JOURNAL

OF

Volume7, Number

Mary

Ann

THE

Liebert,AMERICANCOLLEGEOFTOXICOLOGY

6,1988inc.,

Publishers

5

Final Report on the Safety
Assessment of Steareth-2, -4, -6,-7, -10, -11, -13, -15, and -20
The steareth group is a series of compounds
prepared by reacting stearyl
alcohol with ethylene oxide to form polyoxyethylene
stearyl ethers. Steareths
are waxy solids used primarily as emulsifiers in cosmetics at concentrationsof
up to 25%.
Steareth-2 and -10 were nontoxic to rats in acute oral toxicity studies. In
subchronic
testing, steareth-20 was nontoxic to rabbits when administereddermally at concentrationsof 4%. Steareth-2 and -10, at concentrationsof up
to 60% in water, were at most mildly irritating to rabbit eyes and only mild
irritants when tested in cosmetic formulations
at concentrationsof up to 60%.
Structurally
similar polyoxyethylene
alkyl ethers were neither mutagenic
nor tumor promoters.
Steareth-2, -10, and -20 in water were neither primary irritants nor sensitizers to human skin. Steareth-20 was not phototoxic.
On the basis of the available data it is concluded that steareths-2, -4, -6, -7,-10, -11, -13, -15, and -20 are safe as cosmetic ingredientsin the present
practices of use and concentration.

CHEMISTRY
Definition

and StructureS

teareth (CAS No. 9005-00-9) is the Cosmetic, Toiletry and Fragrance Association (CTFA) adopted name for a series of polyethylene
glycol ethers ofstearyl alcohol. These cosmetic ingredients conform to the formulaCH&H,),,CH,(OCH,CH,),OH
where n has an average value that ranges from 2 (as in the case of steareth-2)
to 20 (i.e., steareth-20).(l)Other names for steareth include polyethylene glycol stearyl ether, polyoxyethylene
stearyl ether, polyethylene glycol octadecyl ether, polyethylene
881

882

COSMETIC

INGREDIENTREVIEWglycol octadecanol ether, polyoxyethylene
octadecyl ether, and stearyl alcohol
ethoxylate. In addition to the generic CAS No. 9005-00-9 for the entire stearethseries, steareth-6 (3,6,9,12,15,18-hexaoxahexatriacontan-l-01)
has the CAS No.
2420-29-3.“-3)
Numerous trade names for the steareth series are presented
elsewhere.(‘s3)

MethodThe steareths
alcohol?

are

CHX(CH,),,CHLOH+

Stearyl alcohol

preparedof Manufacturebyreacting

H2CYO/CH2~

ethylenewithstearylCH3(CH,),,CH,(OCH,CH,),OH
polyoxyethylene

ethylene oxide

Chemicaloxidestearyl ether(Steareth)and Physical Properties

Steareths-2, -10, and -20 are waxy solids. (‘) They are soluble in ethanol andother lower alcohols and insoluble in mineral oil and coal tar hydrocarbons.(5’6)
Water solubility varies and increases with increasing ethylene oxide content.(5,7)
These compounds have a range in average molecular weight from 358 forsteareth-2
to 1150 for steareth-20.
In cosmetic-grade
steareth (-2, -10, -2O),
approximately
95% of the alkyl chain is stearyl (C,,), with smaller amounts
consistingof cetyl (C,,) and “other alkyl groups” (not specified) (Table 1).(5’Analytical

Methods

Analytic methods for the separation and/or determinationof the stearethcompounds include high-performanceliquid chromatography,@spectro-photometry,
and thin-layer chromatography. (lo) Davis(“) has described a sensitive chemical test for the analysis of polyoxyethylene
compounds as well as
for the analysis of products emulsified
with polyoxyethylenes.
The emulsion
stabilityof steareths and other polyethylene
ethers of long-chain, aliphatic
alcohols can be determined by gas chromatography(12) and spectral absorption,(13,“) respectively.

Impurities
Information was not available as to the possible presence of trace amountsof 1,4-dioxane or other impurities
in the steareth compounds.

COSMETIC
The
steareths
are
used
in
emulsifiers.(6,16,17,20,21) Th ese ingredientshigh alkalinity

USE

cosmetic
products
primarilyasare particularly useful in emulsions ofor acidity. PX”) In addition to their use as lipophilic (steareth-2)

ASSESSMENT:TABLE

STEARETHS

883

Chemical and Physical Data for Steareth-2,

1.

Data

-10, and -20

Steareth-2

Description

Steareth- 70

Pale yellow to buff-Whitecolored, waxy solid

Steareth-20
White

to light tan,waxy solid having
a slightly

References

to light

5tan, waxy solid

fatty

odor
Hydroxyl

value

147-l

Ethylene

oxide contact

1.9-2.5

62

70-85

45-60

5

7-T 2

14-22

5
5

(mol EO per mol)
Acid value
Free polyethylene

glycols

Moisture
Free ethyleneoxide

1 .O maximum

1 .O maximum

10 maximum

1.5% maximum

8.0% maximum

10% maximum

5

1 .O% maximum

3.0% maximum

3.0% maximum

5
5100 ppm maximum

100 ppm maximum

100 ppm maximum

Water solubility

Insoluble

Insoluble

Soluble5

Viscosity

2000 CP144 CP15

HLB (hydrophile-lipophile

4.9

15.3

4,15-1912.4

balance)”aThe HLB
attractionthat(hydrophile-lipophileof an emulsifier

is lipophiliccharacteremulsifier;thata high number.

1 to 40. The

HLB

The

a low HLB
midpoint

value is useful

may be expected fromis an expression(or for two phases of a systemin character is assigned

is assigned

ranged frombehavior

balance) of an emulsifier

for water/oil

number,and an emulsifier

is approximately

because it allows

a surfactant

a high value, about 16, will be a solubilizer(i.e.,

a low

of the relative simultaneous

to be emulsified).

10, and the assigneda prediction

An emulsifierthat is hydrophilicof the control

value, about 4, will

for many standard cosmetic

Invalues haveaction or

be a water-in-oil

ingredients).“b’or oil-water(steareth-10 and -20) emulsifiers,(“)
steareths may also be used aswetting agents,@) solubilizers,(“‘)
and nonionic surfactants.(l@ At a use concentration of 1 g of a formulation
containing 5% of a steareth, which in turn
contains 100 ppm free ethylene oxide, the exposure of the consumer is to 5 pg
ethylene oxide.
Data submitted to the Food and Drug Administration(FDA) in 1981 bycosmetic firms participating in the voluntary cosmetic registration
programindicated that steareth-2 was used in a total of 107 cosmetic products.
Steareth-10,-15, and -20 were used in a total of 104 cosmetic formulations(Tables 2 through 6). Products formulated with steareths included personal
cleanlinessproducts and deodorants, as well as suntan, fragrance, skin, eye,and hair preparations. Reported concentrations of steareths in these products
varied from I 0.1% (lowest reported range) to > IO-25% (highest reported
range). The majority of products containing steareth-2 had concentrations
within the ranges of > l-5%or > 0.1-l%.
Steareth-10, -15 and -20 were usedin products mainly in the > l-5%and > 0.1-l%concentration ranges (Tables
2 and 3).(22)The FDA cosmetic product formulation computer printout(22’ is compiled
through voluntary filing of such data in accordance with Title 21 Part 720.4 of
the Code of Federal Regulations. (23) Ingredients are listed in preset concentration ranges under specific product type categories. Since certain cosmetic
ingredients are supplied by the manufacturer at less than 100% concentration
the value reported by the cosmetics formulator may not necessarily reflect thd
actual concentration found in the finished product; the actual concentration isCOSMETIC884
TABLE 2.

Product

Formulation

REVIEW

Data for Steareth-2

rota/no.ofrota/noformulat~ow

containing

in category

ingredient

Eye and facial
preparations

3143

Harr preparations (coloringand noncoloring)

1178

Product category

INGREDIENT

No. of product formulations
concentration

within eachrange (74)>I-5

> 0.1-I

42

2

40

19

2

17

>lO-25>5-10

Face, body, and handskin care preparations(including suntan
preparations)4176

1986 Totals
Sources From

46

1

1

32

12

107

1

i

36

69

Reference 22.

a fraction of that reported to the FDA. Data submitted within the frameworkof preset concentration ranges provides the opportunity for overestimationofthe actual concentration of an ingredient in a particular product. An entry at
the lowest end of a concentration
range is considered the same as one
entered at the highest end of that range, thus introducing the possibilityof a2- to IO-fold error in the assumed ingredient concentration.

TABLE 3.

Product

Formulation

Data for Steareth-IO,-15, and -20
No. of product formulations

rota/ no. of

Total no.

formulations

conta/ningin category

ingredient>I-5> 0.1-I

1571

24

1

23

2044

5

3

2

1377

2

1

463

9

5

4

Hair bleaches

83

2

1

1

Deodorants

259

2

1

1

247

19

18

729

7

2

5

2813

29

II

18

229

5

3

2

104

G

56

Product category
Eye and facial makeup
preparations
Colognes,

toileteach conrentration

withinrange (‘6)
I 0.lwaters, hair

tonics and other hydroalcoholic preparations
Hair condrtioners
shampoosandHair straighteners

and permanents(underarm)

Other personal
products

cleanliness

Skin-cleansing

preparations(cold creams, lotions,liquids, and pads)

1

1Face, body, and handskincare preparations(excluding shaving
preparatrons)
Suntanpreparations

1986 Totals
Source:From

Reference 22

2

ASSESSMENT:STEARETHS

885

ABSORPTIONAND

EXCRETION

No absorption or excretion information
is available for the steareth compounds themselves.
The dermal absorption and excretion of an unspecified alcohol ethoxylate
was studied in the rat. Rapid absorption of the 14C-labeled ethoxylate occurred
after a dose of 12.5 mg/kg was applied to the shaved backs of rats. After 72 h,
29% of the radioactivity administered was excreted in the urine, 11% as 14C02,
and 8% in the feces. Most of the remaining radioactivity was contained in thetissues, organs, and carcass.(24)

MICROBIALAND

ENVIRONMENTALDEGRADATION

Long-chain alcohol polyglycol ethers (alcohol ethoxylates) with the common structural
formulation
R(OCH,CH,),,OH
were studied for microbial
degradation by activated sludge. Two degradation mechanisms were identified: intramolecularscission of the surfactant and w- and P-oxidationof thealkyl chain. Prominent metabolites of stearyl alcohol ethoxylate (seven ethylene oxide units; CAS No. 9005-00-9)
included carboxylated polyethylene
glycols,polyethylene
glycol units, C, fragments,
oxalic acid, and formic
acid.(2526)
The degradation of steareth (CAS No. 9005-00-9) in coastal water ecosystems and the influence of this degradation on biochemical oxygen demand(BOD)
has been evaluated by Bergueiro et al.r2’) Steber and Wierich(25,26)
reported that stearyl alcohol ethoxylate (seven ethylene oxide units; CAS No.
9005-00-9)
undergoes complete biodegradation in the environment.

ANIMALTOXICOLOGY

Acute Toxicity
Oral
The method of Litchfield and WilcoxorG2’) was used to determine
acute oral toxicities in male rats of three polyoxyethylene
stearyl ethers.
following
LD,, values were reportedc4):
Steareth-2,> 25.1 g/kg

Steareth-10,

2.91 g/kg

Steareth-20,

1.92 g/kg

theThe

Treon did not specify whether the reported LD,, values pertained to theundiluted
polyoxyethylene
stearyl ether or to an aqueous solutionof thepolyoxyethylene
stearyl ether (Table 4).
A single oral dose of 25.1 g/kg of steareth-2, 40% in water, was administered to groups of five male (134-144 g) and five female (132-143g) rats todetermine its acute oral toxicity. Sprague-Dawley
CD (Charles River) rats wereAcute Toxicity

TABLE 4.

in Rats

Ingredient

Method of(concentration

dnd whlcle)

Steareth-2

No. of anin,a/s

admmistr~tior~

Unspeclfled

Oral> 25.1 g/kg

Lltchfield

10

OldI

> 25’1 g/kg

Onr

25

Oral

1’ g/kg

FIVP doses from 2.5 to 40.0 g/kg

Unspeciflpd

Oral> 16 g/kg

Methodunspecified

I0

Oral

’ 5 g/kg

One dosrof 5 g/kg,

10

Oral

> IO g/kg

Method and CO,,?,,KYJt.5

Lb

and Wllcoxon,

1947

Reference3(unspec Ifled)-

Stcareth-2dose of 25. I g/kg,

0 of IO died

29

(40% in water)
Steareth-2

30(25% in corn 011)
Steareth-2(unspeciflcd)
Stearethm2

2 of ‘IO died34

One dose of IO g/kg,

2 of IO died,35

one had fibrousrncailng(2.75”& in body lotion
with 2.25% steareth-20)
Stearcth-2(1 .R%In antiperspirant)

tissuehedrt and lungs‘IO

Stearethm2 (0.6%
in mousseOral> 5 rrll,‘kg

One dosp of 5 ml/kg,

6

Oral

37

Oral

> log/kg> 5 ml/kg

Onp dose of IO g/kg, 0 of IO died10

One dose of 5 ml/kg,

0 of 10 died3%

0 of 10 died39

0 of ‘IO died36

conditioner)

Stearethm2

10

Oral

> 5 ml/kg

One dose of 5 ml/kg,

50

lntraperitoncal

0.76 g/kg

Five does, from 0.50 to ‘I.26 g/kg

29

50

intravenous

0.041 g/kg

Five dosr5 from 0’159 to O.‘lOOg/kg

29

Unspecifjed

Oral

2 91 g/kg

Litchfield4(.lO% in normdl sallnr)
Strareth-2(1% In propylene

glycol)Stearrth-IO

and WIlcoxon.

‘I974(unspecified)
Steareth-20

Unspecifjed

Oral
Oral

’ 16 g/kg‘I .92 g/kg

MethodUnspecified
60

Ordl

2.07 g/kg

Six doses from ‘I .26 to 3.98 g/kg

32

25

Oral

2.1g/kg

Five dose\ from 0 3’1 to 5.0 g/kg

33

I0

Oral

> 10 ml/kg

One dose of 10 ml/kg,

0 of ‘IO died

40

40lntraperitoneal

0:190 g/kg

Four doses from 0.126 to 0.25 1 g/kg

32

50

Intravenous

0.164 g/kg

Five doses from 0.‘126 to 0 ‘I 99 g/kg

32

Litchfleld

unsprc ifled
and Wllcoxon,

31
‘1947

4

(unspecified)
Steareth-20(25% in distilledwater)

Steareth-20(25% In corn oil)
Steareth-20(1.5% In moisturizer)
Stearetn-20(‘10% in isotonic

NaCI)

E
m

ASSESSMENT:STEARETHS

887

fasted for 16 h prior to the 14 day observation period. None of the rats diedduring the study (Table 4).(29)
A total of 25 young adult albino rats, Wistar derived, were distributed into
groups of 5, each containing 2 females and 3 males. The body weights ranged
between 200 and 300 g. The five dosage groups received from 2.5 to 40.0 g/kg
of steareth-2 as a 25% corn oil solution and were observed for 14 days. An LD,,
value of 21 g/kg was reported (Table 4).c3’)
An oral LD,,valueof > 16 g/kg in rats was determined for steareth-2 andsteareth-IO
in tests “performed
according to the French regulations
andprotocols.”
Neither the concentrationof steareth-IO or steareth-2 nor thevehicle used was stated, and no protocol for the acute oral toxicity test was
submitted with the data (Table 4).c3’)
Steareth-20, with 0.01% BHA and 0.005% citric acid added as preservatives,
was administeredin a 25% weight per volume dose in distilledwater todetermine the LD,,value.
Doses ranging from 1.26 to 3.98 g/kg were administered to groups of five male and five female Sprague-Dawley
CD (Charles
River) rats that had been fasted for 16 h. The resulting LD,,valueof 2.07 g/kg
was calculated after a 14 day observation period (Table 4).(32)
In another study, steareth-20 was administered as a 25% corn oil solution
to 25 Wistar-derived
young adult albino rats (200-300g). The five dosage
groups, consistingof two females and three males, received doses of 0.31,
0.63, 1.25, 2.50, and 5.00 g/kg. After an observation period of 14 days, an LD,,
value of 2.1 g/kg was determined (Table 4).(33)
A body lotion containing 2.75% steareth-2 and 2.25% steareth-20 was
administered
to Wistar strain rats (206-244 g), five males and five females, todetermine its acute oral toxicity. After 18 h of fasting a single dose of 5 g/kg
was given and the rats were observed for 14 days. Of IO animals, 2 died during
the test. The animals were killed after the test and necropsied, and the 2animals that died during the test had “fibrous
tissue encasing heart andlungs,” whereas the surviving animals’ necropsies were normal (Table 4).(34)
The acute oral toxicity of a roll-on antiperspirant containing 1.8% steareth-2
was determinedin another test. Five female and five male Wistar-derived
albino rats, weighing between 180 and 216 g, were administereda single
IO g/kg dose of the antiperspirant.
The product was “used as received.” Of
the IO rats in the study, 2 died. After the 14 day observation period theanimals were killed and subjected to necropsy. One of the 2 rats that diedduring the test was found to have “fibrous
tissue encasing the heart andlungs” (Table 4).(35)A mousse (conditioner)
containing 0.6% steareth-2 was given to fivefemale and five male rats in a dose of 5.0 ml/kg. The initial body weight of
the rats varied between 184 and 269 g. The animals were observed for 14 days
following
dosage and killed and necropsied after the test period. All IO rats
survived the test. After necropsy, “organs of the thorax and abdomen appeared normal” (Table 4).(36)
In another study, a mousse formulation
containing 0.6% steareth-2 wastested for its acute oral toxicity. Six rats, three males and three females, were
fed a single IO g/kg dose of the mousse. The rats weighed between 200 andCOSMETIC

888

INGREDIENTREVIEW

284 at the beginning of the 14 day observation period. All six rats survived andwere killed at the conclusion of the test. Upon necropsy no gross changes
were found in the organs of the thorax and abdomen (Table 4).(37)
An acute oral toxicity test was performed on a mousse conditioner
containing 0.6% steareth-2. The formulation was administeredin a 5 ml/kg dose
to five male and five female rats. The rats weighed from 202 to 208 g. All 10 of
the rats survived the test, and following
the 14 day observation period theanimals were killed and necropsied. Following necropsy, “organs of the thorax
and abdomen appeared normal” (Table 4).c3’)
A mousse (conditioner)
formulation
containing 0.6% steareth-2 was fed
in a dose of 5.0 ml/kg to five male and five female rats. All IO of the rats
(200-209g) survived the administrationof the formulation.
After an observation period lasting 14 days, the rats were killed and necropsied and all findings
were reported as normal (Table 4).(39)
A rat oral toxicity test was performed for a light yellow, cream moisturizer
containing 1.5% steareth-20. Fasted Charles River Fischer 344 rats, five males
and five females, which weighed between 120 and 190 g, were used in the
study. Each animal received a single dose, by gavage, of IO ml of the undiluted
moisturizer
per kg body weight. No signs of toxicity were observed during the
2 week study and none of the animals died. The investigators found “a single
IO ml/kg dose of this formulation
represents a nonlethal, nontoxic dose inrats” (Table 4).c4’)
lntraperitoneal
Steareth-2, as a 10% weight per volume solution
in normal saline, wasadministered
to Wistar SPF rats in an evaluation of acute intraperitoneal
toxicity. Five dosage groups of five female and five male rats were fasted for
16 h prior to the test. The doses ranged from 0.50 to 1.26 g/kg, and theanimals were observed for 14 days. An intraperitoneal
LD,,valueof 0.76 g/kg
was calculated (Table 4).(29)
In another study, steareth-20 was given to four dosage groups of five maleand five female Wistar SPF rats. Doses of a 10% weight per volume solution ofsteareth-20 in isotonic sodium chloride ranged from 0.126 to 0.251 g/kg. Aftera 14 day observation period an LD,,valueof 0.190 g/kg was calculated (Table(32)
4).
Intravenous
A 1% weight per volume solution of steareth-2 in propylene glycol wasadministered
to five groups of 10 rats, five females and five males. These
Wistar SPF rats were fasted for 16 h prior to being given the doses ranging
from 0.0159 to 0.100 g/kg. The resulting
LD,, value of 0.041 g/kg was
calculated after a 7 day observation period (Table 4).(“)
In another study, steareth-20 in a 10% weight per volume solution
inisotonic sodium chloride was given to five dosage groups of Wistar SPF rats.
The groups, made up of five females and five males, had been fasted for 16 hprior to the test. After a 7 day observation period, an LD,,valueof 0.164 g/kg
was calculated (Table 4).(32)ASSESSMENT:STEARETHS

889

Irritation
OcularThree groups of six rabbits each were used to evaluate the eye irritation
potential of steareth-2, -10, and -20. The Draize(“‘) test methodology was
employed.
A 60% aqueous solution
or dispersionof the polyoxyethylene
stearyl ether was instilled in a single 0.1 ml dose in one eye of each rabbit; theuntreated eye served as a control. The treated eyes of an unspecified numberof rabbits received a water rinse (20 ml) 2 s following
instillationof the test
material; the treated eyes of the remaining animals received no water rinse.
Ocular irritation was assessed at 1, 24, 48, 72, and 96 h and at 7 days. Scoresobtained by the Draize system were interpreted according to the terminologyof Kay and Calandra. (42) This classification consists of eight descriptive ratings
with increasing intensity of irritation as follows: (1) nonirritating,(2) practicallynonirritating,(3) minimally irritating, (4) mildly irritating, (5) moderately irritating, (6) severely irritating, (7) extremely irritating, and (8) maximally irritating.
In rabbits given no water rinse, steareth-IO was “practically nonirritating”
tothe conjunctiva, whereas steareth-2 and -20 were “minimallyirritating” to the
conjunctiva. In rabbits given a water rinse, all three ethers were “nonirritating”
to the conjunctiva. No irritation of the cornea or iris was observed in rinsed or
nonrinsed eyes (Table 5).(“)
In another rabbit eye irritation study, steareth-2 was tested on six young
healthy adult albino rabbits according to the procedure described in 16 CFR
1500.42. The test material, 100 mg, was placed in one eye of each rabbit, andthe other eye served as a control. The eyes were examined, and the ocular
reactions were recorded 24, 48, and 72 h after the instillationof the test
material and again 7 days after the test. No effects were observed in the iris orcornea, although one rabbit had conjunctival
redness. The score for thisindividual rabbit was 2 of a possible 20; the score represented a case in which
the “vessels
are definitely
injected above normal.” The conjunctival effects
cleared during
the 7 day observation
period. The investigators
reportedsteareth-2 “is not an irritant to the rabbit eye” (Table 5).c30)
Steareth-2, in solutions of 60, 40, and 10% weight per volume in distilledwater, was instilled into rabbit eyes. Nine eyes, three with a water rinse andsix withouta water rinse, were used for each solution.
The eyes were
examined and the observations scored at 1, 24, 48, 72, and 96 h after the
instillationof the test material and again after 7 days. None of the solutions inrinsed eyes produced scored reactions, whereas the reactions produced by the
60% solutionin unrinsed eyes had a total score of 3.3 of a possible 110.0.
Reactions produced by both the 40 and 10% solutions had, of 110.0 possible, ascore of 0.3. According to the classification
scheme of Kay and Calandra, as
described earlier, the 60% solution was “minimallyirritating” in unrinsed eyesand “nonirritating”
in eyes rinsed 2 s after exposure. Both the 40 and 10%
solutionswere “nonirritating”
In rinsed and nonrinsed eyes (Table 5).(29)
Two groups of six rabbits each were used to test the eye irritancy of 10%
solutionsof steareth-2 and steareth-IO in water. Into one eye of each rabbit
0.10 ml of either solution was instilled; the other untreated eye served as aTABLE S.

Ocular Irritation
Degree of ,rrit~tion

testedSteareth-2

and conc/usions(MAO/“)

No. ofMaterid/

Steareth concentration
60% in water

rabtxts
6

MethodReferences 41

No water r1rxc
Minimally

Irritating

Water rinse
NonirritatIng

R~J~~KTJCC,1

and 42
Unspecified

6

16 CFR: ‘1500.42, nowater rinse

60% in distIlled

940% in distilled

99ModifiedDralze”“;Modified

Draize(“‘;also Reference 42

water‘10% in water

Drake”“;

al\o Reference 42

water
10% in distilled

Modifiedalso Reference 42

water

6

Modified

Draize’4”;

Not an Irritantto the rabbit eye

30(2.0 of 110.0)
Minimally

irritatrng(3.3 of 110.0)

Nonlrrltdting

19(0.0 of 110.0)

Nonirritating

NonirrItating(0.3 of ‘I’I0.0)

29(0.0 of ‘II0 0)

Nonirritating

Nonirritating(0.3 of ‘1’10.0)

29(0.0 of I 10.0)(6.7 of -1’10)31
8

no water rime
2.75% in body lotion

6

Modified

Draize’““;no water rinse

with 2.25% steareth-20

Not an otular

irntant34

to rabbits(0.3 of ‘l10.0)

1.8% in antiperspirant

9

Modified

Draize’““;no water rinseconditioner
0.6% in mousse
conditioner
0.6% in mousse

Modified

Draize”‘);Draize”‘);

35

to rabbits(6.0 of 110.0)

no water rinse
Modified

6

Mild ocular irritant(3.3 of ‘110.0)

0.6% in mousse(5 7 of 1’lO.O)(2.0 of 110.0)

36
38

no water rinse
Modified

DraizeC4’);

no water rinse(15.4 of ‘1’10.0)

f

37

2
r,
i?
0
;
5
n
?
;;
s

0.6% in mousse

9

Modified

Draize’“”6References 41(‘I 7.0 of 110.0)(11.8 of 110.0)

39

Practically nonirrltdting

Nonirritating

4

conditioner
Steareth-10

60% in waterand 42
10% in water

Modified

Draizp”“‘;(4.3 of 1100)

31

no water rinse
Steareth-20

60% in water

References 41

Mlnlmally

irritating

Nonirritating4

and 42
Unspecified

I6 CFR and ‘I 500 42;
no water rinse

60% in distllled

Modiflrd

Dralze””

water
4% in texturizing
conditioner

Moderate irntant to the rabbit
Minimally

irritating

Nonirritating(0.7 of ‘i’IO.0)
Unspecified

14 doses of 0.1 ml
via unspeciffed33

eye (23.0 of 110 0)

Slight conjunctivitis
throughout

32(0.0 of ‘i’IO.0)
43

study

procedure
4% in texturizing
conditioner

Unspeci-

14 doses of 0 ‘I ml

fied

via un\peclfled

6

0.1 ml in one eye

Slight conjunctivitis
throughout

43

study

procedure
4% in pink, creamy
cosmetic

via unspecified

Slight “conjunctival
hyperemia”

44

in 4 of 6 rabbits

procedure
4% in pink, creamy

6

0.7 ml in one eye
via unspeciflcd

cosmetic

Slight“conjunctival

hyperemia”

44

In 4 of 6 rabbits

procedure
1.5% in moisturizer“Maximumaverage ocular irritation

6

0.1 ml in one eye

Slight conjunctivitis

via unspecified

6 rabbits, cleared

procedureby 24 hin 6 of

40

2
z
z
z
..
Y
2
7
m

892

COSMETIC

INGREDIENTREVIEW

control. The treated eyes that did not receive a water rinse were observed 1, 2,
3, 4, and 7 days after the instillationof the test solution. The average ocularindex (AOI) score, measured after 24 h, was 6.7 for steareth-2 and 4.3 forsteareth-10 of a 110 possible maximum (Table 5).(3”A roll-on antiperspirant formulation containing 1.8% steareth-2 was tested
for ocular irritancy using nine New Zealand albino rabbits weighing between
1.8 and 2.4 kg. The antiperspirant was used “as received,” and 0.1 ml of theformulation
was instilled into the rabbit eyes. Three of the rabbits received a
30 ml water rinse 15 s after the instillationof the product. In the group thatreceived no water rinse the maximum score was 3.3 of 110 possible, and forthe rinsed eyes the maximum score was 2.0. The investigators found that theformulation
was a “mild ocular irritant to rabbits under the conditions of thistest” (Table 5).(35)
Each of two formulations of mousse conditioner containing 0.6% steareth-2
was instilled into the eyes of six rabbits. Scores were recorded 1, 24, 48, and 72
h and 7 and 14 days after the test. In both tests, 0.1 ml of the product was
instilled into the eyes and the eyes were not rinsed with water. The maximum
mean score for one test was 6.0 of 110.0, and the scores ranged from 2 to 12 of110.(36’ In the other test the maximum mean score was 5.7 of 110.0 and therange was from 4 to 6 of 110. (38) All the observed effects involved the
conjunctiva alone, and all had cleared by the 72 h observation period (Table
5).

In another study, 0.1 ml of a mousse conditioner containing 0.6% steareth-2
was instilled
into the eyes of three rabbits. The eyes were not rinsed withwater. The reactions were observed and scored at 1, 24, 48, and 72 h and 7 and
14 days after the instillation.
The maximum mean irritation score was 15.4 of
110.0, and individual scores ranged from 2 to 22 of 110. Cornea1 effects wereobserved in one rabbit, and all three rabbits had conjunctival
effects. All
reactions had cleared by the 72 h observation period (Table 5).(37)
Steareth-2, 0.6% in a mousse conditioner formulation, was instilled as a 0.1
ml dose to the eyes of nine rabbits. The resulting reactions were scored at 1,
24, 48, and 72 h as well as 7 and 14 days after the test. The eyes of three of thenine rabbits were rinsed with water 15 s after the instillationof the product. In
the unrinsed eyes four of the rabbits had cornea1 lesions, and all six of theanimals had conjunctival lesions, The maximum mean irritation score for theunrinsed eyes was 11.8 of 110.0, and all the lesions had cleared by the 7 day
observation period. In the rinsed eyes, the maximum mean score was 17.0 of
110.0. All three of the rabbits had scores for conjunctival lesions, and two of
the animals had cornea1 lesions. All the reactions had cleared by the 7 day
observation period (Table 5).(39)A body lotion formulation containing 2.75% steareth-2 and 2.25% steareth20 was tested for its eye irritation
potential. Six New Zealand white rabbits
each received an application of 0.1 ml of the formulation in one eye; the othereye remained untreated and served as a control. The eyes did not receive awater rinse. The reactions were scored 24, 48, and 72 h after the instillationofthe body lotion. A score of 0.3 of a maximum of 110 was reported, and all theeffects had cleared by the 48 h observation period. The investigators reported

ASSESSMENT:STEARETHS

893

that “this test article is not an ocular irritant to rabbits under conditions of thistest” (Table 5).(34)
Steareth-20 was instilled into one eye of six young adult albino rabbits inanother test of eye irritation potential, The administrationof the sample was
not followed by a water rinse, and the untreated eye served as a control. The
procedure, as described in 16 CFR 1500.42, calls for observation and recordingof the toxic eye effects at 24, 48, and 72 h and at 7 days after the instillation.
Cornea1 effects were observed in one animal with a rating of 0 of 80 at 24 h
and 5 of 80 on day 7. Two animals had irideal effects with scores of 5 of 10 at
24 h; one of these animals had a score of 5 of 10 after 7 days, whereas theeffect in the other animal had cleared by this time. Conjunctival effects wereobserved in all six of the animals with a range of scores at 24 h of 8-14 of 20,
and after 7 days, of 2-8 of 20. In total the animals had a range of scores,
maximum value of 110, from 8 to 19 at 24 h, 8 to 21 at 4 h, 4 to 23 at 72 h, and0 to 13 after 7 days. Steareth-20, as tested earlier, was reported as a moderate
irritant to the rabbit eye when the instillationof the test material was notfollowed by a water rinse (Table 5),c3j)
The eyes of nine rabbits were exposed to a 60% w/w solution of steareth-20
in distilledwater. Into one eye of each rabbit 0.1 ml of the solution
was
instilled;
the other untreated eye served as a control. Six of the rabbits
received no water rinse; three of the rabbits had their eyes rinsed with 20 mlof water 2 s after the instillationof the test material. The eyes were observed
and the reactions scored 1, 24, 48, 72, 96, and 168 h after the test. No cornea1
or iridial effects were observed in the nine rabbits. The maximum score for the
conjunctiva was 0.7 of a maximum of 110 for the unrinsed eyes; the rinsed
eyes had no conjunctival effects. Steareth-20 (60%), according to the classification of Kay and Calandra as described earlier, was “minimallyirritating”
inunrinsed eyes and “nonirritating”
in rinsed eyes (Table 5).(32)
A comparative ocular irritation
study was completed for a texturizing
conditioner versus a texturizing conditioner base, both formulations
contained
4% steareth-20.
Rabbits received 14 doses of 0.1 ml of the product via anunspecified
procedure. The results reported by the investigatorsstated that“both formulations
elicited slight conjunctivitis
which persisted intermittently
throughout
the study.” No cornea1 or iridial effects were observed (Table
5).(43)

Two formulationsof a pink creamy cosmetic containing 4% steareth-20
were submitted for acute ocular irritation testing. New Zealand albino rabbits,
three of each sex, were used to test each formulation.
Each rabbit was treatedonce in one eye with 0.1 ml of the full-strength
formulation.
It was not stated
how many, if any, of the animals received a water rinse. Ocular reactions wereobserved and scored 1, 24, 48, and 72 h and also 7 days after the instillationofthe product. One formulation
caused slight conjunctival
hyperemia to develop within
1 h in 4 of 6 rabbits. The rabbits treated with the otherformulation
had slight conjunctivitis
1 h after the treatment. All the effects
from both formulations
cleared within 24 h (Table 5).cb4)
Six New Zealand albino rabbits were used to evaluate the acute ocular
irritation
potential for a moisturizer
formulation
containing 1.5% steareth-20.

P

TABLE

6.

Rabbit Skin Irritatron
Degree ofMdtefid/testedSteareth-2

Stedreth

concentration

NOOf

fdbbitS

MethodP/I”

irritdtlorl

Reference

60% in aqueous solution

6

Drarze”“;24 h patch

1.o

Mild irritant

4

60% In aqueous solution

6

Draize’““;

24 h patch

1.0

Mild irritant

29

40% in aqueous solution

6

Draizer”“;24 h patch

0.17

Mild irritant

29‘10% in aqueous solution

6

Draizc”“;24 h patch

0.0

Nonirritant

29

Unspec ifred

6

Draize”“,24 h patch

0.13

Nonirritant

30

ModrfredDraize”“;0.1

10% in aqueous solution

Unspec rfied

31

24 h patch
2.75% steareth-2

and2.25% steareth-20

inbody lotion
l.8% in roll-on

6

24 h

occlusive

0.50

Draire’““;6occlusive patch
Draize’““; 24 h patch

24 h

0.0

34

Not a primary35

irntant
0.92

Not a primary

39

8

37

$

irritant

conditioner
0.6% in mousse

Not a primary
irritantpatch

6

antiperspirant
0.6% in mousse

Drarzer”‘;

6

Draize”“;24 h patch

0.59

Slight6

Modified

Draize’““,

0.13

Not a pnmary

irritant

conditioner
0.6% In mousse

5

0.6% in mousse

6

Modified

Draizer4”;

0.33

Not a primary
irritant

4 h occlusive patch

conditioner
Steareth-IO

irritant

4 h occlusive patch

conditioner

24 h patch

0.17

DraizeC4”;

0.3

Mrld irritant

36
38

s

4

E
R

60% rn aqueous solution

6

Draizer4”;‘10% in aqueous solution

Unspecified

Modified

60% in aqueous solution

6

Draize’“‘);

24 h patch

0.0

Nonirritant

4

60% in aqueous solution

6

Draizer”‘;

24 h patch

0.0

Nonirritant

32

31

24 h patch
Steareth-20

2

5
n
?
;
s

Unspecified

6

Draize(“);

24 h patch

0.83

Mild Irritant

33

5.0% in solid

4

Drairr”‘);

24 h

2.8

Mild irntant

45

1.8

Mild Irritant46

antiperspirant

occlusiw

patch,

same rabbits used totest another formulation at the sametime
5.0% in solid

4

Draire”“;24 hocclusive

antiperspirant

patch,

same rabbits used to1

test another formu-

5

latlon at the ~drn~time
3

4% in pink, creamy

Four daily 0.5 mI

30

44

78

44

3.‘1

40

doses for 7

cosmetic-

days; same rabbits as
used withformulation
3

4% in pink, creamy
cosmetic

below

Four daily 0.5 ml
doses for 7days; same rabbits as
used withformulation‘1.5% in moisturizer

3

above

Four daily 0.5 ml
dose\ for 7
days“Primary

irritationindex (maximum= 8.0).

-

8%

COSMETIC

INGREDIENTREVIEW

Each animal was treated once in one eye with a dose of 0.1 ml of theundiluted
formulation.
It was not stated whether the eyes received a waterrinse. The ocular reactions were observed and scored 1 h after treatment andon days 1, 2, 3, and 7. Slight conjunctivitis
developed in all the treated eyes 1 h
after the treatment. No other signs of irritation were reported (Table 5).(40)
DermalThe Draize procedure was used to assess the skin-irritating
effects ofsteareth-2-10 and -20.c4’) The three polyoxyethylene
stearyl ethers were each
evaluated’at a concentration of 60% in aqueous solution
or dispersion.
A
1 inch patch containing 0.5 ml of one of the test solutions or dispersions
wasapplied to intact and abraded sites of the clipped skin of six albino rabbits.
After 24 h, the patch was removed and the treated site graded for skinirritation.
The treated site was scored a second time 48 h following
patch
removal. A primary irritationindex * value was calculated for each material
from scores of irritation based on a scale of 0 (no erythema or edema) to 8
(severe erythema and edema). The primary irritation index scores for steareth-2
and -10 were 1.00 and 0.17, respectively, indicating mild skin irritation.
The
was 0.0 indicating
no skinprimary
irritationindex score for steareth-20
irritation(Table 6). c4) The report did not indicate whether these scores were
for the first or second evaluation (grading) and whether the scores related tointact or abraded sites.
In order to test their dermal irritancy, three solutions of steareth-2; 60, 40,
and 10% weight per volume in water, were applied to the skin of New
Zealand albino rabbits. Using the Draize 1959 procedure, 0.5 ml of eachsolution was placed on a 1 inch square of gauze and applied to the skin of six
rabbits. Three of the rabbits for each solution had intact skin; the other three
had abraded skin. The bandages were removed after 24 h and the reactions to
the test solution were scored then and again after 72 h. The scores, based on
the scale described earlier, were averaged for both time periods and for both
intact and abraded skin. The primary irritation index values reported were 1.0
for the 60% solution, 0.17 for the 40% solution, and 0.0 for the 10% solution.
The 60 and 40% solutions
were classified as “mild irritants,”
and the 10%
solution was classified as a “nonirritant”(Table 6).(29)
Steareth-2
at an unspecified
concentration
was tested for its dermal
irritation
potential. The method was patterned after the 16 CFR 1500.41
descriptionof the Draize 1959 procedure. This acute skin irritation test was
performed on six adult albino rabbits. Steareth-2, 0.5 ml or 0.5 g, was introduced under a 1 inch square of gauze to the shaved backs of the animals, Theskin on half of the animal was left intact and the skin on the other side wasabraded. The patches were removed and the reactions scored 24 h and again
72 h after the administrationof the steareth-2. The primary irritation
index

*The

primary

irritation

whole;

it is calculated

numberof animals

index (Pll) is a value depicting the average skinby adding the irritation

tested.

scoresof all animals

responseof the test group as aand then dividing

the total by the

ASSESSMENT:STEARETHS

897

value was reported as 0.13 and was averaged over both time periods and intact
and abraded sites. Steareth-2 was not an irritant to rabbit skin (Table 6).(30)
A modified Draize’“‘) procedure was used to determine the dermal irritancy of steareth-2 and steareth-10 in 10% aqueous solutions.
Each solution,
0.5 ml, was applied under gauze measuring 6.2 cm2 in area to the shaved backsof an unspecified number of rabbits. Half the shaved skin of each animal wasabraded and the other half remained intact. The patches were removed after
24 h, and the reactions were scored then and again after 72 h using the scale
described earlier. Averaged for both time periods and both intact and abradedsites, the primary irritation index value was 0.1 for the steareth-2 solution and
0.3 for the steareth-10 solutions (Table 6).(31)
A body lotion formulation containing 2.75% steareth-2 and 2.25% steareth20 was tested for primary dermal irritation in rabbits. The lotion was used asreceived in a modification of the procedure described by Draize in 1959. Six
albino New Zealand rabbits were prepared by shaving their backs and slightly
abrading half the shaved skin. The lotion, 0.5 ml, was applied to the backs
under an occlusive patch. The dermal reactions were scored on a scale as
described earlier, after the patches were removed at 24 h and again after 72 h.
The reported primary irritationindex score was 0.50 and was averaged overboth time periods and both intact and abraded sites. The investigators
reported the lotion “is not a primary dermal irritant to rabbits under conditionsof this test” (Table 6).(34)
A modified Draize procedure was used to test the dermal irritancy of aroll-on antiperspirant
formulation containing 1.8% steareth-2. Three male andthree female New Zealand albino rabbits were used for the test; the skin on
the backs was shaved and half of it slightly abraded; the other half remained
intact. A single application of 0.5 ml of the antiperspirant was applied underan occlusive
patch to both intact and abraded sites. The patches were
removed after 24 h and the reactions scored both at 24 and 72 h after theapplication of the patches. The primary irritation index was 0.0, indicating that“is not a primary irritant to rabbits under
the antiperspirant
formulation
conditionsof this test” (Table 6).(35)
Two mousse formulations,each containing 0.6% steareth-2, were tested
for their dermal irritancy. Each sample was applied to intact and abraded sites
on the skin of six rabbits. The dermal reactions were scored at 24 and 72 h
after the application of the sample. One formulation
had a primary irritationindex of 0.92 reported,(39) and the primary irritation index was reported as 0.59
for the other formulation.(37) The PII scores were averages calculated from thescores for both the 24 and 72 h time periods and the intact and abraded sites.
The former was considered “not a primary skin irritant,” whereas the latter
was classified as “being slightly irritating to the skin” (Table 6).
In two other studies, two formulationsof mousse conditioner each containing 0.6% steareth-2 were also tested for their dermal irritation
potential.
One formulation
was applied in an occlusive patch for 4 h to the intact andabraded skin of six rabbits; the reactions were scored 24 and 72 h after theapplication of the sample. The primary irritation index score was 0.13, indicating that the formulation “is not a primary skin irritant”.(36’ The other mousse
conditioner
preparation was placed into contact with the intact and abraded

898

COSMETIC

INGREDIENTREVIEWskin of six rabbits for 4 h. After the 24 and 72 h observation periods, theprimary irritation index was calculated as 0.33, again indicating that the sample“is not a primary skin irritant “(38) Both PII scores were averaged over the
intact and abraded sites as well as both time periods (Table 6).
A 60% aqueous dispersion of steareth-20, with 0.01% BHA and 0.005% citricacid added as preservatives, was applied to the skin of New Zealand albino
rabbits to determine its dermal irritancy. The dispersion, 0.5 ml, was placed on
a 1 inch piece of gauze and applied to the bare skin of the rabbit. Six rabbits,
three with intact skin and three with abraded skin, received such patches. The
patches were removed after 24 h and the reactions scored then and again after
72 h. All scores reported for both intact and abraded skin at both time periods
were zero. On the scale described earlier, the investigators found the dispersion of steareth-20 is “nonirritating”(Table 6).(32)
A primary skin irritation
study with rabbits was undertakenwith anunspecified concentration of steareth-20. The method employed in this study
was patterned after the Draize procedure described in 16 CRF 1500.41. The
material, 0.5 ml or 0.5 g, was placed on the shaved skin of six adult albino
rabbits. The skin on half of the back of each rabbit was abraded; the other halfremained intact. The patches, made of 1 inch square gauze, were removed
after 24 h and scored then and again after 72 h. The scale used was describedin an earlier portion of this section, and a primary irritation index value of 0.83
was reported; the PII was averaged over both sites and time periods. The test
material, steareth-20, was a mild irritant to the rabbit skin (Table 6).(33)
A solid antiperspirant
formulation
containing 5.0% steareth-20 was tested
for dermal irritancy. Occlusive patches containing 0.5 ml of the undiluted
antiperspirant
were applied to the clipped skin of four New Zealand whiterabbits. The adult rabbits weighed between 1.4 and 2.1 kg. Two patches wereapplied to each rabbit; one was on intact skin, and the other was placed on
abraded skin. These same four rabbits were being used to test another solid
antiperspirant
at the same time as this test. It was not stated whether the othersolid antiperspirant
formulation
contained steareth-20. The dermal reactions
were observed after 24 h, when the patches were removed, and again after
72 h. A primary irritationindex score was 2.8, averaged for both intact andabraded sites as well as both time periods, and the investigators reported theformulation
was “mildly irritating” (Table 6).(45)Four New Zealand white rabbits were used to test the dermal irritation
potential of a solid antiperspirant
formulation
containing 5.0% steareth-20. A
dose of 0.5 g of the undiluted antiperspirant
was applied under occlusive
patches to two sites per rabbit, one abraded and one intact. Another solid
antiperspirant
was being tested on the same rabbits at the same time. It was
not stated whether the other antiperspirant formulation contained steareth-20.
The primary irritationindex score was reported as 1.8 after observing andscoring the sites at 24 and 72 h. The PII value was averaged to include bothtime periods and skin conditions (intact or abraded). Using the scale describedearlier, this formulation would be considered “mildly irritating” (Table 6).(46)
Two formulationsof a pink, creamy cosmetic containing 4% steareth-20
were tested for their acute dermal irritation
potentials. Three New ZealandASSESSMENT:STEARETHS

899

albino rabbits were used to compare the irritancy of the two different
formulationsof the cosmetic. Four daily 0.5 ml doses of each formulation
were placed on opposite sides of the three rabbits, and the dermal irritation
was evaluated daily for 7 days. Slight erythema was noted on all treatmentsites 1 day after the initial application, which developed into well-definederythema and slight edema after 3 days. The irritation
persisted, and slightdesquamation was observed after 7 days on the test. Both formulations
causeda pink stain to develop on the treated skin. The primary irritation index score
reported was 3.0 for one formulation and 2.8 for the other (Table 6).(44)Three New Zealand albino rabbits were used to evaluate the dermal
irritancy of a moisturizer
formulation containing 1.5% steareth-20. The back of
the animals were shaved, and four daily doses of the undiluted cosmetic wereapplied to the shaved area. It was not stated whether the sites treated wereabraded or intact skin. Dermal reactions were evaluated daily for 7 days. Slightto well-definederythema and slight edema developed 24 h after the first
application, moderate to severe erythema developed after 3-4 days, and mild
desquamation was observed by day 7. An irritation index of 3.1 was calculated
for the moisturizer
formulation (Table 6).(30)

Subchronic
DermalA 3 month dermal toxicity study was conducted on a cosmetic formulation
containing
4% steareth-20. A total of 30 New Zealand white rabbits weredivided into three dosage groups each containing five males and five females.
One group was the untreated control, whereas the other two groups received
doses of 4.4 mg/cm2 per 5.6% body surface area and 6.6 mg/cm2 per 11.2%
body surface area. These doses were chosen to represent factors of 4 and 12,
respectively,
over the maximum anticipated human exposure of 2.2 mg/cm2
per 2.8% body surface area. The determinationof human exposure was madeon the assumptionthat a 55 kg person would use 1.0 g of the formulationeach day to cover an approximate area on the face of 450 cm2 or 2.8% of the
body surface area. The animals were treated daily with the test material andobserved daily for changes in behavior or appearance. Observationsof theskin were also made each day, and the reactions were scored for dermal
irritation
using the standard Draize scale as described in the dermal irritation
sectio of this report. Body weights, feed consumption,clinical chemistry,hematologic
studies, urinalyses,organ weights, and gross and microscopic
evaluation of organs and tissues were the other monitored parameters. The
cosmetic formulation
caused persistent well-defined
to moderate erythema,slight edema, and slight desquamation. A single male animal receiving a doseof 4.4 mg/cm’ per day died of purulent pneumonia after 43 days of the test.
The results of clinical chemistry and hematologic studies conducted on all
animals involved in the study were negative for any toxicologically significant
findings. The male rabbits in the two groups receiving doses of the formulation had a slightincrease in liver weight
relative to the controls.
No

900

COSMETIC

INGREDIENTREVIEW

treatment-relatedchanges other than mild inflammation at the application sitewere found by histopathologic
examination. The investigators
reported that
“under the conditions of this test, there was no evidence of systemic toxicity
that would contraindicate the use of [the cosmetic product].” The irritation to
the skin observed in the rabbits was thought not to indicate a potential hazard
in humans.(47)Forty New Zealand white rabbits were used in a 3 month, subchronic
toxicity study of a cosmetic formulation
containing 4% steareth-20, administered dermally. The four dosage groups each contained five males and fivefemales and consisted of an untreated control group, a vehicle control group,and two treatment groups receiving 7.5 mg/cm2 per 10% body surface areaand 15 mg/cm2 per 10% body surface area. The doses selected represent
multiplesof 132 and 268 over the anticipated maximum human exposure of
2.25 mg/cm2 per 0.25% body surface area. The vehicle control was applied at
the highest dose; it was not stated whether the vehicle control contained
steareth-20.
The animals were observed daily for changes in appearance or
behavior. They were also observed and scored for dermal irritation each day.
The other monitored parameters included body weight, feed consumption,
hematology, clinical chemistry, organ weight, enzyme induction, and grossand microscopic evaluation of tissues and organs. A single female rabbit diedof pneumonia after 83 days on the test in the vehicle control group. The
investigators
reported that “the death was not treatment related.” Both dosesof the cosmetic caused less dermal irritation than the vehicle control. Dermal
irritationof rabbits in the vehicle control group ranged from slight to severe
erythema, slight to moderate edema, and slight to moderate desquamation.
Rabbits in both dosage groups of the cosmetic formulation
had reactions
ranging from slight to moderate erythema and slight to moderate edema.
These dermal irritation reactions were the only treatment-relatedefects observed. The investigators
reported that under the conditions of this test thecosmetic formulation caused no systemic toxicity and only slight to moderatedermal irritation.(“@MUTAGENICITY
No mutagenicity
informationon the steareth compounds themselvesisavailable.
An alcohol ethoxylate with an unspecified alcohol chain length and an
average value of six ethylene oxide units was tested for its mutagenic potential. In an acute dominant lethal assay, male mice were given oral doses of
either 100, 500, or 1000 mg/kg of the ethoxylate. In a subacute dominantlethal assay, male mice were given oral doses of either 20, 100, or 200 mg/kg
of the ethoxylate.
The mutagenic indices did not significantly
vary fromcontrol values.(24)
Hamsters were given oral doses of 80, 400, or 800 mg/kg of the alcohol
ethoxylate described earlier. The animals were killed at 6, 24, or 48 h after thedose was given. No significant differences in chromosomal anomalies werenoted in the bone marrow cells of the hamsters.‘2”

ASSESSMENT:STEARETHS

901

Human leukocytes were incubated for 18, 24, and 48 h with
tions of 2, 20, or 100 PI/kg of the alcohol ethoxylate. No significant
mal anomalies were observed.(24)concentrachromoso-

CARCINOGENICITY
A polyoxyethylene
alkyl ether (PAE) was tested to determine its carcinogenic and cocarcinogenic properties.
The length of the alkyl chain andnumber of ethylene oxide units were not stated and the formula was listed as
R-O(CH,CH,O),H.
The PAE was tested in a solution of 50% in benzene. A
drop of the solution was painted on the skin of mice twice each week for 1
year. PAE alone did not produce skin tumors in mice.(49)

CLINICAL
DermalASSESSMENT OF SAFETY
Irritationand Sensitization

A Schwartz
patch test was conducted to determine the skin irritation
potential of steareth-2, -10, and -20. A cotton dressing saturated with one of
the test materials (60% in aqueous solution) was applied to the skin of 200
human subjects by means of an elastic adhesive patch. The dressing wasallowed to remain in contact with the skin for 72 h. A second 72 h occlusive
dressing was applied to the original exposure site 10 days after the initial
application. Steareth-2, steareth-10, and steareth-20 produced no skin irritation(Table 7).(“)
Steareth-2 in a concentration of 60% in water was used in a prophetic
patch test to determine its potential for dermal irritation and sensitizationinhumans. A 1 inch piece of cotton twill was covered with the solution andapplied to the skin of the human subjects with an elastic adhesive patch 2
inch square. The patch was left in contact with the skin for a 72 h period. After
this time period the patch was removed and the treated skin observed. The
solution
was reapplied in exactly the same manner to the same area of skin
IO-14 days after the removal of the first patch. After the second 72 h time
period that the solution was left in contact with the skin the dermal reactions
were once again observed. None of the 200 subjects tested reacted to either
patch test. The 60% solutionof steareth-2 in water was neither a primarydermal irritant nor a sensitizer
to humans (Table 7).(29)
A white foam mousse conditioner containing 0.6% steareth-2 was tested toassess its irritancy
potential to human skin caused by repetitive
topicalapplication.
The sample, in a 1 :2 dilution
in water, was applied to theforearms of 17 volunteer men and women between 18 and 65 years of age.
These same volunteers were also being tested at the same time with five othercosmetic formulations
not containing steareth-2. The procedure used was amodificationof that described by Kligman and Frosch.(58) A plastic cup 16 mm
in diameter was filled with cotton cloth onto which 0.2 ml of the sample had

COSMETIC

902

INGREDIENTREVIEW

been placed. The cup was then applied to the forearm using a nonocclusive
tape. The cup was left in place for 24 h the first day of the test and then for
6 h for the remaining 6 days of the test; the reactions were scored after theremoval of the cup on all 7 days of the study. The scale used measured
erythema from values of 1, slight spotty or diffuse redness, to 4, very red withedema; scaling from values of 1, fine scaling, to 3, severe scaling with large
flakes; and fissuresfrom values of 1, fine cracks, to 3 wide cracks withhemorrhage or exudation. For the formulation tested, the values ranged from 0
to 2 for erythema and 0 to 1 for scaling and fissures over all 17 subjects tested.

TABLE 7.

ClinicalAssessmentof Safety: Human Dermal

Irrrtation,

Sensitization,

and Photosensitizatron

No. ofIngredientType of test

Steareth-2Reference

Results and Comments

subjects

-

SIPTd

200

No skin irritation

SIP1

200

No skin reactions,

4(60% in water)
29

not a primary irritantor a skin sensitizer
A 24 h patch,

Steareth-2

followed(0.6% in mousse

Total mean irritation25

No reaction to moderate erythema attributed

50

1.353 of 10.0

patches over 7 days

condrtioner)

Phototoxrcrty,

Steareth-2(2.75%

17

by SIX 6 h

one exposurein a tan

product with 2.25%

to the erythema dosage of UV-6;

of UV-B56

not photo-

toxic or a primary irritantlightsteareth-20)
Steareth-IO

SIP1

200

No skin Irritation

4

51PT

200

No skin irritatron

4

SIP7

200

No skrn rrntation,(60% rn water)
Steareth-20(60”/, in water)
32

not a primary irritantor a skin sensitizer
205

RIPTb

Steareth-20

Four reactions during induction

phase, 13 reac-

51

tions at challenge, not a primary irritant(4% In a cosmetic)or an allergic contact sensitizer
200

RIPT

Seven reactrons during

Inductionphase, one

52

reac.tion at challenge, not a prrmary Irritantor an allergrc contact sensitizer
Cumulative

irritation

test,

11

lrritatron

25

RIPT

54

score 24 of 630; mild material

wrth no evidence of cumulative

21 daysTwo reactions during rnduction

irritation

phase, no reactions at challenge, not a dermal irritant55

orsensitizer
189

RIP7

Steareth-20(1.5?& in a moistureDuringinductionphase 21 reactions;53

9 reactrons at challenge; not an allergic
contact sensitrzer

lotion)Photoallergy,

Steareth-20(4% in a cosmetic)

RIPT

3’1

reactrons on all Irradiated sites

with IJV-A and UV-B

durrng inductron

during induction,

challenge; not an inducer of contact photo-

UV-A only at challenge
Phototoxicity,

SIPT

with UV-A exposure
aSingle-insult

patch test.

‘Repeatpatch test

insultSlight17~~~~~---

allergy, contact dermatitis,10

No reactions,
Irritant

55

phase; no reactrons ator sensitization

not a contact dermal photo-57

ASSESSMENT:STEARETHS

903

The total mean irritation score reported was 1.353 of a maximum of 10 (Table
7). t50)
A prophetic patch test was conducted using a 60% solution of steareth-20
in water. The solution was placed on a 1 inch square of cotton twill that wasthen applied to the skin of the human subjects with an elastic adhesive patch.
The patch remained in contact with the skin for 72 h, after which it wasremoved and the dermal reactions observed. A second patch was applied inexactly the same manner 8 days after the removal of the first patch, and skin
was evaluated again after a contact period of 72 h. Of the 200 subjects tested,
none reacted to either the first or second application. The 60% solution ofsteareth-20 was neither a skin sensitizer
nor a primary irritant to human skin
(Table 7).(32)
A cosmetic formulation containing 4% steareth-20 was used in a repeatedinsult patch testing study based on a modified Draize-Shelanski
method. The
study was conducted on healthy men and women ranging in age from 18 to65; 205 subjects completed the 6 week testing period. The undiluted cosmetic,
0.1 g, was placed in occlusive patches on the upper back or inner upper armof the subjects. During the first 3 week induction period the patches wereapplied on Monday, Wednesday, and Friday to be left on for 24 h, and thereactions were scored from these patches prior to the application of the next
patch. In the fourth week patches were applied on Monday and the reactions
read 48 h after the application on Wednesday of week 4. On Monday of week
6 the final challenge patch tests were applied, 1 to the original testing site and
1 to a previously untreated site. These challenge patches were left in contact
with the skin for 48 h and were scored then and again 72 h after they wereapplied. The patch sites were scored on a scale with values of 0 (negative),
I+ (erythema only), 2+ (erythema and edema or induration), 3+ (erythema,
edema or induration, and vehiculation),and 4+ (erythema, edema or induration, bulla (blisters), with or without ulceration). After the second and the fifth
induction
patches, 1 of 205 subjects had a I+
reaction. Following
the sixth
and seventh induction patches, 1 of 205 subjects had a 2+ reaction. Following
the challenge patch testing, 9 of 204 subjects and 3 of 205 subjects had a I+
reaction 48 h after the patch was applied to the original and unteated site,
respectively. At the challenge untreated site after 72 h, 1 of 205 subjects had aI+reaction and none of the subjects reacted to the challenge patch at theoriginal site after this time. The investigators found the test product did notappear to be an allergic contact sensitizer
or a primary irritant (Table 7).‘5’)
A repeated insult patch test using a modified Draize-Shelanski
methodwas conducted on a cosmetic formulation
containing 4% steareth-20. The
procedure used was the same as described in the previous paragraph, with the
exception that semiocclusive
patches were used and the challenge patches
were applied to previously
untreated sites only. After induction
patchesnumbered 2, 7, 8, 9, and 10, one of the 200 subjects completing the study had
a I+reaction. A single subject had a 2+ reaction following
the fourth
induction patch. Another 2 subjects had a I+ reaction after the fifth induction
patches. No reactions were observed from the challenge patch after 48 h, and
1 of 200 subjects had I+
reactions to the challenge patch at the 72 hobservation period. The investigators reported the rare I+
and 2+ reactions

904

COSMETIC

INGREDIENTREVIEWin the testingof the formulation
were irritantin nature and were notconsideredclinically significant.
Therefore,
the test product was neither a
primary irritant nor an allergic contact sensitizer(Table 7).ts2)
A moisturizing
lotion formulation
containing 1.5% steareth-20 was tested
using a modified
Draize-Shelanski
method as described in the previous
paragraphs, The challenge patches were applied only to previously untreatedsites. After the third induction patch, 1 of 189 had a I+ reaction and 2 of 189
had 2+ reactions. Following
the fourth patch, 1 of 189 subjects had a 2+
reaction. After the fifth induction patch, 2 of 188 subjects had I+
reactions.
Following the sixth induction patch, 3 of 188 subjects had a I+ reaction and 2of 188 had 2+ reactions. After the seventh induction patch, 3 of 188 subjects
had I+
reactions and 1 of 188 had a 2+ reaction. After the eighth induction
patch 5 subjects had skin reactions; 3 of 187 had I+
reactions and 2 of 187
had 2+ reactions. A single subject had a I+ reaction after the tenth induction
patch. After the challenge patch on the untreated site, 1 of 189 had a I+
reaction and 1 of 189 had a 2+ reaction following
the 48 h contact andobservation
period. After the 72 h observation
period, 6 of 189 had I+
reactions and 1 of 189 had a 2+ reaction. The reactions of 3 subjects wereexplained as caused by a cumulative irritation
reaction, multiple cutaneousallergic reactions in the past, and moderately severe hand dermatitis.
The
remaining I+ and rare 2+ reactions “were judged to be irritant in nature, andare not considered to be clinically significant.”
The cosmetic formulation was
not an allergic contact sensitizer (Table 7).(53)A human skin test of cumulative irritation was performed for a cosmetic
formulation
containing 4% steareth-20. A panel of 11 subjects, 1 male and 10
females with an age range of 18-59 years, was used to test the irritancy of 10
test materials simultaneously.
The scores for 1 panelist were not included in
the calculations because that panelist was believed to be presensitizedto acommon ingredient in all the cosmetic formulations
tested. The sample, 0.2
ml, was applied under a closed patch for 23 h for 21 consecutive days. The
skin reactions were observed 1 h after the removal of each patch for a total of
22 days. The sample containing the steareth-20
had a score of 24 of a
maximum possible of 630. This formulation was a mild material with “essentially no evidence of cumulative irritation under conditions of the test” (Table
7).(54)

A formulation
containing 4% steareth-20 was used in a repeat insult patch
test to determine
its skin irritationand sensitization
potential. Occlusive
patches containing 0.2 g of the undiluted cosmetic were applied to the upperback of the subjects, ranging in age from 18 to 65, and were left on for 24 hfollowed by a 24 h nontreatment period. The patches were applied for a totalof nine times every Monday, Wednesday, and Friday for 3 weeks. The skinreactions were scored before the next induction patch was applied. After a 2
week nontreatment
period a challenge patch was applied to a previously
untreated site for 24 h and the reactions were scored then and again 48 and
72 h after the patch was applied. After the second induction patch, 1 of 27
subjects had a faint, minimal reaction. Following the seventh induction patch,
1 of 26 subjects had a faint, minimal reaction. None of the 25 subjects
completing the study had any reaction to the challenge patch, The formula-ASSESSMENT:STEARETHS

tion did not induce either dermal irritation(Table 7).(55)905

or sensitizationin human subjects

Photosensitization
The phototoxicityof two different cosmetic formulations
was tested using
human panelists and a xenon-mercury
arc lamp. This type of lamp emits
ultraviolet-A(UV-A), UV-B, and some UV-C light with a wavelength range of
260-620
nm. With a Mylar sheet as a filter, only UV-A light reaches the
subject; both the UV-B and UV-C light is filtered out. One formulation
was awhite cream tanning product containing 2.75% steareth-2 and 2.25% steareth20; the other formulation
was a yellow cream sunblock containing 3.30%
steareth-2 and 2.70% steareth-20. A group of 25 adult female panelists completed the study. On the first day of the test, three sets of two patches eachcontaining 0.3 ml of either of the test products were applied to the thigh ofeach panelist. The other thigh was exposed to the UV light for a range of timeintervals from 10 to 60 s in order to calculate the minimal erythemic dose(MED) for each individual. On the second day of the study the patches were
removed and the irritation
scored from *, barely perceptible, through 3,
severe, for both erythema and edema. Following the scorings the patches of
the test materials were reapplied and left in contact with the skin for 30
minutes. The patches were then removed and the skin cleansed with acetone.
One of the three test areas for each formulation
was exposed to 1 MED of
unfiltered
UV light; the second was exposed to 6 MED of UV light filteredthrough a Mylar film. The third patch for each product was not exposed to the
UV light and was covered with a light-occlusive
patch for the next 24 h. To
serve as a control, one untreated site was exposed and scored the same way as
the treated sites. All the test sites were scored again for dermal reactions on
the third and fourth day of the test. Scores ranging from 0, no reaction, to 2,
moderate erythema, were observed 24 and 48 h after the UV light exposure,and similar responses were observed in the controls. The investigators foundno indication that either of the samples was phototoxic or a primary irritantwhen compared to untreated sites. Any irritation
observed at the treatmentsites was reported to be caused by the erythema dosage used to challenge
each site (Table 7).c5’)
A white cream cosmetic formulation containing 4% steareth-20 was tested
for its potential to induce contact photoallergy
in humans. A total of 31
subjects, 6 men and 25 women ranging in age from 18 to 64 years, completed
the test. A series of nine occlusive induction patches containing 0.2 g of theundiluted cosmetic was applied to both forearms of the subjects on Mondays,
Wednesdays,
and Fridays for 3 weeks. Each patch remained in place for 24 h,
at which time the subject returned to the laboratory, the patches were
removed, and the dermal reactions scored. A scale ranging from 0 (noreaction) to 4 (fiery colored erythema, marked edema, and substantial vehiculation far beyond the patch margins) was used for the scoring. The designatedforearm was then irradiated and scored again immediately after the irradiation,and the other arm served as an unirradiated control. The irradiation was 15
minutes of UV-A light from four F40 BL fluorescent tubes and the lesser ofCOSMETIC

906

INGREDIENTREVIEW

two MEDs or 120 s of UV-B irradiation from the Solarium 300 lamp. The testsites were marked with gentian violet, and the same sites were repatched until
the nine induction patches and irradiations were complete. After a nontreatment period of approximately 2 weeks, challenge patches were applied to apreviously
untreated site and the original patch sites were observed again.
Each subject reported to the laboratory again 24 h later, at which time thepatches were removed and the reactions scored. The designated forearm wasthen irradiated with UV-A light only. The reactions were scored immediately
after the irradiation and then again 24 and 48 h later. A single subject had a
two-level
reaction 24 h after the second irradiation,and he was judged apresensitizedreactor and was removed from the test. All but the aforementioned subject had slight reactions on the irradiated sites during the induction
phase. Several subjects also had slight transient
reactions on the control
irradiated site with no test material applied. All irradiated sites had a slighttanning response. Slight reactions were observed in several subjects on thesites to which the formulation was applied but that did not receive irradiation.
No reactions were observed at the challenge testing. This formulation“did
not induce contact dermal photoallergy or contact dermatitis or sensitizationin human subjects” (Table 7).(55)
In another study a white creamy cosmetic formulation
containing 4%steareth-20 was tested to determine its phototoxicity
potential in humans. A
total of two men and eight women, with ages ranging from 26 to 58 years,
completed the study. Occlusive patches each containing approximately 0.2 gof the undiluted cosmetic were applied to both forearms of the subjects. The
patch was left in contact with the skin for 24 h, at which time it was removed
and the dermal reactions were scored. The designated forearm was thenirradiated with UV-A light from four F40 BL fluorescent tubes for an unspecified amount of time. The dermal reactions were scored immediately after theirradiation and again after 24 to 48 h. No reactions were observed on either
forearm during any part of the study. The cosmetic test material did not
induce a contact dermal phototoxic response in humans (Table 7).(57)

SUMMARY
The steareth group is a series of compounds prepared by reacting stearyl
alcohol with ethylene oxide to form polyoxyethylene
stearyl ethers. The
number of oxyethylene units corresponds to the number of the steareth (i.e.,
steareth-2).
These compounds are generally waxy solids soluble in lower
alcohols and insoluble in hydrocarbons.
Steareths are primarily used as emulsifiersin cosmetics. In 1986, steareth-2
was used in 107 cosmetic products, and steareth-10, -15, and/or -20 were used
in a total of 104 cosmetic products. The products formulated with steareths
included personal cleanlinessproducts and deodorants as well as suntan,
fragrance, skin, eye, and hair preparations. The maximum reported concentration in use was 25%.
Microbial and environmental
degradation breaks down the steareths into
metabolites
including carboxylated polyethylene glycols, polyethylene glycol
units, C, fragments, and oxalic and formic acids.

ASSESSMENT:STEARETHS

907

Steareth-2 and -10 were nontoxic to rats in acute oral toxicity studies bothat concentrationsof 40% in water and in formulations.
Steareth-20
wasnontoxic in formulations
and had an oral LD,, value in rats of approximately
2.0 g/kg at concentrations of 25% in corn oil or water. Steareth-2 had an IP(10% in saline) LD,,valueof 0.76 g/kg and an IV (1% in propylene glycol) LD,,
value of 0.041 g/kg in rats. Steareth-20 (10% in saline) had an IP LD,,valueof0.190 g/kg and an IV LD,,valueof 0.164 g/kg in rats.
In subchronic testing, steareth-20 was nontoxic to rabbits when administered dermally at concentrations of 4% in a cosmetic formulation.
Steareth-2 and -10, at concentrations of up to 60% in water, were at mostmildly and minimally irritating, respectively, to rabbit eyes. Steareth-20 was amoderate ocular iritant to rabbits at an unspecified concentration.
Steareth-2 and -10 were at most mild irritants to rabbit skin when tested incosmetic formulations
and at concentrations of up to 60% in water. Steareth-20
was a mild dermal irritant to rabbits in a 60% aqueous solution and a moderate
irritant in cosmetic formulations.
A structurally
undefined polyoxyethylene
alkyl ether was neither carcinogenic nor was it a tumor promoter. An unspecified alcohol ethoxylate was
nonmutagenic
in three separate assays.
Steareth-2, 60% in water, was not a primary irritant or a sensitizer to humanskin. In clinical studies of cosmetic formulations,steareth-2, 0.6% in a mousse,
was a mild irritant and was not phototoxic at a concentration of 2.75% with
2.25% steareth-20 in a body lotion. Steareth-10 was not an irritant to humanskin at a concentration of 60% in water. Steareth-20, at concentrations of up to
60% in water and in cosmetic formulations,
was neither an irritant nor asensitizer
and was not phototoxic to human skin.
DISCUSSION
The Cosmetic Ingredient Review Expert Panel decided that the data on
steareth-2, -10, and -20 are sufficient for a decision to be made on the entire
steareth group, including steareth-4, -6, -11, -13, and -15 because of thechemical similarityof all the steareths.
An alcohol ethoxylate of unspecified chain length was not mutagenic inthree separate studies. Because of structuralsimilarities,
the expert panel
considers the data on the alcohol ethoxylate sufficient so that mutagenicity
testing of the steareth group is not required.
CONCLUSION
One the basis of the data included in this report, the CIR Expert Panelconcludes that steareth-2, -4, -6, -7, -10, -11, -13, -15, and -20 are safe as
cosmetic ingredients in the present practices of use and concentration.
ACKNOWLEDGEMENT
Nancy J. Toy, Scientific Analyst and Writer, prepared the technical analysis
used by the expert panel in developing this report.

!I08

COSMETIC

INGREDIENTREVIEW

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Ingredient

Cosmetic

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(March

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Industry

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Cosmetic

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Director,

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Availablerant. (3-13-33).

troner).

Biological

74-81.

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810, Washington,

37. CTFA.

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IngredientDirector,

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(Aug.

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of unpublished

Cosmetic

Industry

Industry

Available

810, Washington,

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A simplified

75(l),

D.C. 20005.

(Nov.

35. CTFA.

aspects. An. Quim.

49(3), 530-7.

P. (1979).

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Washington,

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LA JORDANA,%, 99-112.

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Kinetic

DE

D.C. 20005.

810, Washington,(3-13-6).

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F. (June 1947).

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plants, Appt. Environ.

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submission

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Washington,

31. CTFA.

CASARES,of Brij and Myrj series.

J. Pharmacol.

(Jan. 1974).

Available(3-13-S).

M.,

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34

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in microbial

27. BERGUEIRO.

29. CTFA.

POP

Dermaltoxicity.

In: Appraisal

Assoc. of Food and Drug Officialsof the Safety of Chemidsof U.S. Baltimore,in Foods,

MD: The Editorial

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KAY,

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(July 5, 1982). Industry(3-13-13).

Available

810, Washington,

Available

810, Washington,
45. CTFA.

of unpublished
Cosmetic

submission

for review: Director,of unpublished
Cosmetic

rabbit eye irritation

Review, 1110 Vermont

Ave., N.W.,

data. Acute dermal and ocular irritation

Ingredientstudy.
Suite

Review, 1110 Vermont

Ave., N.W.,

data. Dermal

study

study.
Suite

D.C. 20005.

(March3, 1980).

Industry

antiperspirant.

(3-3-79).

Available for review: Director,

N.W.,

data. Comparative

Ingredient

D.C. 2ooO5.

44. CTFA. (Sept. 5, 1979). industry(3-13-21).

submission

for review: Director,

Suite 810. Washington,

submission

D.C. 2OCO5of unpublished
Cosmetic

Ingredientirritationof a solid

Review, 1110 Vermont

Ave.,

COSMETIC

910
46. CTFA.

(March3, 1980).

Industry

antiperspirant.

(3-3-80).

Available for review: Director,

N.W.,
47. CTFA.
study

Suite 810, Washington,(June 1981).
In rabbits.

Ave., N.W.,
48. CTFA.

formulation
Director,

submission
Available

Suite 810, Washington,(Oct. 1983). Industry
admrnistered
Cosmetic

49. YAMAMOTO,

H. (1977).

data. Dermal

Cosmeticof unpublishedfor review

Ingredientirritation

study

of a solid

Review, 1110 Vermont

Ave.,

data Subchronic

Director,

Cosmetic(three month)

Ingredientdermal toxicity

Review, 1110 Vermont

D.C. 20005.

submission
dermally

Ingredientpolyoxy-ethylene-alkyl

of unpublished

REVIEW

D.C. 20005.

Industry(3-13-22).

submission

INGREDIENTof unpublished
to New

Review,

1110 Vermont

Carcinogenic

data. Three month subchronic

Zealandwhite

Ave., N.W.,

and cocarcinogenic

ether and potassium

rabbits.

(3-13-14).

toxrcity

Suite 810, Washington,

test of detergents

study of a

Available

forreview:

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soap) on the skin of mouse (abstract). J. Nara. Med. Assoc.

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Cosmetic

IngredientIndustry

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Review,

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1110 Vermont

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810, Washington,

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51. CTFA.

(Sept.

Available

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for

Washington,
52. CTFA.

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for

Washrngton.
53. CTFA.

industry

review:

Availableof

Cosmetic

unpublished

Ingredienttest. (3-13-17).

1110

insultVermont

patch test.
Ave.,

N.W.,

(3-13-23).
Suite

8’10,

data. Repeat

Review,

1110

insultVermont

patch test.
Ave.,

N.W.,

(3-13-16).
Suite

810,

of

Cosmetic

unpublished

Ingredient

data

Revrew,

Repeatinsult‘1110 Vermont

patch test.
Ave.,

N.W.,

(3-13-20).
Suite

810,

submissionof unpublished
Cosmetic

data. Human

Ingredientskincumulative

irritation

test.

Ave., N.W.,

Suite

and repeat insult

patch

Review, 1110 Vermont

D.C. 20005.
Industry

submissionof unpublished

Available for review. Director,

Suite 810, Washington,(Nov.

submission

for review: Director,(June 20, 1983).

Cosmetrc

data. Photoallergy

Ingredient

Review, 1110 Vermont

Ave., N.W..

D.C. 20005.

28. 1977). Industry

submissionof unpublrshrd

Director,

Cosmetrc

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Review.

(June 30, 1983). Industry

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Review.

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data. Repeat

Review,

D.C. 20005.

810, Washington,

56. CTFA.

Ingredientsubmission

Director,(June 15, 1982). Industry(2-13-15).
55. CTFA.

Industry

review,: Director,
1983).

for

Washington,
54. CTFA.

of unpublished

Cosmetic

D.C. 20005.

(Feb.

Available

Director,

D.C. 20005.

(AprilAvailable

review:

data. Phototoxicity

I I IO Vermont

Ave., N.W.,

test. (3-13-12).
Suite

Available

810, Washington,

D.C. 20005.
57. CTFA

for revrew:

Director,

Cosmetic

data. Phototoxrcity

11’10 Vermont

Ave., NW.,

test. (3-13-18).
Suite

Available

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D.C. 20005.
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irritancy

A.M.

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A new method

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the