j. Soc.Cosmet.

Chem.,40, 321-333 (November/December

1989)

Comedogenicity andirritancyof commonly

usedingredients
in skincare products

JAMESE. FULTON, JR., AcneResearch

Institute,1236 Somerset,
NewportBeach,CA 92660.

Received
September
3, 1989. Presented
at theSouthern
CaliforniaSection,
CaliforniaChapter,Society
ofCosmetic
Chemists,Spring1989.

Synopsis
A survey,usingthe rabbitear, of the comedogenicity and irritancyof severalgroupsof skin careproducts
indicates
that manycontainfollicularand surfaceepithelialirritatingingredients. Theseingredients fall
into severalchemicalclasses.Certaingeneralizations can be deducedby examiningthe results:(1) me-
dium-chain-length fattyacidsaremorepotentthanshort-or long-chain fattyacidsin producingfollicular
keratosis,
(2) the comedogenicity and irritancyof an organicmaterialcanbe reducedby combiningthe
moleculewith a polarsugaror a heavymetal, (3) increasing the degreeof ethoxylationin a moleculetends
to reducethe comedogenicity and irritancyof the chemical,and (4) the longerchainlipids, i.e., waxes,
appeartoolargeto producea reaction.By followingthe guidelinesdeveloped in thisstudy,it is possible
to
formulatenonirritating,noncomedogenic moisturizers,sunscreens, hair pomades,cosmetics,and condi-
tioners.

INTRODUCTION

The possibilityof comedogenicity and irritancyof facialskin careproductshasbeen

well documented (1- 3). Becauseof thiswork andan increasing publicawareness,
facial
productsthat are lesscomedogenic are now becomingavailable(4). However, other
skin careproductssuchas hair conditioners, hair pomades,moisturizers,sunscreens,
and evenacnetreatmentproductsmay be a sourceof cosmeticacne.By taking these
productsapart,testingtheir ingredients,andputtingthembacktogetherandretesting
them, an extensiveingredientlisting hasbeencreated.By studyingthis list, the cos-
metic chemistcan beginto be selectivein developingformulasfor lessirritating and
lesscomedogenic products.
The rabbit ear assayhasbeenusedsincethe mid-1950sas a methodof measuring
follicularkeratinizationby externallyappliedcompounds (5). The advantage of this
rapidscreening tool is that it takesonlytwo weeksto developfollicularimpactions in
the rabbitear, whileit maytakesixmonthsto develop similarreactions on humanskin.
The disadvantage of the modelis its extremesensitivity.The fragile,protectedepithe-
lium of the inner ear is extremelysensitive.Not everythingthat irritatesthis model
will alsoirritate humanskin. However,this extensivescreening of cosmeticformula-
321
322 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

tionsand their ingredientswould not havebeenpossiblewithout the useof this animal

model.We havenowextendedthemodelto includean indexof surface skinirritancyas
well asof follicularhyperkeratosis.

METHODS

Ingredientsare mixed in propyleneglycolat a 9 to 1 dilution for testingunlessother-

wise indicated(10% concentration).A colonyof New Zealandalbinorabbitsthat has
geneticallygoodearsand is freefrom mitesis used.Threerabbits,weighingtwo to
threekilograms,areusedfor eachassay.Animalsarehousedsinglyin suspended cages
and fed Purina Rabbit Chow and water ad libitum. Animals are maintained on a 12-hour
light and 12-hourdarkcycle.A doseof 1 ml of the testmaterialis appliedandspread
oncedaily to the entireinnersurfaceof oneearfive daysper weekfor two weeks.The
oppositeuntreatedearof eachanimalservesasan untreatedcontrol.Follicularkeratosis
is judged both macroscopically (visually)and microscopically with a micrometerto
measurethe width of the follicularkeratosis.The macroscopic responseis determined
by averagingthe measurements of the width of six folliclesusinga Mitutoyo Dial
Micrometer(#536-724). A similarmicroscopic micrometermeasurement is obtained
by averagingthe width of six folliclesundera magnificationof 430 x aftera 6-ram
biopsyspecimenis fixedin formalin,sectioned at six microns,and stainedwith hema-
toxylin-eosin.The resultsare then combinedon a scaleof oneto five:
Micrometerreading Grade
0.009 in or less 0 No significantincreasein follicularkeratosis
0.010 in-.014 in 1

0.015 in-.019 in 2 A moderate increase in follicular keratosis

0.020 in-.025 in 3

0.025 in-.029 in 4 An extensive increasein follicular keratosis

0.030 in or more 5

Grade5 is the presenceof largecomedones throughoutthe ear, similarto thoseinduced

by the applicationof our standard"positive"testingagent, isopropylmyristate.As
reportedin our previousstudies,a minimal gradeof 0 to 1 is not considered
significant.
Grade2 to 3 is borderline.However,a gradeof 4 to 5 is uniformallyreproduceable and
consideredpositive.
The irritancyproducedby the repeated applicationof a chemicalor skincareproducton
the surfaceepidermisin the rabbit earis alsoevaluatedon a similarscaleof 0 to 5. The
gradesare summarizedasfollows:
0 No irritation
1 Few scales,no erythema
2 Diffusescaling,no erythema
3 Generalizedscalingwith erythema
4 Scaling,erythema,andedema
5 Epidermalnecrosisand slough
To studythe effectsof differentvehicleson comedogenicity
and irritancy,severalfatty
acidsand the D&C red pigment#36 are reexamined in differentsolvents.The fatty
 COMEDOGENICITY 323

acids are dissolvedin either a volatile solvent or sunflower oil. The D&C red #36
pigmentis testedin mineraloil, propylene
glycol,polyethylene
glycol400, andpen-
taerythritaltetra capra/caprylate.

RESULTS AND DISCUSSION

Cosmeticacnewasfirst reportedby Frenchdermatologists in the mid-forties.They

reportedon brilliantinesandhairpomades causingflareupson the templeandforehead
facialregions.They attributedthe problemsto impuritiesin the brilliantines(6). In
1970, Kligman requestedthat Gerd Piewig and I examineover 700 men to find some
with normal facial skin. Much to our chagrin, the majority had cosmeticacne(7).
About 70% showedsomeevidenceof follicularkeratoses on the foreheadand temples.
Occasionallythe eruptionswere noted on the cheeksdown to the jawline area. The
lesionswereusuallynoninflammatory, closedcomedones. A few lesionsdevelopedinto
small inflammatorypapules.However,therewereno casesof severe,cysticinflamma-
tory acne. Histologically, the comedones from pomadeacne caseswere identical to
biopsies takenfrom comedones of classicacnevulgarispatients.In surveyingthe hair
carepreparations,we felt that the actualingredientsand not tracecontaminants were
offenders. Interestingly,veryfew of the subjects
attributedtheir folliculareruptionsto
their daily useof a hair pomade.This studystimulatedus to examineotherskin care
productsand ingredients.
In 1972 Kligman and Mills reportedon acnecosmetica in their surveyat the AcneClinic
at the Universityof Pennsylvania (1). Approximatelyonethird of the adult womenhad
a low-grade,persistentacnein the cheekarea, consistingof closedcomedones quite
similarto thosefoundin pomadeacne.This appearedmorefrequentlyin womenafter
agetwentyand may explainoneof the reasons for epidemicadult acnein womenin the
1970sand 1980s.In 1976 and 1984, Fultonpublishedresultson actualcosmetic lines
andon ingredients,andproposed the development of noncomedogenic cosmetics
using
ingredientsthat werenonoffenders in the rabbitearassay(2,3). Severalmajorcosmetic
manufacturers have now producedthesetypesof products.However, our screening
indicatesthat work is still neededon manyskin careformulations.
It becameapparentduringour research into potentialnoncomedogenic ingredientsthat
several hypotheses couldbedeveloped: (1) In orderforan ingredientto becomedogenic,
it must penetrateinto the follicle, and (2) once in the follicle, the chemicalmust
producethe follicularreactionof "retentionhyperkeratosis" (8). In addition, the overall
penetratibilityof the moleculemayberelatedto (1) the water/oilpartitioncoefficient of
the compound(HLB balance)and (2) the relativemolecularweight of the ingredient.
The ingredientappearsto havethe mostpotentialif it is fairly solublein bothwaterand
oil (HLB around10 to 12) and hasa rangeof molecularweight between200 and 300.
The comedogenicity of an ingredientmay be reducedby addinga large constituent
(i.e., polymersof PEGs), by addinga chargedmolecule(i.e., sugars),or by addinga
heavymetal (i.e., zinc or lithium). This often relatesto raisingthe HLB balanceto
above 12.

Examplesof this conceptof water/lipidsolubilityandmolecularweightsareapparentin

eachclassof chemicals examined(TableI). Amongthe lanolins,the classicanhydrous
lanolinsare not as comedogenicas the moderatelyethoxylatedderivatives(laneth 10).
324 JOURNAL OF THE SOCIETYOF COSMETICCHEMISTS

Table I
IngredientsandTheir Comedogenicity
and Irritancy

Grade (0- 5) Grade (0- 5)

Ingredient Comedo.
? Irrit. ½ Ingredient Comedo.? Irrit.½

I. Lanolins and derivatives Myristylalcohol 2 4

Acetylatedlanolin 0 0 Cetyl alcohol 2 2
Acetylatedlanolinalcohol 4 2 Isocetylalcohol 4 4
Anhydrouslanolin 0-1' 0 Cetearylalcohol 2 1
Lanolin alcohol 0-2* 0 Oleylalcohol 4 2
Lanolin oil 0-1' 0 Stearylalcohol 2 2
PEG 16 lanolin (Solulan 16) 4 3 Cetearylalcoholq-
PEG 75 lanolin 0 0 ceteareth 20 4
Laneth- 10 2 1 Ceteareth-20 2 3
PPG 12 PEG 65 lanolin oil 2 0 Propyleneglycol 0 0
Butyleneglycol 1 0
II. Fattyacidsandtheir derivatives Hexyleneglycol 0-2* 0-
Caprylicacid 1 3
PG caprylate/caprate 2 2
Capricacid 2 2
Lauric acid 4
PG dicaprylate/caprate 1 0
PG dipelargonate 2 2
Myristic acid 3 0 PG laurate 0 3
Palmitic acid 2 0
PG monostearate 0- 3 0-
Stearic acid 2 - 3' 0
Eicosanoic acid 2 0
Ethyleneglycol
monostearate 0 0
Behenic acid 0 0
Glucoseglutamate 0 0
Ascorbylpalmitate 2 0 Sorbitol 0 0
Behenylerucate 0 0 Sorbitan laurate 1- 2' !- 2
Butyl stearate 3 0
Sorbitansesquinoleate 0- !* 0
Cetyl acetate 4 2 Sorbitan oleate 3 0
Cetyl esterNF 1 1 Sorbitan stearate 0
Cetyl palmitate 0 0 Sorbitan isostearate 1-2' 0
Decyl oleate 3 0 PEG 40 sorbitan laurate 0 0
Di (2 ethylhexyl)succinate 2 0
Polysorbate20 0 0
Dioctyl malate 3 1
Polysorbate80 0 0
Dioctyl succinate 3 2
Glycerin 0 0
Diisopropyladipate 0 0
Glycereth-26 0 0
Diisopropyldimerate 0 0
Glyceryl-3-diisostearate 4 0
Ethylhexylpalmitate 4 0
GlycerylstearateNSE 1 0
Ethylhexylpelargonate 2 3
GlycerylstearateSE 3 2
Isodecyloleate 2- 3' 1- 2
Glyceryltricapylo/caprate 1 1
Isopropylisostearate 5 0
Behenyltriglyceride 0 0
Isopropyllinolate 4 2
Pentaerythritaltetra
Isopropyl myristate 5 3 isostearate 2 0
Isopropylpalmitate 4 1
Pentaerythrital
tetracapra/
Isostearylneopentanoate 3 3
caprylate 0 0
Isostearylisostearate 4 1
Wheat germglyceride 3 2
Myristyl lactate 4 2
Polyglyceryl-
3-diisostearate 4 0
Myristyl myristate 5 2
Polyethyleneglycol(PEG
Octyldodecylstearate 0 0
400) ! 0
Octyldodecylstearoyl Sucrose distearate 0 2
stearate 0 0
Sucrose stearate 0 0
Stearylheptanoate 4 0
PEG 120 methyl glucose
Tridectyl neopentanoate 0 3 dioleate 0 0
III. Alcohols•sugarsand their derivatives PEG 8 stearate 3
SD alcohol 40 0 0 PEG 20 stearate ! 0
Isopropylalcohol 0 0 PEG 100 stearate 0 0
 COMEDOGENICITY 325

Table I (continued)

Grade (0-5) Grade (0 - 5)

Ingredient Comedo.•- Irrit. :• Ingredient Comedo.•- Irrit.:•

PEG 100 distearate 2 0 Sesame oil 3(1)** 0

PEG 150 distearate 2 0 Corn oil 3 0
PEG 200 dilaurate 3 2 Avocado oil 3(2) 0
Laureth-4 5 4 Eveningprimroseoil 3 2
Laureth-23 3 0 Mink oil 3(2)
Steareth-2 2 2 Soybeanoil 3 0
Steareth- 10 4 3 Shark liver oil 3 2
Steareth-20 2 1 Cotton seed oil 3 2
Steareth- 100 0 0 Peanut oil 2 0
Oleth-3 5 2 Olive oil 2(1) 0
Oleth-5 3 2 Sandalwood seed oil 2 0
Oleth- 10 2 1 Almond oil 2(I) 0
Oleth-20 1 0 Apricot kernel oil 2(1) 0
Oleth-3 phosphate 2 2 Hydrogenated
Triacetin 0 0 polyisobutane 1 2
PPG 5 Ceteth 10 phosphate 4 2 Castor oil 1 0
PPG 2 myristyl propionate 3 2 Hydrogenatedcastoroil 1 0
PPG 10 cetyl ether 3 1 Chaulmoograoil 1 0
PPG 30 cetyl ester 0 0 Babassu oil 1 0
PPG 50 cetyl ester 0 0 Squalane 1 0
PEG 78 glyceryl Maleatedsoybeanoil 0 0
monococoate 0 1 Safflower oil 0 0
PEG 8 castor oil 1 1 Sunflower oil 0 0
PEG 40 castor oil 0 0 Mineral oil 0-2 0
Polypentaerythrital
tetralaurate 0 0 VII. Pigments
D & C red #3
IV. Waxes D & C red #4
Candelilla wax 1 0 D & C red #6
Carnuba wax 1 0 D & C red #7
Ceresin wax 0 0 D & C red #9
Beeswax 0- 2 * 0 D & C red # 17
Lanolin wax 1 0 D & C red # 19
Jojobaoil 0-2* 0 D & C red #21
Sulfatedjojobaoil 3 2 D & C red #27
Emulsifyingwax NF 0 0- 2' D & C red #30
D & C red #33
V. Thickeners
D & C red #36
Carboxymethylcellulose 0 0 D & C red #40
Carboxypropylcellulose 1 0 Ultamarine violet
Hydroxypropylcellulose 1 0 Iron oxides
Magnesiumaluminum Carmine
silicate 0 0
Titanium dioxide
Carbomer 940 1 0
Bentonite 0 0 VIII. Silicones
Kaolin 0 0 Simethicone
Talc 1 0 Dimethicone
PVP 0 0 Cyclomethicone
VI. Oils* IX. SteroIs
Cocoa butter 4 0 Cholesterol 0
Coconut butter 4 0 Soyasterol 0
Hydrogenatedvegetableoil 3 0 Peg 5 soyasterol 0

(continued)
326 JOURNALOF THE SOCIETYOF COSMETICCHEMISTS

Table I (continued)

Grade (0-5) Grade (0 - 5)

Ingredient Comedo.
? Irrit.$ Ingredient Comedo.? Irrit.

Peg 10 soyasterol 0 1 XlI. Miscellaneous

Choleth24 0 0 Octyl dimethylPABA 0 0
Sterolesters 0 0 Oxybenzone 0 0

Phytantriol 2 2 Octylmethoxycinnamate 0 0
Octyl salicylate 0 0
X. Vitamins
andherbs Acetone 0 0
A & D additive 2 0
0 0
Tocopherol* 0-3' 0-3' Ethyl
ether
Tocopheryl
acetate 0 0 Diethylene
glycol 0 0
Black
walnut
extract 0 0 monoethyl
ether
Papain 0 0 Ethylene
glycol
Chamomile
extract 0 0 monomethyl
ether 0 0
Vitamin
Apalmitate 1-3' 1-3' (EGME) 4 3
Panthenol 0 0 Xylene
Lithium stearate 1 0

XI. Preservativesand additives Magnesium stearate 1 0

Methylparaben 0 0 Zinc oxide 1 0

0 0
Propylparaben 0 0 Zinc stearate
2 0
Phenoxyethyl
paraben 0 0 Triethanolamine
Allantoin 0 0 Stearic acid: TEA 3 2
Hydantoin Amoniomethylpropinate 0 0
0 0
Sodiumhyaluronate 0 0 Sodium
PCA
Chondroitinsulfate 0 0 Hydrolyzedanimalprotein 0 0

Precipitatedsulfur 0 0
Water-soluble sulfur 3 0

? Comedogenicity or abilityof testsubstance

to producefollicular
hyperkeratosis.
$ Irritancyor abilityof testsubstanceto producesurface
epithelial
irritation.
* Resultsdependon sourceof raw material.
** Parentheses
indicateresultsusing"reftned"oil.

The higherethoxylated derivatives with HLBsabove12 aremorewater-soluble and

noncomedogenic andnonirritating (PEG 75 lanolin).Two of the lanolinderivatives
studiedrequirespecialcomments: (1) Theacetylatedlanolinalcoholsarebothcomedo-
genicandirritating,not because of the acetylated
lanolinbut because of the cetyl
acetateadditive(Figure1), and(2) PEG 16 lanolin(Solulan16) is quitecomedogenic
andirritating,perhaps
secondary to thecombinationofnonlanolin additives:
ceteth-16,
oleth-16, and steareth-16.
Amongthefattyacidsandesters a similaranalogy
isfound.Themid-chain-lengthfatty
acids,suchaslauricacidandmyristicacidanditsanalogscause
folliclehyperkeratosis.
Asthemolecular weightof thefattyacidbecomeslargerandtheeffective
chargeof the
overallmoleculeis reduced,lessfollicularreactionis produced.When the fatty acidis
esterifiedwith a small- to mid-sizealcohol,the combinationbecomesmorepotent than
the fatty aciditself.The cousinsof isopropyl
myristate,suchasmyristylmyristate,
isopropyl isostearate,
isostearyl
neopentanoate,
butylstearate,
anddecyloleate,areall
comedogenic (Figure2). Also,whenbranched-chain
fattyacidsareused,thederivatives
maybemorecomedogenic. Largemolecularweightesters,
suchasbehenyl erucate
and
cetylpalmitate,arenot a problem.
 COMEDOGENICITY 327

Figure 1. The key ingredientis acetylated

lanolinalcohol
-- cetylacetate--is not onlycomedogenic,
but
it is also an irritant.

Similar analogiesare apparentwith the alcohols,ethers,glycols,and sugars.Short-

chainalcoholsdo not causea reaction.The mid-chain-lengthalcoholsare comedogenic
and moreirritating than their fatty acidanalogs(Figure3). In the glycolseries,as the
hydrocarbon component becomes moredominant,the compoundis moreeffectiveat
producingcomedones. The puresugarsarenoncomedogenic. However,if theyarecom-
binedwith penetratingfatty acids,they may becomefollicularirritants.Also, if they
are combinedwith anotherirritant, as in glycerylstearate(SE), which containsadded
sodiumor potassiumstearate,the combinationbecomes morecomedogenic. The in-
creasing additionof polyethylene glycolsto the fatty acidsincreases
the HLB balance,
reducesthe follicularirritancy,and appearsto preventhyperkeratosis. An exampleis
the oleth3, 5, 10, 20 series(Figure4).
Among the waxes,the hydrocarbon chainsappeartoo long to penetrateunlessthe wax
is modified,suchasin sulfatedjojobaoil. In the caseof beeswaxes
and jojobaoils, some
commercialpreparations are more comedogenic than others.This suggestsmore con-
taminantsor irritants in someof the preparations.Emulsifyingwax NF may be irri-
tating, dependingon the concentration of longer-chainalcoholssuchas cetearylal-
cohol.

Chemicalssuchas cellulosicpolymers,the silicates,and the carbomersusedin the

pharmaceutical
and cosmeticindustryto thickenlotionsand creamsare not usuallya
problem.The clays,bentonite,and kaolinarealsonot a problem.Neither is talc.
Clinically,naturaloilssuchascocoabutterandcoconutbutterhavelongbeenknownto
causeproblemswith pomadeacne.This is confirmedin the rabbit ear assay.Also,
328 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

- OCTYLDODECYL
ISOPROPYLMYRISTATE STEAROYL
STEARATE

Figure 2. Ingredienttesting in the rabbit ear assay--the macroscopicview of the resultsfrom testing
isopropylmyristate.Microscopic examinationconfirmedthe comedogenicity seenvisually.Note that the
ingredientis alsoan irritant compared
to a potentialsubstitute,octyldodecylstearoylstearate.

hydrogenated
vegetableoil (Crisco
©) appearsto containresidualirritating lipids.
Among the naturaloils suchas sesameoil, avocadooil, and mink oil, the resultsare
improvedwhena morerefinedoil is used.However,it seemseasierto usesaffloweroil
and sunfloweroils, which are naturallylesscomedogenic. Mineral oil presentsa com-
plex problem:somesources are acceptable;othersare not.
D&C red colorsrepresenta perplexingmixture of differenttypesof red dyesand pig-
ments. Someare mildly comedogenic; othersare not. The commonpigmentsusedin
powderblushers (D&C red #6, bariumlake;D&C red #7, calciumlake;andD&C red
#9, bariumlake)arerelativelynoncomedogenic. However,the vehicleis alsoparticu-
larly importantfor the D&C red colors.A dry compressedpowderor powdersuspended
in an evaporatingvehiclesuchaspropyleneglycolmay be noncomedogenic. The same
dyeincorporated
intoa nonevaporating
oil canbecomedogenic
(TableII, Figure5).
Carmine,whichis a red dye obtainedfrom insectwings,is noncomedogenic andmay
be usedasa substitute.The iron oxides,chromiumhydroxide,andtitaniumdioxideare
not a problem.
The silicones andsteroIsdo not appearto be a problem.Amongthe vitamins,tocoph-
erol is a follicularirritant. Tocopherolhasbeenadvocated by the laymanfor yearsto
increase woundhealingand reducescarformation.However,it shouldnot be usedon
acne-prone skin because of its potentialto producefollicularhyperkeratosis.
The deriva-
tive, tocopherylacetate,is noncomedogenic, andresearch needsto bedoneto seeif it is
an acceptablesubstitute.
 COMEDOGENICITY 329

.,.

&t,
Cosoz ISOCETYL ALCOHOL

..

.,
;,

.'-".
, r•tl'.,.,'/'

Figure 3. The brsnched-½h•in

•l½oholis more½ornedo•eni½
•nd moreirrit•tin• th•n the
•l½ohol.

As for the miscellaneous

items,the usualsunscreenactiveingredients
arenoncomedo-
genic. Amongchemicalsolvents,acetone,ether, and EGME are not problems,but
xyleneis comedogenic andan irritant.Whenmetallicbases,suchaslithium, magne-
sium,andzincstearate, areaddedto the fattyacids,the metalappears
to preventthe
comedogenic reaction.Amongbases,triethanolamine is morecomedogenicthanami-
nomethylpropylamine.The classicformulation of a cold cream often involvesa salt
bridgebetweenstearicacidandtriethanolamine. In testingdifferentratios[4:1, 1:1,
1:4] of stearicacidto triethanolamine
(stearicacid:TEA)in a coldcreambase,all com-
binationswerefoundto be comedogenic.
The influence
of thevehicleor solvent
onthecomedogenicity andirritancyof a chem-
icalappears
quitesignificant.Forexample,theuseof rapidlyevaporatingvehicles such
asacetoneor etherreducesthe comedogenicityof fatty acidswhencompared to the
resultsobtainedwith sunfloweroil, a nonvolatilevehicle(Table III). The effectson
irritancy are reversed.Fatty acidsare lessirritating when deliveredin a nonvolatile
vehicle.As with the fatty acids,the vehicleor carrierfor the D&C red pigmentis
extremelyimportant.Whereasthe D&C red colormay be noncomedogenic in volatile
propyleneglycol,it may be morecomedogenic
in mineraloil. Possible
alternatives
for
mineraloil, suchaspentaerythritaltetracapra/caprylateandpolyethylene glycol400,
alsoreducethe comedogenicity of the redcolor(TableII). We havechosen propylene
glycolasthe routinediluentfor thesestudies,asit graduallyevaporates and leavesa
concentrateof the rawmaterialto be tested.Also,lot afterlot of propylene
glycolhas
provento be nonirritatingand noncomedogenic.
330 JOURNAL OF THE SOCIETYOF COSMETICCHEMISTS

OLETH-iO

OLETH.
2

Figure4. Oleth-3compared to oleicacid.Theinitialadditions

of ethylene
glycolsto potentially
comedo-
genicandirritatingingredients
appearto increase
thispropensity. Furtheradditionsof ethylene
glycols,
such as oleth-10 and oleth-20, tend to reduce reactions.

Someingredientcombinations--forexample,the combination of glycerylstearate

with
potassium stearate
(available
commerciallyasglycerylstearate
S.E.) andalsothe combi-
nation of D&C red #36 and mineral oil--appear more comedogenic than the indi-
vidual compounds themselves.
Thesesynergisticreactionsneedto be studiedfurther.
 COMEDOGENICITY 331

Table II
Comedogenicity
of D&C Red #36 Dye in DifferentVehicles
Grade (0- 5)

Comedo. lrrit.

D&C red #36 in mineral oil 3 0

D&C red #35 in pentaerythrital
tetracaprdcaprylate 2 0

D&C #36 in propyleneglycol 1 0

D&C red #36 in PEG 400 0 0

The oppositeis alsopossible.For example,the combinationproducedby the ingredient

D&C red #36 and the vehiclepolyethylene glycolis lesscomedogenic
than D&C red
#36 whenincorporated into othervehicles.The cosmeticchemistmay be ableto take
advantageof thesefindingsin the future to customdesignnoncomedogenic products.

SUMMARY

Thesestudiesindicatethat skin carepreparations that are nonirritatingand noncome-

dogeniccan be made.Nonreactiveingredientscanbe usedto makeelegantproducts,
and borderlineingredientscanbe combinedwith otheringredientsto reducethe reac-
tionsto acceptable
levels.In spiteof theseguidelines,newformulations mustalwaysbe
examinedwith the rabbit earassaybeforethe cosmeticchemistcanbe assuredthat his
ideas work.

Figure 5. The comedogenicityof D&C red #36 whenincorporated into two differentvehicles.The ve-
hiclemayincreaseor decrease
an ingredient's
ability to producefollicularhyperkeratosis.
332 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Table III
Effectsof the Solventon Comedogenicity
and/orIrritancyof FattyAcids

Organicsolvent* Sunfloweroil
Grade (0- 5) Grade (0- 5)

Fattyacids Comedo. Irrit. Comedo. Irrit.

Caproicacid 0 4 2 2
Caprylicacid 1 3 1 1
Capricacid 2 2 3 1
Lauric acid 3 1 4 1
Myristicacid 1 0 3 0
Palrnitic acid 0 1 2 0
Stearic acid 0 1 2 0
Archidic acid 1 1 2 0
Behenic acid 1 0 1 0

* Ethyl etheror acetone.

The rabbitearassayremainsimportantto the rapidevaluationof newingredients

and
the cosmeticchemist'sformulations.Both the visualand microscopicevaluationsof the
rabbitearneedto be donesimultaneously (9). Materialsfoundto be noncomedogenic
in
the rabbit assayappearto be noncomedogenic in the human model (10). Whether
highly comedogenic ingredientsin the rabbit ear assayare alwayscomedogenicin
humansstill remainsuncertain.Currently,it is moreprudentto avoidtheseoffenders.
The majoroffenders, suchasisopropylmyristate,acetylated lanolinalcohol,andlauric
acid derivativessuchas laureth-4, shouldbe usedwith cautionin skin careproducts.
We are not convincedof the statementthat lower concentrations of thesecompounds
canbe safelyusedwith no comedogenic consequences (11). Humanskinstudieshave
beenusedto give that statementcredence, but the backskin of humanvolunteers is
relativelyinsensitive
(7). However,whentherabbitearassay is positivebut thehuman
back skin resultsare negativeafter only eight weeks'exposure,the resultsfrom the
rabbitearassay shouldnot be dismissed.The reaction maytakelongeror thebackskin
may not be the idealtestingsurface.
An additional"bonus"of the rabbit ear assayis detectionof the potentialof an ingre-
dient or finishedproductto producean epithelialirritant reaction.It is easyto keep
trackof the surfaceirritancywhiledoingthe follicularstudies.The stratumcorneumof
the rabbitearis verythin andundeveloped.This resultsin an extremesensitivity of the
skinto exposure
to irritants.If thistestfindingis confirmed
by others,we mayfind it
unnecessary
to usethe Draizerabbitdermalirritancytest.
This paperis meantto be a surveyof the ingredients usedin skin careand hair care
products.The surveyis not at all definitivebut simplydesignedto stimulateresearch,
sothat new noncomedogenic productswill becomeavailablefor thoseof uswith acne-
pronecomplexions.Thissubject hasrecentlyreceived anexcellentreviewby theAmer-
icanAcademyof DermatologyInvitationalSymposium on Comedogenicity (12).

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 COMEDOGENICITY 333

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