appendix i - miljøstyrelsen pbt... · shc/ts 2-3/0304 annex 4. high production volume pbs...

SHC/TS 2-3/030 1

Appendix I

To

Identification of potential PBTs and vPvBs by use of

QSARs.

NB: Annex 1 and Annex 2 are included in the paper: "Identification of potential

PBTs and vPvBs by use of QSARs."

Annex 3

High production Volume PBs according to P-selection 2 and BCF-Connell

Annex 4: QSAR-predictions and IUCLID: High production Volume PBs identified by QSAR compared to ECB automated PB selection

on IUCLID data (including summary)

Annex 5:

Number of substances selected according to P-selection 1 and 2 and Log Kow

Annex 6: Persistency: Usefulness of QSARs for prediction of persistency of vP and P.

Annex 7: Bioaccumulation potential of HPVC. Details of Expert judgements based on the first initial expert judgement of High Production

Volume substances selected by use of P-selection 2 and BCF Connell > 2000 but not according

to P-selection 2 and BCF Syrecuse > 2000.

Annex 8: Bioaccumulation potential of MPVC

Details of Expert judgements based on the first initial expert judgement of Medium

Production Volume substances selected by use of P-selection 2 and BCF Connell > 2000 but

not according to P-selection 2 and BCF Syrecuse > 2000.

Annex 9:

VPvB/PBT-candidates with significant environmental release potential: vPvB/PBT-candidates in products marketed in Denmark, Finland, Norway or Sweden and

with a significant environmental release potential.

SHC/TS 2-3/030 2

Annex 3: High Production Volume PBs

according to P-selection 2 and BCF-Connell: P2 & 2000< BCF Connell < 5000: CAS BCF

Syracuse BCF Connell

Log Kow

Chemical

58-89-9 309 2089 4,26 Cyclohexane, 1,2,3,4,5,6-hexachloro-, (1alpha,2alpha,3beta,4alpha,5alpha,6beta)-

77-47-4 1514 4786 4,63 1,3-Cyclopentadiene, 1,2,3,4,5,5-hexachloro-

101-61-1 468 2692 4,37 Benzenamine, 4,4'-methylenebis[N,N-dimethyl-

1836-75-5 741 2399 4,32 Benzene, 2,4-dichloro-1-(4-nitrophenoxy)-

2303-17-5 398 4169 4,57 Carbamothioic acid, bis(1-methylethyl)-, S-(2,3,3-trichloro-2-propenyl) ester

5216-25-1 631 3981 4,54 Benzene, 1-chloro-4-(trichloromethyl)-

51338-27-3 724 3981 4,54 Propanoic acid, 2-[4-(2,4-dichlorophenoxy)phenoxy]-, methyl ester

61260-55-7 513 3090 4,43 1,6-Hexanediamine, N,N'-bis(2,2,6,6-tetramethyl-4-piperidinyl)-

68937-41-7 16 4786 9,07 Phenol, isopropylated, phosphate (3:1)

NB Please note that 77-47-4 (hexachlorocyclopentadiene) is a substance on the 4th

priority list

P & BCF Connell > 5000:

CAS BCF Syracuse

BCF Connell

Log Kow

Chemical

50-29-3 41687 45709 6,79 Benzene, 1,1'-(2,2,2-trichloroethylidene)bis[4-chloro-

79-94-7 13490 43652 7,20 Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo-

87-68-3 955 5754 4,72 1,3-Butadiene, 1,1,2,3,4,4-hexachloro-

101-20-2 1175 7943 4,90 Urea, N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)-

115-32-2 1479 28184 5,81 Benzenemethanol, 4-chloro-alpha-(4-chlorophenyl)-alpha-(trichloromethyl)-

117-08-8 759 5012 4,65 1,3-Isobenzofurandione, 4,5,6,7-tetrachloro-

118-74-1 5129 29512 5,86 Benzene, hexachloro-

118-82-1 43 5623 8,99 Phenol, 4,4'-methylenebis[2,6-bis(1,1-dimethylethyl)-

119-47-1 4571 25704 7,97 Phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-

128-69-8 13183 38905 6,26 Perylo[3,4-cd:9,10-c'd']dipyran-1,3,8,10-tetrone

133-49-3 7079 30903 5,91 Benzenethiol, pentachloro-

2312-35-8 1413 21878 5,57 Sulfurous acid, 2-[4-(1,1-dimethylethyl)phenoxy]cyclohexyl 2-propynyl ester

5102-83-0 10 22387 8,11 Butanamide, 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2,4-dimethylphenyl)-3-oxo-

5468-75-7 10 45709 7,02 Butanamide, 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2-methylphenyl)-3-oxo-

5567-15-7 10 26915 7,94 Butanamide, 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(4-chloro-2,5-dimethoxyphenyl)-3-oxo-

6358-85-6 10 45709 7,05 Butanamide, 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-N-phenyl-

39489-75-3 2951 18197 5,42 Phenol, 2,4-dichloro-5-nitro-, carbonate (2:1) (ester)

41556-26-7 1349 45709 6,92 Decanedioic acid, bis(1,2,2,6,6-pentamethyl-4-piperidinyl) ester

70660-55-8 10 38905 6,24 1-Naphthalenamine, 4-[(2-bromo-4,6-dinitrophenyl)azo]-N-(3-methoxypropyl)-

NB Please note that 79-94-7 (tetrabromobisphenol) is a substance on the 4th

priority list

Use categories of the above substances should be checked (e.g. according to IUCLID and data from

Nordic / the Danish Product Register)

SHC/TS 2-3/030 3

Annex 3 (cont.):

High Production Volume PBs

according to P-selection 2 and BCF-Syracuse:

P & 2000< BCF Syracuse < 5000:

CAS BCF Syracuse

BCF Connell

Log Kow

Chemical

119-47-1 4571 25704 7,97 Phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-

39489-75-3 2951 18197 5,42 Phenol, 2,4-dichloro-5-nitro-, carbonate (2:1) (ester)

P & BCF Syracuse > 5000:

CAS BCF Syracuse

BCF Connell

Log Kow

Chemical

50-29-3 41687 45709 6,79 Benzene, 1,1'-(2,2,2-trichloroethylidene)bis[4-chloro-

79-94-7 13490 43652 7,20 Phenol, 4,4'-(1-methylethylidene)bis[2,6-dibromo-

118-74-1 5129 29512 5,86 Benzene, hexachloro-

128-69-8 13183 38905 6,26 Perylo[3,4-cd:9,10-c'd']dipyran-1,3,8,10-tetrone

133-49-3 7079 30903 5,91 Benzenethiol, pentachloro-

NB Please note that 79-94-7 (tetrabromobisphenol) is a substance on the 4th

priority list

SHC/TS 2-3/030 4

Annex 4. High Production Volume PBs identified by QSAR compared to ECB

automated PB selection on IUCLID data.

A very first preliminary comparison based on the first check of the available experimental IUCLID

data (has to be checked, whether it also contains certain QSAR data !) and the QSAR selections

presented above (cf. Annex 3) indicates the following:

Of the 28 HPVC selected in the QSAR P-selection 2 by the BCF Connell model (BCF > 2000)

two substances are also selected based on experimental IUCLID data: hexachlorobenzene &

hexachlorobutadiene.

6 HPVC are furthermore selected based on IUCLID, but not according to the QSAR-selection. The

substances are mentioned below, with an indication of why it was not selected by using the QSAR-

selection method:

Two anthracene derivatives. Not selected by QSARs due to lack of a discrete chemical

structure, i.e. not included in the QSAR exercise

TBTO. Not selected because organo-metals cannot in general be predicted reliably by the

QSARs and thus not included in the QSAR exercise

Sodium acetate - this IUCLID based selection must be wrong !

Dodecylphenol is not predicted to be highly persistent (BIOWIN2 = 0.9, MITIDEG 2 = 0.527

and BIOWIN 3 = 2.9) and possibly also not highly bioaccumulative due to metabolisation

(BCF-Syracuse = 478 (substances with a long aliphatic carbon chain are based on empirical

BCF-data predicted to be much less bioaccumulated than predicted by their high log Kow and

are treated as a special chemical class in the Syracuse model ( cf. Meyland W.M. et al. (1999):”

Improved Method for Estimating Bioconcentration/Bioaccumulation Factor from Octanol/Water

Partitioning Coefficient” Environ. Toxicol. Chem. 18(4), 664-72.), BCF-Connell = 38904, log

Kow = 7.46)

2,4,6-trichlorophenol is predicted to be highly persistent (BIOWIN2 = 0.007, MITIDEG 2 =

0.04 & BIOWIN 3 = 2.199) but not bioaccumulative (BCF-Syracuse = 54; BCF-Connell = 223

& log Kow = 3.45)

The data quality (experimental as well as the QSAR predictions) of the latter two substances should

be checked.

Of the residual 26 substances identified as potential PBTs or vPvBs by using QSARs but not by

data in IUCLID:

13 substances have neither B- nor P-data in IUCLID

6 substances have only B- but no P-data in IUCLID

5 substances have P but no B-data in IUCLID

and

for one substance (triallate (CAS 2303-17-5) ) both P- and B-data are available in IUCLID, but do

not clearly indicate that the P- and B-criteria are fulfilled

and

for another substance (tetrabromobisphenol-A (CAS 79-94-7)) both P- and B-data are available in

IUCLID, but the B-data do not fulfill the B-criterion (BCF> 2000)

SHC/TS 2-3/030 5

Annex 4 (cont.) High Production Volume PBs identified by QSAR compared to ECB automated

PB selection on IUCLID data P

1

(core) B

Fejl!

Ukendt

argument for

parameter.

(core)

CAS BPP2 BPP3 BCFSYR BCFCON Name

PB-substances according to IUCLID data and QSAR

2 2 87683 0,00 1,58 955 5754 Hexachlorobuta-1,3-diene

2 2 118741 0,00 1,33 5129 29512 Hexachlorobenzene

Substances PB according to QSAR but not P or not B according to IUCLID

2 0 79947 0,00 1,35 13490 43652 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol

2 -1 133493 0,00 1,54 7079 30903 Pentachlorobenzenethiol

2 -1 5567157 0,00 -0,17 10 26915 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(4-chloro-2,5-dimethoxyphenyl)-3-oxobutyramide]

2 -1 41556267 0,00 1,00 1349 45709 Bis(1,2,2,6,6-pentamethyl-4-piperidyl)$sebacate

2 -1 61260557 0,01 1,58 513 3090 N,N'-bis(2,2,6,6-tetramethylpiperidin-4-yl)hexane-1,6-diamine

0 0 2303175 0,00 1,96 398 4169 Tri-allate

0 -1 68937417 1,00 2,13 16 4786 Phenol,$isopropylated,$phosphate$(3:1)

-1 2 115322 0,00 1,02 1479 28184 Dicofol

-1 1 50293 0,00 1,20 41687 45709 Clofenotane

-1 1 1836755 0,00 1,93 741 2399 Nitrofen

-1 0 58899 0,00 1,52 309 2089 Gamma-HCH$or$gamma-BHC

-1 0 77474 0,00 1,35 1514 4786 Hexachlorocyclopentadiene

-1 0 2312358 0,19 2,15 1413 21878 Propargite

Substances PB according to QSAR with no data in IUCLID

-1 -1 101202 0,00 1,88 1175 7943 Triclocarban

-1 -1 101611 0,01 2,05 468 2692 N,N,N',N'-tetramethyl-4,4'-methylenedianiline

-1 -1 117088 0,00 1,74 759 5012 Tetrachlorophthalic$anhydride

-1 -1 118821 0,00 1,45 43 5623 2,2',6,6'-tetra-tert-butyl-4,4'-methylenediphenol

-1 -1 119471 0,15 1,91 4571 25704 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol

-1 -1 128698 0,00 1,53 13183 38905 Perylene-3,4:9,10-tetracarboxylic$dianhydride

-1 -1 5102830 0,00 0,22 10 22387 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2,4-dimethylphenyl)-3-oxobutyramide]

-1 -1 5216251 0,00 1,75 631 3981 Alpha,alpha,alpha,4-tetrachlorotoluene

-1 -1 5468757 0,00 0,43 10 45709 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2-methylphenyl)-3-oxobutyramide]

-1 -1 6358856 0,00 0,68 10 45709 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-N-phenylbutyramide]

-1 -1 39489753 0,00 1,06 2951 18197 Bis(2,4-dichloro-5-nitrophenyl)$carbonate

-1 -1 51338273 0,94 2,06 724 3981 Methyl$2-(4-(2,4-dichlorophenoxy)phenoxy)propionate

-1 -1 70660558 0,00 1,20 10 38905 4-[(2-bromo-4,6-dinitrophenyl)azo]-N-(3-methoxypropyl)naphthalen-1-amine

Please note that the basis for this comparison is the substances selected by P-selection 2 and a predicted BCF-Connell >

2000, because this gives the highest number of selected substances. We suggest however to modify this method of

selection as described in the text.

1 The first two columns indicate fulfilment of P and B-criteria (>2000) on the basis of IUCLID data in an automated

data retrieval and evaluation routine performed by ECB (2001). A negative value indicates no test available. Zero

indicates that available test data do not fulfil criteria (for P or B). Positive values indicate that available test data do

fulfil the criteria.

SHC/TS 2-3/030 6

Annex 4 (cont.).

Summary of provisional comparison of QSAR-

and IUCLID-data retrieval based PB-selections of HPVC

QSAR: IUCLID: No. of PB-HPVC2 Comments:

Yes Yes 1 - 2

Yes No 1 - 6 * Data quality to be checked

Yes No P and/or

no B data 24** Check data availability

beyond IUCLID

No Yes 2 3 Data quality to be checked

* one substance not fulfilling P according to IUCLID but QSAR based on P-selection 2 and BCF <

2000 according to IUCLID but QSAR Bs & Bc > 2000

5 substances no IUCLID P data, QSAR based P-selection 2 fulfilled & BCF < 2000 according to

IUCLID but QSAR Bc > 2000 - however Bs < 2000.

** For substances with either experimental P or B data: available experimental P data (IUCLID)

agreed with QSAR P-selection 2 in four out of a total of five cases and experimental B data

(IUCLID) agreed with Bs -predictions in three and all cases, whereas Bc predictions disagreed.

2 The number of selected substances differs depending on the employed BCF model - in all cases here P-selection 2 was

performed (cf. the text) 3 3 more substances were not covered by the QSAR selection and one more substance had obviously unreliable data in

IUCLID that indicate, that this substance is a PB-candidate (cf. the text)

SHC/TS 2-3/030 7

Annex 5.

Number of substances selected according to P-selection 1 and

2 and Log Kow:

EINECS: MPVC: HPVC: P-selection 1 : ( )

& log Kow > 4:

(6906)

3593

(623)

369

(91)

39

P-selection 1

& 4<log Kow<5:

1084

119

15

P-selection 1

& log Kow > 5:

2509

250

24

P-selection 2 : ( )

& log Kow > 4:

(7666)

4029

(730)

401

(97)

41

P-selection 2

& 4< log Kow< 5:

1195

131

16

P-selection 2

& log Kow > 5:

2834

270

25

Note that the total number of substances selected by P-selection 1 and 2 respectively appears

in parentheses in the first and third row. Note also that these selection algoritms is only

included for illustrative purposes and are not preferred.

SHC/TS 2-3/030 8

Annex 6

Persistency:

Usefulness of QSARs for prediction of persistency of vP and P. Doubts have been expressed regarding the usefulness of employing the suggested QSARs for

prediction of vPs and P. The main arguments were that,

whereas the combination of QSARs (BIOWIN 2 and MITIDEG 2) employed in P-selection 2

limits the number of false predictions of not ready biodegradable substances, it may still exclude

identification of a very high percentage of not ready biodegradable substances.

BIOWIN 3 has not been externally validated and should be left out from use. Thus an option

would be if QSARs can be used at all to use P-selection 5 instead of the recommended one, P-

selection 2.

It has also been doubted whether QSARs for degradability may be needed at all, because a

requirement for experimental ready biodegradability tests on all substances > 1 tpa may be

decided (cf. the work of the testing and assessment working group).

Response:

1) If a requirement of ready biodegradability testing is later on decided for all substances > 1 tpa,

then it will still only be possible to distinguish between ready and not ready degradable

substances. Acquiring such degradability data on ALL substances > 1 tpa may realistically also

take a considerable number of years. In relation to doubt of the usefulness of employing QSARs

for predicting potential vP/ Ps, it could be asked: what is the alternative ?

2) It has furthermore to be realised that the purpose of the QSAR prediction is NOT to identify all

not readily degradable substances, but to identify those of the not readily degradable

substances with a sufficiently long half-life for mineralisation that they should be regarded as

potentially fulfilling the vP- and P-criteria. That is why the two QSAR-models for predicting

not ready biodegradability are combined with the model for prediction of a long mineralisation

half-life.

3) The number of substances falsely excluded by the QSARs for prediction of not ready

biodegradability for BIOWIN 2 and MITIDEG 2 has been summarised in relation to external

validations (cf. p. 7-8). Furthermore our own external validation study (referred to on p. 7) has

been circulated to the TGD rev. working group for information. Based on this it is obvious that

for one of the models the number of exclusions by using only one of the models are around 50

%, whereas for the other one it is around 20 %. When these two models are used in combination

however, the percentage of excluded not readily biodegradable substances will be significantly

lower ! So even if the purpose is to identify the not readily biodegradable substances, the

percentage of the wrongly excluded substances would be considerably lower than for

application of each of the models individually.

4) This is also obvious from a special exercise we have made now due to the doubts expressed:

We have investigated the number of identified not readily biodegradable substances using the

QSAR models on the updated and extended MITI I database: cf. the table below:

Number of substances in the MITI database: 894 substances

Number of substances in the MITI database

with a discrete structure (and thus a SMILES): 850 substances

SHC/TS 2-3/030 9

Number of substances:

MITI I: number of

experimentally not readily deg.:

449 % of not readily degradable substances identified by

the QSARs:

BIOWIN 2 < 0.5: 252 56 %

MITIDEG 2 < 0.5: 390 87 %

BIOWIN 2<0.5 or

MITIDEG 2<0.5:

403 90 %

It is obvious that the use of the combination of BIOWIN 2 and MITIDEG 2 is identifying the

highest percentage of the not readily biodegradable substances. Use of MITIDEG 2 alone has

however almost the same high percentage of identification of the not readily biodegradable

substances. Use of the combination of models is however not more complicated to do than

using the MITIDEG 2 model alone, and because of this the slightly better performance of the

use of BIOWIN 2 and MITIDEG 2 in combination is preferred.

Please note that the BIOWIN-models were NOT created based on the endpoint ready

biodegradability but rather on the endpoint rapid biodegradability, whereas MITIDEG-models

were created for prediction of biodegradability in the MITI I test.

If the substances included in this exercise are representative for all EINEC substances, only

around 10 % of the not readily biodegradable substances are NOT identified by using the

combination of BIOWIN 2 and MITIDEG 2 as done in P-selection 2. It is however emphasised

that P-selection 2 by intention in addition employed BIOWIN 3 prediction of a long

mineralisation half-life (cf. point 2 above) and that the final PB selection 2 is also heavily

influenced by the use of BCF-models.

5) In relation to the use of the combination of QSAR-models for

prediction of vP and P, we have also now investigated how often the prediction regarding ready

biodegradability is in discrepancy with the QSAR used for predicting a long mineralisation half-

life (the table indicates number of substances, the total number of substances on EINECS, the

MPVC- and HPVC- lists which are included in this modelling exercise

EINECS

(46706)

MPVC:

(4165)

HPVC:

(1351)

BIOWIN 2>0.5 and MIDEG 2>0.5

31515

1458

578

(BIOWIN 2 > 0.5 and MITIDEG2 > 0.5) and

BPP3 < 2.2

249

5

5

% of substances predicted readily degradable

also predicted having a long mineralisation

half-life:

0.8 %

0.3 %

0.4 %

NB: It is noted that the negation of the algorithm (BIOWIN 2 <0.5 or MITIDEG 2 < 0.5) is the algorithm (BIOWIN 2 >

0.5 and MITIDEG 2 > 0.5)

The percentages of substances which are excluded in P-selection 2 that has been employed also

include substances predicted to have a long mineralisation half-life, but which are at the same

time predicted of being readily biodegradable (cf. the table above). The substances with such

conflicting predictions have been excluded from being regarded as fulfilling the persistency

criterion. Of course it cannot be documented based on experimental evidence, which of these

conflicting predictions are wrong simply because experimental data on mineralisation half-life

in the environment are not available. It is however most likely that the prediction of a long

mineralisation half-life is wrong in these cases, because the model for mineralisation half-life

has not been externally validated contrary to the models relating to ready biodegradability.

When the latter two models are used in combination as has been done to identify potential

SHC/TS 2-3/030 10

vPvBs and PBTs, it is furthermore obvious that the number of falsely excluded not readily

biodegradable substances is low indeed (cf. point 4 above).

In conclusion: the very low percentages of conflicting predictions between the models used

for prediction of not ready biodegradability (BIOWIN 2 and MITIDEG 2) and the model

for prediction of long mineralisation half-life (BIOWIN 3) gives an overall confidence in

the P-selection 2 algorithm used for identification of vPs and Ps.

6) In relation to the models for prediction of ready biodegradability it should be kept in mind that

the endpoint ready biodegradability only relates to the result from an experimental screening test

of the potential for rapid degradability. Substances which are toxic to bacteria at the high

concentration of the test substance which are used in these screening tests for ready

biodegradability comes out as being not readily biodegradable, simply because the test substance

inhibit the bacteria, and thus the degradation in the test system. According to experience however

such substances may be rapidly biodegradable at environmentally realistic low concentrations.

Thus the model BIOWIN 2 which has been developed for identification of rapid biodegradation

may "rightly" exclude some of the rapidly biodegradable substances which are not readily

biodegradable due to toxicity only.

7) A new not yet published data analysis on more than 300 new substances notified to the US EPA

indicates that application of BIOWIN 3 just as BIOWIN 2 and MITIDEG 2 employed here also

identifies not readily biodegradability reliably (Bob Boethling,, USEPA, pers. com.).

8) Finally the use of these QSARs4 for prediction of vP & P has been agreed after lengthy

discussions in an OSPAR working group and the TGD rev. working group. It furthermore seems

that there is general acceptance to use the text of the marine TGD in relation to the vPvB and

PBT issues, including the use of QSARs and experimental screening data.

4 and in particular a validated BIOWIN-model for prediction of not ready biodegradability and the BIOWIN 3-model

for prediction of long environmental half-life

SHC/TS 2-3/030 11

Annex 7 Bioaccumulation potential of HPVC

Details of Expert judgements based on the first initial expert judgement of High

Production Volume substances selected by use of P-selection 2 and BCF Connell

> 2000 but not according to P-selection 2 and BCF Syrecuse > 2000.

The following pages contain only output reports from Multicase META PC v. 1.0 estimates of

mammalian metabolism including percent, SMILES and LogP estimates for the first breakdown

products. Only the first step is included (e.g. each metabolite is not followed all the way to the final

excretion product.)

The predictions are followed by expert judgements in bold type:

The first expert performed the evaluation initially on all substances selected by P-selection 2 and

BCF-Connell > 2000 but not BCF_Syracuse > 2000 as described in the section on Comparison of

B-selections.

Then the second expert made his evaluation on the substances indicated by the first expert to be

potentially resistant to biotransformation. Where the results seemed equivocal, this is presented as

“Partial” meaning that a conclusion could not be reached, or “Partial no significant” where initial

metabolism seemed likely to lead to a product that was still accumulative.

After this the experts went through two rounds of fine tuning the expert judgements focussing on

judgements that differed. The final judgement of the two experts is indicated in bold types.

For these high volume chemicals, the structures of the initial metabolites are also shown for

illustration.

SHC/TS 2-3/030 12

% META log file

Employed database: Mammal

-----------------------

Results for compound N1 (line #1): 58-89-9

S3. C6H5OCl5 Smiles Code: ClC1C(C(C(C(C1Cl)=O)Cl)Cl)Cl

MW = 270.371 log P: 3.05 Yield: 100.00%

s4. Cl- Smiles Code: MW = 35.453 log P: N/A Yield: 100.00%

(Expert 1: Metabolizes)

(Expert 2: Connell OK = no metabolism, substance is lindane !)

(Expert 1: O.K. as a PBT by me! But mammals dechlorinate it by P450 monooxygenase)

(Expert 2: no further comments)

Cl

Cl

Cl

Cl

Cl

Cl

S3

O

Cl

Cl

Cl

Cl

Cl

S4-Cl

________________________________________________________________________________

________________

SHC/TS 2-3/030 13



[10.3.1-2] GSH conjugation of benzylic/allylic halides

[20.2] Non-specific hydration and opening of aziridine rings


S2. C5SCl5SG

Smiles Code: ClC1=C(C(S(CC(C(=O)NCC(=O)O)NC(=O)CCC(N)C(=O)O))(Cl)C(Cl)=C1Cl)Cl

MW = 577.932 log P: 0.81 Yield: 11.45%


S4. C5OCl4 Smiles Code: ClC1=C(C(C(Cl)=C1Cl)=O)Cl

MW = 217.867 log P: 2.41 Yield: 8.41%



(Expert 2: inbetween = partial or not significant metabolism)

(Expert 1: Dechlorination by glutathione transferases and hydrolysis. But one of first

metabolites (S4) is highly resonant and may cycle, so I agree with “partial or not significant”)


Cl

ClCl

Cl

Cl

Cl

S3-Cl

S2

S

SG

Cl

Cl

Cl

Cl

Cl

S4 Cl

O

Cl

Cl

Cl

________________________________________________________________________________

________________

SHC/TS 2-3/030 14




[5.11-18] Reduction of terminal aliphatic trihalides

[0.6.7-8] Decomposition of "beta-aminonitroso"



S7. C14H8OCl4

Smiles Code: ClC1=CC=C(C=C1)C1(C(O1)(Cl)Cl)C1=CC=C(C=C1)Cl

MW = 334.031 log P: 5.82 Yield: 15.52%

[0.6.7-8] Decomposition of "beta-aminonitroso"

S2. C14H8OCl5C6H9O6

Smiles Code:

ClC1=CC=C(C=C1)C(C(Cl)(Cl)Cl)(C1=CC=C(C=C1)Cl)O(C%99C(O)C(O)C(O)C(C(=O)O)O%9

9)

MW = 547.265 log P: 2.26 Yield: 7.92%

[11.2.1] Glucuronic O-conjugation: alkyl alcohol

S4. C14H9O2Cl3

Smiles Code: ClC1=CC=C(C=C1)C(C(Cl)=O)(C1=CC=C(C=C1)Cl)O

MW = 315.586 log P: 4.23 Yield: 7.92%


(Expert 1: Only partial or no significant metabolism)

(Expert 2: Connell OK = no metabolism, substance is dicofol !)

(Expert 1: Some metabolism, but slow and still a PTB)


HO

Cl

Cl

Cl

Cl

Cl

S4-Cl

S3

O Cl

Cl

Cl

Cl

S5

HO

Cl

O

Cl

Cl

S2

OC6H9O6

Cl

Cl

Cl

Cl

Cl

________________________________________________________________________________

________________

SHC/TS 2-3/030 15


S4. C29H43O2C6H9O6

Smiles Code:

OC1=C(C(C)(C)C)C=C(C=C1C(C)(C)C)CC1=CC(C(C)(C)C)=C(C(C(C)(C)C)=C1)O(C%99C(O)

C(O)C(O)C(C(=O)O)O%99)

MW = 601.445 log P: 5.34 Yield: 34.32%

[11.2.2] Gluc acid O-conjugation of aryl/vinyl alcohols

S2. C29H44O3

Smiles Code:

OC1=C(C(C)(C)C)C=C(C=C1C(C)(C)C)C(O)C1=CC(C(C)(C)C)=C(C(C(C)(C)C)=C1)O

MW = 440.672 log P: 8.61 Yield: 25.21%

[0.7.1.7-9] Double keto to enol tautomerization

S5. C29H44O5S

Smiles Code:

OC1=C(C(C)(C)C)C=C(C=C1C(C)(C)C)CC1=CC(C(C)(C)C)=C(C(C(C)(C)C)=C1)OS(O)(=O)=O

MW = 504.735 log P: 8.45 Yield: 25.21%

[12.2] O-sulfation of aryl/vinyl alcohols



(Expert 1: I don’t really trust my prediction – so “partial or not significant” is o.k. but this is

a very bulky structure that may not cross cell membranes.)

(Expert 2: no further

comments)

H

O

O

H

root: S1

S

3

H

OO

C6H9

O6

root: S1

S

2

H

O

O

H

O

H

root: S1

S

4

O

S

H

O

O

O

root: S1

________________________________________________________________________________

________________

SHC/TS 2-3/030 16


S11. C7H10ONSCl3 Smiles Code: ClC(CSC(NC(C)C)=O)=C(Cl)Cl

MW = 262.587 log P: 2.99 Yield: 50.72%

S12. C3H6O Smiles Code: C(C)(C)=O MW = 58.081 log P: 0.27

Yield: 50.72%

S9. C3HOCl3 Smiles Code: ClC(C=O)=C(Cl)Cl MW = 159.400

log P: 1.85 Yield: 13.10%

S10. C7H15ONS Smiles Code: SC(N(C(C)C)C(C)C)=O MW = 161.268

log P: 1.56 Yield: 13.10%

S13. C3H3SCl3 Smiles Code: ClC(CS)=C(Cl)Cl MW = 177.480

log P: 3.16 Yield: 12.05%

S7. C6H15N Smiles Code: N(C(C)C)C(C)C MW = 101.193

log P: 1.41 Yield: 12.05% [7] Hydrolysis of any amide

s14. CO2 Smiles Code: C(=O)=O MW = 44.010 log P: 1.43

Yield: 12.05%

S8. C10H16ONS2Cl2SG

Smiles Code:

ClC(CSC(N(C(C)C)C(C)C)=O)=C(S(CC(C(=O)NCC(=O)O)NC(=O)CCC(N)C(=O)O))Cl

MW = 609.826 log P: 0.90 Yield: 6.02%

[10.3.4] GSH conjugation of dichloroalkenes


(Expert 2: agrees with Expert 1)

Cl

SN

ClCl

O

S11 Cl

SNH

ClCl

O

S12

O

S9

Cl

Cl

ClO

S10

SH

N

O

S13

Cl

SH

Cl

Cl

S5

NH

S14

O

C

O

S6

Cl

S

SN Cl

SG

O

________________________________________________________________________________

________________

SHC/TS 2-3/030 17


S2. C4SCl5SG

Smiles Code: C(Cl)(S(CC(C(=O)NCC(=O)O)NC(=O)CCC(N)C(=O)O))=C(C(Cl)=C(Cl)Cl)Cl

MW = 565.920 log P: 1.37 Yield: 100.00%

[10.3.4] GSH conjugation of dichloroalkenes


Cl

ClCl

Cl Cl

Cl

S2 Cl

S

SG

Cl

Cl Cl

Cl

________________________________________________________________________________

________________

Results for compound N7 (line #7): 117-08-8: (No metabolism)

(Expert 1: No metabolisation)


(Expert 1: Wouldn’t make much difference, but what would the partial metabolit(s) be?)

(Expert 2: I thought the double bonds could be attacked by epoxidation, be it at a slow rate…)

________________________________________________________________________________

________________

SHC/TS 2-3/030 18








S2. C7H4SCl3SG

Smiles Code: ClC1=CC=C(C=C1)C(S(CC(C(=O)NCC(=O)O)NC(=O)CCC(N)C(=O)O))(Cl)Cl

MW = 535.080 log P: 0.84 Yield: 10.52%


S4. C7H4OCl2 Smiles Code: ClC1=CC=C(C=C1)C(Cl)=O

MW = 175.015 log P: 2.23 Yield: 7.73%


S5. C7H5Cl3 Smiles Code: ClC1=CC=C(C=C1)C(Cl)Cl MW = 195.477

log P: 3.44 Yield: 5.92%




(Expert 1: It is removal of the first chlorine atom from the methyl group by glutathione

transferase that is critical. I believe it will occur. After that the path to soluble excretion

products is quite straightforward.)

(Expert 2: again it is the rate that made be judge the substance as ‘inbetween’, I do not

question the metabolic pathway and agree in that with Expert 1)

Cl

Cl

Cl

Cl

S3-Cl

S4

Cl

O

Cl

S2

S

SG

Cl

Cl

Cl

S5

Cl

Cl

Cl

________________________________________________________________________________

_______________

SHC/TS 2-3/030 19


S4. C27H33O5P

Smiles Code:

P(OC1=CC=CC(C(C)C)=C1)(OC1=CC(C(CO)C)=CC=C1)(OC1=CC=CC(C(C)C)=C1)=O

MW = 468.535 log P: 5.59 Yield: 48.64%

[0.7.1] General enol-keto tautomerization


S3. C27H33O5P

Smiles Code:

P(OC1=CC=CC(C(C)C)=C1)(OC1=CC(C(O)(C)C)=CC=C1)(OC1=CC=CC(C(C)C)=C1)=O

MW = 468.535 log P: 5.90 Yield: 40.20%



(Expert 1: Partial or no significant metabolism)


O

P O

O

O

S4

O

P O

O

OH

O

S3

O

P O

O

OH

O

S2

O

P O

O

OH O

________________________________________________________________________________

________________

SHC/TS 2-3/030 20

Annex 8 Bioaccumulation potential of MPVC

Details of Expert judgements based on the first initial expert judgement of

Medium Production Volume substances selected by use of P-selection 2 and BCF

Connell > 2000 but not according to P-selection 2 and BCF Syrecuse > 2000.

Multicase META PC v. 1.0 predictions for mammalian metabolism for medium production volume chemicals. See

Annex 6 on HPV chemicals for explanation. In this Annex figures of metabolic pathway figures have not been included.

% META log file

Employed database: Mammal

-----------------------

Results for compound N1 (line #1): 115-27-5 s3. Cl- Smiles Code: MW = 35.453 log P: N/A Yield: 100.00%

[0.4.4] Decomposition of nitrosocarbinolamine



S2. C9HO3Cl5

Smiles Code: ClC1=C(C2(C3C(OC(C3=C1C2(Cl)Cl)=O)=O)Cl)Cl

MW = 334.371 log P: 1.86 Yield: 22.55%

[0.4.4] Decomposition of nitrosocarbinolamine

(Expert 1: Partial or no significant)

(Expert 2: Connell OK = partial or not significant metabolism)

Results for compound N2 (line #2): 626-39-1 (No metabolism)

(Expert 1: No metabolism)

(Expert 2: Connell OK = no metabolism)

Results for compound N3 (line #3): 634-66-2 S3. C6H2OCl4 Smiles Code: ClC1=C(C2C(O2)C(Cl)=C1Cl)Cl

MW = 231.894 log P: 2.99 Yield: 41.15%

[3.8.1] Epoxidation of double bond

S2. C6H2OCl4 Smiles Code: ClC1=C(C=C(O)C(Cl)=C1Cl)Cl

MW = 231.894 log P: 4.20 Yield: 32.51%

[0.7.2.1] General enamine-imine tautomerization

S4. C6H2SCl3SG

Smiles Code: ClC1=C(C=CC(S(CC(C(=O)NCC(=O)O)NC(=O)CCC(N)C(=O)O))=C1Cl)Cl

MW = 521.053 log P: 1.01 Yield: 26.34%

[10.6.4] Substitution of activated vinyl/aryl halide by GSH


(Expert 2: Connell OK = partial or not significant metabolism NB this compound is tetrachlorobenzene)

(Expert 1: This is 1,2,3,4-terachlorobenzene which should metabolize via P450 hydroxylation and epoxidation

leading to soluble products. The other isomers of tetrachlorobenzene won’t metabolize.)

(Expert 2: still I wonder how fast the metabolism will take place, I do agree that it will take place, but doubt the

rate and extent!)

SHC/TS 2-3/030 21

Results for compound N4 (line #4): 13014-24-9 s3. Cl- Smiles Code: MW = 35.453 log P: N/A Yield: 96.88%







S2. C7H3SCl4SG

Smiles Code: ClC1=CC=C(C=C1Cl)C(S(CC(C(=O)NCC(=O)O)NC(=O)CCC(N)C(=O)O))(Cl)Cl

MW = 569.525 log P: 1.50 Yield: 8.66%


S4. C7H3OCl3 Smiles Code: ClC1=CC=C(C=C1Cl)C(Cl)=O

MW = 209.460 log P: 2.90 Yield: 6.36%


S5. C7H4Cl4 Smiles Code: ClC1=CC=C(C=C1Cl)C(Cl)Cl

MW = 229.922 log P: 4.11 Yield: 4.87%


(Expert 1: Partial metabolism)


Results for compound N5 (line #5): 13171-00-1 S2. C17H24O2

Smiles Code: C1=C(C(C)=O)C2=C(C=C1C(C)(C)C)C(C)(C)CC2O

MW = 260.380 log P: 3.84 Yield: 27.93%


S6. C17H26O

Smiles Code: C1=C(C(O)C)C2=C(C=C1C(C)(C)C)C(C)(C)CC2

MW = 246.396 log P: 4.62 Yield: 21.38%

[5.3] Reduction of aryl/vinyl alkyl ketone (enones)

S3. C17H24O2

Smiles Code: C1=C(C(C)=O)C2=C(C=C1C(C)(C)C)C(CO)(C)CC2

MW = 260.380 log P: 3.69 Yield: 16.90%


S4. C17H24O2

Smiles Code: C1=C(C(C)=O)C2=C(C=C1C(CO)(C)C)C(C)(C)CC2

MW = 260.380 log P: 3.69 Yield: 16.90%


S5. C17H24O2

Smiles Code: C1=C(C(C)=O)C2=C(C=C1C(C)(C)C)C(C)(C)C(O)C2

MW = 260.380 log P: 3.84 Yield: 16.90%




Results for compound Nx (line #x): 14295-43-3 (No metabolism)



SHC/TS 2-3/030 22


Smiles Code: C1=C(C)C(C(C)=O)=CC2=C1C(C)(C)C(O)(C2(C)C)C

MW = 260.380 log P: 4.13 Yield: 35.04%


[0.9.1-2][0.9.6][0.9.7-8]

S3. C17H24O2

Smiles Code: C1=C(CO)C(C(C)=O)=CC2=C1C(C)(C)C(C2(C)C)C

MW = 260.380 log P: 3.83 Yield: 21.83%

[0.7.1.2-5] Tautomerization of benzylic/allylic ketone

S6. C17H26O

Smiles Code: C1=C(C)C(C(O)C)=CC2=C1C(C)(C)C(C2(C)C)C

MW = 246.396 log P: 4.76 Yield: 16.72%


S2. C17H24O2

Smiles Code: C1=C(C)C(C(C)=O)=CC2=C1C(CO)(C)C(C2(C)C)C

MW = 260.380 log P: 3.83 Yield: 13.21%


S5. C17H24O2

Smiles Code: C1=C(C)C(C(C)=O)=CC2=C1C(C)(C)C(C2(C)C)CO

MW = 260.380 log P: 3.83 Yield: 13.21%



(Expert 2: Connell OK = partial or not significant metabolism, MAY BE SOME MORE METABOLISM THAN

INITIALLY JUDGED, HOWEVER STILL DOUBTS ON FAST METABOLISM)

(Expert 1: I think you are right about “Partial or non significant.” There should be several possibilities of

monooxygenase transformation, but they don’t lead to any rapidly excretable products.)


Results for compound N7 (line #7): 37853-59-1 S3. C8H5O2Br3 Smiles Code: BrC1=CC(Br)=C(C(Br)=C1)OCC=O

MW = 372.840 log P: 3.89 Yield: 100.00%

S4. C6H3OBr3 Smiles Code: OC1=C(C=C(C=C1Br)Br)Br

MW = 330.802 log P: 4.10 Yield: 100.00%


(Expert 2: Connell OK = partial or not significant metabolism, WHAT IS ARGUMENT FOR EXPERT 1’S

JUDGEMENT)

(Expert 1: Hydroxylation of the aliphatic ether linkage should occur in mammals if it is bioavailable at all – it is

pretty insoluble, and with a theoretical (low energy conformation) length of around 13-14 Angstroms, may not

cross cell membranes.)

(Expert 2: the length is not a problem per se for prohibiting uptake across cell membranes, fatty acids up to 30-

40 Angstroms length may be taken up, the cross-section of this substances however is in my opinion small

enough to pass the membranes; regarding the hydroxylation of the ether linkage, I thought of that too, but

thought it would occur only at a slow rate because of potential shielding of the aromatic rings…)

SHC/TS 2-3/030 23

Results for compound N8 (line #8): 57018-04-9 S2. C9H11O4PSCl2

Smiles Code: ClC1=C(C(Cl)=CC2(C1O2)C)OP(OC)(OC)=S

MW = 317.129 log P: 3.73 Yield: 24.52%


S7. C8H9O3PSCl2

Smiles Code: ClC1=C(C(Cl)=CC(C)=C1)OP(O)(OC)=S MW = 287.103

log P: 3.65 Yield: 22.22%

[10.10] Glutathione detoxication phosphoroester

s9. CH2O Smiles Code: C=O MW = 30.026 log P: -0.05

Yield: 19.16%

S3. C9H11O4PSCl2

Smiles Code: ClC1=C(C2(C(O2)C(C)=C1)Cl)OP(OC)(OC)=S

MW = 317.129 log P: 3.73 Yield: 17.03%


S6. C9H11O4PCl2

Smiles Code: ClC1=C(C(Cl)=CC(C)=C1)OP(OC)(OC)=O MW = 285.065

log P: 2.49 Yield: 8.51%

[3.7.1] Desulfurization of organophosphosulfur compound.


(Expert 2: agrees with Expert 1: metabolizes)

Results for compound N9 (line #9): 65879-43-8 S5. C9H10O4NCl Smiles Code: ClC1=CC(OC(C)C)=C(C=C1O)N(=O)=O

MW = 231.637 log P: 2.89 Yield: 61.40%

S6. C3H6O Smiles Code: C(C)(C)=O MW = 58.081 log P: 0.27

Yield: 61.40%

S4. C12H16O3NCl

Smiles Code: ClC1=CC(OC(C)C)=C(C=C1OC(C)C)N=O MW = 257.719

log P: 3.67 Yield: 26.73%

[5.10] Reduction of aryl/vinyl nitro to nitroso



(Expert 1: Hydroxylation of the propoxy groups leading to low logp substances which can be further broken

down.)

(Expert 2: may be so…)

SHC/TS 2-3/030 24

Results for compound N10 (line #10): 67564-91-4 S13. C20H33O2N

Smiles Code: C1=CC(C(C)(C)C)=CC=C1CC(CNCC(OC(C=O)C)C)C

MW = 319.491 log P: 4.71 Yield: 29.48%

S14. C14H20O Smiles Code: C1=CC(C(C)(C)C)=CC=C1CC(C=O)C

MW = 204.315 log P: 3.89 Yield: 21.94%

S15. C6H13ON Smiles Code: N1CC(OC(C1)C)C MW = 115.177

log P: 0.44 Yield: 21.94%

S12. C20H33O2N

Smiles Code: C1=CC(C(C)(C)C)=CC=C1CC(CN(CC(C)=O)CC(O)C)C

MW = 319.491 log P: 4.47 Yield: 13.14%

S6. C20H33O2N

Smiles Code: C1=CC(C(C)(C)C)=CC=C1CC(O)(CN1CC(OC(C1)C)C)C

MW = 319.491 log P: 4.74 Yield: 12.25%


[0.9.1-2][0.9.6][0.9.7-8]

S2. C20H33O2N

Smiles Code: C1=CC(C(C)(C)C)=CC=C1C(O)C(CN1CC(OC(C1)C)C)C

MW = 319.491 log P: 4.45 Yield: 5.54%




(Expert 1: Opening of the heterocyclic ring will led to lower logp substances, but final metabolism may be a slow

process)


Results for compound N11 (line #11): 116-29-0 S2. C12H6O3SCl4

Smiles Code: ClC1=CC=C(C=C1O)S(C1=CC(Cl)=C(C=C1Cl)Cl)(=O)=O

MW = 372.056 log P: 4.95 Yield: 100.00%




(Expert 1: What would it metabolize to?)

(Expert 2: epoxidation of aromatic ring with single chlorine!?)

Results for compound N12 (line #12): 117-18-0 S2. C6HONCl4 Smiles Code: ClC1=CC(Cl)=C(C(N=O)=C1Cl)Cl

MW = 244.893 log P: 4.27 Yield: 100.00%




SHC/TS 2-3/030 25

Results for compound N13 (line #13): 611-75-6 S6. C14H20ON2Br2

Smiles Code: C1(CCCCC1)C(C1=C(C(Br)=CC(Br)=C1)NO)(C)N

MW = 392.136 log P: 3.77 Yield: 19.17%

[3.6.8] N-hydroxylation of aryl/vinyl amine

[4.1.x] N-hydroxylation of aromatic/vinyl primary amines

S5. C16H22ON2Br2

Smiles Code: C1(CCCCC1)C(C1=C(C(Br)=CC(Br)=C1)N)(C)NC(C)=O

MW = 418.174 log P: 4.28 Yield: 11.05%

[14.1] N-acetylation of primary aliphatic amines

S8. C14H20O3N2SBr2

Smiles Code: C1(CCCCC1)C(C1=C(C(Br)=CC(Br)=C1)NS(O)(=O)=O)(C)N

MW = 456.199 log P: 3.77 Yield: 11.05%

[12.4] N-sulfation of aryl/vinyl amines

S3. C14H20ON2Br2

Smiles Code: C1(CCCCC1)C(C1=C(C(Br)=CC(Br)=C1)N)(C)NO

MW = 392.136 log P: 4.11 Yield: 8.12%

[4.1.1] N-hydroxylation of prim, sec aliphatic amines

S4. C15H22N2Br2

Smiles Code: C1(CCCCC1)C(C1=C(C(Br)=CC(Br)=C1)N)(C)NC

MW = 390.164 log P: 4.59 Yield: 8.12%

[13.1.1] N-methylation of aliphatic primary amines

S7. C14H19N2Br2C6H9O6

Smiles Code: C1(CCCCC1)C(C1=C(C(Br)=CC(Br)=C1)N(C%99C(O)C(O)C(O)C(C(=O)O)O%99))(C)N

MW = 552.909 log P: 0.65 Yield: 8.12%

[11.4.1] Gluc acid N-conjugation of aryl/vinyl primary amine




Smiles Code: O=C1C=C(C(CC(C)(C)C)(C)C)C(C=C1C(CC(C)(C)C)(C)C)=O

MW = 332.531 log P: 6.51 Yield: 63.17%

[0.6.9-10] Decomposition of "beta-aminonitrosoamine"

S4. C22H37O2C6H9O6

Smiles Code: OC1=CC(C(CC(C)(C)C)(C)C)=C(C=C1C(CC(C)(C)C)(C)C)O(C%99C(O)C(O)C(O)C(C(=O)O)O%99)

MW = 511.320 log P: 3.27 Yield: 14.04%



(Expert 2: inbetween = partial or not significant metabolism, substance is 1,4-Benzenediol, 2,5-bis(1,1,3,3-

tetramethylbutyl)- and does not contain amino-group; how can “Decomposition of "beta-aminonitrosoamine"”

take place?)

(Expert 1:: Don’t know where the amino group came from (program bug). The prediction is for glucoronyl and

sulfotransferase conjugation of the hydroxyl groups leading to excretion. Alternatively, could form a quinone

which would not metabolize well. Hard to call)


SHC/TS 2-3/030 26

Results for compound N15 (line #15): 976-56-7 S12. C17H29O4P

Smiles Code: CCOP(CC1=CC(C(C)(C)C)=C(C(C(C)(C)C)=C1)O)(O)=O

MW = 328.392 log P: 3.94 Yield: 24.16%

s13. C2H4O Smiles Code: C(C)=O MW = 44.054 log P: 0.02

Yield: 24.16%

S11. C19H33O5P

Smiles Code: CCOP(CC12C=C(C(C(C1O2)C(C)(C)C)=O)C(C)(C)C)(OCC)=O

MW = 372.446 log P: 4.43 Yield: 22.22%

S10. C19H33O5P

Smiles Code: CCOP(CC1=CC(C(C2(C1O2)C(C)(C)C)=O)C(C)(C)C)(OCC)=O

MW = 372.446 log P: 4.43 Yield: 16.32%

S8. C19H32O4PC6H9O6

Smiles Code: CCOP(CC1=CC(C(C)(C)C)=C(C(C(C)(C)C)=C1)O(C%99C(O)C(O)C(O)C(C(=O)O)O%99))(OCC)=O

MW = 533.219 log P: 1.00 Yield: 11.11%


S4. C19H33O5P

Smiles Code: CCOP(C(O)C1=CC(C(C)(C)C)=C(C(C(C)(C)C)=C1)O)(OCC)=O

MW = 372.446 log P: 4.28 Yield: 8.16%


S9. C19H33O7PS

Smiles Code: CCOP(CC1=CC(C(C)(C)C)=C(C(C(C)(C)C)=C1)OS(O)(=O)=O)(OCC)=O

MW = 436.508 log P: 4.12 Yield: 8.16%



(Expert 2: agrees with Expert 1: metabolizes)

SHC/TS 2-3/030 27

Results for compound N16 (line #16): 979-02-2 s16. C2H4O2 Smiles Code: OC(C)=O MW = 60.053 log P: -0.19

Yield: 23.55% [6.1] Hydrolysis of aliphatic esters

S2. C23H32O4

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4C3C(O)C=C1CC(CC2)OC(C)=O)C)C

MW = 372.509 log P: 4.26 Yield: 13.03%



S3. C23H32O4

Smiles Code: C12(C3CCC4(C(C(C)=O)=CC(O)C4C3CC=C1CC(CC2)OC(C)=O)C)C

MW = 372.509 log P: 4.26 Yield: 13.03%



S17. C21H28O2

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4C3CC=C1CC(CC2)=O)C)C

MW = 312.456 log P: 4.53 Yield: 11.12%

S14. C23H34O3

Smiles Code: C12(C3CCC4(C(C(O)C)=CCC4C3CC=C1CC(CC2)OC(C)=O)C)C

MW = 358.526 log P: 5.04 Yield: 6.21%


S15. C21H30O2

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4C3CC=C1CC(O)CC2)C)C

MW = 314.472 log P: 4.32 Yield: 6.21%

[6.1] Hydrolysis of aliphatic esters

S4. C23H32O4

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4C3CC=C1CC(CC2)OC(C)=O)CO)C

MW = 372.509 log P: 4.11 Yield: 4.91%


S5. C23H32O4

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4C3CC=C1CC(CC2)OC(C)=O)C)CO

MW = 372.509 log P: 4.11 Yield: 4.91%


S7. C23H32O4

Smiles Code: C12(C3(O)CCC4(C(C(C)=O)=CCC4C3CC=C1CC(CC2)OC(C)=O)C)C

MW = 372.509 log P: 4.41 Yield: 4.91%


S8. C23H32O4

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4C3(O)CC=C1CC(CC2)OC(C)=O)C)C

MW = 372.509 log P: 4.41 Yield: 4.91%


S9. C23H32O4

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4(O)C3CC=C1CC(CC2)OC(C)=O)C)C

MW = 372.509 log P: 4.41 Yield: 4.91%


S10. C23H32O4

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4C3CC=C1CC(CC2O)OC(C)=O)C)C

MW = 372.509 log P: 4.26 Yield: 4.91%


S11. C23H32O4

Smiles Code: C12(C3CC(O)C4(C(C(C)=O)=CCC4C3CC=C1CC(CC2)OC(C)=O)C)C

MW = 372.509 log P: 4.26 Yield: 4.91%


S12. C23H32O4

Smiles Code: C12(C3CCC4(C(C(C)=O)=CCC4C3CC=C1CC(C(O)C2)OC(C)=O)C)C

MW = 372.509 log P: 4.26 Yield: 4.91%


S13. C23H32O4

Smiles Code: C12(C3C(O)CC4(C(C(C)=O)=CCC4C3CC=C1CC(CC2)OC(C)=O)C)C

MW = 372.509 log P: 4.26 Yield: 4.91%


(Expert 1: Partial metabolisation)



SHC/TS 2-3/030 28

S19. C24H38O4

Smiles Code: C12(C3CCC4(C(C(CC4C3CC=C1CC(CC2)O)C)C(O)COC(C)=O)C)C

MW = 390.568 log P: 4.59 Yield: 15.23%

[5.2] Reduction of aliphatic ketones

[19.2] Reduction of ketones

s23. C2H4O2 Smiles Code: OC(C)=O MW = 60.053 log P: -0.19


S20. C24H34O3

Smiles Code: C12(C3CCC4(C(C(CC4C3CC=C1C=CCC2)C)C(COC(C)=O)=O)C)C

MW = 370.537 log P: 5.47 Yield: 10.97%

[5.1] Dehydration of aliphatic alcohols

S21. C24H34O3

Smiles Code: C12(C3CCC4(C(C(CC4C3CC=C1CC=CC2)C)C(COC(C)=O)=O)C)C

MW = 370.537 log P: 5.47 Yield: 10.97%


S24. C22H32O3

Smiles Code: C12(C3CCC4(C(C(CC4C3CC=C1CC(CC2)O)C)C(C=O)=O)C)C

MW = 344.499 log P: 3.93 Yield: 7.02%

(Expert 1: Partial metabolisation)


Results for compound N18 (line #18): 1478-61-1 S2. C15H9O2F6C6H9O6

Smiles Code: OC1=CC=C(C=C1)C(C(F)(F)F)(C(F)(F)F)C1=CC=C(C=C1)O(C%99C(O)C(O)C(O)C(C(=O)O)O%99)

MW = 513.009 log P: 1.38 Yield: 57.65%


S3. C15H10O5F6S

Smiles Code: OC1=CC=C(C=C1)C(C(F)(F)F)(C(F)(F)F)C1=CC=C(C=C1)OS(O)(=O)=O

MW = 416.298 log P: 4.50 Yield: 42.35%


(Expert 1: Partial or no significant metabolisation)


SHC/TS 2-3/030 29

Results for compound N19 (line #19): 2309-94-6 S12. C18H17O3N6Br

Smiles Code: BrC1=CC(N(=O)=O)=CC(C#N)=C1N=NC1=CC=C(C=C1NC(CC)=O)NCC

MW = 445.279 log P: 6.35 Yield: 34.03%


Yield: 34.03%

S8. C3H6O2 Smiles Code: C(CC)(O)=O MW = 74.080 log P: 0.20

Yield: 16.30% [7] Hydrolysis of any amide

S11. C13H21ON3 Smiles Code: NC1=CC=C(C=C1NC(CC)=O)N(CC)CC

MW = 235.332 log P: 1.61 Yield: 16.30%

[5.21] Reduction of di(aryl/vinyl) azo compounds

S6. C20H21O4N6Br

Smiles Code: BrC1=CC(N(=O)=O)=CC(C#N)=C1N=NC1=CC=C(C=C1N(O)C(CC)=O)N(CC)CC

MW = 489.332 log P: 5.47 Yield: 11.98%

[3.6.8] N-hydroxylation of aryl/vinyl amine [0.95.30]

S7. C17H17O2N6Br

Smiles Code: BrC1=CC(N(=O)=O)=CC(C#N)=C1N=NC1=CC=C(C=C1N)N(CC)CC

MW = 417.268 log P: 5.99 Yield: 8.15%

[7] Hydrolysis of any amide

S9. C20H21O2N6Br

Smiles Code: BrC1=CC(N=O)=CC(C#N)=C1N=NC1=CC=C(C=C1NC(CC)=O)N(CC)CC

MW = 457.333 log P: 6.36 Yield: 8.15%


S10. C7H4O2N3Br Smiles Code: BrC1=CC(N(=O)=O)=CC(C#N)=C1N

MW = 242.033 log P: 1.53 Yield: 8.15%


S4. C20H21O4N6Br

Smiles Code: BrC1=CC(N(=O)=O)=CC(C#N)=C1N=NC1=CC=C(C=C1NC(C(O)C)=O)N(CC)CC

MW = 489.332 log P: 5.49 Yield: 5.99%




Results for compound N20 (line #20): 3380-34-5 S3. C12H6O2Cl3C6H9O6

Smiles Code: ClC1=CC(Cl)=C(C=C1)OC1=CC=C(C=C1O(C%99C(O)C(O)C(O)C(C(=O)O)O%99))Cl

MW = 466.320 log P: 0.63 Yield: 47.74%


S4. C12H7O5SCl3

Smiles Code: ClC1=CC(Cl)=C(C=C1)OC1=CC=C(C=C1OS(O)(=O)=O)Cl

MW = 369.610 log P: 3.75 Yield: 35.07%




SHC/TS 2-3/030 30

Results for compound N21 (line #21): 5590-18-1 S2. C22H6O3N4Cl8

Smiles Code:

ClC1=C(C(Cl)=C2C(NC(C2=C1Cl)=NC1=CC2C(O2)(C=C1)N=C1C2=C(C(Cl)=C(C(Cl)=C2C(N1)=O)Cl)Cl)=O)Cl

MW = 657.942 log P: 10.43 Yield: 31.44%


S4. C22H6O3N4Cl8

Smiles Code:

ClC1=C(C(Cl)=C2C(NC(C2=C1Cl)=NC1=CC=C(C=C1)N=C1C2=C(C(Cl)=C(C(Cl)=C2C(N1O)=O)Cl)Cl)=O)Cl

MW = 657.942 log P: 9.77 Yield: 31.44% [0.95.32] [0.95.30]

S5. C22H8O3N4Cl8

Smiles Code:

ClC1=C(C(Cl)=C2C(NC(C2=C1Cl)=NC1=CC=C(C=C1)N=C(N)C1=C(C(Cl)=C(C(Cl)=C1C(O)=O)Cl)Cl)=O)Cl

MW = 659.958 log P: 11.85 Yield: 21.40%


S3. C22H6O3N4Cl8

Smiles Code:

ClC1=C(C(Cl)=C2C(NC(C2=C1Cl)=NC1=CC=C(C=C1)N(=O)=C1C2=C(C(Cl)=C(C(Cl)=C2C(N1)=O)Cl)Cl)=O)Cl

MW = 657.942 log P: 9.75 Yield: 15.72%

[3.9.1] N-oxidation of aryl/vinyl imine



Results for compound N22 (line #22): 6406-56-0 S7. C6H7O3NS Smiles Code: NC1=CC=C(S(O)(=O)=O)C=C1

MW = 173.192 log P: 0.15 Yield: 45.79%


S5. C12H11O3N3S

Smiles Code: NC1=CC=C(N=NC2=CC=C(S(O)(=O)=O)C=C2)C=C1

MW = 277.304 log P: 3.74 Yield: 22.90%


S2. C22H15O4N4SC6H9O6

Smiles Code:

N(C1=C(C=CC2=CC=CC=C12)O(C%99C(O)C(O)C(O)C(C(=O)O)O%99))=NC1=CC=C(N=NC2=CC=C(S(O)(=O)=

O)C=C2)C=C1

MW = 609.234 log P: 4.78 Yield: 11.45%


S4. C10H9ON Smiles Code: NC1=C(C=CC2=CC=CC=C12)O

MW = 159.189 log P: 1.96 Yield: 11.45%


S6. C16H13ON3

Smiles Code: N(C1=C(C=CC2=CC=CC=C12)O)=NC1=CC=C(N)C=C1

MW = 263.302 log P: 5.56 Yield: 11.45%


S3. C22H16O7N4S2

Smiles Code:

N(C1=C(C=CC2=CC=CC=C12)OS(O)(=O)=O)=NC1=CC=C(N=NC2=CC=C(S(O)(=O)=O)C=C2)C=C1

MW = 512.523 log P: 7.90 Yield: 8.41%




SHC/TS 2-3/030 31

Results for compound N23 (line #23): 6407-78-9 S2. C18H18ON4

Smiles Code: C1=CC=C(C=C1)N1NC(C)=C(N=NC2=CC=C(C=C2C)C)C1=O

MW = 306.370 log P: 5.53 Yield: 100.00%

[0.7.2.2] General imine-enamine tautomerization



Results for compound N24 (line #24): 6410-30-6 S7. C18H13O5N3

Smiles Code: C(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=CC(N(=O)=O)=C2)=C1O)(O)=O

MW = 351.321 log P: 7.22 Yield: 22.37%


S10. C7H8O2N2 Smiles Code: NC1=CC(N(=O)=O)=CC=C1C

MW = 152.154 log P: 1.37 Yield: 22.37%


S3. C24H17O5N4Cl

Smiles Code: ClC1=CC=C(C=C1)N(O)C(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=CC(N(=O)=O)=C2)=C1O)=O

MW = 476.880 log P: 7.80 Yield: 16.44%


S4. C24H16O4N4ClC6H9O6

Smiles Code:

ClC1=CC=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=CC(N(=O)=O)=C2)=C1O(C%99C(O)C(O)C(O)C(

C(=O)O)O%99))=O

MW = 637.653 log P: 3.72 Yield: 11.19%


S6. C6H6NCl Smiles Code: ClC1=CC=C(C=C1)N MW = 127.574


S8. C24H17O3N4Cl

Smiles Code: ClC1=CC=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=CC(N=O)=C2)=C1O)=O

MW = 444.881 log P: 8.69 Yield: 11.19%


S9. C17H13O2N2Cl

Smiles Code: ClC1=CC=C(C=C1)NC(C1=CC2=CC=CC=C2C(N)=C1O)=O

MW = 312.758 log P: 4.09 Yield: 11.19%


S2. C24H17O5N4Cl

Smiles Code: ClC1=CC=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(CO)C=CC(N(=O)=O)=C2)=C1O)=O

MW = 476.880 log P: 7.79 Yield: 8.22%


S5. C24H17O7N4SCl

Smiles Code:

ClC1=CC=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=CC(N(=O)=O)=C2)=C1OS(O)(=O)=O)=O

MW = 540.943 log P: 6.83 Yield: 8.22%




SHC/TS 2-3/030 32


Smiles Code: C(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=C(C=C2)N(=O)=O)=C1O)(O)=O

MW = 351.321 log P: 7.22 Yield: 19.77%


S12. C7H8O2N2 Smiles Code: NC1=CC=C(C=C1C)N(=O)=O

MW = 152.154 log P: 1.37 Yield: 19.77%


S5. C25H20O5N4

Smiles Code: C1=CC(C)=C(C=C1)N(O)C(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=C(C=C2)N(=O)=O)=C1O)=O

MW = 456.462 log P: 7.52 Yield: 14.52%


S6. C25H19O4N4C6H9O6

Smiles Code:

C1=CC(C)=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=C(C=C2)N(=O)=O)=C1O(C%99C(O)C(O)C(O)C(

C(=O)O)O%99))=O

MW = 617.235 log P: 3.44 Yield: 9.88%


S8. C7H9N Smiles Code: C1=CC(C)=C(C=C1)N MW = 107.156


S10. C25H20O3N4

Smiles Code: C1=CC(C)=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=C(C=C2)N=O)=C1O)=O

MW = 424.463 log P: 8.41 Yield: 9.88%


S11. C18H16O2N2

Smiles Code: C1=CC(C)=C(C=C1)NC(C1=CC2=CC=CC=C2C(N)=C1O)=O

MW = 292.340 log P: 3.82 Yield: 9.88%


S3. C25H20O5N4

Smiles Code: C1=CC(C)=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(CO)C=C(C=C2)N(=O)=O)=C1O)=O

MW = 456.462 log P: 7.52 Yield: 7.26%


S4. C25H20O5N4

Smiles Code: C1=CC(CO)=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=C(C=C2)N(=O)=O)=C1O)=O

MW = 456.462 log P: 7.52 Yield: 7.26%


S7. C25H20O7N4S

Smiles Code:

C1=CC(C)=C(C=C1)NC(C1=CC2=CC=CC=C2C(N=NC2=C(C)C=C(C=C2)N(=O)=O)=C1OS(O)(=O)=O)=O

MW = 520.525 log P: 6.56 Yield: 7.26%




SHC/TS 2-3/030 33


Smiles Code: ClC1=CC=C(C(N=NC2=C(C(C(NC3=CC=CC=C3O)=O)=CC3=CC=CC=C23)O)=C1)Cl

MW = 452.300 log P: 8.89 Yield: 31.09%


Yield: 31.09%

S7. C7H9ON Smiles Code: NC1=CC=CC=C1OC MW = 123.156


S9. C18H16O3N2

Smiles Code: NC1=C(C(C(NC2=CC=CC=C2OC)=O)=CC2=CC=CC=C12)O

MW = 308.340 log P: 3.45 Yield: 19.13%


S4. C24H16O3N3Cl2C6H9O6

Smiles Code:

ClC1=CC=C(C(N=NC2=C(C(C(NC3=CC=CC=C3OC)=O)=CC3=CC=CC=C23)O(C%99C(O)C(O)C(O)C(C(=O)O)O

%99))=C1)Cl

MW = 643.100 log P: 4.02 Yield: 9.57%


S6. C17H10O3N2Cl2

Smiles Code: ClC1=CC=C(C(N=NC2=C(C(C(O)=O)=CC3=CC=CC=C23)O)=C1)Cl

MW = 361.187 log P: 8.17 Yield: 9.57%


S8. C6H5NCl2 Smiles Code: ClC1=CC=C(C(N)=C1)Cl MW = 162.019

log P: 2.33 Yield: 9.57%





Smiles Code: NC1=CC=C(C=C1)NC1=CC=C(C=C1N(=O)=O)N(=O)=O

MW = 274.238 log P: 2.67 Yield: 45.30%


S4. C24H16O5N5C6H9O6

Smiles Code:

C1=CC=C(C=C1)C1=C(C=CC(N=NC2=CC=C(C=C2)NC2=CC=C(C=C2N(=O)=O)N(=O)=O)=C1)O(C%99C(O)C(O

)C(O)C(C(=O)O)O%99)

MW = 632.206 log P: 4.27 Yield: 11.33%


S6. C24H17O4N5

Smiles Code: C1=CC=C(C=C1)C1=C(C=CC(N=NC2=CC=C(C=C2)NC2=CC=C(C=C2N=O)N(=O)=O)=C1)O

MW = 439.434 log P: 8.42 Yield: 11.33%


S7. C24H17O4N5

Smiles Code: C1=CC=C(C=C1)C1=C(C=CC(N=NC2=CC=C(C=C2)NC2=CC=C(C=C2N(=O)=O)N=O)=C1)O

MW = 439.434 log P: 8.42 Yield: 11.33%


S8. C12H11ON Smiles Code: C1=CC=C(C=C1)C1=C(C=CC(N)=C1)O

MW = 185.228 log P: 2.53 Yield: 11.33%


S3. C24H17O6N5

Smiles Code:

C1=CC=C(C=C1)C1=C(C=CC(N=NC2=CC=C(C=C2)N(O)C2=CC=C(C=C2N(=O)=O)N(=O)=O)=C1)O

MW = 471.433 log P: 6.90 Yield: 8.32%

[3.6.8] N-hydroxylation of aryl/vinyl amine

S5. C24H17O8N5S

Smiles Code:

C1=CC=C(C=C1)C1=C(C=CC(N=NC2=CC=C(C=C2)NC2=CC=C(C=C2N(=O)=O)N(=O)=O)=C1)OS(O)(=O)=O

MW = 535.496 log P: 7.39 Yield: 8.32%





SHC/TS 2-3/030 34

S6. C16H13O4N4Cl3

Smiles Code: ClC1=CC(N(=O)=O)=CC(Cl)=C1N=NC1=CC=C(C=C1Cl)N(CC=O)CCO

MW = 431.665 log P: 6.41 Yield: 27.21%

[16.1.1] Oxidation of primary aliphatic alcohol

S11. C14H11O3N4Cl3

Smiles Code: ClC1=CC(N(=O)=O)=CC(Cl)=C1N=NC1=CC=C(C=C1Cl)NCCO

MW = 389.628 log P: 6.86 Yield: 25.37%

s12. C2H4O2 Smiles Code: C(CO)=O MW = 60.053 log P: -0.92

Yield: 25.37%

S8. C16H13O3N4Cl3

Smiles Code: ClC1=CC(N(=O)=O)=CC(Cl)=C1N=NC1=CC=C(C=C1Cl)N(C=C)CCO

MW = 415.666 log P: 7.01 Yield: 16.59%


S10. C10H15O2N2Cl Smiles Code: NC1=CC=C(C=C1Cl)N(CCO)CCO

MW = 230.696 log P: 0.64 Yield: 14.75%


S7. C16H15O3N4Cl3

Smiles Code: ClC1=CC(N=O)=CC(Cl)=C1N=NC1=CC=C(C=C1Cl)N(CCO)CCO

MW = 417.682 log P: 6.18 Yield: 7.38%


S9. C6H4O2N2Cl2 Smiles Code: ClC1=CC(N(=O)=O)=CC(Cl)=C1N

MW = 207.017 log P: 2.32 Yield: 7.38%




Results for compound N29 (line #29): 27137-85-5 (Model inappropriate – structure contains Silicon)



S6. C5H3SCl2SG

Smiles Code: C1(S(CC(C(=O)NCC(=O)O)NC(=O)CCC(N)C(=O)O))(Cl)C=C(Cl)C=C1

MW = 474.597 log P: -0.42 Yield: 37.26%


s5. SCl3I- Smiles Code: Cl(Cl)(Cl)SI MW = 265.327 log P: 2.53

Yield: 16.16%



S7. C5H3OCl Smiles Code: C1(C=CC(Cl)=C1)=O MW = 114.532

log P: 1.18 Yield: 13.69%


S2. C5H3OSCl5I

Smiles Code: Cl(Cl)(Cl)(C1(Cl)C=C(Cl)C2C1O2)SI MW = 415.312

log P: 4.46 Yield: 9.32% [3.8.1] Epoxidation of double bond

S3. C5H3S2Cl4ISG

Smiles Code: Cl(Cl)(Cl)(C1(S(CC(C(=O)NCC(=O)O)NC(=O)CCC(N)C(=O)O))C=C(Cl)C=C1)SI

MW = 704.471 log P: 1.71 Yield: 9.32%


(Expert 1: No estimate – contains Silicon)



Smiles Code:

ClC1=CC(Cl)=C(C(Cl)=C1)N1NC(NC(C2=CC=CC(NC(COC3=CC=C(C=C3C(C)(C)CC)C(C)(C)CC)=O)=C2)=O)=C

C1=O

MW = 672.057 log P: 7.86 Yield: 100.00%

[0.7.2.2] General imine-enamine tautomerization

(Expert 1: Partial metabolization)


Results for compound N31 (line #31): 52179-28-9 S8. C13H14O3Cl2

Smiles Code: C1(C(C1)C1=CC=C(C=C1)OC(C(O)=O)(C)C)(Cl)Cl

SHC/TS 2-3/030 35

MW = 289.161 log P: 3.47 Yield: 41.85%




[0.4.1-2] Decomposition of hydroxamide


Yield: 33.25%

S10. C15H17O3Cl

Smiles Code: C1(Cl)=C(C1)C1=CC=C(C=C1)OC(C(OCC)=O)(C)C

MW = 280.754 log P: 3.93 Yield: 15.29%

[0.4.1-2] Decomposition of hydroxamide

S6. C15H18O4

Smiles Code: C1(C(C1)C1=CC=C(C=C1)OC(C(OCC)=O)(C)C)=O

MW = 262.308 log P: 2.89 Yield: 11.23%




Results for compound N32 (line #32): 52320-66-8 S12. C16H13O5N4Cl

Smiles Code: ClC1=CC=C(C(N(=O)=O)=C1)N=NC(C(C)=O)C(NC1=CC=C(C=C1)O)=O

MW = 376.759 log P: 4.57 Yield: 23.88%


Yield: 23.88%

S9. C18H19O5N4Cl

Smiles Code: ClC1=CC=C(C(N(=O)=O)=C1)N=NC(C(O)C)C(NC1=CC=C(C=C1)OCC)=O

MW = 406.829 log P: 5.44 Yield: 23.51%

[5.2] Reduction of aliphatic ketones

[19.2] Reduction of ketones

S7. C8H11ON Smiles Code: NC1=CC=C(C=C1)OCC MW = 137.183


S5. C18H17O6N4Cl

Smiles Code: ClC1=CC=C(C(N(=O)=O)=C1)N=NC(C(C)=O)C(N(O)C1=CC=C(C=C1)OCC)=O

MW = 420.812 log P: 4.52 Yield: 11.05%


S4. C18H17O6N4Cl

Smiles Code: ClC1=CC=C(C(N(=O)=O)=C1)N=NC(O)(C(C)=O)C(NC1=CC=C(C=C1)OCC)=O

MW = 420.812 log P: 4.83 Yield: 7.52%

[3.6.10] C-hydroxylation of aromatic amine

S6. C10H8O5N3Cl

Smiles Code: ClC1=CC=C(C(N(=O)=O)=C1)N=NC(C(C)=O)C(O)=O

MW = 285.645 log P: 3.83 Yield: 7.52%


S8. C18H17O4N4Cl

Smiles Code: ClC1=CC=C(C(N=O)=C1)N=NC(C(C)=O)C(NC1=CC=C(C=C1)OCC)=O

MW = 388.814 log P: 5.41 Yield: 7.52%




SHC/TS 2-3/030 36

Results for compound N33 (line #33): 52583-53-6 S12. C16H15O3N5Br2

Smiles Code: N(C1=CC(Br)=C(C(Br)=C1)N=NC1=C(C=C(C=C1)NCC)NC(C)=O)(=O)=O

MW = 485.138 log P: 7.13 Yield: 30.20%


Yield: 30.20%

S2. C18H19O4N5Br2

Smiles Code: N(C1=CC(Br)=C(C2(C1O2)Br)N=NC1=C(C=C(C=C1)N(CC)CC)NC(C)=O)(=O)=O

MW = 529.191 log P: 6.44 Yield: 14.47%


s8. C2H4O2 Smiles Code: C(C)(O)=O MW = 60.053 log P: -0.19


S11. C12H19ON3 Smiles Code: NC1=CC=C(C=C1NC(C)=O)N(CC)CC

MW = 221.305 log P: 1.22 Yield: 14.47%


S6. C18H19O4N5Br2

Smiles Code: N(C1=CC(Br)=C(C(Br)=C1)N=NC1=C(C=C(C=C1)N(CC)CC)N(O)C(C)=O)(=O)=O

MW = 529.191 log P: 6.25 Yield: 10.63%


S7. C16H17O2N5Br2

Smiles Code: N(C1=CC(Br)=C(C(Br)=C1)N=NC1=C(C=C(C=C1)N(CC)CC)N)(=O)=O

MW = 471.154 log P: 7.16 Yield: 7.23%


S9. C18H19O2N5Br2

Smiles Code: N(C1=CC(Br)=C(C(Br)=C1)N=NC1=C(C=C(C=C1)N(CC)CC)NC(C)=O)=O

MW = 497.192 log P: 7.14 Yield: 7.23%


S10. C6H4O2N2Br2

Smiles Code: N(C1=CC(Br)=C(C(Br)=C1)N)(=O)=O MW = 295.919

log P: 2.70 Yield: 7.23%


S3. C18H19O4N5Br2

Smiles Code: N(C1=CC(Br)=C(C(Br)=C1)N=NC1=C(C=C(C(O)=C1)N(CC)CC)NC(C)=O)(=O)=O

MW = 529.191 log P: 6.72 Yield: 5.31%




SHC/TS 2-3/030 37

Results for compound N34 (line #34): 52829-07-9 S8. C19H35O4N

Smiles Code: N1C(C)(C)CC(CC1(C)C)OC(CCCCCCCCC(O)=O)=O

MW = 341.495 log P: 3.92 Yield: 38.45%


S9. C9H19ON Smiles Code: C1(O)CC(C)(C)NC(C)(C)C1

MW = 157.258 log P: 1.04 Yield: 27.56%


S10. C9H17ON Smiles Code: C1(CC(C)(C)NC(C)(C)C1)=O

MW = 155.242 log P: 1.25 Yield: 24.67%

S4. C29H54O4N2

Smiles Code: N1C(C)(C)CC(CC1(C)C)OC(CCCCCCCCC(OC1CC(C)(C)N(C)C(C)(C)C1)=O)=O

MW = 494.765 log P: 6.56 Yield: 18.00%

[13.2.1] N-methylation of aliphatic secondary amines

S2. C28H52O5N2

Smiles Code: N1C(CO)(C)CC(CC1(C)C)OC(CCCCCCCCC(OC1CC(C)(C)NC(C)(C)C1)=O)=O

MW = 496.737 log P: 4.94 Yield: 10.89%


S5. C28H52O5N2

Smiles Code: N1C(C)(C)CC(CC1(C)C)OC(CCCCCCC(O)CC(OC1CC(C)(C)NC(C)(C)C1)=O)=O

MW = 496.737 log P: 4.96 Yield: 10.89%


S6. C28H52O5N2

Smiles Code: N1C(C)(C)CC(CC1(C)C)OC(CCCCCC(O)CCC(OC1CC(C)(C)NC(C)(C)C1)=O)=O

MW = 496.737 log P: 4.96 Yield: 10.89%


S7. C28H52O5N2

Smiles Code: N1C(C)(C)CC(CC1(C)C)OC(CCCCC(O)CCCC(OC1CC(C)(C)NC(C)(C)C1)=O)=O

MW = 496.737 log P: 4.96 Yield: 10.89%




Results for compound N35 (line #35): 54112-23-1 s14. CO2 Smiles Code: C(=O)=O MW = 44.010 log P: 1.43

Yield: 42.11%

S7. C6H11ON Smiles Code: N1C(CCCCC1)=O MW = 113.161


S8. C20H23O2N3

Smiles Code: C1(N(C(NC2=CC=C(C=C2)CC2=CC=C(C=C2)N)=O)CCCCC1)=O

MW = 337.425 log P: 2.88 Yield: 25.27%


S13. C27H32O5N4

Smiles Code: C1(N(C(NC2=CC=C(C=C2)CC2=CC=C(C=C2)NC(NC(CCCCC=O)=O)=O)=O)CCCCC1)=O

MW = 492.580 log P: 3.56 Yield: 15.87%

S5. C27H34O5N4

Smiles Code: C1(N(C(NC2=CC=C(C=C2)CC2=CC=C(C=C2)NC(NCCCCCC(O)=O)=O)=O)CCCCC1)=O

MW = 494.596 log P: 3.86 Yield: 10.28%

[7] Hydrolysis of any amide dic_xxx

S4. C27H32O5N4

Smiles Code: C1(N(C(NC2=CC=C(C=C2)CC2=CC=C(C=C2)N(O)C(N2C(CCCCC2)=O)=O)=O)CCCCC1)=O

MW = 492.580 log P: 2.43 Yield: 6.19%


S2. C27H32O5N4

Smiles Code: C1(N(C(NC2=CC=C(C=C2)C(O)C2=CC=C(C=C2)NC(N2C(CCCCC2)=O)=O)=O)CCCCC1)=O

MW = 492.580 log P: 2.45 Yield: 3.09%




SHC/TS 2-3/030 38


Smiles Code: C1(O)=C(CC2=CC(C)=CC(C(C)(C)C)=C2O)C=C(C)C=C1C(C)(C)C

MW = 340.510 log P: 7.28 Yield: 77.96%

[6.3] Hydrolysis of aryl/vinyl ester

S7. C3H4O2 Smiles Code: C(O)(C=C)=O MW = 72.064 log P: 0.03

Yield: 38.98% [6.3] Hydrolysis of aryl/vinyl ester



(Expert 1: Esterase to the biphenol, followed by glucoronide conjugation and excretion – but I doubt it somewhat

– so agree with “partial or not significant.)


Results for compound N37 (line #37): 61847-48-1 s16. CH2O Smiles Code: C=O MW = 30.026 log P: -0.05

Yield: 33.81%

S15. C32H22O6N4Cl2

Smiles Code:

ClC1=CC=C(C(NC(C2=CC=C(C(N=NC3=C(C(C(NC4=C(C=CC=C4)O)=O)=CC4=CC=CC=C34)O)=C2)C(OC)=O)

=O)=C1)Cl

MW = 629.461 log P: 9.44 Yield: 19.98%

S11. C32H22O6N4Cl2

Smiles Code:

ClC1=CC=C(C(NC(C2=CC=C(C(N=NC3=C(C(C(NC4=C(C=CC=C4)OC)=O)=CC4=CC=CC=C34)O)=C2)C(O)=O)

=O)=C1)Cl

MW = 629.461 log P: 9.72 Yield: 17.29%


S8. C7H9ON Smiles Code: NC1=C(C=CC=C1)OC MW = 123.156


S10. C27H21O7N3

Smiles Code:

C(C1=CC=C(C(N=NC2=C(C(C(NC3=C(C=CC=C3)OC)=O)=CC3=CC=CC=C23)O)=C1)C(OC)=O)(O)=O

MW = 499.484 log P: 7.66 Yield: 12.30%


S14. C18H16O3N2

Smiles Code: NC1=C(C(C(NC2=C(C=CC=C2)OC)=O)=CC2=CC=CC=C12)O

MW = 308.340 log P: 3.45 Yield: 12.30%


S5. C33H23O6N4Cl2C6H9O6

Smiles Code:

ClC1=CC=C(C(NC(C2=CC=C(C(N=NC3=C(C(C(NC4=C(C=CC=C4)OC)=O)=CC4=CC=CC=C34)O(C%99C(O)C(O

)C(O)C(C(=O)O)O%99))=C2)C(OC)=O)=O)=C1)Cl

MW = 820.261 log P: 4.58 Yield: 6.15%


S7. C26H17O6N3Cl2

Smiles Code:

ClC1=CC=C(C(NC(C2=CC=C(C(N=NC3=C(C(C(O)=O)=CC4=CC=CC=C34)O)=C2)C(OC)=O)=O)=C1)Cl

MW = 538.348 log P: 8.72 Yield: 6.15%


S9. C6H5NCl2 Smiles Code: ClC1=CC=C(C(N)=C1)Cl MW = 162.019


S13. C15H12O3N2Cl2

Smiles Code: ClC1=CC=C(C(NC(C2=CC=C(C(N)=C2)C(OC)=O)=O)=C1)Cl

MW = 339.180 log P: 2.88 Yield: 6.15%




SHC/TS 2-3/030 39


Smiles Code: OC1=CC=C(C=C1)C(CC(C1=CC=C(C=C1)C(C)(C)C)=O)=O

MW = 296.369 log P: 4.08 Yield: 76.35%


Yield: 76.35%



Results for compound N39 (line #39): 71617-28-2 S17. C11H16O2N3Cl

Smiles Code: NC1=CC(Cl)=C(C=C1NC(C)=O)NCC(C)O MW = 257.722

log P: 1.04 Yield: 21.18%


S18. C14H11O3N5Cl2

Smiles Code: ClC1=CC(N(=O)=O)=CC=C1N=NC1=CC(Cl)=C(C=C1NC(C)=O)N

MW = 368.181 log P: 5.27 Yield: 12.92%

S19. C3H6O2 Smiles Code: C(C(C)O)=O MW = 74.080 log P: -0.51

Yield: 12.92%

S20. C17H15O3N5Cl2

Smiles Code: ClC1=CC(N(=O)=O)=CC=C1N=NC1=CC(Cl)=C(C=C1NC(C)=O)N=CCC

MW = 408.247 log P: 7.98 Yield: 11.92%

s11. C2H4O2 Smiles Code: C(C)(O)=O MW = 60.053 log P: -0.19


S10. C15H15O3N5Cl2

Smiles Code: ClC1=CC(N(=O)=O)=CC=C1N=NC1=CC(Cl)=C(C=C1N)NCC(C)O

MW = 384.224 log P: 5.93 Yield: 5.30%


S12. C17H17O3N5Cl2

Smiles Code: ClC1=CC(N=O)=CC=C1N=NC1=CC(Cl)=C(C=C1NC(C)=O)NCC(C)O

MW = 410.263 log P: 5.91 Yield: 5.30%


S16. C6H5O2N2Cl Smiles Code: ClC1=CC(N(=O)=O)=CC=C1N

MW = 172.572 log P: 1.65 Yield: 5.30%




Results for compound N40 (line #40): 72968-71-9 s18. CH2O Smiles Code: C=O MW = 30.026 log P: -0.05

Yield: 35.24%

S12. C22H27O4N7S

Smiles Code: S1C(C(O)=O)=C(C(C#N)=C1N=NC1=C(C)C(C#N)=C(N=C1NCCCOC)NCCCOC)C

MW = 485.569 log P: 7.01 Yield: 22.02%


s13. CH4O Smiles Code: CO MW = 32.042 log P: -0.55


S14. C19H21O3N7S

Smiles Code: S1C(C(OC)=O)=C(C(C#N)=C1N=NC1=C(C)C(C#N)=C(N=C1N)NCCCOC)C

MW = 427.488 log P: 5.22 Yield: 19.11%

S15. C4H8O2 Smiles Code: C(CCOC)=O MW = 88.107 log P: 0.21

Yield: 19.11%

S17. C22H27O4N7S

Smiles Code: S1C(C(OC)=O)=C(C(C#N)=C1N=NC1=C(C)C(C#N)=C(N=C1NCCCO)NCCCOC)C

MW = 485.569 log P: 6.15 Yield: 17.62%

S16. C22H25O4N7S

Smiles Code: S1C(C(OC)=O)=C(C(C#N)=C1N=NC1=C(C)C(C#N)=C(N=C1NCCC=O)NCCCOC)C

MW = 483.553 log P: 6.33 Yield: 11.28%




SHC/TS 2-3/030 40

S10. C11H20N2S5 Smiles Code: CC(C)(C)CCCCCSSC1=NN=C(SS)S1

MW = 340.615 log P: 5.69 Yield: 29.04%

S11. C9H18O Smiles Code: C(CCCCC(C)(C)C)=O MW = 142.243

log P: 2.70 Yield: 29.04%

S3. C20H38ON2S5

Smiles Code: CC(C)(C)CCCCCSSC1=NN(=O)=C(SSCCCCCC(C)(C)C)S1

MW = 482.859 log P: 9.27 Yield: 14.81%

[3.9.1] N-oxidation of aryl/vinyl imine



Results for compound N42 (line #42): 335-36-4 (No metabolism) (Expert 1: No metabolism)


Results for compound N43 (line #43): 335-67-1 S3. C10H4O3NF15

Smiles Code: FC(C(C(C(C(C(C(C(NCC(O)=O)=O)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F

MW = 471.124 log P: 3.10 Yield: 37.11%

[8.1] Glycination of pri, sec, tert aliphatic acids

S4. C8HONF15GLM

Smiles Code: FC(C(C(C(C(C(C(C(N(C(C(=O)O)CCC(=O)N))=O)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F

MW = 542.204 log P: 3.24 Yield: 37.11%

[9.1] Glutamation of pri,sec, tert aliphatic acids:

S2. C8O2F15C6H9O6

Smiles Code:

FC(C(C(C(C(C(C(C(O(C%99C(O)C(O)C(O)C(C(=O)O)O%99))=O)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F

MW = 590.845 log P: 1.67 Yield: 25.77%

[11.1.1] Glucuronic O-conjugation of carboxylic acid












SHC/TS 2-3/030 41

Results for compound N47 (line #47): 2991-51-7 S8. C10H4O4NF17S

Smiles Code: OC(CNS(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(=O)=O)=O

MW = 557.185 log P: 4.08 Yield: 35.51%


Yield: 35.51%

s10. C2H2O3 Smiles Code: OC(C=O)=O MW = 74.036 log P: -0.96

Yield: 16.11%

S6. C14H11O5N2F17S

Smiles Code: N(CC(O)=O)C(CN(S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(=O)=O)CC)=O

MW = 642.291 log P: 3.49 Yield: 16.11%


S7. C12H8O3N2F17SGLM

Smiles Code:

N((C(C(=O)O)CCC(=O)N))C(CN(S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(=O)=O)CC)=O

MW = 713.370 log P: 3.63 Yield: 16.11%


S11. C10H6O2NF17S

Smiles Code: N(S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(=O)=O)CC

MW = 527.202 log P: 6.84 Yield: 16.11%

S5. C12H7O4NF17SC6H9O6

Smiles Code:

O((C%99C(O)C(O)C(O)C(C(=O)O)O%99))C(CN(S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(

=O)=O)CC)=O

MW = 762.011 log P: 2.07 Yield: 11.19%


(Expert 1. Partial or no significant metabolism)


Results for compound N48 (line #48): 3825-26-1 S3. C10H4O3NF15

Smiles Code: N(CC(O)=O)C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)=O

MW = 471.124 log P: 3.10 Yield: 37.11%


S4. C8HONF15GLM

Smiles Code: N((C(C(=O)O)CCC(=O)N))C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)=O

MW = 542.204 log P: 3.24 Yield: 37.11%


S2. C8O2F15C6H9O6

Smiles Code:

O((C%99C(O)C(O)C(O)C(C(=O)O)O%99))C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)=O

MW = 590.845 log P: 1.67 Yield: 25.77%




SHC/TS 2-3/030 42

Results for compound N49 (line #49): 13417-01-1 S10. C12H11O2N2F17S

Smiles Code: S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(NCCCNC)(=O)=O

MW = 570.271 log P: 6.89 Yield: 49.46%


Yield: 49.46%

S8. C11H6O3NF17S

Smiles Code: S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(NCCC=O)(=O)=O

MW = 555.212 log P: 6.47 Yield: 16.79%

s9. C2H7N Smiles Code: N(C)C MW = 45.085 log P: 0.05

Yield: 16.79%

S12. C8H2O2NF17S

Smiles Code: S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(N)(=O)=O

MW = 499.147 log P: 5.87 Yield: 9.91%

S13. C5H11ON Smiles Code: C(CCN(C)C)=O MW = 101.150

log P: 0.49 Yield: 9.91%



Results for compound N50 (line #50): 25268-77-3 S9. C13H8O4NF17S

Smiles Code: S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(NCCOC(C=C)=O)(=O)=O

MW = 597.250 log P: 6.98 Yield: 48.53%


Yield: 48.53%

S6. C3H4O2 Smiles Code: OC(C=C)=O MW = 72.064 log P: 0.03


S7. C9H4O2NF17S

Smiles Code: S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(NC)(=O)=O

MW = 513.175 log P: 6.45 Yield: 25.09%

S8. C5H6O3 Smiles Code: C(COC(C=C)=O)=O MW = 114.102

log P: 0.16 Yield: 25.09%

S11. C11H6O3NF17S

Smiles Code: S(C(C(C(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)(N(CC=O)C)(=O)=O

MW = 555.212 log P: 5.75 Yield: 14.81%



Results for compound N51 (line #51): 38850-60-1 S16. C13H17O5N2F13S2

Smiles Code: FC(C(C(C(C(C(S(N(CCCNC)CCCS(O)(=O)=O)(=O)=O)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F

MW = 592.398 log P: 4.81 Yield: 41.27%


Yield: 41.27%

S10. C12H12O6NF13S2

Smiles Code: FC(C(C(C(C(C(S(N(CCC=O)CCCS(O)(=O)=O)(=O)=O)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F

MW = 577.340 log P: 4.39 Yield: 14.01%

S12. C9H8O5NF13S2

Smiles Code: FC(C(C(C(C(C(S(NCCCS(O)(=O)=O)(=O)=O)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F

MW = 521.275 log P: 4.70 Yield: 14.01%

s11. C2H7N Smiles Code: N(C)C MW = 45.085 log P: 0.05

Yield: 14.01%

S13. C5H11ON Smiles Code: C(CCN(C)C)=O MW = 101.150

log P: 0.49 Yield: 14.01%

S14. C11H13O2N2F13S

Smiles Code: FC(C(C(C(C(C(S(NCCCN(C)C)(=O)=O)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F

MW = 484.282 log P: 5.64 Yield: 8.27%

S15. C3H6O4S Smiles Code: C(CCS(O)(=O)=O)=O MW = 138.143

log P: -0.44 Yield: 8.27%



SHC/TS 2-3/030 43

Annex 9: vPvB/PBT-candidates with significant environmental release

potential: vPvB/PBT-candidates in products marketed in Denmark, Finland, Norway and

Sweden with a significant environmental release potential.

Denmark:

Number of substances in each exposure potential category in DK (Danish Product Register Data 2002)

Exposure

Score: Number of

preparations Volume

Number of use categories

Number of industry categories

Low 25 30 32 26

Medium 21 15 14 9

High 1 2 1 12

Table 4b Exposure potential of individual substances

CAS

DK Product Register

Number of preparations

Volume Number of use

categories

Number of industry

categories

50-29-3 Low Low Low Low


77-47-4

78-63-7

79-94-7 Low Medium Low Medium

81-98-1

85-22-3

87-83-2

93-46-9

115-27-5 Medium Low Low Low

115-32-2


117-08-8

117-18-0


118-82-1 Medium Low Medium High

119-47-1 Medium Medium Medium High

128-69-8 Medium Medium Low High

128-83-6

128-87-0

129-73-7

133-14-2

133-49-3

135-91-1

139-60-6

152-11-4

298-57-7



335-57-9

335-67-1


355-43-1

SHC/TS 2-3/030 44

CAS

DK Product Register



categories

Number of industry

categories

375-72-4

423-50-7

507-63-1

512-04-9

611-75-6

626-39-1

632-79-1

634-66-2

678-26-2

732-26-3 Medium Medium Medium Medium

850-92-0

903-19-5

979-02-2


1173-09-7


1582-09-8 Low Medium Low Low

1639-60-7



2212-81-9

2309-94-6


2781-00-2

2795-39-3 Medium Low Medium Medium


3006-86-8

3147-75-9

3278-89-5

3739-67-1

3810-80-8

3825-26-1 Medium Low Low Low

3846-71-7 Medium Medium Medium Medium

3851-87-4


4051-63-2 Medium Medium Low High

4162-45-2


5216-25-1

5285-60-9

5590-18-1 High High Medium High


6410-30-6 Medium Medium Low Low

6410-38-4

6731-36-8 Low Medium Low Medium

08-02-7139

12223-91-5

13014-24-9

13171-00-1 Medium Low Low Medium

13417-01-1

13680-35-8 Medium Low Low Medium



15958-61-9

SHC/TS 2-3/030 45

CAS

DK Product Register



categories

Number of industry

categories

16699-20-0

17540-75-9 Medium Low Medium Medium


18254-13-2


23593-75-1

25155-25-3



26748-47-0

27137-85-5

29312-59-2


30707-68-7

31188-91-7

35578-47-3


37853-59-1

38521-51-6

38850-60-1

39489-75-3

40567-16-6

41604-19-7

41999-84-2

42074-68-0

43076-30-8

50679-08-8

50772-29-7


52179-28-9

52434-90-9

52740-90-6

53184-75-1

53928-30-6



55525-54-7

58997-88-9

59447-55-1

61167-58-6

64131-85-7

65294-17-9

67564-91-4

68937-41-7 Medium Medium High High


72968-71-9

89347-09-1 Medium High Medium Medium

SHC/TS 2-3/030 46

Finland:

Number of substances in each exposure potential category in Finnish Product Register 2002)

Exposure

Score: Number of

preparations Volume

Number of use categories

Number of industry categories

Low 19 7 19 21

Medium 2 5 2

High

Table 4b Exposure potential of individual substances

CAS

FIN Product Register



categories

Number of industry

categories

50-29-3

58-89-9

77-47-4


79-94-7

81-98-1

85-22-3

87-83-2

93-46-9

115-27-5

115-32-2

116-29-0

117-08-8

117-18-0

118-74-1

118-82-1

119-47-1 Low - Low Low

128-69-8

128-83-6

128-87-0

129-73-7


133-49-3

135-91-1

139-60-6


298-57-7

307-34-6

335-36-4

335-57-9

335-67-1

355-42-0

355-43-1

375-72-4

423-50-7

507-63-1

512-04-9

611-75-6 Low - Low Low

626-39-1

SHC/TS 2-3/030 47

CAS




categories

Number of industry

categories

632-79-1

634-66-2

678-26-2

732-26-3

850-92-0

903-19-5

979-02-2

1068-27-5

1173-09-7

1478-61-1 Low - Low Low

1582-09-8 Low - Low Low

1639-60-7

1691-99-2

2094-98-6

2212-81-9

2309-94-6

2475-31-2

2781-00-2

2795-39-3

2991-51-7

3006-86-8


3278-89-5

3739-67-1

3810-80-8

3825-26-1


3851-87-4


4051-63-2

4162-45-2

4378-61-4

5216-25-1


5590-18-1

6407-78-9

6410-30-6

6410-38-4

6731-36-8

08-02-7139

12223-91-5

13014-24-9

13171-00-1

13417-01-1


14295-43-3

15323-35-0

15958-61-9

16699-20-0

17540-75-9

18181-80-1

18254-13-2


23593-75-1 Low - Low Low

SHC/TS 2-3/030 48

CAS




categories

Number of industry

categories


25268-77-3

25973-55-1 Medium Medium Medium Low

26748-47-0

27137-85-5

29312-59-2

29398-96-7

30707-68-7

31188-91-7

35578-47-3

36861-47-9

37853-59-1 Low - Low Low

38521-51-6

38850-60-1

39489-75-3

40567-16-6

41604-19-7

41999-84-2

42074-68-0

43076-30-8

50679-08-8

50772-29-7

51630-58-1

52179-28-9

52434-90-9

52740-90-6

53184-75-1

53928-30-6

54079-53-7

54914-37-3

55525-54-7

58997-88-9

59447-55-1

61167-58-6

64131-85-7

65294-17-9

67564-91-4 Low - Low Low

68937-41-7 Medium - Medium Low

70321-86-7 Low - Low Low

72968-71-9


SHC/TS 2-3/030 49

Norway:

Results from the Norwegian Products Register (Data from year 2001)

CAS No Available to consumers



categories

Number of industry

categories

25973-55-1 Yes High Medium Medium Medium



128-69-8 No High Medium Medium Low

68937-41-7 Yes Medium Medium Medium Medium

119-47-1 Yes Medium Low Medium Medium

4051-63-2 No High Medium Low Low

3846-71-7 No High Medium Low Low

2991-51-7 Yes Medium Low Medium Medium

70321-86-7 No Medium Low Medium Medium

3864-99-1 No Medium Low Medium Low

732-26-3 No Low Low Medium Low

78-63-7 No Low Medium Low Low

89347-09-1 No Low Low Medium Low



1691-99-2 No Medium Low Low Low

118-82-1 Yes Low Low Medium Low

14295-43-3 No Medium Low Low Low

6731-36-8 No Low Low Low Low



15323-35-0 Yes Low Low Low Low



SHC/TS 2-3/030 50

Sweden: Results from the Swedish Products Register (Data from year 2000)

CAS nr Available to

Annual Number of

consumers volume preparations ind branches

product types

58-89-9 79-94-7 No High Medium Low Medium 81-98-1 87-83-2 78-63-7 No Medium Medium Low Medium 50-29-3 77-47-4 No Low Low Low Low

118-82-1 Yes Medium Medium Medium Medium 93-46-9

128-83-6 128-87-0 118-74-1 135-91-1 129-73-7 128-69-8 No Low Low Low Low 85-22-3

119-47-1 Yes Medium Medium High High 139-60-6 133-49-3 No Low Low Low Low 115-32-2 115-27-5 No High Low Low Low 116-29-0 No Low Low Low Low 117-18-0 117-08-8 133-14-2 No Medium Low Low Low 152-11-4 298-57-7 307-34-6 No Low Low Low Low 335-67-1 335-57-9 335-36-4 No Low Low Low Low 375-72-4 355-43-1 355-42-0 423-50-7 507-63-1 512-04-9 611-75-6 No Low Low Low Low 632-79-1 634-66-2 626-39-1 678-26-2 732-26-3 Yes Medium Medium Medium Medium 850-92-0 903-19-5 979-02-2

1068-27-5 No High Medium Low Low 1173-09-7 1478-61-1 No Low Medium Low Medium 1582-09-8 1639-60-7 No Low Low Low Low 1691-99-2 2094-98-6 2212-81-9 No Low Low Low Low 2309-94-6 No Low Low Low Low 2475-31-2 No Low Low Low Low 2795-39-3 No Low Low Low Low 2781-00-2 Yes Low Low Low Low 3006-86-8 No Medium Low Low Low 2991-51-7 Yes Low Medium Medium High 3147-75-9 3278-89-5 3739-67-1 3810-80-8 3851-87-4 3864-99-1 Yes Medium Medium Medium High 3846-71-7 No Medium Low Low Low

SHC/TS 2-3/030 51 3825-26-1 No Low Low Low Low 4051-63-2 No Low Medium Low Low 4162-45-2 4378-61-4 Yes Medium Medium Medium Medium 5216-25-1 5285-60-9 No Medium Low Low Low 5590-18-1 No Medium Medium Medium Low 6407-78-9 Yes Low Low Low Low 6410-38-4 6410-30-6 6731-36-8 No Medium Low Low Low 7139-02-8

12223-91-5 13014-24-9 13171-00-1 No Low Low Low Low 13417-01-1 13680-35-8 No Low Low Low Medium 14295-43-3 No Medium Low Low Low 15323-35-0 15958-61-9 16699-20-0 17540-75-9 No Low Low Low Low 18181-80-1 18254-13-2 20241-76-3 No Medium Medium Low Low 23593-75-1 25155-25-3 No High Medium Low Medium 25268-77-3 No Medium Low Low Low 25973-55-1 Yes Medium Medium Medium Medium 26748-47-0 27137-85-5 29312-59-2 29398-96-7 No Low Low Low Low 30707-68-7 31188-91-7 35578-47-3 36861-47-9 No Medium Low Low Low 37853-59-1 No Low Low Low Low 38521-51-6 38850-60-1 39489-75-3 40567-16-6 41604-19-7 41999-84-2 42074-68-0 43076-30-8 50679-08-8 50772-29-7 51630-58-1 52179-28-9 52434-90-9 52740-90-6 53184-75-1 53928-30-6 54079-53-7 No Low Low Low Low 54914-37-3 No Low Low Low Low 55525-54-7 58997-88-9 59447-55-1 61167-58-6 64131-85-7 65294-17-9 67564-91-4 No Medium Low Low Low 68937-41-7 Yes Medium Medium Medium High 70321-86-7 No Medium Medium Medium Medium 72968-71-9 No Low Low Low Low 89347-09-1 Yes Medium Medium Medium Medium

appendix i - miljøstyrelsen pbt... · shc/ts 2-3/0304 annex 4. high production volume pbs...

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