trimethyl-cyclohexyl salicilate LPV New-8 21245-02-3 2-ethyl-hexyl-4-dimethyl-
aminobenzoate LPV
New-8/10
36861-47-9 3-(4-Methylbenzylidene)camphor LPV
New-8 131-57-7 2-hydroxy-4-methoxy-benzophenone
LPV
New-8 99-96-7 p-Hydroxybenzoic acid LPV New-8 99-76-3 Methyl p-Hydroxybenzoate LPV New-8 120-47-8 ethyl 4-hydroxybenzoate LPV New-8 94-13-3 n-propyl p-hydroxybenzoate LPV New-10 15087-24-8 3-Benzylidene camphor (3-BC) LPV New-10 131-55-5 Benzophenone-2 (Bp-2), 2,2',4,4'-
tetrahydroxybenzophenone LPV
New-12 10043-35-3 Boric acid HPV New-17 1582-09-8 Trifluralin HPV New-28 100-02-7 4-nitrophenol HPV New-28 106-44-5 4-nitro-3-phenylphenol HPV
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Substance found on ECB-ESIS list, but neither LPV or HPV (Production volume < 10 ton/year Will be evaluated in the present study No. CAS Name Existing labeling (ESIS) 549 485-72-3 Formononetin 548 491-80-5 Biochanin A 300 1806-29-7 2,2'-Dihydroxybiphenyl = 2,2'-Biphenol 301 92-88-6 4,4'-Dihydroxybiphenyl = 4,4'-Biphenol 309 2051-60-7 PCB 1 (2-Chlorobiphenyl) 311 2050-68-2 PCB 15 (4,4'-Dichlorobiphenyl) 313 2051-61-8 PCB 2 (3-Chlorobiphenyl) 315 2051-62-9 PCB 3 (4-Chlorobiphenyl) 233 104-51-8 n-Butylbenzene 235 25167-81-1 Dichlorophenol 238 87-26-3 2-sec-Pentylphenol = 2-(1-Methylbutyl)phenol 239 1131-60-8 4-Cyclohexylphenol 240 1009-11-6 4-Hydroxy-n-butyrophenone 241 70-70-2 4-Hydroxypropiophenone 242 104-40-5 4-Nonylphenol (4-NP) 243 20427-84-3 4-Nonylphenoldiethoxylate (NP2EO) 245 99-71-8 4-sec-Butylphenol = 4-(1-Methylpropyl)phenol 247 7786-61-0 4-vinylguaiacol (4-VG) 248 2628-17-3 4-vinylphenol (4-VP) 249 27986-36-3 Ethanol, 2-(nonylphenoxy)- 250 1322-97-0 Ethanol, 2-(octylphenoxy)- = Octylphenolethoxy-
late
255 27193-28-8 Phenol, (1,1,3,3-tetramethylbutyl)- = Octylphenol 256 27985-70-2 Phenol, (1-methylheptyl)- 257 3884-95-5 Phenol, 2-(1,1,3,3-tetramethylbutyl)- 258 17404-44-3 Phenol, 2-(1-ethylhexyl)- 259 18626-98-7 Phenol, 2-(1-methylheptyl)- 260 37631-10-0 Phenol, 2-(1-propylpentyl)- 261 949-13-3 Phenol, 2-octyl- 262 3307-00-4 Phenol, 4-(1-ethylhexyl)- 263 1818-08-2 Phenol, 4-(1-methylheptyl)- 264 3307-01-5 Phenol, 4-(1-propylpentyl)- 268 25013-16-5 tert.-Butylhydroxyanisole (BHA) 270 84-75-3 Di-n-hexyl phthalate (DnHP) = Dihexylphthalate
(DHP)
272 131-16-8 Di-n-propylphthalate (DprP) = Dipropylphthalate 273 4376-20-9 Mono 2 ethyl hexylphthalate (MEHP) 274 131-70-4 Mono-n-butylphthalate 275 33204-76-1 2,6-cis-Diphenylhexamethylcyclotetrasiloxane -
2,6-cis-[(PhMeSiO)2(Me2SiO)2][
277 56-33-7 Diphenyltetramethyldisiloxane PhMe2-SiOSiMe2Ph
278 10448-09-6 Phenylheptamethylcyclotetrasiloxane [(PhMe-SiO)(Me2SiO)3]
279 28994-41-4 Phenyl-2-hydroxyphenylmethane = 2-Benzylphenol = o-Benzylphenol
284 3373-03-3 1,1-Bis(4-hydroxyphenyl)-n-heptane 285 24362-98-9 1,1-Bis(4-hydroxyphenyl)-n-hexane 288 6807-17-6 2,2-Bis(4-hydroxyphenyl)-4-methyl-n-pentane R60: May impair fertility 289 77-40-7 2,2-Bis(4-hydroxyphenyl)-n-butan = Bisphenol B 290 14007-30-8 2,2-Bis(4-hydroxyphenyl)-n-hexane
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No. CAS Name Existing labeling (ESIS) 292 52479-85-3 2,3,4,3',4',5'-Hexahydroxybenzophenon 294 611-99-4 4,4'-Dihydroxybenzophenon 297 81-92-5 2-[Bis(4-hydroxyphenyl)methyl]benzylalkohol =
Phenolphthalol
298 77-09-8 3,3'-Bis(4-hydroxyphenyl)phthalid = Phenol-phthaleine
321 1125-78-6 5,6,7,8-Tetrahydro-2-naphthol = 6-Hydroxytetralin 322 15231-91-1 6-Bromo-2-naphthol 323 530-91-6 Tetrahydronaphthol-2 335 303-38-8 2,3-dihydroxybenzoicacid (2,3-DHBA) 337 490-79-9 2,5-dihydroxybenzoicacid (2,5-DHBA) 342 537-98-4 Ferulic acid (FA) 343 533-73-3 Hydroxyhydroquinone 346 7400-08-0 p-Coumaric acid (PCA) 348 463-56-9 Thiocyanate 409 26401-75-2 Phenol, 2-sec-octyl- 411 27214-47-7 Phenol, 4-sec-octyl- 552 545-55-1 TEPA 328 53-96-3 n-2-fluorenylacetamide 178 50-18-0 Cyclophosphamide 179 682-80-4 Demefion 220 6164-98-3 Chlordimeform 223 25550-58-7 Dinitrophenol 375 70393-85-0 Glufosinate-ammonium 222 96-12-8 Dibromochloropropane (DBCP) R60: May impair fertility 377 121-29-9 Pyrethrin 365 83-05-6 p,p'-DDA 667 114369-43-6 Fenobucanazole 170 14868-03-2 Bis-OH-MDDE New-8 33704-61-9 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)indanone New-8 94-26-8 n-Butyl p-Hydroxybenzoate New-28 2581-34-2 3-methyl-4-nitrophenol
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Substances not found on ECB - ESIS list and therefore excluded from the evaluation
No. CAS Name 229 135505-63-4 4-Hydroxyphenyl-di-a-naphthylmethane 230 630-95-5 Diphenyl-a-naphthylcarbinol 339 57-12-5 Cyanide 513 20291-73-0 1,9-Dimethylphenanthrene 515 58024-06-9 2,8-Dihydroxy-4b,5,6,10b,11,12-hexahydrochrysene 522 5684-12-8 Dehydrodoisynolacid = Bisdehydrodoisynolacid 303 53905-30-9 2-Hydroxy-2',5'-dichlorobiphenyl 304 53905-29-6 3-Hydroxy-2',5'-dichlorobiphenyl 305 53905-28-5 4-Hydroxy-2',5'-dichlorobiphenyl 306 23719-22-4 4-Hydroxy-2-chlorobiphenyl 308 28034-99-3 4-Hydroxy-4'-chlorobiphenyl 310 2050-67-1 PCB 11 (3,3'-Dichlorobiphenyl) 316 13029-08-8 PCB 4 (2,2'-Dichlorobiphenyl) 317 34883-43-7 PCB 8 (2,4'-Dichlorobiphenyl) 318 11104-28-2 PCB Aroclor 1221 319 11141-16-5 PCB Aroclor 1232 479 34883-39-1 2,5-Dichlorobiphenyl 481 34883-41-5 3,5-Dichlorobiphenyl 484 56858-70-9 4,4'-Dihydroxy-2'-chlorobiphenyl 489 79881-33-7 4-Hydroxy-2',6'-dichlorobiphenyl 246 94-06-4 4-sec-Pentylphenol = 4-(1-Methylbutyl)phenol = p-sec-amylphenol 276 30026-85-8 Diphenylhexamethylcyclotetrasiloxane [(PhMeSiO)2(Me2SiO)2] 281 2081-08-5 1,1-Bis(4-hydroxyphenyl)ethane 282 2081-32-5 1,1-Bis(4-hydroxyphenyl)-iso-pentane 283 4731-84-4 1,1-Bis(4-hydroxyphenyl)-n-butane 286 1576-13-2 1,1-Bis(4-hydroxyphenyl)-n-propane 299 4081-02-1 Bis(4-Hydroxyphenyl)phenylmethane 340 482-49-5 Doisynolic acid 392 1805-61-4 4-iso-Pentylphenol = 4-(3-Methylbutyl)phenol 408 1331-54-0 Phenol, (2-ethylhexyl)-
433 31751-59-4 2,4-trans-Diphenyltetramethylcyclotrisiloxane - 2,4-trans-[(PhMeSiO)2(Me2SiO)]
434 33204-77-2 2,6-trans-Diphenylhexamethylcyclotetrasiloxane - 2,6-trans-[(PhMeSiO)2(Me2SiO)2]
435 51134-25-9 Diphenyltetramethylcyclotrisiloxane [(PhMeSiO)2(Me2SiO)] 436 35964-76-2 o-Tolylheptamethylcyclotetrasiloxane [(o-TolylMeSiO)(Me2SiO3)] 437 17156-72-8 Phenylhexamethylcyclotetrasiloxane [(PhHSiO)(Me2SiO)3] 438 17964-44-2 PhMe[SiCH2CH2SiMePhO] 439 92569-29-4 1,1-Bis(4-hydroxyphenyl)-2-ethyl-n-butane 441 1844-00-4 1,1-Bis(4-hydroxyphenyl)-iso-butane 442 7615-24-9 2,2,5,5-Tetra(4-hydroxyphenyl)-n-hexane 444 3555-19-9 2,2-Bis(4-hydroxyphenyl)-3-methyl-n-butane 445 41709-94-8 2,2-Bis(4-hydroxyphenyl)-n-heptane 446 6052-90-0 2,2-Bis(4-hydroxyphenyl)-n-octane 447 4204-58-4 2,2-Bis(4-hydroxyphenyl)-n-pentane 448 31127-54-5 2,3,4,4'-Tetrahydroxybenzophenon 449 10196-77-7 3,3-Bis(4-hydroxyphenyl)-n-hexane 450 3600-64-4 3,3-Bis(4-hydroxyphenyl)-n-pentane 451 7425-79-8 4,4-Bis(4-hydroxyphenyl)-n-heptane 453 21388-77-2 4-Hydroxyphenyl-4'-methoxyphenylmethane 454 57547-76-9 5,5-Bis(4-hydroxyphenyl)-n-nonane 455 59176-75-9 6,6-Bis(4-hydroxyphenyl)-n-undekane
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No. CAS Name 456 10193-50-7 Bis(3-hydroxyphenyl)methane 466 115489-12-8 1,1-Bis(4-hydroxyphenyl)-1-(4-methoxyphenyl)ethane 467 1571-75-1 1,1-Bis(4-hydroxyphenyl)-1-phenylethane 470 791-92-4 4-Hydroxy-triphenylmethane 471 115481-73-7 Bis(4-hydroxyphenyl)[(2-phenoxysulfonyl)phenyl]methane 473 4865-83-2 1,3-Bis(4-hydroxyphenyl)pentane 474 2549-50-0 1,3-Bis(4-hydroxyphenyl)propane 475 85-95-0 2,4-Bis(4-hydroxyphenyl)-3-ethylhexane 477 140131-31-3 3,5-Bis(4-hydroxyphenyl)heptane 510 553-39-9 2-Hydroxy-6-naphthylpropionacid 546 NoCAS052 Allenolic acid 514 573-22-8 1-Oxo-1,2,3,4-tetrahydrophenanthrene 144 76578-14-8 Quizalofop-ethyl 341 64529-56-2 Ethiozin 167 3567-62-2 1-(3,4-Dichlorophenyl)-3-methylurea 349 463-77-4 Carbamate 369 17356-61-5 1-(3,4-Dichlorophenyl)-3-methoxyurea 146 34113-46-7 o,p'-DDA 352 65148-76-7 3-MeO-o,p'-DDA 357 65148-77-8 5-MeO-o,p'-DDA 172 2132-70-9 MDDE 372 75938-34-0 Mono-OH-MDDE 373 28463-03-8 Mono-OH-Methoxychlor
New-7 125116-23-6 Metconazole New-12 1303-96-4 Borax
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Substances with no CAS number + (? substances) and therefore excluded from the evaluation
No. CAS Name 516 NoCAS089 2,8-dihydroxy-5,6,11,12,13,14-hexahydrochrysene 491 NoCAS126 4-hydroxy-3,5-dichlorobiphenyl 394 NoCAS016 4-Nonylphenoxycarboxylic acid (NP1EC) 395 NoCAS013 4-tert-Pentylphenol = p-tert-Amylphenol 399 NoCAS015 Nonylphenolcarboxylic acid 400 NoCAS017 Nonylphenolethoxylate carboxylic acid 404 NoCAS106 nonylphenolethyleneoxyphosphate 405 NoCAS014 Octylphenol-5-ethoxylate 440 NoCAS025 1,1-Bis(4-hydroxyphenyl)-2-n-propylpentane 452 NoCAS026 4,4-Bis(4-hydroxyphenyl)-n-octane 476 NoCAS030 2,4-Bis(4-hydroxyphenyl)-3-ethylpentane 374 NoCAS108 1-methyl-2-methylcarbamoylvinyldimethyl phosphate 383 NoCAS009 Indole(3.2-b)carbazole (ICZ) 376 NoCAS122 Metalodemeton 382 NoCAS130 Febuconazole
New-8 NoCAS Benzophenone derivatives
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A P P E N D I X J
References to studies and reports on endocrine disruption incorporated in the database
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A P P E N D I X K
Manual for the VEIW version of the EDC Database
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Manual for the VIEW version of the EDS Database
Updated 2006 by DHI Water & Environment
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CONTENTS
ABBREVIATIONS ...................................................................................................................232
1 INTRODUCTION.......................................................................................................233 1.1 Installing the EDS database ......................................................................................233
2 WORKING WITH THE EDS DATABASE ..................................................................233 2.1 Start Menu.................................................................................................................233 2.2 Selection of chemicals and type of data ....................................................................234 2.3 Short overview window..............................................................................................234 2.4 Pre-print Short overview............................................................................................234 2.5 Details window ..........................................................................................................234 2.6 Print preview of the details ........................................................................................235 2.7 Categorisation Window .............................................................................................235 2.8 EUSES calculations ..................................................................................................235 2.9 Datasheets................................................................................................................235
ANNEX 1: EXPLANATION OF THE FIELDS IN THE EDS DATABASE..................................236
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ABBREVIATIONS
EM 1999 and EM 2002 EDS Expert meeting 1999 and 2002
BKH 2000 BKH 2000 report
RPS BKH 2002 BKH 2003 report
DHI 2000 Underlying report
DQ Data Quality 1 – 2 – 3 – 4:
DQ1 • Good data quality, fulfilling all (important) criteria
DQ2 • Sufficient data quality, study fulfilling most of the (important) criteria
DQ3 • Insufficient data quality, study cannot be used for identification
DQ4 • Not evaluated
CAT1, 2, 3a or 3b Category 1, 2, 3 or 4
CAT1 At least one study providing evidence of endocrine disruption in an intact organism. Not a formal weight of evidence approach.
CAT2 Potential for endocrine disruption. In vitro data indicating potential for en-docrine disruption in intact organisms. Also includes effects in-vivo that may, or may not, be ED-mediated. May include structural analyses and metabolic considerations.
CAT3a No scientific basis for inclusion in list (ED studies available but no indications on ED effects)
CAT3b Substances with no or insufficient data gathered
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1 INTRODUCTION
The EDS database is the result of three studies on the identification of Endocrine Dis-rupters for further research, conducted by RPS BKH Consulting Engineers in 1999-2000 and 2002 and by DHI in 2006. All three studies have been contracted by the Euro-pean Commission DG Environment E1. The EDS database holds information for more than 500 chemicals on Human health and Wildlife relevant data concerning both Endocrine disrupting effects and Systemic toxic-ity. Furthermore, the results of categorisations prepared by experts at two separate EU Expert meetings on endocrine disrupters held on 27-28 September 1999 and 9-10 Sep-tember 2002 are included. The EDS database gives the opportunity to select (groups of) chemicals, view and print all available effects data, identified key-studies, categorisa-tions and qualifying remarks given by experts. More information on the data in the EDS database, the evaluation and categorisation procedure can be found in the RPS BKH re-port 2002 and the DHI report 2006. If you have any questions or comments to these instructions or the EDS database, please do not hesitate to contact us via ([email protected])
1.1 Installing the EDS database
Two separate EDS database versions are developed for Access 2000 and Access 2003. Depending on the operating system and Office package installed on your computer, the appropriate version of the EDS database plus the help.doc file must be copied to a sepa-rate directory (e.g. C:\EDSdatabase\…).
After having copied the Access file to your computer, make sure to remove the read-only option under properties (in file manager).
2 WORKING WITH THE EDS DATABASE
The database can be opened in Access using Office version 2000 or 2003. In this man-ual, not all options in the different Windows are explained. However, most of these op-tions are self-explanatory.
2.1 Start Menu
After opening the EDS database, the ‘Start Menu’ is activated. This menu consists of a number of options including a ‘View module’. Other options are ‘Categorisation’ which gives the results of the categorisation plus qualifying remarks; ‘References’ and ‘Litera-ture sources’. In principle, the view module consists of 5 windows: 1. Selection of chemicals and type of data (Human Health or Wildlife relevant)
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2. Short overview of the data 3. Pre-print Short overview 4. Details of the data 5. Pre-print of the details 6. Results of EUSES calculations (CAT1 and CAT2) 7. Datasheets for CAT1 substances
2.2 Selection of chemicals and type of data
The first window in the View Module can be used to select chemical(s) of interest. This window includes the ‘Identified chemicals’ form and the ‘Selected chemicals’ form. To start the search, chemicals can be selected using the chemical name field, the CAS number field or chemical group field. Using the ‘chemical names’ field, chemicals can be selected using parts of their names and adding wild cards (*). Chemicals are identified when the button next to the selection field is applied. Here-after in the ‘Identified chemicals’ form, all chemicals will appear that have been attrib-uted to the selection made. Using the options, one or more chemicals can be (de)selected. After selecting the option ‘Human Health’ or ‘Wildlife’ relevant data, the next window can be opened, choosing the window ‘short overview’ or immediate to ‘details’ or de-tails on key studies. It should be emphasised that the EDS database does NOT contain effects data on all chemicals. In some cases, categorisation is based on data available for ‘reference’ chemicals only.
2.3 Short overview window
This window gives a short overview of the studies available on the selected chemical(s). Fields included in this overview are explained in Annex 1. This window has a number of options to select specific types of data such as in-vivo or in-vitro ED-related data, systemic toxicity data and key studies (if available). Other available options to choose from are: ‘Pre-print Short overview’, Details of se-lected studies, the overview of the categorisation or change the selection of chemicals
2.4 Pre-print Short overview
This window gives the opportunity to print out a short overview of all data on the se-lected chemicals. To print or close the window, a temporary BAR appears.
2.5 Details window
This window is subdivided into 4 tab-sheets and gives extended information on the se-lected studies and the four parts of the expert evaluation.
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Tab-sheet one shows Part 1 of the expert evaluation: Identification of key studies with details of a study and the Tag-field Key study. In a separate Tab-sheet, also the refer-ence and source of information are included plus information on whether the primary reference will be available at the expert meeting. The fields included in this tab-sheet are explained in Annex 1. Part 2: Evaluation of the Data quality of the key studies includes free fields for the ex-perts to fill in their reasoning on the quality of the specific study. Parts 3 and 4: Categorisation of the chemicals plus qualifying remarks and Additional considerations include free fields with the experts reasoning on the categorisation of a chemical. The Details window has a number of options to select specific types of data such as ED-related studies, systemic toxicity studies, DQ1 and DQ2 studies etc. Furthermore, options are available to go to ‘Print preview’, ‘Short overview’ of the se-lected studies, go to ‘Categorisation’ or to change the selection of chemicals.
2.6 Print preview of the details
This Window gives an overview of all details of selected studies including data quality, categorisation and remarks.
2.7 Categorisation Window
The ‘Categorisation’ form shows all categorisations based on Human Health and Wild-life relevant data and overall categorisation, of chemicals incorporated in the EDS data-base including the event when the categorisation was applied. The form gives the possibility to select chemicals categorised at specific events such as Expert meeting 1999 or 2002 (EM 1999 or EM 2002), categorisation given in the BKH 2000 report or RPS BKH 2002 report, and DHI 2006 report. Additionally, specific Categories can be selected (CAT1, CAT2, CAT3 (BKH 2000 report) CAT3a and CAT3b (explanation see Annex 1). All these lists or the complete list can be printed. Hereafter, additional information on the selected chemicals can be viewed selecting ‘Qualifying remarks’, ‘Short overview’ or ‘Details’.
2.8 EUSES calculations
For the CAT1 and CAT2 substances assessed in the 2006 project, it is possible to see/print the results of the EUSES calculations including the physical-chemical proper-ties used for the calculations.
2.9 Datasheets
For the CAT1 substances assessed in the 2006 project, it is possible to see/print a data-sheet summarizing the properties of the substance, the EUSES calculations, and the conclusion on the assessment.
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ANNEX 1: EXPLANATION OF THE FIELDS IN THE EDS DATABASE
Field Explanation: Recno Record code in the database
for example: GPh001 (Gitte Peterson– author; H – human relevant ED data; 001 – first record); LBw021 (Lamert van Breemen– author; W – wildlife relevant ED data 021 – 21 record); GPsh059 (Gitte Peterson– author; SH – systemic toxicity); CGse311 (Christa Groshart– author; SE – systemic Ecotoxicity). The code is unique.
Chemno Chemical number: each chemical has a number, which can be found in the Totlist. So there is no need to type the chemical name
Test type Human health relevant data included are epidemiological, in-vitro and in-vivo experiments. In-vivo studies are sometimes subdivided into ACUTE, REP (Repro-duction) or RDT (Repeated Dose Toxicity). Wildlife relevant data are field, in-vitro and in-vivo experiments.
Test method OECD ... or other procedures used for the test Species/receptor Information such as: species, strain, age, weight, gender, cell type.
e.g. rat, Salmon or Human MCF-7 cells Exposure route Food, water, oral, intraperitoneal, subcutaneous ... Dose-conc. Numerical value of the amount of substance applied Unit Unit of the dose or concentration applied Relative Potency Endocrine effects related to a reference substance as for example estradiol:
In the remarks field, it should be made clear how this ratio is calculated Effect Effect parameter tested, e.g. feminized females, testicular or ovarian effects hor-
mone effects, thyroid effect (a listing of effect parameters is given in Annex 1) Criterion NOEL (No observed effect level), LOEL (lowest observed effect level), ED (effect
dose), LC50 (lethal concentration 50%), NOEC (No observed effect concentra-tion), TDlow (lowest toxic dose) The exposure concentration/dose preferably referred to the LOEL if available. If more criteria were reported, these were put in the remarks field
Code The data have been given a code (class) to combine the different groups of ef-fects. The following groups of effects are distinguished:
e: Suspected endocrine effects on (anti) estrogenic (anti) androgenic pi: Effect on pituitary organ re: Retinoid effects th: Effects on thyroid organ y: Reproductive/teratogenic effects z: Other systemic toxicity effects
The code was combined with a ‘-‘ or ‘+’ sign (e.g. +e). The ‘-‘ sign attached to the experiment-code stands for no effects at all concentrations tested, whereas the ‘+’ sign refers to the observation that effects were found in the experiment.
RefID Reference code of the experiment (a first three letters of first author, year, and if there are more publications of the same author in one year use a letter a, b, c, d etc.)
SourceID Source code of the experiment, like the Ref ID.
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Field Explanation: Remarks Detailed information on experimental design and test results. If on ED there is a
NOEC and LOEC or NOEL and LOEL is available, then put the NOEC/NOEL in the remarks field and LOEC/LOEL in the criteria field. Other information in the remarks field is: • Exposure period (e.g. 21 days, 2 generations ...)/ frequency • Number of test concentrations plus levels • Test system (static/renewal/flow through) • Details on types of effects • Concentrations measured/analyse • Life stage • Details on critical window
Data Quality DQ1: good data quality, fulfilling all (important) criteria; DQ2: sufficient data quality, study fulfilling most of the (important) criteria; DQ3: insufficient data quality, study cannot be used for identification; DQ4: not evaluated
Evaluation Data Quality
Relevance effect parameter: • Relation ED effects with mechanistic cause Test reliability: • Use of validated protocols (analysis, test procedure) • Experimental design: controls, concentration range • Test species: suitability, health, life stage... • Analysis of results: statistics • Dose – Response relationship ED potency: • Comparison with indicator hormone activity (e.g. estradiol), if available
CATEGORY CAT1 At least one study providing evidence of endocrine disruption in an intact organism. Not a formal weight of evidence approach.
CAT2 Potential for endocrine disruption. In vitro data indicating potential for en-
docrine disruption in intact organisms. Also includes effects in-vivo that may, or may not, be ED-mediated. May include structural analyses and metabolic considerations
CAT3a No scientific basis for inclusion in list, based on data in the ED database
(ED studies available but no indications on ED effects) CAT3b Substances with no or insufficient data gathered. CAT3 No scientific basis for inclusion in list or Substances with no or insufficient
data gathered (BKH 2000 report) Qualifying re-marks
Coherence of results ED related tests; • ‘other ED evidence is supporting’ • ‘other evidence is lacking’ • ‘other evidence is contradicting’ Qualifying remarks may also concern the identification certain "groups" of sub-stances with an overall ED categorisation on the basis of reference substances;
Additional con-siderations
• The amount of ED evidence • ED Potency • Comparison with systemic toxicity
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A P P E N D I X L
Updated ranked priority list
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CAS No. NAME Human health Wildlife Overall cate-
gorization NoCAS 040 4-Hydroxy-3,3',4',5'-
tetrachlorobiphenyl CAT1 CAT2 CAT1
53905-33-2 4-Hydroxy-2,2',5'-trichlorobiphenyl CAT1 CAT2 CAT1 4400-06-0 4-Hydroxy-3,4',5-trichlorobiphenyl CAT1 CAT2 CAT1 67651-37-0 3-Hydroxy-2',3',4',5'-
tetrachlorobiphenyl CAT1 CAT2 CAT1
100702-98-5 4,4'-Dihydroxy-2,3,5,6-tetrachlorobiphenyl
CAT1 CAT2 CAT1
13049-13-3 4,4'-Dihydroxy-3,3',5,5'-tetrachlorobiphenyl
CAT1 CAT2 CAT1
4329-12-8 m,p'-DDD CAT1 CAT3b CAT1 72-54-8 p,p'-DDD CAT1 CAT3b CAT1 8068-44-8 Clophen A50 CAT1 CAT2 CAT1 65148-75-6 5-MeO-o,p'-DDD CAT1 CAT3b CAT1 NoCAS 036 PCB Aroclor 1016 CAT1 CAT1 CAT1 54991-93-4 Clophen A30 CAT1 CAT2 CAT1 53-19-0 o,p'-DDD CAT1 CAT2 CAT1 NoCAS 037 PCB 126 (3,3',4,4',5-
Pentachlorobiphenyl) CAT1 CAT1 CAT1
118174-38-2 6-Methyl-1,3,8-trichlorodibenzofuran CAT1 CAT2 CAT1 56614-97-2 3,9-Dihydroxybenz(a)anthracene CAT1 CAT2 CAT1 65148-72-3 4-MeO-o,p'-DDT CAT1 CAT3b CAT1 65148-73-4 5-OH-o,p'-DDT CAT1 CAT3b CAT1 65148-74-5 5-MeO-o,p'-DDT CAT1 CAT3b CAT1 57-97-6 7,12-Dimethyl-1,2-benz(a)anthracene CAT1 CAT2 CAT1 56-49-5 3-Methylcholanthrene CAT1 CAT3b CAT1 NoCAS 038 Mixture of 2,3,4,5-tetrachlorobiphenyl
(PCB 61), 2,2',4,5,5'-octachlorobiphenyl (PCB 101) and 2,2',3,3',4,4',5,5'-octachlorobiphenyl (PCB 194)
CAT1 CAT1 CAT1
7099-43-6 5,6-Cyclopento-1,2-benzanthracene CAT1 CAT2 CAT1 NoCAS 039 PCB 104 (2,2',4,6,6'-
Pentachlorobiphenyl) CAT1 CAT1 CAT1
35693-99-3 PCB 52 (2,2';5,5'-Tetrachlorobiphenyl) CAT1 CAT1 CAT1 NoCAS 042 PCB 122 (2,3,3',4,5 -
Pentachlorobiphenyl) CAT1 CAT1 CAT1
2971-36-0 Bis-OH-Methoxychlor = 1,1,1-trichloro-2,2-bis(4-hydroxyphenyl)ethane (HTPE)
CAT1 CAT1 CAT1
38380-07-3 PCB 128 (2,2',3,3',4,4'-Hexachlorobiphenyl)
CAT1 CAT1 CAT1
NoCAS 041 PCB 105 (2,3,3',4,4' -Pentachlorobiphenyl)
CAT1 CAT1 CAT1
67651-34-7 4-Hydroxy-2',3',4',5'-tetrachlorobiphenyl
CAT1 CAT2 CAT1
50-32-8 Benzo[a]pyrene CAT1 CAT2 CAT1 9006-42-2 Metiram (Metiram-complex) CAT1 CAT3b CAT1 55702-46-0 PCB 21 (2,3,4-Trichlorobiphenyl) CAT1 CAT1 CAT1 32809-16-8 Procymidon CAT1 CAT3b CAT1 87-86-5 Pentachlorophenol (PCP) CAT1 CAT3b CAT1 608-73-1 Hexachlorocyclohexane = HCH mixed CAT3b CAT3b CAT1
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CAS No. NAME Human health Wildlife Overall cate-
gorization 319-85-7 Beta-HCH CAT2 CAT1 CAT1 9016-45-9 Nonylphenolethoxylate CAT2 CAT1 CAT1 72-43-5 Methoxychlor CAT1 CAT1 CAT1 85535-84-8 Short chain chlorinated paraffins CAT1 CAT3b CAT1 72-43-5 p,p'-Methoxychlor CAT1 CAT1 CAT1 8018-01-7 Mancozeb CAT1 CAT3b CAT1 60168-88-9 Fenarimol CAT1 CAT2 CAT1 10453-86-8 Resmethrin CAT1 CAT3b CAT1 52918-63-5 Deltamethrin CAT1 CAT2 CAT1 30668-06-5 1,3-Dichloro-2,2-bis(4-methoxy-3-
methylphenyl)propane CAT1 CAT1 CAT1
21087-64-9 Metribuzin CAT1 CAT3b CAT1 72-55-9 p,p'-DDE CAT1 CAT1 CAT1 12642-23-8 PCT Aroclor 5442 CAT1 CAT1 CAT1 65148-80-3 3-MeO-o,p'-DDE CAT1 CAT3b CAT1 11081-15-5 Phenol, isooctyl- CAT1 CAT1 CAT1 14962-28-8 4-Hydroxy-2',4',6'-trichlorobiphenyl CAT1 CAT2 CAT1 37680-65-2 PCB 18 (2,2',5-Trichlorobiphenyl) CAT1 CAT1 CAT1 2971-22-4 1,1,1-Trichloro-2,2-bis(4-
chlorophenyl)ethane CAT1 CAT1 CAT1
65148-82-5 5-MeO-o,p'-DDE CAT1 CAT3b CAT1 3424-82-6 o,p'-DDE CAT1 CAT2 CAT1 101-53-1 Phenyl-4-hydroxyphenylmethane = 4-
Benzylphenol = p-Benzylphenol CAT1 CAT3b CAT1
84-66-2 Diethyl phthalate (DEP) CAT1 CAT3b CAT1 84-61-7 Dicyclohexyl phthalate (DCHP) CAT1 CAT2 CAT1 65148-83-6 o,p'-DDA-glycinat = N-[(2-
chlorophenyl)(4-chlorophenyl)acettyl]glycin
CAT1 CAT3b CAT1
14835-94-0 o,p'-DDMU CAT1 CAT3b CAT1 85535-85-9 Intermediate chain chlorinated paraf-
fins CAT1 CAT3b CAT1
65148-81-4 4-MeO-o,p'-DDE CAT1 CAT3b CAT1 65277-42-1 Ketoconazol CAT1 CAT3b CAT1 5103-73-1 Cis-Nonachlor CAT2 CAT1 CAT1 608-93-5 Pentachlorobenzene CAT1 CAT3b CAT1 1918-02-1 Picloram CAT1 CAT3b CAT1 63-25-2 Carbaryl CAT1 CAT2 CAT1 43216-70-2 3-OH-o,p'-DDT CAT1 CAT3b CAT1 50585-41-6 2,3,7,8-TeBDD CAT1 CAT2 CAT1 886-50-0 Terbutryn CAT1 CAT3b CAT1 39765-80-5 Trans-Nonachlor CAT2 CAT1 CAT1 7012-37-5 PCB 28 (2,4,4'-trichlorobiphenyl) CAT1 CAT1 CAT1 31508-00-6 PCB 118 (2,3',4,4',5-
pentachlorobiphenyl) CAT1 CAT1 CAT1
1806-26-4 Phenol, 4-octyl- CAT1 CAT1 CAT1 12002-48-1 Trichlorobenzene CAT1 CAT3b CAT1 91465-08-6 Cyhalothrin (@Karate) CAT1 CAT3b CAT1 82657-04-3 Bifenthrin (@Talstar) CAT1 CAT3b CAT1 1689-83-4 Ioxynil CAT1 CAT3b CAT1 NoCAS 088 PCB180 2,2',3,4,4',5,5'-
heptachlorobiphenyl CAT1 CAT1 CAT1
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CAS No. NAME Human health Wildlife Overall cate-
gorization 789-02-6 o,p'-DDT CAT1 CAT1 CAT1 NoCAS 127 2,4-6-trichlorobiphenyl CAT1 CAT2 CAT1 94-82-6 2,4-dichlorophenoxybutyric acid = 2,4-
DB CAT1 CAT3b CAT1
NoCAS 128 3,4',5-trichlorobiphenyl CAT1 CAT2 CAT1 72-33-3 Mestranol CAT1 CAT2 CAT1 106-89-8 Epichlorohydrin (1-chloro-2,3-
epoxypropane) CAT1 CAT3b CAT1
NoCAS 087 PCB138 2,2',3,4,4',5'-hexachlorobiphenyl
CAT1 CAT1 CAT1
25036-25-3 2,2'-bis(2-(2,3-epoxypropoxy)phenyl)-propane
CAT3b CAT1 CAT1
106-93-4 Dibromoethane (EDB) CAT1 CAT3b CAT1 NoCAS 092 PCB 114 (2,3,4,4',5-
pentachlorobiphenyl) CAT1 CAT1 CAT1
NoCAS 096 1,1-trichloro-2,2-bis(4-hydroxyphenyl)ethane (HPTE)
CAT1 CAT1 CAT1
NoCAS 097 4-OH-2,2',4',5,5'-pentachlorobiphenyl CAT1 CAT2 CAT1 122-14-5 Fenitrothion CAT1 CAT2 CAT1 1022-22-6 p,p'-DDMU CAT1 CAT3b CAT1 104-40-5 4-Nonylphenol (4-NP) CAT1 CAT1 CAT1 25013-16-5 tert.-Butylhydroxyanisole (BHA) CAT1 CAT1 CAT1 1131-60-8 4-Cyclohexylphenol CAT1 CAT3b CAT1 99-96-7 p-Hydroxybenzoic acid CAT1 CAT3b CAT1 131-55-5 Benzophenone-2 (Bp-2), 2,2',4,4'-
tetrahydroxybenzophenone CAT1 CAT1 CAT1
13593-03-8 Quinalphos = Chinalphos CAT1 CAT1 CAT1 15087-24-8 3-Benzylidene camphor (3-BC) CAT1 CAT1 CAT1 94-26-8 n-Butyl p-Hydroxybenzoate CAT1 CAT1 CAT1 94-13-3 n-propyl p-hydroxybenzoate CAT1 CAT1 CAT1 556-67-2 Cyclotetrasiloxane CAT1 CAT3b CAT1 99-76-3 Methyl p-Hydroxybenzoate CAT1 CAT3b CAT1 1582-09-8 Trifluralin CAT1 CAT2 CAT1 36861-47-9 3-(4-Methylbenzylidene)camphor CAT1 CAT3a CAT1 96-45-7 Ethylene Thiourea (ETU) CAT1 CAT1 CAT1 92-69-3 4-Hydroxybiphenyl = 4-Phenylphenol CAT1 CAT3b CAT1 5466-77-3 2-ethyl-hexyl-4-methoxycinnamate CAT1 CAT1 CAT1 131-18-0 Di-n-pentylphthalate (DPP) = Dipen-
tylphthalate CAT1 CAT3b CAT1
96-12-8 Dibromochloropropane (DBCP) CAT1 CAT3b CAT1 120-47-8 ethyl 4-hydroxybenzoate CAT1 CAT1 CAT1 10043-35-3 Boric acid CAT1 CAT2 CAT1 7400-08-0 p-Coumaric acid (PCA) CAT1 CAT3b CAT1 1634-04-4 methyl tertiary butyl ether (MTBE) CAT1 CAT2 CAT1 27193-28-8 Phenol, (1,1,3,3-tetramethylbutyl)- =
Octylphenol CAT1 CAT1 CAT1
6164-98-3 Chlordimeform CAT1 CAT3b CAT1 77-09-8 3,3'-Bis(4-hydroxyphenyl)phthalid =
Phenolphthaleine CAT1 CAT3b CAT1
131-70-4 Mono-n-butylphthalate CAT1 CAT3b CAT1 4376-20-9 Mono 2 ethyl hexylphthalate (MEHP) CAT1 CAT3b CAT1
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CAS No. NAME Human health Wildlife Overall cate-
gorization 92-88-6 4,4'-Dihydroxybiphenyl = 4,4'-
Biphenol CAT1 CAT2 CAT1
1113-02-6 Omethoate CAT1 CAT3b CAT1 33204-76-1 2,6-cis-
Diphenylhexamethylcyclotetrasiloxane - 2,6-cis-[(PhMeSiO)2(Me2SiO)2][
CAT1 CAT3b CAT1
77-40-7 2,2-Bis(4-hydroxyphenyl)-n-butan = Bisphenol B
CAT1 CAT3b CAT1
611-99-4 4,4'-Dihydroxybenzophenon CAT1 CAT1 CAT1 131-56-6 2,4-Dihydroxybenzophenon = Res-
benzophenone CAT1 CAT1 CAT1
50-18-0 Cyclophosphamide CAT1 CAT3b CAT1 26354-18-7 2-propenoic acid, 2-methyl-, methyl
ester = Stannane, tributylmeacrylate CAT2 CAT1 CAT1
50-29-3 DDT (technical) = clofenotane CAT1 CAT1 CAT1 2385-85-5 Mirex CAT1 CAT2 CAT1 8001-35-2 Toxaphene = Camphechlor CAT1 CAT2 CAT1 143-50-0 Kepone (Chlordecone) CAT1 CAT2 CAT1 12789-03-6 Chlordane CAT1 CAT2 CAT1 57-74-9 Chlordane (cis- and trans-) CAT1 CAT2 CAT1 26636-32-8 Tributyltinnaphthalate CAT2 CAT1 CAT1 50-29-3 p,p'-DDT = clofenotane CAT1 CAT1 CAT1 3563-45-9 1,1,1,2-Tetrachloro-2,2-bis(4-
chlorophenyl)ethane (tetrachloro DDT)
CAT2 CAT1 CAT1
58-89-9 Gamma-HCH (Lindane) CAT1 CAT2 CAT1 1983-10-4 Stannane, tributylfluoro- CAT2 CAT1 CAT1 95-76-1 3,4-Dichloroaniline CAT2 CAT1 CAT1 26239-64-5 Stannane, tribu-
tyl[[[1,2,3,4,4a,4b,5,6,1 CAT2 CAT1 CAT1
25154-52-3 Phenol, nonyl- CAT1 CAT1 CAT1 24124-25-2 Stannane, tributyl[(1-oxo-9,12-
octadecad CAT2 CAT1 CAT1
2155-70-6 Tributyl[(2-methyl-1-oxo-2-propenyl)oxy]stannane
CAT2 CAT1 CAT1
330-55-2 Linuron (Lorox) CAT1 CAT3 CAT1 36631-23-9 Stannane, tributyl = Tributyltin naphta-
late CAT2 CAT1 CAT1
2437-79-8 PCB 47 (2,2',4,4'-Tetrachlorobiphenyl) CAT1 CAT1 57117-31-4 2,3,4,7,8-Pentachlorodibenzofuran
(2,3,4,7,8-PeCDF) CAT1 CAT1
688-73-3 Tributyltin hydride CAT2 CAT1 CAT1 56-35-9 Tributyltin oxide = bis(tributyltin) oxide CAT2 CAT1 CAT1 NoCAS 050 Tributyltin compounds CAT2 CAT1 CAT1 NoCAS 051 Triphenyltin CAT3 CAT1 CAT1 99-99-0 4-Nitrotoluene CAT1 CAT3 CAT1 3090-35-5 Stannane, tributyl[(1-oxo-9-
octadecenyl) CAT2 CAT1 CAT1
NoCAS 099 Tributyltincarboxylate CAT2 CAT1 CAT1 1746-01-6 2,3,7,8-Tetrachlorodibenzo-p-dioxin
(2,3,7,8-TCDD) CAT1 CAT1
NoCAS 101 Tributyltinpolyethoxylate CAT2 CAT1 CAT1
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CAS No. NAME Human health Wildlife Overall cate-
gorization NoCAS 004 PBBs = Brominated Flame retardants
= PBB (mixed group of 209 Conge-ners)
CAT1 CAT1
4342-30-7 Phenol, 2-[[(tributylstannyl)oxy]carbony
CAT2 CAT1 CAT1
4342-36-3 Stannane, (benzoyloxy)tributyl- CAT2 CAT1 CAT1 4782-29-0 Stannane, [1,2-
phenylenebis(carbonyloxy) CAT2 CAT1 CAT1
85409-17-2 Stannane, tributyl-, mono(naphthenoyloxy
CAT2 CAT1 CAT1
2279-76-7 Tri-n-propyltin (TPrT) CAT3 CAT1 CAT1 1461-25-2 Tetrabutyltin (TTBT) CAT2 CAT1 CAT1 900-95-8 Fentin acetate = triphenyltin acetate CAT3 CAT1 CAT1 137-42-8 Metam Natrium CAT1 CAT3 CAT1 34256-82-1 Acetochlor CAT1 CAT3 CAT1 108-46-3 Resorcinol CAT1 CAT3 CAT1 NoCAS 100 Methoxyetylacrylate tinbutyltin, co-
polymer CAT2 CAT1 CAT1
84-74-2 Di-n-butylphthalate (DBP) CAT1 CAT3 CAT1 137-26-8 Thiram CAT1 CAT3 CAT1 12122-67-7 Zineb CAT1 CAT3 CAT1 1912-24-9 Atrazine CAT1 CAT2 CAT1 61-82-5 Amitrol = Aminotriazol CAT1 CAT3 CAT1 50471-44-8 Vinclozolin CAT1 CAT3 CAT1 15972-60-8 Alachlor CAT1 CAT2 CAT1 1836-75-5 Nitrofen CAT1 CAT3 CAT1 100-42-5 Styrene CAT1 CAT3 CAT1 118-74-1 Hexachlorobenzene (HCB) CAT1 CAT3 CAT1 40321-76-4 1,2,3,7,8-Pentachlorodibenzodioxin CAT1 CAT1 85-68-7 Butylbenzylphthalate (BBP) CAT1 CAT3 CAT1 12427-38-2 Maneb CAT1 CAT3 CAT1 117-81-7 Di-(2-ethylhexyl)phthalate (DEHP) CAT1 CAT3 CAT1 80-05-7 2,2-Bis(4-hydroxyphenyl)propan =
4,4'-isopropylidenediphenol = Bisphe-nol A
CAT1 CAT1 CAT1
53469-21-9 PCB Aroclor 1242 CAT1 CAT1 12672-29-6 PCB Aroclor 1248 CAT1 CAT1 32598-13-3 PCB 77 (3,3',4,4'-Tetrachlorobiphenyl) CAT1 CAT1 35065-27-1 PCB 153 (2,2',4,4',5,5'-
Hexachlorobiphenyl) CAT1 CAT1
1336-36-3 PCB CAT1 CAT1 11097-69-1 PCB Aroclor 1254 CAT1 CAT1 11096-82-5 PCB Aroclor 1260 (Clophen A60) CAT1 CAT1 32774-16-6 PCB 169 (3,3',4,4',5,5'-
Hexachlorobiphenyl) CAT1 CAT1
140-66-9 4-tert-Octylphenol=1,1,3,3-Tetramethyl-4-butylphenol
CAT1 CAT1 CAT1
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CAS No. NAME Human health Wildlife Overall cate-
gorization 125652-14-4 6-n-Propyl-1,3,8-
trichlorodibenzofuran CAT3b CAT2 CAT2
131167-13-0 2-Bromo-1,3,7,8-tetrachlorodibenzodioxin
CAT3b CAT2 CAT2
103124-72-7 8-Bromo-2,3,4-trichlorodibenzofuran CAT3b CAT2 CAT2 112344-57-7 8-Methyl-2,3,7-
trichlorodibenzodioxin CAT3b CAT2 CAT2
172485-97-1 6-Methyl-2,3,8-trichlorodibenzofuran CAT3b CAT2 CAT2 172485-98-2 8-Methyl-1,3,7-trichlorodibenzofuran CAT3b CAT2 CAT2 172485-96-0 8-Methyl-1,3,6-trichlorodibenzofuran CAT3b CAT2 CAT2 109333-33-7 2-Bromo-3,7,8-
trichlorodibenzodioxin CAT3b CAT2 CAT2
125652-16-6 6-Ethyl-1,3,8-trichlorodibenzofuran CAT3b CAT2 CAT2 97741-74-7 7-Bromo-2,3-dichlorodibenzodioxin CAT3b CAT2 CAT2 125652-13-3 6-i-Propyl-1,3,8-
trichlorodibenzofuran CAT3b CAT2 CAT2
125652-12-2 6-t-Butyl-1,3,8-trichlorodibenzofuran CAT3b CAT2 CAT2 139883-51-5 6-Methyl-2,3,4,8-
tetrachlorodibenzofuran CAT3b CAT2 CAT2
139883-50-4 8-Methyl-1,2,4,7-tetrachlorodibenzofuran
CAT3b CAT2 CAT2
172486-00-9 8-Methyl-2,3,4,7-tetrachlorodibenzofuran
CAT3b CAT2 CAT2
56-55-3 Benz(a)anthracene CAT2 CAT2 CAT2 172485-99-3 8-Methyl-2,3,7-trichlorodibenzofuran CAT3b CAT2 CAT2 51630-58-1 Fenvalerate CAT2 CAT2 CAT2 116-06-3 Aldicarb CAT2 CAT3b CAT2 16752-77-5 Methomyl CAT2 CAT3b CAT2 2597-11-7 1-Hydroxychlordene CAT2 CAT3b CAT2 93-76-5 2,4,5-T = 2,4,5-
Trichlorophenoxyaceticacid CAT2 CAT3b CAT2
470-90-6 Chlorfenvinphos CAT3a CAT2 CAT2 584-79-2 Bioallethrin = d- trans allethrin CAT2 CAT3b CAT2 109333-32-6 2,8-Dibromo-3,7-
dichlorodibenzodioxin CAT3b CAT2 CAT2
26002-80-2 Fenothrin = sumithrin CAT2 CAT3b CAT2 50585-40-5 2,3-Dibromo-7,8-
dichlorodibenzodioxin CAT3b CAT2 CAT2
69409-94-5 Fluvalinate CAT2 CAT3b CAT2 52645-53-1 Permethrin CAT2 CAT3b CAT2 88378-55-6 3,5-Dichlorophenylcarbaminacid-(1-
carboxy-1-methyl)-allyl CAT2 CAT3b CAT2
83792-61-4 N-(3,5-Dichlorophenyl)-2-hydroxy-2-methyl-3-butenacidamid
CAT2 CAT3b CAT2
72490-01-8 Fenoxycarb CAT3b CAT2 CAT2 14409-72-4 4-Nonylphenolnonaethoxylat (Tergi-
tol NP 9) CAT3b CAT2 CAT2
50585-46-1 1,3,7,8-Tetrachlorodibenzodioxin CAT3b CAT2 CAT2 52315-07-8 Cypermethrin CAT3a CAT2 CAT2 2593-15-9 Etridiazole CAT2 CAT3b CAT2 21725-46-2 Cyanazine CAT2 CAT3b CAT2 30560-19-1 Acephate CAT2 CAT2 CAT2
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CAS No. NAME Human health Wildlife Overall cate-
gorization 13171-21-6 Phosophamidon CAT2 CAT3b CAT2 7287-19-6 Prometryn CAT2 CAT3b CAT2 123-88-6 Triadimenol CAT2 CAT3b CAT2 52-68-6 Trichlorfon = Dipterex CAT2 CAT3b CAT2 1689-84-5 Bromoxynil CAT2 CAT3b CAT2 NoCAS 115 1,3,7,8-TeBCDD CAT3b CAT2 CAT2 NoCAS 112 1,2,4,7,8-PeCDD CAT3b CAT2 CAT2 109333-34-8 1,2,3,7,8-PeBDD CAT3b CAT2 CAT2 103456-39-9 TeBDD CAT3b CAT2 CAT2 319-86-8 Delta-HCH CAT2 CAT3b CAT2 1563-66-2 Carbofuran CAT2 CAT2 CAT2 7786-34-7 Mevinphos = Phosdrin CAT3a CAT2 CAT2 51-03-6 Piperonyl butoxide CAT3b CAT2 CAT2 25085-99-8 Bisphenol A-diglycidylether polymer
(mw<700) CAT3b CAT2 CAT2
131-57-7 2-hydroxy-4-methoxy-benzophenone
CAT2 CAT2 CAT2
2051-61-8 PCB 2 (3-Chlorobiphenyl) CAT2 CAT3b CAT2 2051-60-7 PCB 1 (2-Chlorobiphenyl) CAT2 CAT3b CAT2 1806-29-7 2,2'-Dihydroxybiphenyl = 2,2'-
Biphenol CAT2 CAT2 CAT2
81-92-5 2-[Bis(4-hydroxyphenyl)methyl]benzylalkohol = Phenolphthalol
CAT2 CAT3b CAT2
6807-17-6 2,2-Bis(4-hydroxyphenyl)-4-methyl-n-pentane
CAT2 CAT3b CAT2
2581-34-2 3-methyl-4-nitrophenol CAT2 CAT3b CAT2 14007-30-8 2,2-Bis(4-hydroxyphenyl)-n-hexane CAT2 CAT3b CAT2 100-02-7 4-nitrophenol CAT2 CAT3b CAT2 3115-49-9 4-nonylphenoxy acetic acid CAT2 CAT2 CAT2 99-71-8 4-sec-Butylphenol = 4-(1-
Methylpropyl)phenol CAT2 CAT2 CAT2
20427-84-3 4-Nonylphenoldiethoxylate (NP2EO)
CAT2 CAT2 CAT2
84-69-5 Diisobutylphthalate CAT2 CAT3b CAT2 2051-62-9 PCB 3 (4-Chlorobiphenyl) CAT2 CAT3b CAT2 131-54-4 2,2'-Dihydroxy-4,4'-
dimethoxybenzophenon CAT2 CAT3b CAT2
121-29-9 Pyrethrin CAT2 CAT3b CAT2 84-75-3 Di-n-hexyl phthalate (DnHP) = Di-
hexylphthalate (DHP) CAT2 CAT3b CAT2
83-05-6 p,p'-DDA CAT2 CAT2 CAT2 131-16-8 Di-n-propylphthalate (DprP) =
Dipropylphthalate CAT2 CAT3b CAT2
106-44-5 p-cresol CAT2 CAT3b CAT2 2597-03-7 Elsan = Dimephenthoate CAT3b CAT2 CAT2 106340-44-7 Tetrabromodibenzofuran (TeBDF) CAT2 CAT2 107555-93-1 1,2,3,7,8-Pentabromodibenzofuran CAT2 56-38-2 Parathion = Parathion(-ethyl) CAT2 CAT3 CAT2 121-75-5 Malathion CAT2 CAT2 CAT2 298-00-0 Methylparathion CAT3 CAT2 CAT2 39801-14-4 Photomirex CAT2 CAT3 CAT2
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gorization 333-41-5 Diazinon CAT3 CAT2 CAT2 75-15-0 Carbon disulphide CAT2 CAT3 CAT2 330-54-1 Diuron CAT2 CAT3 CAT2 36734-19-7 Iprodione CAT2 CAT3 CAT2 115-32-2 Dicofol = Kelthane CAT3 CAT2 CAT2 60-51-5 Dimethoate CAT2 CAT3 CAT2 94-75-7 2,4-Dichlorophenoxy acetic acid
(2,4-D) CAT2 CAT2 CAT2
1570-64-5 4-chloro-2-methylphenol CAT2 CAT3 CAT2 33213-65-9 Endosulfan (beta) CAT2 CAT2 CAT2 959-98-8 Endosulfan (alpha) CAT2 CAT2 CAT2 115-29-7 Endosulfan CAT2 CAT2 CAT2 27304-13-8 Oxychlordane CAT2 CAT3 CAT2 72-20-8 Endrin CAT2 CAT2 CAT2 60-57-1 Dieldrin CAT2 CAT2 CAT2 309-00-2 Aldrin CAT2 CAT2 CAT2 28553-12-0 diisononyl phthalate = 1,2-
Benzenedicarboxylic acid, diisononyl ester (DINP)
CAT2 CAT3 CAT2
10605-21-7 Carbendazim CAT2 CAT3 CAT2 67747-09-5 Prochloraz CAT2 CAT3 CAT2 71998-72-6 1,3,6,8-Tetrachlorodibenzofuran CAT2 CAT2 33284-53-6 PCB 61 (2,3,4,5-
Tetrachlorobiphenyl) CAT2 CAT2
70362-47-9 PCB 48 (2,2',4,5-Tetrachlorobiphenyl)
CAT2 CAT2
38411-22-2 PCB 136 (2,2',3,3',6,6'-Hexachlorobiphenyl)
CAT2 CAT2
38380-08-4 PCB 156 (2,3,3',4,4',5-Hexachlorobiphenyl)
CAT2 CAT2
NoCAS 043 Octabrominated diphenyl ether (oc-taBDE)
CAT2 CAT2
NoCAS 044 Decabrominated diphenyl ether (decaBDE)
CAT2 CAT2
NoCAS 045 Pentabrominated diphenyl ether (pentaBDE)
CAT2 CAT2
26761-40-0 Diisodecyl phthalate CAT2 CAT3 CAT2 1675-54-3 2,2'-bis(4-(2,3-
epoxypropoxy)phenyl)propane = 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane
CAT2 CAT3 CAT2
74-83-9 Methylbromide (bromomethane) CAT2 CAT3 CAT2 NoCAS 046 2,2',4,4'-Tetrabrominated diphenyl
ether (2,2',4,4'-tetraBDE) CAT2 CAT2
43121-43-3 Triadimefon CAT2 CAT3 CAT2 58802-20-3 1,2,7,8-Tetrachlorodibenzofuran CAT2 CAT2 709-98-8 Propanil CAT2 CAT3 CAT2 98-54-4 4-tert-Butylphenol CAT2 CAT2 CAT2 51207-31-9 2,3,7,8-Tetrachlorodibenzofuran CAT2 CAT2 57117-41-6 1,2,3,7,8-Pentachlorodibenzofuran CAT2 CAT2 120-83-2 2,4 Dichlorophenol CAT2 CAT3 CAT2 76-44-8 Heptachlor CAT2 CAT3 CAT2 83704-53-4 1,2,3,7,9-Pentachlorodibenzofuran CAT2 CAT2
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CAS No. NAME Human health Wildlife Overall cate-
gorization 90-43-7 o-phenylphenol CAT2 CAT2 CAT2 127-18-4 Perchloroethylene CAT2 CAT3 CAT2 122-34-9 Simazine CAT2 CAT3 CAT2 137-30-4 Ziram CAT2 CAT2 CAT2 59-50-7 4-chloro-3-methylphenol CAT2 CAT3 CAT2 32598-12-2 PCB 75 (2,4,4',6-
Tetrachlorobiphenyl) CAT2 CAT2
67733-57-7 2,3,7,8-Tetrabromodibenzofuran CAT2 CAT2
CAS No. NAME Human health Wildlife Overall cate-
gorization 2921-88-2 Chlorpyrifos CAT3a CAT3b CAT3a 3734-48-3 Chlordene CAT3a CAT3b CAT3a 40487-42-1 Pendimethalin CAT3a CAT3b CAT3a 35367-38-5 Diflubenzuron CAT3a CAT3b CAT3a 919-86-8 Demeton-s-methyl CAT3a CAT3b CAT3a 62-73-7 Dichlorvos CAT3a CAT3b CAT3a 1024-57-3 Heptachlor-epoxide CAT3a CAT3b CAT3a 92-52-4 Diphenyl CAT3a CAT3b CAT3a 17804-35-2 Benomyl CAT3a CAT3b CAT3a 11141-17-6 Azadirachtin CAT3a CAT3b CAT3a 299-84-3 Ronnel = fenchlorfos CAT3a CAT3b CAT3a 22248-79-9 Tetrachlorvinphos = Gardona CAT3a CAT3b CAT3a 71751-41-2 Abamectin CAT3a CAT3b CAT3a 33089-61-1 Amitraz CAT3a CAT3b CAT3a 51276-47-2 Glufosinate CAT3a CAT3b CAT3a 2439-99-8 Glyphosate CAT3a CAT3b CAT3a 3554-44-0 Imazalil CAT3a CAT3b CAT3a 301-12-2 Oxydemeton-methyl CAT3a CAT3b CAT3a 19044-88-3 Oryzalin CAT3a CAT3b CAT3a 545-55-1 TEPA CAT3a CAT3b CAT3a 537-98-4 Ferulic acid (FA) CAT3a CAT3b CAT3a 104-51-8 n-Butylbenzene CAT3a CAT3b CAT3a 314-40-9 Bromacil CAT3a CAT3b CAT3a
CAS No. NAME Human health Wildlife Overall cate-
gorization 29082-74-4 Octachlorostyrene CAT3b CAT3b CAT3b 88-85-7 Dinoseb CAT3b CAT3b CAT3b 107534-96-3 Tebuconazole CAT3b CAT3b CAT3b 74115-24-5 Clofentezine = chlorfentezine CAT3b CAT3b CAT3b 119-61-9 Benzophenone CAT3b CAT3b CAT3b 76674-21-0 Flutriafol CAT3b CAT3b CAT3b NoCAS 121 Epiconazol CAT3b CAT3b CAT3b 55179-31-2 Bitertanol CAT3b CAT3b CAT3b 106-47-8 4-chloroaniline CAT3b CAT3b CAT3b 69806-50-4 Fluazifop-butyl CAT3b CAT3b CAT3b 9014-90-8 Poly(oxy-1,2-ethanediyl), alpha-
sulfo-omega-nonylphenoxy CAT3b CAT3b CAT3b
88671-89-0 Myclobutanil CAT3b CAT3b CAT3b
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gorization 53792-11-3 4-(4-Hydroxyphenyl)-2,2,6,6-
tetramethylcyclohexanecarbonacid CAT3b CAT3b CAT3b
23950-58-5 Pronamide CAT3b CAT3b CAT3b 85535-86-0 Long chain chlorinated paraffins CAT3b CAT3b CAT3b 117-84-0 1,2-Benzenedicarboxylic acid, dioctyl
ester CAT3b CAT3b CAT3b
1335-87-1 Halowax 1014 CAT3b CAT3b CAT3b 117-84-0 Di-n-octylphthalate (DnOP) CAT3b CAT3b CAT3b 103-23-1 Bis(2-ethylhexyl)adipate CAT3b CAT3b CAT3b 135-19-3 2-Naphthol CAT3b CAT3b CAT3b NoCAS 027 2,2,6,6-Tetramethyl-4,4-bis(4-
hydroxyphenyl)-n-heptan CAT3b CAT3b CAT3b
82-68-8 Pentachloronitrobenzene (PCNB) CAT3b CAT3b CAT3b 80844-07-1 Ethofenprox CAT3b CAT3b CAT3b 2717-05-5 Heptaoctatrikosan-1-ol, 23-
(nonylphenoxy)3,6,9,12,15,18,21-nonylphenolmonoethoxylate
CAT3b CAT3b CAT3b
4685-14-7 Paraquat = 1,1'-dimethyl-4,4'-bipyridinium
CAT3b CAT3b CAT3b
60207-90-1 Propiconazole CAT3b CAT3b CAT3b 108-05-4 Vinyl acetate CAT3b CAT3b CAT3b 120068-37-3 Fipronil CAT3b CAT3b CAT3b 66230-04-4 Esfenvalerate CAT3b CAT3b CAT3b 119446-68-3 Difenoconazole CAT3b CAT3b CAT3b 142-59-6 Nabam CAT3b CAT3b CAT3b NoCAS 008 Epoxiconazole CAT3b CAT3b CAT3b 117718-60-2 Thiazopyr CAT3b CAT3b CAT3b 29091-21-2 Prodiamine CAT3b CAT3b CAT3b 66246-88-6 Penconazole CAT3b CAT3b CAT3b 68-12-2 Dimethylformamide (DMFA) CAT3b CAT3b CAT3b 2212-67-1 Molinate CAT3b CAT3b CAT3b 94361-07-6 Cyproconazole CAT3b CAT3b CAT3b 28994-41-4 Phenyl-2-hydroxyphenylmethane =
2-Benzylphenol = o-Benzylphenol CAT3b CAT3b
10448-09-6 Phenylheptamethylcyclotetrasiloxane [(PhMeSiO)(Me2SiO)3]
CAT3b CAT3b CAT3b
1322-97-0 Ethanol, 2-(octylphenoxy)- = Octyl-phenolethoxylate
CAT3b CAT3b CAT3b
56-33-7 Diphenyltetramethyldisiloxane PhMe2-SiOSiMe2Ph
CAT3b CAT3b
17404-44-3 Phenol, 2-(1-ethylhexyl)- CAT3b CAT3b CAT3b 1818-08-2 Phenol, 4-(1-methylheptyl)- CAT3b CAT3b CAT3b 18626-98-7 Phenol, 2-(1-methylheptyl)- CAT3b CAT3b CAT3b 26401-75-2 Phenol, 2-sec-octyl- CAT3b CAT3b CAT3b 1009-11-6 4-Hydroxy-n-butyrophenone CAT3b CAT3b 14868-03-2 Bis-OH-MDDE CAT3b CAT3b 87-26-3 2-sec-Pentylphenol = 2-(1-
Methylbutyl)phenol CAT3b CAT3b
7786-61-0 4-vinylguaiacol (4-VG) CAT3b CAT3b CAT3b 2628-17-3 4-vinylphenol (4-VP) CAT3b CAT3b CAT3b 25167-81-1 Dichlorophenol CAT3b CAT3b CAT3b 620-92-8 Bis(4-hydroxyphenyl)methane CAT3b CAT3b
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gorization 70-70-2 4-Hydroxypropiophenone CAT3b CAT3b 303-38-8 2,3-dihydroxybenzoicacid (2,3-
DHBA) CAT3b CAT3b
530-91-6 Tetrahydronaphthol-2 CAT3b CAT3b 2540-82-1 Formothion CAT3b CAT3b 70393-85-0 Glufosinate-ammonium CAT3b CAT3b 114369-43-6 Fenbuconazole CAT3b CAT3 25550-58-7 Dinitrophenol CAT3b CAT3b 79-44-7 Dimethyl carbamyl chloride CAT3b CAT3b 490-79-9 2,5-dihydroxybenzoicacid (2,5-
DHBA) CAT3b CAT3b
949-13-3 Phenol, 2-octyl- CAT3b CAT3b CAT3b 463-56-9 Thiocyanate CAT3b CAT3b 53-96-3 n-2-fluorenylacetamide CAT3b CAT3b 1222-05-5 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-
hexamethylcyclopenta(g)-2-benzopyrane
CAT3b CAT3b CAT3b
13171-00-1 4-Acetyl-1,1-dimethyl-6-tert.-butylindane
CAT3b CAT3b
33704-61-9 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)indanone
CAT3b CAT3b CAT3b
118-56-9 3,3,5-trimethyl-cyclohexyl salicilate CAT3b CAT3b CAT3b 533-73-3 Hydroxyhydroquinone CAT3b CAT3b 27214-47-7 Phenol, 4-sec-octyl- CAT3b CAT3b 24362-98-9 1,1-Bis(4-hydroxyphenyl)-n-hexane CAT3b CAT3b 3373-03-3 1,1-Bis(4-hydroxyphenyl)-n-heptane CAT3b CAT3b 90-15-3 1-Naphthol CAT3b CAT3b 1125-78-6 5,6,7,8-Tetrahydro-2-naphthol = 6-
Hydroxytetralin CAT3b CAT3b
15231-91-1 6-Bromo-2-naphthol CAT3b CAT3b 682-80-4 Demefion CAT3b CAT3b CAT3b 21245-02-3 2-ethyl-hexyl-4-dimethyl-
aminobenzoate CAT3b CAT3b CAT3b
52479-85-3 2,3,4,3',4',5'-Hexahydroxybenzophenon
CAT3b CAT3b
27985-70-2 Phenol, (1-methylheptyl)- CAT3b CAT3b CAT3b 27986-36-3 Ethanol, 2-(nonylphenoxy)- CAT3b CAT3b CAT3b 3307-00-4 Phenol, 4-(1-ethylhexyl)- CAT3b CAT3b CAT3b 3307-01-5 Phenol, 4-(1-propylpentyl)- CAT3b CAT3b CAT3b 37631-10-0 Phenol, 2-(1-propylpentyl)- CAT3b CAT3b CAT3b 3884-95-5 Phenol, 2-(1,1,3,3-tetramethylbutyl)- CAT3b CAT3b CAT3b 2050-68-2 PCB 15 (4,4'-Dichlorobiphenyl) CAT3b CAT3b