safety evaluation of gums and thickeners used in cosmetic ... · formulation de produits...

International Journal of Cosmetic Science 4 . 5 3 - 6 6 (1982)

Safety evaluation of gums and thickeners used in cosmetic for mu lations

J . P. GUILLOT*, J. Y . GIAUFFRETI, M . C. MARTINI$, J. F. GONNET* and G. SOULE*, “Institut Francais de Recherches et Essais Biologiques, Lyon/Les Oncins, 692 10 I’Arbresle, tProduits de Beauti Lancaster (Service Recherche), 7 avenue d’Ostende, Monte Carlo, and SInstitut de Pharmacie Industrielle (Option Cosmktique), 8 avenue Rockefeller, 69008 Lyon, France

Received 3 August I981

Key words: Irritation. eye. \kin, gelatin, cqetable mucilages. inorganic colloids, synthetic polymers.

Synopsis Safety tests have been carried ou t on gunis and thickeners, continuing a study involving commonly used cosmetic ingredients ( I , 2.3,4). The ocular and cutaneous tolerance tests have been conducted on the rabbit following the official French methods (5 ,6) but with some complements or modifications ( I , 2 , 3 , 4, 7). The test substances (listed in Table 1) were products from various suppliers and {if different types and grades. None of the fifty samples tested provoked pathological lesions of the ocular mucous membrane; nevertheless, corneal irritation was noted with silicates, silica and bentonite, probably due to mechanical effect, when applied at relatively high concentration. The highest score on the primary cutaneous irritancy test (moderately irritant) was that for the gelled volatile hydrocarbon solvents. The repeated application test was continued for 6 weeks: no significant pathological reaction was observed. Only a slight intolerance was noted with the gels of volatile hydrocarbons and isopropyl myristate, but the irritant reactions were significantly reduced compared to those previously observed with the pure oils (1, 2). Consequently, based on these data. it can be concluded that the use of gums and thickeners involved in this publication prcsents no hazard for the skin.

Evaluation toxicologique d’agents gelifints et 6paississants utilises en cosmetologie

Resume Faisant suite i une s6rie de travaux rdaliscs sur les principaux corps gras entrant dans la formulation de produits cosmktiqucs ( I , 2 . 3,4), cette 6tude concerne les agents g6lifiants et dpaissants genkralement incorpor6s dam Ic but de stabiliser les preparations ou d’am81- iorer leurs caracteres organolcptiqucs.

Les 50 6chantillons test& figurent dans le Tableau I. 11s appartiennent aux principaux types utilids, savoir: mucilages v6gC.tau.L. collo’ides inorganiques et polymires synth6- tiques. Les essais de tol6ranccs oculaire e’ cutan6e ont 6t6 effect& selon les methodes officielles franpises ( 5 , 6 ) mais avec quelques compl6ments ou modifications (1 ,2 ,3 ,4 , 7). Au niveau de la muqueuse oculaire, certains produits tels que les silicates, la silice, la bcn- tonite irritent la muqueuse oculaire, vraisernblablement par effet abrasif, lorsqu’ils sont utilis6s concentration relativement 6levdt:. Au niveau de l’irritation cutan6e primaire, les indices obtenus sont dans I’enscmble faibles except6 pour les gels de solvants hydrocar- bones volatils (moyennement irritants sous pansement occlusif). Apris applications it&- atives pendant 6 semaines, seuls les gels de solvants hydroearbonCs volatils et de myristate d’isopropyle ont montrd unc l d g h intolPrance, confirmant ainsi les rksultats obtenus

0142-5463/82/0400-0053 $02.00 0 1982 International Journal of Cosmetic Science

53

54 J. P. Guillot et al.

(1,2). On peut, en consCquence, conclure que l'utilisation des agents gilifiants et hpaissis- sants, faisant l'objet de cette publication, parait dCnuCe de tout inconv6nient au niveau cutani.

I N T R O D U C T I O N

Continuing preceding work on the safety evaluation of cosmetic ingredients in common use (1 , 2, 3, 4), this publication involves gums and thickening agents. Several types of gums and thickeners are widely employed in cosmetic, toiletry and pharmaceutical formulations and some date back many centuries such as, for example, starch, casein, tragacanth and other natural products. More recently, the introduction of synthetic thickeners and polymeric derivatives has considerably expanded the fields of application and has enabled formulating chemists to have a broad range of choice.

The types available may be classified as follows:

substances of animal origin - gelatin, casein, etc., vegetable gums and related semi-synthetic materials - algin, aloe, cellulose derivatives, locust bean, guar, etc., inorganic compounds - bentonites, silicates, silica, etc., synthetic polymers - vinyl polymers (including polyvinyl alcohol, carboxyvinylpolymer, polyvinylpyrrolidone) polyacrylamide, polyethylene glycol resins, etc.

From each of which representative samples were involved in this study. These materials are used for their thickening, binding, suspending, film forming and

stabilizing effects. They have multiple properties, reacting in different ways to such variables as temperature, pH, degree of polymerization, sunlight, storage, impurities and preservatives.

EXPE R I M E N TA L P ROC E D U R E

Materials The test substances consisted of fifty ingredients and, whenever possible, samples from various suppliers and of different grades were evaluated. It was however impossible within the constraints of the investigation to test several lots from the same supplier. A qualitative selection was purposely not made as it was desirable to study raw materials readily available on the market.

The materials studied are given in Table I. The choice of concentrations has been motivated by obtaining a consistency allowing an

easy application.

Physico-chemical analysis With regard to the physicochemical parameters scored, the specifications of tested materials can be considered as corresponding to those regularly employed in industry. The infrared spectroscopy, used for identification, did not show noticeable differences for similar compounds from different manufacturers.

Manufacturing procedures of dilutions/dispersions Most of the gums and thickeners used are in powdered form and a dilution/suspension was necessary for the safety evaluation tests. Solutions or dispersions of water soluble/dispersible

Strfety ajgums and thickeners 55

Table 1. Raw materials tested, Loncentration\ m d rample reference numbers

TYPC Chemical name or CTi A adopted iiiiine Ref. Conc. ”/o W/W number

~~ ~-~

I Gelatin 5 110

I1 Sodium alginate (Algin)

I11

Cellulose derivatives

Cellulose gum (CMC)

Cellulose (microcrystalline L clluluse)

Hydroxyethylcellulow (H t (

Quaternium-19 (cationic k l l < )

Hydroxypropyi cellulose ( 1 I tY’)

Methylcellulose (MC)

Vegetable mucins

Aloe

Locust bean gum

Guar gum

Tara gum

Xanthan gum*

Bentonite (colloidal aluminium silicate c l a ~ I

Quaternium-l8bentonite

Quaternium-1 8-hectorite

Organically modified clay mastergels Lanolin oil (and) isopropyl palmitatc (anti) stearalkonium hectorite (and) propylenr ,,arbonate

Castor oil (and) stearalkonium hectorite I md) propylene carbonate Isopropyl myristate (and) stearalkonium hectorite (and) propylene carbonate

Mineral spirits (and) quaternium-18 hectorite (and) pr opylene carbonate Caprylic/capric triglyceridc (and) stearalk onium hectorite (and) propylene carbonate

Montmorillonite (complex silicate clay )

2 111 2 112 2 113

4 114 1 115

10 116

10 117

118 119 120 121 122

123 124 125

5 126

I 127

2 128 2 129 1 130

1 131

1 132 1 133

5 134 10 135

5 136

5 137

As supplied 138

As supplied 139

As supplied 140

As supplied 141

As supplied 142

10 143


Table I. continued

Type Chemical name or CTFA adopted name Kef.

Conc. % W/W number

IV

Kaolin (native hydrated aluminium silicate) 50 144

Magnesium aluminium silicate (complex colloidal)

10 145 10 146

Silica 9 147

Polyvinyl alcohol

Carboxyvinylpolyrner (carbomer)

10 148 10 149 10 150

1 151 1 152 1 153

Petroleum distillate (and) aluminium polyoxystearate As supplied 154

Polyacrylamide 5 155

Polyethylene glycol resin (PEG-7M) 10 156

Polyvinylpyrrolidone (PVP) 10 157 10 158 10 159

*Produced by a pure-culture fermentation of a carbohydrate with Xanthomonas campesbis.

gums and thickeners are generally prepared by adding the powder at a steady rate to the vortex of rapidly stirred water. Stirring is continued until a smooth dispersion/solution is obtained, or at least until a l l the particles are evenly suspended. The final consistency de- pends on the method of preparation, i.e. the length and rate of stirring, the varying amounts of work input, the use of heat, etc. Gelatin, the vegetable gums and most of the synthetic polymers tested are in this category of water soluble/dispersible substances, Some of the materials used do not form true solutions. Magnesium aluminium silicate (complex colloidal), for example, swells and expands in water to form a thixotropic colloidal dispersion. This property is reversible. Colloidal clays also absorb water but do not dissolve. Bentonite, a native hydrated colloidal aluminium silicate clay, has a strong affinity for water and some grades may absorb several times their volume. One (no. 135) out of the two sampIes of bentonite involved in this study was tested dispersed in water. The second sample (no. 134) was prepared using the following formula:

gellant 5% W/W, mineral oil 46% W/W, water 45.8% W/W, ethanol3% W/W, parabens 0.2% W/W,

the same formulation being employed for quaternium-18-bentonite and quaternium-18- hectorite.

The organically modified clay ‘mastergels’ (products .nos 138-142) and the sample no. 154 have been applied as supplied.

h f e t y of gums and thickeners 57

According to the suppliers’ information, the corriposition is approximately as follows:

gellant 10% w/w; solvent (mineral oil, castor oil. etc.) polar additive (propylene carbollate)

87% W/W; 3% W/W.

Finally, because some gums are prone to microbid attack, preservatives have been added (sodium parabens 0.1 5%; propylparabens 0.05%. the dilutions freshly prepared every week, stored in a cool place and protected against LJV.

Safety evaluation methods The ocular and cutaneous tolerance was cvaluated the rabbit using the following tests: determination of the ocular irritation index (011); determination of the primary cutaneous irritation index under patch-test (HI); determination of the cumulative irritation index after repeated exposures.

The test procedure is described in the Journal Ojticiel de la Republique Frangaise (5, 6 ) but the following additions or modifications have been made (1 ,2 ,3 ,4 ,7 ) .

Ocular irntation test Reading after 1 h, in addition to those o t 74 h. 3 d‘iys, 3 days, 4 days and 7 days. Photo- motor reflex study. Use of a 2% aqueoub solution of fluorescein to help to demonstrate the presence of corneal opacity and to evaluate the extent of surface attack. Qualitative evaluation of any ulceration or granulation. bse o f an ophthalmoscope and a retinograph. Inter- pretation of the results using an evaluation scale froni 0 to 110 (Kay and Calandra modified) (8).

Primary cutaneous im’tation test Use of occlusive patches ‘Neodermotest‘ 1 king of the patches using absorbent gauze held in place by adhesive tape. Housing in individual cages Modification of the interpretation of mean scores - non irritant, less than 0.5. slightly ii-ri tmt, 0.5-2.0.

Cumulative cutaneous irritation test Reduction of the length of treatment: from 3 month:, to 6 weeks. Application of 2 ml of the test substance per animal, instead of 2 ml per kilo. I‘wo test substances are applied as such daily (5 days a week) for 6 weeks, on the right and left flanks respectively of the 3 rabbits, wiping off the excess of substance with gauze. Daily readings expressed as a weekly average. Qualitative evaluation of thickening and dryness uf 1 he skin. Histological examination after 6 weeks of treatment. Study of recovery from cutaneous injuries, by stopping application for 7 days and examining the skin after this rest.

Interpretation o f results The results given in the tables call for several comments. For the ocular irritation test, only the acute ocular irritation index (AOlI) is expressed. For the primary cutaneous irritation test, duplicate assays were monitored in many cases 111 order to ensure significant results: the mean index is given in the tables. Foi the 6-week ;urndative irritation test, the data is a ‘rCsumB ’ of macroscopic and histological findings. thcy correspond to the most characteristic phenomena observed on all animals. The mean irntation index for each animal is calculated by adding up the erythema and oedema scores obtained each week (from five daily readings) and the mean maximum irritation index (MMI I ) is given in the tables.


The interpretation of the results was carried out using the following principles:

Ocular iwitation index (OII). A compound does not provoke any significant injury to the eye mucous membrane when no opacity of the cornea occurs and when the ocular index is less than 15.

Aimary cutaneous irritation index (PII). The result is deemed satisfactory if the index is less than 0.5, but it is still acceptable if it is not greater than 1, taking into account experi- mental practice.

CbmuEative cutaneous irritation index (CII). Concerning the skin response to repeated exposures, the interpretation is more complex because, for some series of products tested after several applications, erythema was noted lasting until the final test. It was observed that vesicles appeared for spasmodic or prolonged periods, as well as papules, maculae or patches of erythema. However, if the presence of vesicles is an allergic reaction in the human, it would appear that this is not applicable to the rabbit, because in this event 60-7076 of cosmetics would appear to contain allergy-inducers. It appears that this is due to an occlusive film formed by the remaining material in spite of all the precautions taken to remove the excess of product. The pores in the skin of rabbit are more dilated than those of human skin and materials tend to accumulate in these cavities. Furthermore, these products when applied under the same conditions to hairless or normal rats, provoke the appearance of vesicles.

To ensure a proper evaluation of skin irritancy, it is necessary that macroscopic observations show comparable results on all animals involved because orthoergic reactions give a collective response contrary to sensitization. It is important that reactions are observed over the total epidermis area treated and not just at localized points.

Histological examinations carried out on two biopsies for each rabbit should confirm the macroscopic observations.

Because the rabbit skin is more responsive than human skin, this procedure is necessary to eliminate individual or local reactions and to take into consideration only the pathological lesions.

RESULTS A N D DISCUSSION (TABLES I l - X )

Table II. Gelatin

6-week cumulative cutaneous irritation Ref' no. % *'I1 'I1 (macroscopic and histological evaluation) Compound

~~ ~

Gelatin 110 5 5.66 0 Relatively well tolerated (MMII = 1.00)

Table Ill. Sodium aleinate

6-week cumulative cutaneous irritation Ref* no* % 'I1 (macroscopic and histological evaluation) Compound

Sodium alginate 111 2 3.00 0 Relatively well tolerated (MMII = 0.67) (Akin) 112 2 9.17 0 Very well tolerated (MMII = 0)

113 2 5.50 0.08 Relatively well tolerated (MMII = 0.67)

A011 = Acute ocular irritation index. PI1 = Primary cutaneous irritation index. MMII = Mean maximum cutaneous irritation index

Su.fet.v of gums and thickeners 59

Table IV. ('ellulow dcri\.ltives

6-week cumulative cutaneous irritation (macroscopic and histological evaluation) Compounds Ref.no. Conc.% AOII PI1

-

Cellulose gum 114 4 7 X ? 0.88 Relatively well tolerated (MMII = 0.67)

(sodium CMC) 115 1 5 0 Kelatively well tolerated (MMII = 1.00)

116 10 6 1 - 4 ) Well tolerated (MMII = 0.34)

117 10 5 I 0.08 Relatively well tolerated (MMII = 0.67) Cellulose

(microcrystalline)

Hydroxy-e thy1 118 2 6 1 7 0.08 Well tolerated (MMII = 0.34)

cellulose 119 2 -, 5 0 0.1 3 Relatively well tolerated (MMII = 1.00)

Quaternium-19 120 6 10.00 0.08 Relatively well tolerated (MMII = 1.34)

(cationic HEC) 121 5 8.(lO 0 1 3 Relatively well tolerated (MMII = 1.34)

Hydroxy-propyl 122 2 5 3 3 0.13 Relatively well tolerated (MMII = 0.67)

cellulose

Me thylcellulose 123 2 X I 7 0.04 Well tolerated (MMII = 0.34)

124 2 I l l 5 0 0.08 Very well tolerated (MMII = 0)

125 2 6.82 0.21 Relatively well tolerated (MMII = 0.67)

Table V. Vcgetablc mucilages

Compound 6-week cumulative cutaneous irritation

Ref' no. Cone' ' ''I (macroscopic and histological evaluation) . . -~

Aloe 126 5 9 I 7 0.63 Well tolerated (MMII = 0.34)

Locust bean 127 1 5.h' u Very well tolerated (MMII = 0)

Guar

128 2 7.17 0 Very well tolerated (MMII = 0)

129 2 9.17 0 Very well tolerated (MMIl = 0) 130 1 7 3 3 0.08 Very well tolerated (MMlI = 0)

Tara 131 1 6.(1(1 0.33 Very well tolerated (MMII = 0)

Table VI Xanthan gum

6-week cumulative cutaneous irritation Ref' no. ' 'I1 (macroscopic and histological evaluation) Compound

132 1 2.51) 0.13 Very well tolerated (MMII = 0)

133 1 5 83 0.1 3 Very well tolerated (MMII = 0) Xanthan gum

-.

AOII = Acute ocular irritation indrv PI1 = Primary cutaneous mitation index. MMII = Mean maximum cutaneou\ irritation index.

Tab

le V

II In

orga

nic

com

poun

ds

L

.b c?

(mac

rosc

opic

and

his

tolo

gica

l eva

luat

ion)

5 d

6-w

eek

cum

ulat

ive

cuta

neou

s irr

itatio

n C

ompo

und

Ref

. no.

C

onc.

%

A01

1 PI

1 .b c?

(mac

rosc

opic

and

his

tolo

gica

l eva

luat

ion)

5 d

6-w

eek

cum

ulat

ive

cuta

neou

s irr

itatio

n C

ompo

und

Ref

. no.

C

onc.

%

A01

1 PI

1

Ben

toni

te

Q

134

5 11

.33

0.13

K

elat

ivel

y w

ell t

oler

ated

(MM

II =

1.0

0)

2 13

5 10

A

ssay

1 =

15.

17 (c

orne

al o

paci

ty

0.04

W

ell t

oler

ated

(M

MII

= 0

.34)

-+ Fa 5

in tw

o ra

bbits

) A

ssay

2 =

14.

50 (c

orne

al o

paci

ty

in th

ree

rabb

its)

Qua

tern

ium

-18

bent

onite

13

6 5

11.3

3 0.

08

Rel

ativ

ely

wel

l tol

erat

ed (

MM

II =

1.3

4)

Qua

tern

ium

-18

hect

orite

13

7 5

10.1

7 0.

17

Rel

ativ

ely

wel

l tol

erat

ed (

MM

II =

1.3

4)

Mod

ified

hec

torit

e (a

nd):

Lano

lin o

il 13

8 As

sup

plie

d C

asto

r oil

139

As s

uppl

ied

12.6

7 8.

50

1.25

1.

83

Rel

ativ

ely

wel

l tol

erat

ed (

MM

II =

1.6

7)

Rel

ativ

ely

wel

l tol

erat

ed (

MM

II =

2.0

0)

Isop

ropy

l myr

ista

te

140

As s

uppl

ied

Ass

ay 1

= 1

2.33

(sl

ight

cor

neal

A

ssay

1 =

0.9

2 Sl

ight

into

lera

nce:

orth

oerg

ic re

actio

n op

acity

in tw

o ra

bbits

) A

ssay

2 =

14.

50 (s

light

cor

neal

op

acity

in

one

rabb

it)

A01

1 = A

cute

ocu

lar i

rrita

tion

inde

x.

PI1 =

Prim

ary

cuta

neou

s irr

itatio

n in

dex.

M

MII

= M

ean

max

imum

cut

aneo

us i

rrita

tion

inde

x.

Ass

ay 2

= 1

.08

Ope

n te

st =

0

(MM

II =

2.6

7)

Tabl

e V

I I I.

Inor

gani

c co

mpo

unds

Com

poun

d R

ef. n

o.

Con

c. %

A

OII

6-

wee

k cu

mul

ativ

e cu

tane

ous

irri

tatio

n (m

acro

scop

ic a

nd h

isto

logi

cal e

valu

atio

n)

PI1

Mod

ified

hec

tori

te (a

nd):

Min

eral

spi

rits

14

1 A

s sup

plie

d A

ssay

1 =

16.

83 (s

light

cor

neal

A

ssay

1 =

2.8

3 Sl

ight

into

lera

nce

(MM

II =

2.0

0)

opac

ity in

five

rabb

its)

Ass

ay 2

= 1

7.17

(sl

ight

cor

neal

op

acity

in th

ree

rabb

its)

Ass

ay 2

= 3

.25

Ope

n te

st =

2.1

7

Cap

ry li

c/ca

pric

tri

glyc

erid

c

Von

trno

rillo

nite

Kao

lin

142

As

supp

lied

11.0

0 0.

83

Rel

ativ

ely

wel

l tol

erat

ed (M

MII

= 2

.00)

143

10

12.0

0 0.

46

Kel

ativ

ely

wel

l to

lera

ted

(MM

II =

0.6

7)

144

50

12.8

3 (s

light

cor

neal

opa

city

in

thre

e ra

bbits

)

0 V

crq

wel

l tol

erat

ed (

MM

II

0)

14'

11

1

ii 6

7

I1

Kel

atir

clt

wel

l to

lera

ted

(\f\ljI

II 6')

@ %

2 2 & p

.t"

(slig

ht L

orne

al o

paci

ty i

n to

ur

rabb

its)

(slig

ht c

orne

al o

paci

ty in

fou

r ra

bbits

)

I46

10

19.6

7 0

Wel

l tol

erat

ed (M

MII

= 0

.33)

Q

A01

1 =

Acu

te o

cula

r ir

rita

tion

inde

x PI

1 =

Prim

ary

cuta

neou

s ir

rita

tion

inde

x.

MM

II =

Mea

n m

axim

um c

utan

eous

irri

tatio

n in

dex.

c) s

??

r;'

2 2

Q

E 2

Tabl

e IX

. In

orga

nic

com

poun

ds

Com

poun

d R

ef. n

o.

Con

c. %

A

011

6-w

eek

cum

ulat

ive

cuta

neou

s ir

rita

tion

m (m

acro

scop

ic a

nd h

isto

logi

cal e

valu

atio

n)

c1

PI1

a Si

lica

147

9 A

ssay

1

0 R

elat

ivel

y w

ell t

oler

ated

(M

MII

= 0.

67)

1 h

: 16

.33*

24

h :

lO.O

Ot

*Slig

ht c

orne

al o

paci

ty in

fou

r rab

bits

?

Sla

t cor

neal

opa

city

in o

ne ra

bbit

Ass

ay 2

1

h :

22.1

7*

24 h

: 1

0.61

t *C

orne

al o

paci

ty in

six

rabb

its

?Slig

ht c

orne

al o

paci

ty in

one

rabb

it

A01

1 =

Acu

te o

cula

r ir

rita

tion

inde

x.

PI1 =

Prim

ary

cuta

neou

s ir

rita

tion

inde

x.

MM

II =

Mea

n m

axim

um c

utan

eous

irri

tatio

n in

dex.

Tabl

e X

. Sy

nthe

tic

poly

mer

s

Com

poun

d R

ef. n

o.

Con

c. 70

A

OII

PI

1

~~

~

6-w

eek

cum

ulat

ive

cuta

neou

s ir

rita

tion

(m

acro

scop

ic an

d hi

stol

ogic

al e

valu

atio

n)

Poly

viny

l alc

ohol

14

8 10

11

.00

0.04

14

9 10

7.

17

0.08

15

0 10

9.

50

0.42

Car

boxy

-vin

ylpo

lym

er

151

15 2

15

3

1 8.

83

0.08

1

9.33

0

1 11

.00

0.04

Rel

ativ

ely

wel

l tol

erat

ed (M

MII

= 1

.OO)

R

elat

ivel

y w

ell t

oler

ated

(MM

II =

1.0

0)

Rel

ativ

ely

wel

l tol

erat

ed (M

MII

= 1

.OO)

Rel

ativ

ely

wel

l tol

erat

ed (

MM

II =

1 .O

O)

Rel

ativ

ely

wel

l tol

erat

ed (M

MII

= 1

.OO)

V

ery

wel

l to

lera

ted

(MM

II =

0)

Pctr

oleu

in d

istil

latc

land

) 15

4 .4s s

uppl

ied

5.00

A

ssay

1 =

3.00

R

elat

ivel

y w

ell

tole

rate

d (M

MII

= 1 .OO)

alum

iniu

m p

nlyo

\yct

eara

tc

.4S

Yd

y 2

3.33

O

pen

test

= 1

.2 I

Poly

acry

lam

ide

I55

5 6.

17

0.04

R

elat

ivel

y w

ell

tole

rate

d (M

MII

= 1

.Oo)

Poly

ethy

lene

~lv

col re

rin

I56

10

4.00

0

I’V P

I5

7 1 ii

4.83

(I

158

10

4.00

0

159

10

4.83

0

Wel

l tol

erat

cd W

MII

= 0

67)

t,

Rel

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The gums and thickening agents involved in this study can be considered as safe and the few reactions observed were generally mild.

None of the fifty test substances provoked pathological lesions of the ocular mucous membrane. Nevertheless, corneal irritation was noted with bentonite, silica, silicates and with the isopropyl myristate and mineral oil mastergels. This irritation, probably due to a mechanical effect, occurs when the substances are applied at relatively high concentration (equal or greater than 10%). The mild reactions observed with some other materials could be due to the slightly alkaline pH of the applied preparations (presence of sodium parabens). The mean acute ocular irritation index was 6.83 (maximum 10.50) for the vegetable mucilages and gelatin, 14.12 (maximum 22.17) for the inorganic compounds, and 7.14 (maximum 11.00) for the synthetic polymers.

The highest scores (moderately irritant) for the primary cutaneous irritancy were those of the organically modified clay mastergels and the sample of mineral spirits gelled by aluminium polyoxystearate. It must be noted that these values are significantly higher than those previously obtained with the corresponding oils, tested neat under patch, and this could be explained by the presence of propylene carbonate (to be proved). The mean primary cutaneous irritation index was 0.09 (maximum 0.63) for the vegetable mucilages and gelatin, 0.93 (maximum 3.25) for the inorganic compounds, and 0.59 (maximum 3.33) for the synthetic polymers.

No significant severe reaction was macroscopically and histologically observed after daily application for 6 weeks. Only a slight intolerance was noted for the gelled mineral spirits and isopropyl myristate tested as supplied. This leads to the following remarks:

(1) The irritant reactions are lessened when these substances are applied without patch. (2) The irritation previously obtained with mineral spirits and isopropyl myristate is

significantly reduced for the gelled oils and, consequently, it seems that gellants have protec- tive effects on the skin.

(3) The filmforming or occlusive properties of a thickener will not a priori be a cause of intolerance.

CONCLUSION

Based on these data, it can be concluded that the use of gums and thickeners involved in this publication presents no hazard for the skin.

ACKNOWLEDGMENTS

All histological examinations were performed and interpreted by Dr J. Guilane, Dermatolo- gist. The authors also gratefully acknowledge the technical assistance of C. Clement, L. Ferrero, J. Charroy, N. Chaussard, J. Y. Guyot and D. Thiry.

REFERENCES

1 . Guillot, J. P., Martini, M. C1. and Giauffret, J . Y. Safety evaluation of cosmetic raw materials.J. SOC. Comet . Chem. 28 311-393 (1917) .

2 . Guillot, J. P., Giauffret, J. Y. et Martini, M. C1. Etudes de toldrances oculaire et cutanee chez le lapin

Szjety of gums and thickeners 65

de diffirentes matikres premi6res utilisdes en cosmktologie zt provenant de fabrications diverses. 2dme partie: les huiles vdgktales, animales et min6rales. Inf . J. Cosrnet. Sci. 1 27-57 (1979).

3. Guillot, J. P., Giauffret, J. Y., Martini, M. Cl., Gonnet, J . 1.’ et Soul&, G. Etudes de tolhances oculaire et cutanbe chez le lapin de diffdrents dchantillons d’esters d’acides gras. Int . J . Cosrnet. Sci. 1 265-290 (1 979).

4. Guillot, J. P., Giauffret, J. Y., Martini, M. (I., Gonnct, .I t . et SoulB, G. Etude toxicologique chez l’animal de diffkrents Bchantillons de lanoline anhydre, de lanoline modifiBe et de ddrivds de lanoline. Int . X Comet. Sci. 2 1-38 (1980).

5 . Journal Officiel de la Rdpublique Franqaise du 21/4/7 1 ~ Bdition Lois et Ddcrets ct du 5/6/73, Bdition Documents Administratifs. Mdthodes officielles d’analyse des cosmitiques et produits de beaut&

6. Journal Officiel de la RBpublique Franqaise du 11/7/75. Chapitre VIII: produits cosrndtiques et produits d’hygiene corporelle. DBcret d’application i paraitre.

7. Guillot, J. P. Les test de toldrance du Journal Officiel appliquds aux cosmktiques: description som- maire, modifications proposds et rdsultats obtenus sur plus de 600 produits. Purfums, Cosme‘tiques, Arches20 75-88 (1978).

8. Kay, J. H. and Calandra, J. C. Interpretation of eye irritation tests. J. SOC. Cosrnet. Chem. 6 281-289 (1962).