Safety evaluation of gums and thickeners used in cosmetic ... · formulation de produits cosmktiqucs (I, 2. 3,4), ... thickeners are widely employed in cosmetic, toiletry and pharmaceutical
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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; never- theless, 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 sig- nificant 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 thick- eners 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 com- pounds 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
56 J. P. Guillot et al.
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 ben- tonite 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 eval- uation 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.
58 J. P. Guillot et al.
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 obser- vations 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
ativ
ely
we
ll to
lcra
ted
(MM
II ~
1 U
O)
~1
Rel
ativ
ely
wel
l tol
erat
ed (M
MII
= 1
.OO)
,o
R
elat
ivel
y w
ell t
oler
ated
(MM
II =
1.3
4)
2 % ‘c 5 3
a A
OII
= A
cute
ocu
lar
irri
tati
on in
dex.
PI
1 =
Pri
mar
y cu
tane
ous
irri
tati
on in
dex.
M
MII
= M
ean
max
imum
cut
aneo
us ir
rita
tion
inde
x.
G? & B *+
x
R’
2 s rp
64 J. P. Guillot et al.
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 mechan- ical 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 alumin- ium 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 cu- taneous 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 syn- thetic 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).
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