Safety Assesment Butylene Glycol

International Journal of Toxicology, 25(Suppl.
2):1–89, 2006
Copyright c American College of Toxicology
ISSN: 1091-5818 print / 1092-874X online
DOI: 10.1080/10915810600964618
Annual Review of Cosmetic Ingredient Safety

Assessments—2004/20051
The Cosmetic Ingredient Review (CIR) program Expert Chloroxylenol

Panel has assessed the safety of almost 1300 cosmetic ingredi- Diisopropanolamine, Isopropanolamine, Triisopropanolamine,
ents since its inception in 1976. These safety assessments were and Mixed Isopropanolamines
published in the Journal of Environmental Pathology and Tox- Dioctyl Adipate and Diisopropyl Adipate
icology in 1980, the Journal of the American College of Toxi- Formaldehyde
cology, from 1982 to 1996, and since then in the International Hydrolyzed Collagen
Journal of Toxicology. p-Hydroxyanisole
Because information relevant to the safety of ingredients may Isostearyl Neopentanoate
have become available since early safety assessments were pub- 2-Nitro- p-Phenylenediamine and 4-Nitro-o-Phenylenediamine
lished, the CIR Expert Panel has initiated a re-review process. Oleic Acid, Lauric Acid, Palmitic Acid, Myristic Acid, Stearic
If new information is thought to be available or if a long period Acid
of time has passed, the CIR Expert Panel may initiate a search Panthenol and Pantothenic Acid
for relevant new data. p-Phenylenediamine
In some cases, newly available data are largely redundant Phenyl Trimethicone
with the data available in the original safety assessment. In other Propylene Carbonate
cases, there are new safety data. If the CIR Expert Panel decides Propyl Gallate
to not reopen a safety assessment, this finding is summarized and Polyvinylpyrrolidone/Vinyl Acetate Copolymer
announced publicly. To assure that the scientific community is Safflower Oil
aware of any new information and the decision to not reopen, Sodium Borate and Boric Acid
this Annual Review of Cosmetic Ingredient Safety Assessments Sodium Dehydroacetate and Dehydroacetic Acid
is prepared. Sodium Lauryl Sulfoacetate
A reference list is provided that updates the available pub- Sodium Sesquicarbonate, Sodium Bicarbonate, and Sodium
lished literature and includes any unpublished data made avail- Carbonate
able since the original safety assessment. The re-review also Stearyl Alcohol, Oleyl Alcohol, and Octyl Dodecanol
captures information on the industry’s current practices of in- Toluene
gredient use, updating the data available in the earlier report. Toluenesulfonamide/Formaldehyde Resin
Although this material provides the opinion of the CIR Expert Tragacanth Gum
Panel regarding the new data described, it does not constitute a Vinyl Acetate/Crotonic Acid Copolymer
full safety review. Zinc Phenolsulfonate
The ingredients the CIR Expert Panel reconsidered in
2004/2005, and decided not to reopen are:
Benzethonium Chloride and Methylbenzethonium Chloride BENZETHONIUM CHLORIDE AND
2-Bromo-2-Nitropropane-1,3-Diol METHYLBENZETHONIUM CHLORIDE
Butylated Hydroxyanisole (BHA) A safety assessment of Benzethonium Chloride and Methyl-
Butylene Glycol, Hexylene Glycol, Ethoxydiglycol, and benzethonium Chloride was published in 1985 with the conclu-
Dipropylene Glycol sion that these ingredients are safe at concentrations of 0.5% in
Cetearyl Octanoate (Ceteraryl Ethylhexanoate) cosmetics applied to the skin, and up to 0.02% for cosmetics
Cholesterol used in the eye area (Elder 1985). New studies, along with the
updated information below regarding types and concentrations
of use, were considered by the CIR Expert Panel. The Panel
Received 2 May 2006; accepted 14 August 2006.
1
Reviewed by the Cosmetic Ingredient Review Expert Panel. Ad- determined to not reopen this safety assessment.
dress correspondence to Director, Cosmetic Ingredient Review, 1101 Benzethonium Chloride is a quaternary ammonium salt
17th Street, NW, Suite 412, Washington, DC 20036, USA. used as an antimicrobial agent, cosmetic biocide, deodorant
1
2 SAFETY ASSESSMENTS—2004/2005
TABLE 1
Historical and current cosmetic product uses and concentrations for Benzethonium Chloride and historical uses of
Methylbenzethonium Chloride
1981 uses 2002 uses 1981 concentrations 2003 concentrations
Product category (Elder 1985) (FDA 2002) (Elder 1985) % (CTFA 2003) %
Benzethonium Chloride
Baby care∗ 1 — >0.1–1 —
Bath* 1 — ≤0.1 —
Eye makeup
Eyeliners 2 — >0.1–1 —
Fragrances
Colognes and toilet waters 6 — >0.1–1 —
Perfumes 3 — >0.1–1 —
Powders 1 — >0.1–1 —
Noncoloring hair care
Conditioners 2 — >0.1–1 —
Sprays/aerosol fixatives 1 — ≤ 0.1 —
Rinses 3 — ≤0.1 —
Shampoos 1 — >0.1–1 —
Tonics, dressings, etc. 1 2 ≤0.1 —
Wave sets 1 — ≤0.1 —
Other noncoloring hair care 2 3 ≤0.1 —
Makeup
Other makeup — — — 0.03
Personal hygiene
Underarm deodorants 11 6 ≤0.1 0.05
Douches 7 1 >0.1–5 —
Feminine deodorants 3 1 ≤0.1 —
Other personal hygiene 7 5 ≤1 0.1–0.3
Shaving
Aftershave lotions 2 3 ≤0.1 —
Mens talcum 2 — ≤1 0.1
Preshave lotions 1 — >0.1–1 —
Other — 1 — —
Skin care
Cleansing creams, lotions, etc. 5 2 ≤1 0.2%
Face and neck skin care 1 —
7∗∗ ≤1∗∗
Body and hand skin care 5 —
Foot powders and sprays — 2 — 0.1
Moisturizers 2 1 ≤0.1 ≤0.1
Paste masks/mud packs 2 — ≤0.1 —
Skin fresheners 13 — ≤1 —
Other skin care 3 4 ≤0.1 —
Suntan products
Suntan gels, creams, liquids and sprays 2 2 ≤0.1 —
Indoor tanning preparations 1 — ≤0.1 —
Total uses/ranges for Benzethonium Chloride 93 39 ≤5 0.03–0.3
Methylbenzethonium Chloride
Baby Care
Lotions, oils, powders, and creams 2 — ≤1 —
COSMETIC INGREDIENT REVIEW 3
TABLE 1
Historical and current cosmetic product uses and concentrations for Benzethonium Chloride and historical uses of
Methylbenzethonium Chloride (Continued)
Fragrances
Colognes and toilet waters 1 — ≤0.1 —
Conditioners 1 — ≤0.1 —
Sprays/aerosol fixatives 6 — ≤0.1 —
Personal hygiene
Underarm deodorants 5 — ≤1 —
Douches 1 — >0.1–1 —
Feminine deodorants 2 — ≤0.1 —
Other personal hygiene 1 — ≤0.1 —
Shaving
Aftershave lotions 4 — ≤1 —
Other shaving 1 — ≤0.1 —
Skin care
Cleansing creams, lotions, etc. 1 — ≤0.1 —
Face and neck creams, lotions, powder and sprays 1 — ≤0.1 —
Moisturizers 1 — ≤0.1 —
Skin fresheners 3 — ≤0.1 —
Suntan
Suntan gels, creams, liquids and sprays 2 — ≤0.1 —
Other suntan 1 — ≤0.1 —
Total uses/ranges for Methylbenzethonium Chloride 33 — ≤1.0 —
∗
No details were provided describing specific product categories.
∗∗
These categories were combined and have since been separated.
agent, or surfactant—suspending agent in cosmetics. In volun- • 1% of soap remaining on human skin after washing
tary reports provided by industry to the Food and Drug Ad- • human dermal absorption of Benzethonium Chloride
ministration (FDA) in 1981, Benzethonium Chloride was used from hand soap formulations = 50%
in 93 cosmetic products, with a maximum concentration up to • Average body weight 40 kg
5% (Elder 1985). In 2002, information provided by industry • No observable effect level (NOEL) of 12.5 mg/kg
to FDA indicated that Benzethonium Chloride was used in 39 day−1 for systemic toxicity from an NTP 13-week der-
cosmetic products (FDA 2002). A survey conducted by the Cos- mal study
metic, Toiletry, and Fragrance Association (CTFA) found that
the maximum use concentration for Benzethonium Chloride was Exposure calculation:
5% in douches (CTFA 2003). The current and historical data on
use as a function of product category are given in Table 1. The 1.5 g/day × 5% × 1% × 50% = 3.75 mg/day
most recent information now constitutes the present use of this 3.75 mg/day/40 kg = 0.09375 mg/kgday−1 maximum
ingredient. possible exposure
Newly available unpublished toxicology data were consid-
ered supportive of the original conclusion. The CIR Expert Panel The NOEL value divided by the maximum possible exposure
did consider an analysis by Blumenthal et al. (1995), in which a yielded a margin of safety of 113 for Benzethonium Chloride.
margin of safety was calculated for Benzethonium Chloride as Methylbenzethonium Chloride is also a quaternary ammo-
an antibacterial agent in consumer handsoaps as follows: nium salt with functions in cosmetics that include antimicrobial
agent, antistatic agent, cosmetic biocide, and deodorant agent.
• Soap usage of 15 g/day (90th percentile of human use In the earlier safety assessment, Methylbenzethonium Chloride
= 10 × 1.5 g). was used in 33 cosmetic products, at a maximum concentra-
• Maximum use concentration of 5% tion up to 1% in baby lotions, oils, powders, and creams, and
in underarm deodorants, douches, and aftershave lotions (Elder Lonza, Inc. 1995a. Acute eye irritation test in the rabbit. SPL project number
1985). Industry reported no uses to the FDA in 2002 (FDA 2002) 102/213. Unpublished data submitted by Toxicology/Regulatory Services,
and CTFA found no uses in its survey (CTFA 2003). Inc., January 8, 2004. (19 pages.)2
Lonza, Inc. 1995b. Magnusson & Kligman maximisation study in the guinea
The historical data on use of Methylbenzethonium Chloride pig. SPL project number 102/213. Unpublished data submitted by Toxicol-
as a function of product category are given in Table 1. Were ogy/Regulatory Services, Inc., January 8, 2004. (36 pages.)2
this ingredient to be used in the future, the CIR Expert Panel Lonza, Inc. 1995c. Developmental toxicity study of Hyamine 1622 in rats. Un-
expects that it would be used at concentrations and in product published data submitted by Toxicology/Regulatory Services, Inc., January
8, 2004. (223 pages.)2
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Lonza, Inc. 1996a. Magnusson-Kligman guinea pig maximization study with
Hyamine 1622. Unpublished data submitted by Toxicology/Regulatory Ser-
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was published in 1980 with the conclusion that this preserva- Boots Co. PLC submitted to EPA. 33 pages.3
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that use concentrations were reported at levels up to 1%. In cosmetic ingredients. Contact Dermatitis 13:258–265.
addition, the action of 2-Bromo-2-Nitropropane-1,3-Diol as a Environmental Protection Agency (EPA). 1995. Reregistration eligibility de-
nitrosating agent was emphasized and data provided demon- cision (RED): Bronopol. (Includes RED facts: bronopol fact sheet). NTIS
strating that it was present in formulations with amines such Report No. PB96188461.
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Studies available since the addendum was completed, along Ms. Kathryn Boyle. July 7, 2003.3
with the updated information regarding uses and use concen- European Commission. 2003. The rules governing cosmetic products in the
trations, were considered by the CIR Expert Panel. The Panel European Union. Volume 1. Cosmetics legislation—Cosmetic products.
http://dg3.eudra.org/F3/home.html. Internet site accessed June 30, 2003.
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atives at concentrations of ≤0.1%. Frequency of use data pro- Everest, R., and C. Williams. 1986a. Bronopol-Boots: In vitro bacterial muta-
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an industry survey in 2003 indicated use in several other product Boots Company PLC submitted to EPA. 19 pages.3
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TABLE 2
Historical and current cosmetic product uses and concentrations for 2-Bromo-2-Nitropropane-1,3-Diol
1976 use 2002 use 1976 concentrations 2003 concentrations
Bath
Bath oils, tablets, and salts 1 — ≤0.1 —
Bubble baths 4 — ≤0.1 —
Bath soaps and detergents 1 — ≤0.1 —
Other bath 5 — ≤0.1 —
Eye makeup
Eyebrow pencil 14 — ≤0.1 —
Eyeliner 11 — ≤0.1 —
Eye shadow 3 — ≤0.1 0.1
Eye makeup remover — — — 0.05
Mascara 6 — ≤0.1 —
Other eye makeup 2 — ≤0.1 —
Fragrances
Colognes and toilet waters — — — 0.03
Perfumes — — — 0.1
Other fragrances 2 — >0.1–1 —
Hair conditioners 22 — ≤0.1–1 —
Rinses 6 — ≤0.1–1 —
Shampoos 9 — ≤0.1 —
Hair tonics, dressings, etc. 3 — ≤0.1–1 —
Other noncoloring hair care 1 1 ≤0.1 —
Hair coloring
Hair dyes and colors 3 — >0.1–1 —
Makeup
Blushers 20 — ≤0.1 0.1
Foundations 6 — ≤0.1 —
Leg and body paints 2 — ≤0.1 —
Lipstick — — — 0.1
Makeup bases 3 — ≤0.1 —
Makeup fixatives 134 — ≤0.1 —
Other makeup 1 — ≤0.1 —
Personal hygiene
Underarm deodorants 2 — ≤0.1 —
Shaving
Aftershave lotion 1 — ≤0.1 0.03
Skin care
Cleansing creams, lotions, etc. 17 — ≤0.1 0.02
Depilatories
Face and neck skin care preparations — —
3∗ >0.1–1*
Body and hand skin care preparations — —
Moisturizers 9 — ≤0.1 —
Night skin care preparations 3 — ≤0.1 —
Paste masks/mud packs 8 — ≤0.1 —
Skin fresheners 3 — ≤0.1 0.01
Other skin care 6 — ≤0.1 0.009
Suntan preparations
Suntan gels, creams, and liquids 3 — ≤0.1–1 0.05
Indoor tanning preparations 1 — ≤0.1 —
Other suntan 1 — ≤0.1 —
Total uses/ranges for 323 1 ≤0.1–1 ≤0.1
2-Bromo-2-Nitropropane-1,3-Diol
∗
These categories were originally combined, but are now separate.
FDA. 2003. Prohibited ingredients and related safety issues. Podmore, P. 2000. Occupational allergic contact dermatitis from both 2-bromo-
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Ford, G. P., and M. H. Beck. 1986. Reactions to quaternium 15, bronopol, and zolinone in spin finish. Contact Dermatitis 43:45.
germall 115 in a standard series. Contact Dermatitis 14:271–274. Rudzki, E., P. Rebandel, and Z. Grzywa. 1993. Occupational dermatitis from
Fransway, A. F., and N. A. Schmitz. 1991. The problem of preservation in the cosmetic creams. Contact Dermatitis 29:210.
1990s: II. Formaldehyde and formaldehyde-releasing biocides: Incidences of Sanyal, A. K., M. Basu, and A. B. Banerjee. 1996. Rapid ultraviolet spec-
cross-reactivity and the significance of the positive response to formaldehyde. trophotometric determination of bronopol: application to raw material analy-
Am. J. Contact Dermatitis 2:78–88. sis and kinetic studies of bronopol degradation. J. Pharmaceut. Biomed. Anal.
Frosch, P. J., I. R. White, R. J. G. Rycroft, et al. 1990. Contact allergy to bronopol. 14:1447–1453.
Contact Dermatitis 22:24–26. Scalia S., S. Simeoni, and E. Bousquet. 2001. Determination of bronopol in cos-
Glass, R., and S. Hewertson. 1993. Study of the excretion, distribution, metic products by HPLC with electrochemical detection. Pharmazie 56:318–
and metabolism of bronopol in the rat: Lab Project Number: DT93077: 320.
RD/RCG.SJH/763474: BHR/006. Unpublished data from Boots Pharmaceu- Schnuch, A., J. Geier, W. Uter, and P. J. Frosch. 1998. Patch testing with preser-
ticals submitted to EPA. 252 pages.3 vatives, antimicrobials, and industrial biocides. Results from a multicentre
Goossens, A., M. H. Beck, E. Haneke, J. P. McFadden, S. Nolting, G. Durupt, study. Br. J. Dermatol. 138:467–476.
and G. Ries. 1999. Adverse cutaneous reactions to cosmetic allergens. Contact Shaw, S. 1997. Patch testing bronopol. Cosmet. Toiletries 112:67–68, 71–73.
Dermatitis 40:112–113. Shehade, S. A., M. H. Beck, and V. F. Hillier. 1991. Epidemiological survey of
Grattan, C. E., R. R. Harman, and R. S. Tan. 1986. Milk recorder dermatitis. standard series patch test results and observations on day 2 and day 4 readings.
Contact Dermatitis 14:217–220. Contact Dermatitis 24:119.
Herzog, J., J. Dunne, R. Aber, M. Claver, and J. G. Marks, Jr. 1988. Milk tester’s Smithson, A. 1984. Bronopol: Data on individual animals in toxicity studies:
dermatitis. J. Am. Acad. Dermatol. 32:1693–1698. Report No. TXA 83082. Unpublished data from Boots Co. LTD (Nottingham,
Hindmarsh, M. 1990. Mortality in calves associated with the feeding of milk England; CDL:252631-A) submitted to EPA, March 7, 1984.3
containing bronopol. Aust. Vet. J. 67:309–310. Steele, C. 1994. Bronopol: Oral (gavage) rat developmental toxicity dose ranging
Irwine, L. 1992a. Bronopol: Oral (gavage). Rabbit developmental toxicity (ter- study. Lab Project Number: TX94032: BON/8/93. Unpublished data from
atogenicity) study: Lab Project Number: BON/3/R. Unpublished data from Boots Pharmaceuticals submitted to EPA. 106 pages.3
Toxicol Laboratories, Ltd. submitted to EPA. 198 pages.3 Storrs, F. J., L. E. Rosenthal, R. M. Adams, et al.1989. Prevalence and relevance
Irwine, L. 1992b. Bronopol: Oral (gavage). Rabbit developmental toxicity (ter- of allergic reactions in patients patch tested in North America 1984 to 1985.
atogenicity) study: Lab Project Number: BON/3/R. Unpublished data from J. Am. Acad. Dermatol. 20:1038–1045.
Toxicol Laboratories, Ltd. submitted to EPA. 200 pages.3 Torresani, C., I. Periti, and L. Beski. 1996. Contact urticaria syndrome from
Jacobs, M. C., I. R. White, R. J. Rycroft, and N. Taub. 1995. Patch testing with formaldenyde with multiple physical urticarias. Contact Dermatitis 35:174–
peservatives at St John’s from 1982 to 1993. Contact Dermatitis 33:247– 175.
254. Wang, H., G. J. Provan, and K. Helliwell. 2002. Determination of bronopol and
Jackson, R., B. Hall, and D. Self. 1992. Bronopol—Environmental fate phase its degradation products by HPLC. J. Pharmaceut. Biomed. Anal. 29:387–392.
4 response: Photodegradation—Water. Unpublished data from Inveresk Re- Wilson, C. L., and S. M. Powell. 1990. An unusual case of allergic contact
search International Ltd. 28 pages.3 dermatitis in a veterinary surgeon. Contact Dermatitis 23:42–43.
Jantova, S., J. Hojerova, B. Hanusova, and M. Mikulasova. 2001. Cytotoxic and
genotoxic activity of certain preservatives in cosmetics. Ceska Slov. Farm.
50:238–242. BUTYLATED HYDROXYANISOLE (BHA)
Kränke, B., C. Szolar-Platzer, and W. Aberer. 1996. Reactions to formaldehyde
A safety assessment of Butylated Hydroxyanisole was pub-
and formaldehyde releasers in a standard series. Contact Dermatitis 35:192–
193. lished in 1984 with the conclusion that this ingredient is safe as
Liggett, M., and B. Parcell 1984. Irritant effects on the rabbit eye of bronules: a cosmetic ingredient in the practices of use (Elder 1984). New
8422D/BTS 186/SE. Unpublished data from Huntingdon Research Center plc studies, along with updated information regarding types and con-
submitted to EPA. 17 pages.3 centrations of use, were considered by the CIR Expert Panel. The
Marks, J. G. Jr., D. V. Belsito, V. A. DeLeo, et al. 1995. North American Con-
Panel determined to not reopen this safety assessment.
tact Dermatitis Group standard tray patch test results (1992 to 1994). Am. J.
Contact Dermatitis 6:160–165. The name of Butylated Hydroxyanisole as listed in the In-
Marks, J. G. Jr., D. V. Belsito, V. A. DeLeo, et al. 1998. North American Contact ternational Cosmetic Ingredient Dictionary and Handbook has
Dermatitis Group patch test results for the detection of delayed-type hyper- been changed to BHA (Pepe et al. 2002).
sensitivity to topical allergens. J. Am. Acad. Dermatol. 38:911–918. BHA functions in cosmetics include antioxidant and fra-
Marks, J. G. Jr., D.V. Belsito, V.A. Deleo, et al. 2000. North American Con-
grance ingredient. It was used in 3217 cosmetic products in
tact Dermatitis Group standard tray patch test results, 1996 to 1998. Arch.
Dermatol. 136:272–273. 1981, with the largest use occurring in lipstick at concentrations
Marks, J. G. Jr., D. V. Belsito, V. A. Deleo, et al. 2003. North American Contact of ≤10% (Elder 1984). In 2002, BHA was used in 1224 cosmetic
Dermatitis Group patch-test results, 1998 to 2000. Am. J. Contact Dermatitis products (FDA 2002), at a maximum use concentration of 0.2%
14:59–62. in colognes, toilet waters, and perfumes (CTFA 2003). Table 3
Palmer, K. 1995. Bronopol: Oral (gavage) rat developmental toxicity study. Final
presents the available use information for BHA. The most recent
report: Lab project numbers: BON/9/R: TXO95007. Unpublished data from
Toxicol Labs Ltd submitted to EPA. 165 pages.3 information now constitutes the present use of this ingredient.
Pepe, R. C., J. A. Wenninger, and G. N. McEwen, Jr., eds. 2002. International
Cosmetic Ingredient Dictionary and Handbook, 9th ed., 201–202, Washing- REFERENCES
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TABLE 3
Historical and current cosmetic product uses and concentrations for BHA
Baby care
Lotions, oils, powders, and creams 1 1 >0.1–1 0.0001
Bath
Oils, tablets, and salts 20 4 ≤0.1 0.0004
Bubble baths 7 — ≤0.1 0.00001
Bath soaps and detergents 2 5 ≤0.1 0.000004
Other bath 10 3 ≤1 0.0001
Eye makeup
Eyebrow pencil 33 51 ≤1 0.0001
Eyeliner 75 399 ≤1 0.1
Eye shadow 410 38 ≤5 0.002
Eye lotion 2 2 ≤0.1 —
Eye makeup remover 11 6 ≤0.1 0.02
Mascara 65 18 ≤1 0.1
Other eye makeup 39 10 ≤1 0.001
Fragrances
Colognes and toilet waters 97 18 ≤1 0.2
Perfumes 62 6 ≤1 0.2
Powders 12 2 ≤0.1 0.0002
Sachets 21 — ≤0.1 —
Other fragrances 24 10 ≤1 0.004
Conditioners 8 5 ≤0.1 0.0002
Sprays 1 — — 0.0001
Shampoos 6 — ≤0.1 0.0005
Tonics, dressings, etc. 10 8 ≤1 0.02
Wave sets 1 — — —
Other noncoloring hair care — — — 0.05
Hair coloring
Other hair coloring 5 1 ≤0.1 —
Makeup
Blushers 176 26 ≤5 0.2
Face powders 98 11 ≤1 0.005
Makeup foundations 119 30 ≤0.1 0.05
Lipstick 1256 279 ≤25 0.2
Makeup bases 64 4 ≤1 0.005
Rouges 48 1 ≤1 0.04
Makeup fixatives 10 — ≤0.1 —
Other makeup 106 23 ≤5 0.05
Nail care
Basecoats and undercoats 1 3 ≤0.1 —
Cuticle softeners 2 2 ≤0.1 0.001
Creams and lotions 4 1 ≤0.1 —
Polish and enamel — — — 0.06
Polish and enamel remover 1 — ≤0.1 —
Other nail care 2 4 ≤0.1 0.004
TABLE 3
Historical and current cosmetic product uses and concentrations for BHA (Continued)
Oral hygiene
Dentifrices — — — 0.01
Personal hygiene
Underarm deodorants 1 1 ≤0.1 0.002
Other personal hygiene 2 4 ≤1 0.002
Shaving
Aftershave lotions 11 2 ≤1 0.006
Preshave lotions 3 — — —
Shaving cream 8 10 ≤0.1 0.0003
Shaving soap 1 — >0.1–1 —
Other shaving 3 — ≤1 0.0003
Skin care
Cleansing creams, lotions, etc. 51 23 ≤1 0.05
Face and neck skin care ∗ 15 ∗ 0.1
77 ≤1
Body and hand skin care 72 0.1
Hormone skin care∗∗ 1 ∗∗
— ∗∗

Moisturizers 111 51 ≤1 0.06
Night skin care 30 26 ≤1 0.04
Paste masks/mud packs 6 3 ≤1 0.004
Skin lighteners∗∗ 11 ∗∗
≤0.1 ∗∗
Skin fresheners 6 2 ≤0.1 —

Wrinkle smoothers∗∗ 6 ∗∗
≤0.1 ∗∗
Other skin care 42 30 ≤1 0.03

Suntan
Suntan gels, creams, and liquids 27 7 ≤1 0.1
Indoor tanning 2 1 ≤0.1 —
Other suntan 9 5 ≤0.1 —
Total uses/ranges for BHA 3217 1224 ≤0.1–25 0.000004-0.2
∗
These categories were combined, but now are listed separately.
∗∗
No longer listed as product categories.
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BUTYLENE GLYCOL, HEXYLENE GLYCOL,
Pepe, R. C., J. A. Wenninger, and G. N. McEwen. 2002. International Cosmetic
Ingredient Dictionary and Handbook, 9th ed. Washington, DC: CTFA. ETHOXYDIGLYCOL, AND DIPROPYLENE GLYCOL
Poulsen, E. 1991. Safety evaluation of substances consumed as technical ingre- A safety assessment was published in 1985 with the conclu-
dients (food additives). Food Addit. Contam. 8:125–134. sion that these ingredients are safe as presently used in cosmetics
Richer, N., M. Marion, and F. Denizeau. 1989. Inhibition of binding of 2- (Elder 1985). New studies, along with updated information re-
acetylaminofluorene to DNA by butylatedhydroxytoluene and butylated hy-
droxyanisole in vitro. Cancer Lett. 47:211–216.
garding types and concentrations of use, were considered by
Romero, F. J., J. Romá, F. Bosch-Morell, B. Romero, J. Segura-Aguilar, A. the CIR Expert Panel. The Panel determined to not reopen this
Lombart-Bosch, and L. Ernster. 2000. Reduction of brain antioxidant defense safety assessment.
upon treatment with butylated hydroxyanisole (BHA) and Sudan III in Syrian Butylene Glycol was reported to be used in 165 cosmetic
golden hamsters. Neurochem. Res. 25(3):389–393. preparations in 1981, with the greatest use occurring in mas-
Sakai, A., N. Miyata, and A. Takahashi. 1997. Promoting activity of 3-tert-
4-hydroxyanisole (BHA) in BALB/3T3 cell transformation. Cancer Lett.
cara, and at concentrations that ranged from less than 0.14%
115:213–220. to greater than 50% (Elder 1985). In 2002, industry reports to
Schilderman, P. A. E. L., E. Rhijnsburger, I. Zwingmann, and J. C. S. Kleinjans. FDA indicated that Butylene Glycol was used in 813 prepara-
1995. Induction of oxidative DNA damage and enhancement of cell prolifer- tions (FDA 2002). An industry survey of use concentrations in
TABLE 4
Historical and current cosmetic product uses and concentrations for Butylene Glycol, Hexylene Glycol, Ethoxydiglycol,
and Dipropylene Glycol
Butylene Glycol
Baby care
Lotions, oils, powders, and creams — 2 — 13
Other baby care — — — 3–4
Bath
Oils, tablets, and salts 1 3 5–10 0.08
Soaps and detergents 1 10 5–10 0.02–1
Other bath 4 20 5–>50 1
Eye makeup
Eyebrow pencils — 1 — 0.007
Eyeliners 3 12 1–5 3–12
Eye shadow 13 3 5–25 2
Eye lotions — 5 — 3–8
Eye makeup remover 4 16 1–5 5
Mascara 34 14 1–10 0.00007–3
Other eye makeup 1 19 1–5 7
Fragrances
Colognes and toilet waters 3 5 0.1–25 4
Perfumes 2 4 1–5 —
Powders — 4 — —
Other fragrances 1 18 5–10 2
Conditioners 5 10 ≤1–10 <1–3
Sprays/aerosol fixatives — — — 3
Permanent waves — 2 — 1
Shampoos 1 9 ≤0.1 1–4
Tonics, dressings, etc. 1 11 1–5 0.02–5
Other noncoloring hair care — 12 — <1–6
Makeup
Blushers 7 — 1–25 —
Face powders 1 2 1–5 2
Foundations 19 66 5–25 6–9
Lipsticks — 4 — 0.2–3
Makeup bases 1 12 5–10 6
Rouges 2 — 5–>50 —
Makeup fixatives — 3 — 6
Other makeup 2 15 5–25 3–4
Nail care
Cuticle softeners 1 3 5–10 —
Creams and lotions — 2 — —
Nail polishes and enamels — 5 — —
Other nail care — 2 — —
Oral hygiene
Other oral hygiene — — — 0.01
Personal hygiene
Underarm deodorants 1 14 10–25 20–30
Other personal hygiene 1 1 1–5 —
(Continued on next page)
TABLE 4
and Dipropylene Glycol (Continued)
Shaving
Aftershave lotions 4 8 0.1–5 0.05–7
Shaving cream — 5 — 1
Other shaving — 5 — —
Skin care
Cleansing creams, lotions, etc. 13 66 ≤0.1–10 0.05–20
Depilatories — — — 4
Face and neck skin care 30 3–7
8∗ ≤ 0.1–>50∗
Body and hand skin care 43 0.01–14
Foot powders and sprays — 4 —
Moisturizers 13 171 ≤0.1–>50 0.02–13
Night skin care 1 23 ≤0.1 3–8
Paste masks/mud packs 3 27 0.1–10 3–12
Skin fresheners 6 16 ≤0.1–5 2–6
Other skin care 7 78 ≤0.1–10 4–89
Suntan products
Suntan gels, creams, liquids, and sprays 1 7 1–5 2–5
Indoor tanning — 18 — 0.5–20
Other suntan — 3 — 5
Total uses/ranges for Butylene Glycol 165 813 ≤0.1–>50 0.00007–89
Hexylene Glycol
Baby care
Other baby care — — — 1
Bath
Oils, tablets, and salts 4 1 5–25 —
Soaps and detergents 3 3 1–5 —
Bubble baths 3 2 0.1–5 —
Other bath — 2 — —
Eye makeup
Eye lotions — 2 — 2
Eye makeup remover 1 20 0.1–1 2
Mascara — 1 — 0.1
Other eye makeup — 3 — 0.8
Fragrances
Other — 1 — —
Conditioners 7 3 0.1–10 4
Permanent waves 1 2 10–25 —
Rinses 1 — 10–25 —
Shampoos 29 12 ≤0.1–10 —
Tonics, dressings, etc. — 2 — 4
Wave sets — 1 — —
Other noncoloring hair care — 2 — —
Hair coloring
Dyes and colors 20 179 1–25 —
TABLE 4
Rinses — 2 — —
Bleaches 1 1 1–5 —
Makeup
Foundations — 4 — 0.3
Lipsticks 0.003
Makeup bases — 1 —
Makeup fixatives — — — 1
Nail care
Nail polish and enamel removers — 1 — —
Personal hygiene
Underarm deodorants 2 — 0.1–1 0.002
Other personal hygiene — 1 — 0.0009
Shaving
Aftershave lotions — — — 0.1–2
Shaving cream — 1 — —
Other shaving — — — 2
Skin care
Cleansing creams, lotions, etc. 4 22 0.1–5 0.005–6
Face and neck skin care 5 0.001–4
1* 1–5*
Moisturizers 3 7 0.1–5 1
Night skin care — 2 — 1–4
Paste masks/mud packs 1 6 5–10 0.3
Skin fresheners 3 2 0.1–5 —
Other skin care 1 6 1–5 3
Suntan
Suntan gels, creams, liquids, and sprays — 6 — 0.01
Other suntan — 2 — —
Total uses/ranges for Hexylene Glycol 85 306 ≤0.1–25 0.0009–6
Ethoxydiglycol
Baby care
Shampoos — — — <1
Lotions, oils, powders, and creams — — — <0.5
Bath
Oils, tablets, and salts — 3 — —
Soaps and detergents — — — 0.6
Bubble baths — 2 — 0.006
Eye makeup
Eye lotions — — — 0.0001–2
Eye makeup remover — 1 — —
Mascara 1 7 0.1–1 —
Other eye makeup — 1 — —
Fragrances
Colognes and toilet waters 3 — 0.1–10 1
Perfumes — — — 1
TABLE 4
Other fragrances — 2 — —
Conditioners 4 11 0.1–5 0.04
Sprays/aerosol fixatives — 4 — 0.00008
Shampoos 1 15 0.1–1 0.02–1
Tonics, dressings, etc. — 4 — 0.03
Wave sets 1 1 1–5 —
Other noncoloring hair care — 4 — 0.4
Hair coloring
Dyes and colors 14 495 1–10 —
Tints 13 — 1–5 —
Bleaches 5 6 1–5 —
Other hair coloring 1 2 1–5 —
Makeup
Blushers — — — 0.0006
Face powders — — — 0.0008
Lipsticks — — — 0.00004
Makeup bases — — — 0.008
Rouges — — — 0.05
Other — — — 0.04
Nail care
Basecoats and undercoats — 1 — —
Nail polish and enamel removers 1 — 5–10 —
Other nail care — — — 42
Personal hygiene
Underarm deodorants — — — 0.2
Douches — — — 0.1
Other personal hygiene — — — 0.3
Shaving
Aftershave lotions 2 2 0.1–1 0.6
Preshave lotions — — — 0.0005
Shaving cream — 2 — 5
Other shaving — 2 — —
Skin care
Cleansing creams, lotions, etc. 14 10 ≤0.1–> 50 0.02–80
3* ≤0.1–1∗
Body and hand skin care 6 0.1–0.5
Moisturizers 3 3 1–10 0.04–3
Night skin care 2 — ≤0.1–5 0.09–10
Paste masks/mud packs 3 2 0.1–25 0.002–8
Skin fresheners 3 — 1–5 5–8
Other skin care 5 14 0.1–10 0.05–53
Skin lighteners∗∗ 1 —∗ —
TABLE 4
Suntan
Suntan gels, creams, liquids, and sprays — 5 — —
Indoor tanning — 10 — 1–5
Other suntan — — — 0.2–9
Total uses/ranges for Ethoxydiglycol 80 622 ≤0.1–> 50 0.00004–80
Dipropylene Glycol
Baby care
Lotions, oils, powders, and creams — 1 — —
Bath
Oils, tablets, and salts 1 3 >50 —
Soaps and detergents — 4 — 0.8
Bubble baths — 1 — 0.03
Eye makeup
Eye lotions — 2 — 0.1–4
Mascara — 7 — —
Fragrances
Colognes and toilet waters 2 — 5–10 7–9
Perfumes 12 4 0.1–>50 0.01–20
Sachets 1 — >50 —
Other fragrances 1 5 >50 4
Conditioners — 8 — 0.2
Sprays/aerosol fixatives 1 — ≤0.1 0.6
Rinses — — — 0.004
Shampoos 1 6 5–10 0.4
Tonics, dressings, etc. 1 3 10–25 0.4
Wave sets 4 4 5–10 —
Hair coloring
Dyes and colors — 10 — —
Other hair coloring — 2 — —
Makeup
Blushers — 1 — 0.08
Lipsticks 4 15 ≤0.1–10 0.03
Makeup bases 1 4 1–5 0.05
Rouges — — — 0.08
Other makeup — 2 — 0.2–7
Nail care
Nail polish and enamel removers — — — 0.004
Personal hygiene
Underarm deodorants 4 25 1–5 8–50
Other personal hygiene — 13 — 1
TABLE 4
Shaving
Aftershave lotions 2 2 0.1–5 3–5
Preshave lotions — — — 0.6
Shaving cream — — — 0.07
Skin care
Cleansing creams, lotions, etc. 4 38 ≤0.1 0.01–12
Face and neck skin care 24 2
3∗ 1–5∗
Foot powders and sprays 1 — 0.1–1 —
Moisturizers 4 39 1–10 7
Night creams, lotions, powder, and sprays — 4 — 2–3
Paste masks/mud packs — 14 — 0.02–0.03
Skin fresheners 2 3 0.1–25 2
Other skin care 1 18 5–10 1–2
Suntan
Suntan gels, creams, liquids and sprays — 5 — —
Indoor tanning — 4 — 1
Total uses/ranges for Dipropylene Glycol 50 304 ≤0.1–>50 0.004–50
∗
This category was combined when the original safety assessment was performed and is now two separate categories.
∗∗
No longer included as a cosmetic product category.
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dose level. These findings suggest that the process of metabolic
of 15 cases with occupational contact dermatitis in the secondary industries.
Environ. Dermatol. 6:22–25. conversion of DEHT to 2-EH, and subsequent hydrolysis to 2-
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Although this study was undertaken to understand 2-EHA
ether as a vehicle for topical delivery of ivermectin. Vet. Res. Commun.
19:309–319. developmental toxicity, the Panel considered that it is rele-
vant to the assessment of Cetearyl Ethylhexanoate. Like DEHT,
Cetearyl Ethylhexanoate must undergo conversion in order to
CETEARYL OCTANOATE (CETEARYL produce 2-EHA. In addition, Cetearyl Ethylhexanoate, as used in
ETHYLHEXANOATE) cosmetics, would have to pass through the stratum corneum and
A safety assessment of Cetearyl Octanoate was published in the epidermis before entering the blood stream, further moder-
1982 with the conclusion that this ingredient is safe as a cos- ating the time course of 2-EHA appearing in the liver. The Panel
metic ingredient in the present practices of use (Elder 1982). recognized that Cetearyl Ethylhexanoate is used in lipsticks and
Studies available since that safety assessment was completed that ingestion is possible from that use. It was the view of the CIR
have been considered by the CIR Expert Panel, along with up- Expert Panel that these considerations would preclude any pos-
dated information regarding uses and use concentrations. The sibility that Cetearyl Ethylhexanoate in cosmetics could present
Panel determined to not reopen this safety assessment. a risk of developmental toxicity.
The terminology for this ingredient in the International Cetearyl Ethylhexanoate was used in 243 cosmetic products
Cosmetic Ingredient Dictionary and Handbook has changed— in 1976 (Elder 1982). The highest concentrations were in eye
Ceteraryl Ethylhexanoate is the current terminology (Pepe et al. makeup, makeup, and skin care preparations. Currently there
2002). are 229 reported uses of Cetearyl Ethylhexanoate reported to
Significant among the new data were data on 2-ethylhexanoic FDA (FDA 2002), with the highest concentrations (up to 35%)
acid (2-EHA), which has been shown to be a liver and develop- in makeup (CTFA 2002). Although current use concentrations
mental toxicant in animal studies at high dose levels. 2-EHA is have increased compared to those reported in 1976, available
a possible metabolite of Cetearyl Ethylhexanoate. skin irritation data show no irritation at concentrations up to
In developmental toxicity studies, it has been postulated that 30%.
2-EHA maternal liver toxicity begins a cascade of effects that Table 5 presents the available use and concentraton informa-
includes metallothionein (MT) induction, zinc accumulation in tion. The most recent information now constitutes the present
the liver due to MT binding, and a resulting zinc deficiency in practices of use.
the developing embryo. In this model, it is the zinc deficiency in
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TABLE 5
Historical and current cosmetic product uses and concentrations for Cetearyl Ethylhexanoate
Product category (Elder 1982) (FDA 2002) (Elder 1982) % (CTFA 2002a) %
Baby care
Bath
Oils, tablets, and salts 1 — Unknown —
Capsules — — — 9
Other bath 2 — 1–10 —
Eye makeup
Eyeliners 1 — 0.1–1 —
Eye shadows 22 4 0–25 26–28
Mascara 6 — 0.1–1 0.07
Other eye makeup 2 3 0.1–5 3–5
Fragrances
Conditioners 5 — 0–5 —
Sprays (aerosol fixatives) 5 5 0–5 —
Straighteners 1 — 0.1–1 —
Rinses 1 — 0.1–1 —
Shampoos — — — 0.2
Tonics, dressings, etc. 1 32 0.1–1 0.1
Wave sets 1 — 1–5 —
Other noncoloring hair 3 2 0–5 —
Makeup
Blushers 19 3 1–25 3
Face powders 10 6 0.1–1 1–4
Foundations — 5 — 0.1–34
Lipstick — 4 — 0.1–8
Makeup bases 25 — 0.1–5 —
Rouges 2 — 5–25 —
Makeup fixatives 1 — 5–10 —
Other makeup 10 — 0.1–5 35
Nail care
Nail creams and lotions 1 — 10–25 —
Personal hygiene
Underarm deodorants — — — 3
Feminine deodorants 1 — 1–5 —
Shaving
Aftershave lotion — 2 — —
Mens talcum — 1 — —
Preshave lotions 1 — 1–5 —
Other shaving 1 — 1–5 —
Skin care
Cleansing creams, lotions, etc. 15 7 >0–10 13
Face and neck skin care 21 3
35* >0–25*
Body and hand skin care 38 3–10
Moisturizers 39 23 0.1–25 2–34
Night skin care 16 13 0.1–10 2–7
Paste masks/mud packs 3 8 0.1–5 —
Skin fresheners 1 2 0.1–1 —
Other skin care 4 21 1–25 6
Suntan
Suntan gels, creams, and liquids 7 9 0-5 0.5–9
Other suntan 1 3 5–10 —
Total uses/ranges for Cetearyl Ethylhexanoate 243 229 0–25 0.07–35
∗
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CTFA. 1993b. Photoallergenicity. Unpublished data submitted by CTFA. May Manninen, A., S. Kröger, J. Liesivuori, and H. Savolainen. 1989. 2-
8 2002.6 Ethylhexanoic acid inhibits urea synthesis and stimulates carnitine acetyl-
CTFA. 1994a. Single Application Patch Test. Unpublished data submitted by transferase activity in rat liver mitochondria. Arch. Toxicol. 63:160–161.
CTFA. May 8 2002.6 Ministry of Health, Labor, and Welfare (MHLW). 2001a. Unofficial translation
CTFA. 1994b. Human Repeat Insult Patch Test. Unpublished data submitted by of MHW Ordinance No. 331, Attached Table 1 [Negative List]. Ministry
CTFA. May 8 2002.6 of Health, Labor and Welfare, Pharmaceutical and Medical Safety Bureau,
CTFA. 1995. Human Repeat Insult Patch Test. Unpublished data submitted by Inspection and Guidance Division, 2-2, 1-chome, Kasumigaseki, Chiyoda-ku,
CTFA. May 8 2002.6 Tokyo 100-8045, Japan.
CTFA 2001a. Report rearding the primary eye irritation of pentaerythrityl MHLW. 2001b. Unofficial translation of MHW Ordinance No. 331, Attached
tetraethylhexanoate; Salacos 5408. Unpublished data provided by CTFA Oc- Table 2 [Restricted List]. Ministry of Health, Labor, and Welfare, Pharma-
tober 22, 2001. 7 pages.6 ceutical and Medical Safety Bureau, Inspection and Guidance Division, 2-2,
CTFA 2001b. Report rearding the primary dermal irritation of pentaerythrityl 1-chome, Kasumigaseki, Chiyoda-ku, Tokyo 100-8045, Japan.
tetraethylhexanoate; Salacos 5408. Unpublished data provided by CTFA Oc- Pennanen, S., and A. Manninen. 1991. Distribution of 2-ethylhexanoic acid in
tober 30, 2001. 5 pages.6 mice and rats after an intraperitoneal injection. Pharmacol. Toxicol. 68:57–59.
CTFA. 2002a. Concentration of use of ethylhexanoate ingredients. Unpublished Pennanen, S., A. Manninen, and H. Savolainen. 1990. Urinary arginine and
data provided by CTFA. Updated October 21, 2002. 6 pages.6 ornithine in occupational exposure to 2-ethylhexanoic acid. Arch. Toxicol.
CTFA. 2002b. Concentration of 2-Ethylhexanoic Acid in Cetearyl Ethylhex- 64:426–427.
anoate. Unpublished data provided by CICD committee of CTFA Sept. 6, Pennanen, S., K. Tuovinen, H. Huuskonen, and H. Komulainen. 1992. The
2002.6 developmental toxicity of 2-ehtylhexanoic acid in Wistar rats. Fundam. Appl.
Eastman Kodak Company. 1992. Initial submission: Dermal corrosivity test of Toxicol. 19:505–511.
2-ethylhexanoic acid in rabbits with cover letter dated 09/28/92. NTIS Report Pennanen, S., K. Tuovinen, H. Huuskonen, V. M. Kosma, and H. Komulainen.
No. OTS0555383. 1993. Effects of 2-ethylhexanoic acid on reproduction and postnatal develop-
Elder, R. L., ed. 1982. Final report on the safety assessment of Cetearyl Oc- ment in Wistar rats. Fundam. Appl. Toxicol. 21:204–212.
tanoate. J. Am. Coll. Toxicol. 1:81–90. Pepe, R. C., J. A. Wenninger, and G. N. McEwen. 2002. International Cosmetic
English, J. C., P. J. Deisinger, and D. Guest. 1998. Metabolism of 2-ethylhexanoic Ingredient Dictionary and Handbook. 9th ed. Washington, DC: CTFA.
acid administered orally or dermally to the female Fischer 344 rat. Xenobiotica Pradhan, M. 2002. Personal communication—toxicologist’s evaluation of toxi-
28:699–714. cological data, exposure levels, and assessment, dated April 11, 2002.6
European Commission. 1999. EEC Cosmetics Directive 76/768/EEC, as Ritter, E. J., W. J. Scott, Jr., J. L. Randall, and J. M. Rittter. 1987. Teratogenicity of
amended through the 26th Adapting Commission Directive 2002/34/EC, An- di(2-ethylhexyl) phthalate, 2-ethylhexanol, 2-ethylhexanoic acid, and valproic
nexes I-VII. Brussels: EEC. http://europa.eu.int/scadplus/leg/en/lvb/l21191. acid, and potentiation by caffeine. Teratology 35:41–46.
htm. Scott, W. J., Jr., M. S. Collins, and H. Nau. 1994. Pharmacokinetic determi-
Faber, W. 2003. Presentation made at the February, 2003 meeting of the CIR nants of embryotoxicity in rats associated with organic acids. Environ. Health
Expert Panel.6 Perspect. 102:97–101.
Food and Drug Administration (FDA). 1984. Cosmetic product formulation and Shell Oil Company. 1992a. Initial submission: two-week oral (dietary admin-
frequency of use data. FDA Database. Washington, DC: FDA. istration) toxicity study of 2-ethylhexanoic acid in the mouse (Final Report)
FDA. 2002. Frequency of use of cosmetic ingredients. FDA database. Washing- with cover letter dated 041792. NTIS Report No. OTS0539188.
ton, DC: FDA. Shell Oil Company. 1992b. Initial submission: two-week oral toxicity study of
Hauck, R. S., C. Wegner, P. Blumtritt, J. H. Fuhrhop, and H. Nau. 1990. Asym- 2-ethylhexanoic acid in the rat (Final Report) with cover letter dated 041792.
metric synthesis and teratogenic activity of (R)- and (S)-2-ehtylhexanoic acid, NTIS Report No. OTS0539183.
Sipi, P., H. Jarventaus, and H. Norppa. 1992. Sister-chromatid exchanges in- Cross, N. L. 1996. Effect of Cholesterol and Other Sterols on Human Sperm
duced by vinyl esters and respective carboxylic acids in cultured human lym- Acrosomal Responsiveness. Mol. Reprod. Dev. 45:212–217.
phocytes. Mutat. Res. 279:75–82. Dehart, D. B., L. Lanoue, G. S. Tint, and K. K. Sulik. 1995. Altered cholesterol
Union Carbide Corporation. 1992a. Initial Submission: Letter from Union Car- biosynthesis in rats: A model for Smith-Lemli-Opitz syndrome. Teratology
bide Corp. to USEPA submitting information on the enclosed 90 day (dietary 51:165.
administration) toxicity study of 2-ethylhexanoic acid in the rat & mouse. Elder, R. L. ed. 1986. Final report on the safety assessment of Cholesterol. J.
NTIS Report No. OTS0543763. Am. Coll. Toxicol. 5:491–516.
Union Carbide Corporation. 1992b. Initial Submission: Letter from Union Food and Drug Administration (FDA). 2002. Frequency of Use of Cosmetic
Carbide Corp. submitting two developmental toxicity studies with 2- Ingredients. FDA database. Washington, DC: FDA.
ethylhexanoic acid in rats and rabbits with attachments. NTIS Report No. Gottschalck, T. E., and G. N. McEwen, Jr., eds. 2004. International Cos-
OTS0539327. metic Ingredient Dictionary and Handbook, 10th ed., 151. Washington, DC:
Wil Research Laboratories, Inc. 2001. A dietary two-generation reproductive CTFA.7
toxicity study of di-2-ethylhexyl terephthalate in rats. Final Report. Unpub- Innis, S. M., and N. C. Haave. 1988. Effect of chronic modification of diet fat
lished data submitted by the American Chemistry Council. 3250 pages.6 and cholesterol during gestation on plasma hormones and hepatic enzyme
activities in rat fetus. Biol. Neonate 53:355–361.
Kurtin, W. E., W. H. Schwesinger, and R. M. Stewart. 1991. Effect of dietary
ethanol on gallbladder absorption and cholesterol gallstone formation in the
prairie dog. Am. J. Surg. 161:470–474.
CHOLESTEROL Lewis, R. J., ed. 2000. Cholesterol. In: Sax’s Dangerous Properties of Industrial
A safety assessment of Cholesterol was published in 1986 Materials. 919. New York: John Wiley & Sons, Inc.
with the conclusion that this ingredient is safe as presently used Lynn, W. S., D. Mathews, A. Thompson, and M. Cloyd. 1988. Role of calcium
in cosmetic products (Elder 1986). The CIR Expert Panel re- and cholesterol in cytotoxicity. Clin. Res. 36:606A.
Mallinkrodt Baker, Incorporated. 2004. MSDS: Cholesterol. Internet site ac-
viewed new studies available since that time, along with updated
cessed http://www.jtbaker.com/msds/englishhtml/c3993.htm. October, 2004.
information regarding types and concentrations of use, and de- Morgan, B. P., and M. Moynihan. 1990. Steroids. In Kirk-Othmer concise ency-
termined to not reopen this safety assessment. clopedia of chemical technology, 4th ed., 1894–1900. New York: John Wiley
According to the entry in the International Cosmetic In- & Sons, Inc.
gredient Dictionary and Handbook, Cholesterol functions as Poulos, A. 1995. Cholesterol in prenatal development. Teratology. 51:286.
Rao, K. N. 1986. Regulatory aspects of cholesterol metabolism in cells with
an emulsion stabilizer, miscellaneous skin-conditioning agent,
different degrees of replication. Toxicol. Pathol. 14:430–437.
and nonaqueous viscocity-increasing agent in cosmetic products Rao, A. V., S. A. Janezic, D. Friday, and C. W. Kendall. 1992. Dietary choles-
(Gottschalck and McEwen 2004). terol enhances the induction and development of colonic preneoplastic lesions
Frequency of use data provided by industry to FDA for 2002 in C57BL/6J and BALB/cJ mice treated with azoxymethane. Cancer Lett.
show that cholesterol is used in 258 cosmetic products (FDA 63:249–257.
Repetto, M., J. C. Maziere, D. Citadelle, R. Dupuis, M. Meier, S. Biade, D.
2002), an increase compared to 145 uses reported in 1981 (Elder
Quiec, and C. Roux. 1990. Teratogenic effect of the cholesterol synthesis
1986). In 1981, Cholesterol use concentrations (again, as re- inhibitor AY 9944 on rat embryos in vitro. Teratology 42:611–618.
ported by industry to FDA) ranged from ≤0.1% to 5% (Elder Ridker, P. M., and T. Michel. 1989. Streptokinase therapy and cholesterol em-
1986). A survey by the Cosmetic, Toiletry, and Fragrance Asso- bolization. Am. J. Med. 87:357–358.
ciation (CTFA) in 2004 found the range of use concentrations Thacker, B. J., B. M. Trivedi, Y. D. Shah, D. A. Shah, P. D. Bharadia, et al. 1988.
Comparative study of different methods of isolation of cholesterol. Indian J.
to be 0.002% to 3%, with majority of products around 0.1%.
Pharm. 50:331–332.
Historical and current cosmetic product uses and concen- Yadav, S., and U. M. Rawal. 1992. Cholesterol and lipid peroxidation in 3beta-(2-
trations for Cholesterol are given in Table 6. The most recent diethylaminoethoxy) androst-5-en-17-one hydrochloride (U18666A) induced
information now constitutes the present practices of use. cataractogenesis in rats. Indian J. Exp. Biol. 30:147–148.
Wrensch, M., L. Gruenke, N. Petrakis, R. Miike, V. Ernster, and J. Craig. 1987.
Breast fluid cholesterol and cholesterol—epoxides relation to breast cancer
risk factors. Am. J. Epidemiol. 126:770.
REFERENCES
Barbu, V., C. Roux, D. Lampert, R. Dupuis, J. Gardette, J. C. Maziere, C.
Maziere, E. Elefant, and J. Polonovski. 1988. Cholesterol prevents the terato-
CHLOROXYLENOL
genic action of AY 9944: Importance of the timing of cholesterol supplemen-
tation to rats. J. Nutri. 118:774–779. A safety assessment of Chloroxylenol was published in 1985
Contag, B. 1991. Specific crystal chemical interactions between carcinogenic with the conclusion that this ingredient was safe as a cosmetic
aromatic compounds and cholesterol. Z. Naturforsch. 46:663–672. ingredient in the practices of use at that time (Elder 1985). New
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2004a. Cholesterol use studies, along with the updated information below regarding
concentration data from industry survey. Unpublished data submitted by
CTFA, 2004 (1 page).7
types and concentrations of use, were considered by the CIR
CTFA. 2004b. Sources of cholesterol. Unpublished data submitted by CTFA, Expert Panel. The Panel determined not to reopen this safety
2004 (1 page).7 assessment.
As given in the International Cosmetic Ingredient Dictionary
and Handbook, the functions of Chloroxylenol in cosmetic prod-
7
Available for review: Director, Cosmetic Ingredient Review (CIR), ucts are now described as a cosmetic biocide, deodorant agent,
1101 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. and preservative (Gottschalck and McEwen 2006).
TABLE 6
Historical and current cosmetic product uses and concentrations for Cholesterol
Bath
Soaps and detergents — 2 — —
Eye makeup
Eyeliners 6 1 >0.1–1 —
Eye shadow 15 — <0.1–1 0.01
Eye lotions — 1 — 0.04–0.3
Mascara 16 2 >0.1–5 —
Other eye makeup 3 4 >0.1–5 —
Fragrances
Other fragrances 1 2 >0.1–1 —
Conditioners 7 13 ≤0.1–1 0.3
Straighteners — — — 0.003
Shampoos 1 5 >0.1–1 —
Tonics, dressings, etc. — 3 — 2
Other noncoloring hair care — 4 — 0.2
Hair coloring
Makeup
Face powders — 3 — —
Foundations 7 7 ≤0.1–1 3
Lipsticks — 5 — 0.1
Makeup bases 12 3 ≤0.1–1 0.02
Rouges — 1 — —
Makeup fixatives — 2 — —
Other makeup 14 4 ≤0.1–1 —
Nail care
Cuticle softeners — 1 — 0.1
Nail polish and enamel removers — 1 — —
Shaving
Aftershave lotions 1 3 >0.1–1 0.1
Other shaving 1 — >0.1–1 —
Skin care
Cleansing creams, lotions, etc. 5 11 ≤0.1–1 1
11* ≤0.1–5*
Moisturizers 19 61 ≤0.1–5 0.005–1
Night skin care 15 24 ≤0.1–5 0.1–1
Wrinkle smoothers** 2 — ≤0.1–5 —
Paste masks/mud packs — 4 — 0.5
Skin fresheners — 3 — —
Other skin care 8 13 ≤0.1–5 —
Suntan
Suntan gels, creams, liquids, and sprays 1 1 >0.1–1 0.02–0.4
Indoor tanning — — — 0.005
Total uses/ranges for Cholesterol 145 258 ≤0.1–5 0.002–3
∗
∗∗
No longer listed as product categories.
In 1984, Chloroxylenol was used as an antimicrobial com- Miner, N., and M. Armstrong. 1994. Comparative ability of various prescription
pound in 93 cosmetic products, with the maximum concentra- and over-the-counter topical antifungal drug products to inhibit growth of C.
tions at up to 5% in fragrance powders, noncoloring shampoos, albicans. Adv. in Wound Care 7:53–56.
Momma, J., K. Takada, Y. Aida, H. Yoshimoto, K. Naito, Y. Suzuki, Y. Nakaji,
and other hair preparations (Elder 1985). In 2002, industry re- Kurokawa, and M. Tobe. 1988. Combined ling-term toxicity and carcino-
ports of Chloroxylenol use to the FDA included 43 cosmetic genicity test of p-chloro-m-xylenol (PCMX) applied to female mouse skin.
products (FDA 2002). Based on an industry survey, CTFA Eisei Shikenjo Hokoku 106:39–47.
(2002) reported that Chloroxylenol was used in cosmetic prod- Mowad, C. 1998. Chloroxylenol causing hand dermatitis in a plumber. Am. J.
Contact Dermatitis 9:128–129.
ucts at a maximum concentration of use of 0.5% in skin cleansing
Newby, C. S., R. M. Barr, M. W. Greaves, and A. I. Mallet. 2000. Cytokine
products. release and cytotoxicity in human keratinocytes and fibroblasts induced by
Table 7 summarizes these data. The most recent information phenols and sodium dodecyl sulfate. J. Invest. Dermatol. 115:292–298.
now constitutes the present practices of use. Papageorgiou, P. P., and A. C. Chu. Chloroxylenol and zinc oxide containing

R
cream (Nels cream ) vs. 5% benzoyl peroxide cream in the treatment of acne
vulgaris. A double-blind, randomized, controlled trial. Clin. Exp. Dermatol.
25:16–20.
REFERENCES Schäfer, E., and K. Bössmann. 1999. Antimicrobial effect of camphorated
Aly, R., and H. I. Maibach. 1988. Comparative antibacterial efficacy of a 2- chloroxylenol (ED84) in the treatment of infected root canals. J. Endod.
minute surgical scrub with chlorhexidine gluconate, povidone-iodine, and 25:547–551.
chloroxylenol sponge-brushes. Am. J. Infect. Control 16:173–177. Schäfer, E., and K. Bössmann. 2001. Antimicrobial efficacy of chloroxylenol
Chan, T. Y. K., and J. A. J. H. Critchley. 1994. Is chloroxylenol nephrotoxic like and chlorohexidine in the treatment of infected root canals. Am. J. Dent.
phenol? A study of patients with DETTOL poisoning. Vet. Human Toxicol. 14:233–237.
36:250–251. Stubbs, W. P., J. R. Bellah, D. Vermaas-Hekman, B. Purich, and P. S. Kubilis.
Cosmetic, Toiletry, and Fragrance Association. 2004. Ingredient use data— 1996. Chlorohexidine gluconate versus chloroxylenol for preoperative skin
chloroxylenol. Unpublished data submitted by CTFA on March 15, 2004. preparation in dogs. Vet. Surg. 25:487–494.
1 page.8 Yamano, T., M. Shimizu, and T. Noda. 2003. Allergenicity evaluation of p-
Davila, J. C., A. Dorantes, S. A. Stavchansky, and D. Acosta. 1991. The cytotox- chloro-m-cresol and p-chloro-m-xylenol by non-radioactive murine local
icity of p-chloro-m-xylenol in primary culture of rat hepatocytes. Pharmaceu. lymph-node assay and multiple dose guinea pig maximization test. Toxicology
Res. 8:656–657. 190:259–266.
Dorantes, A., and S. Stavchansky. 1992. Pharmacokinetic and metabolic dis-
position of p-chloro-m-xylenol (PCMX) in dogs. Pharmaceut. Res. 9:677–
682.
Elder, R. L. 1985. Final report on the safety assessment of chloroxylenol. J. Am.
DIISOPROPANOLAMINE, ISOPROPANOLAMINE,
Coll. Toxicol. 4:147–169.
Food and Drug Administration (FDA). 2002. Frequency of use of cosmetic TRIISOPROPANOLAMINE, AND MIXED
ingredients. FDA database. Washington, DC: FDA. ISOPROPANOLAMINES
Gatti, R., P. Roveri, D. Bonazzi, and V. Cavrini. 1997. HPLC-fluorescence de- A safety assessment of Diisopropanolamine, Triiso-
termination of chlorocresol and chloroxylenol in pharmaceuticals. J. Phar- propanolamine, Isopropanolamine, and Mixed lsopropano-
maceut. Biomed. Anal. 16:405–412.
Goh, C. L. 1989. Contact sensitivity to topical antimicrobials. (ii) Sensitizing
lamines was published in 1987 with the conclusion that these
potentials of some topical antimicrobials. Contact Dermatitis 21:166–171. ingredients are safe as cosmetic ingredients in the present prac-
Gudipati, R. M., and S. A. Stavchansky. 1995. Percutaneous absorption of tices of use and concentration, if not used in products containing
parachlorometaxylenol. Int. J. Pharmaceu. 118:41–45. N-nitrosating agents (Elder 1987). The CIR Expert Panel con-
Holder, I. A., L. Vanderpool, and J. Wesselman. 1985. Para-chloro-meta-xylenol sidered new studies, along with updated information regarding
(PCMX): a new, potential topical antimicrobial agent. J. Burn Care Rehab.
6:58–61.
types and concentrations of use. The Panel determined not to
Lear, J. C., J.-Y. Maillard, P. W. Dettmar, P. A. Goddard, and A. D. Russell. reopen this safety assessment.
2002. Chloroxylenol- and triclosan-tolerant bacteria from industrial sources. No uses of Mixed Isopropanolamines were reported in the
J. Ind. Microbiol. Biotech. 29:238–242. original safety assessment, in frequency of use data collected by
Libow, L. F., A. M. Ruszkowski, and V. A. DeLeo. 1989. Allergic contact der- FDA in 2002 (FDA 2002) or in a recent industry survey (CTFA
matitis from para-chloro-meta-xylenol in Lurosep soap. Contact Dermatitis
20:67–68.
2004).
Malakar, S., and S. Panda. 2001. Post-inflammatory depigmentation follow- Diisopropanolamine reportedly was used in 66 products in
ing allergic contact dermatitis to chloroxylenol. Br. J. Dermatol. 144:1275– 1981, at concentrations of ≤10%, and in 33 products in 2002,
1276. at concentrations of up to 0.7% (from the 2004 survey).
Malaveille, C., G. Brun, and H. Bartsch. 1991. Genotoxicity of ochratoxin A and Isopropanolamine was used in 11 cosmetic products in 1981,
structurally related compounds in Escherichia coli strains: Studies on their
mode of action. In: Mycotoxins, Endemic Nephropathy and Urinary Tract
at concentrations of ≤1%, and in 27 products in 2002, at the
Tumours, ed. M. Castegnaro, R. Pleština, G. Dirheimer, I. N. Chernozemsky, same concentrations (from the 2004 survey).
and H. Bartsch, 261–266. Lyon, France: IARC. Triisopropanolamine had 36 cosmetic uses in 1981, at con-
centrations of ≤ 5%, and 25 uses in 2002, at concentrations up
to 1% (from the 2004 survey).
8
Available for review: Director, Cosmetic Ingredient Review, 1101 Table 8 summarizes the historical and recent uses of Diiso-
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. propanolamine, Isopropanolamine, and Triisopropanolamine in
TABLE 7
Historical and current cosmetic product uses and concentrations for Chloroxylenol
Baby care
Lotions, oils, powders, and creams — — — 0.1
Bath
Soaps and detergents 2 1 >0.1–1 —
Eye makeup
Eye shadow — 1 — —
Eye makeup remover 2 — ≤1 —
Fragrances
Powders 2 — >1–5 —
Conditioners 8 3 ≤1 —
Straighteners 4 — >0.1–1 —
Shampoos 29 3 ≤5 —
Tonics, dressings, etc. 3 6 >0.1–1 —
Other noncoloring hair care 3 — ≤5 —
Hair coloring
Dyes and colors 1 — ≤1 —
Rinses 2 — >0.1–1 —
Makeup
Blushers 1 — >0.1–1 —
Makeup fixatives 1 — >0.1–1 —
Other makeup — 5 — —
Nail care
Basecoats and undercoats 1 — ≤1 —
Cuticle softeners 1 — >0.1–1 —
Oral hygiene
Other oral hygiene — — — 0.4
Personal hygiene
Underarm deodorants 1 1 >0.1–1 —
Feminine deodorants 1 — ≤0.1 —
Other personal hygiene 8 11 ≤1 —
Shaving
Skin care
Cleansing creams, lotions, etc. 5 4 ≤1 0.5
Depilatories 1 — >0.1–1 —
Face and neck skin care — 0.2
7* ≤1∗
Moisturizers — 1 — 0.1
Paste masks/mud packs 2 — ≤1 —
Skin fresheners 1 — ≤1 —
Other skin care 5 3 ≤1 —
Suntan products
Suntan gels, creams, liquids and sprays 1 — 0.1–1 —
Total uses/ranges for Chloroxylenol 93 43 ≤5 0.1–0.5
∗
TABLE 8
Historical and current uses and use concentrations for Diisopropanolamine, Isopropanolamine, and Triisopropanolamine in
cosmetic products
Diisopropanolamine
Fragrances
Colognes and toilet waters 2 1 ≤0.1 —
Other fragrances 13 10 ≤1 —
Conditioners 1 1 >0.1–1 —
Sprays 1 — >1–5 —
Permanent waves 7 3 >0.1–10 —
Wave sets 1 1 >0.1–1 —
Other noncoloring hair care 2 1 >1–5 —
Hair coloring
Hair dyes and colors — 3 — —
Makeup
Makeup foundations 2 — >1–5 —
Other makeup 5 — >0.1–5 —
Shaving
Aftershave lotion 4 2 ≤1 —
Other shaving 2 3 ≤1 —
Skin care preparations
Cleansing creams, lotions, etc. — — — <0.01
Face, body, and hand skin care 10 — >0.1–1 —
Moisturizers 4 — ≤5 —
Night skin care 1 — >0.1–1 —
Paste masks/mud packs 2 1 >0.1–5 —
Skin fresheners 2 1 ≤1 —
Wrinkle smoothers∗∗ 1 —∗∗ >0.1–1 —∗∗
Other skin care 1 1 >0.1–1 —
Suntan preparations
Suntan gels, creams, and liquids 2 — >0.1–1 —
Indoor tanning 1 — >0.1–1 —
Total uses/ranges for Diisopropanolamine 66 33 ≤10 <0.01–0.7
Isopropanolamine
Eye makeup
Eyeliner — 1 — —
Mascara 3 22 ≤1 —
Hair coloring
Hair dyes and colors — — — 1
Shaving
Aftershave lotions 2 — >0.1–1 —
Skin care
Depilatories 1 — ≤0.1 —
Body and hand skin care — 1 — —
Moisturizers 3 1 ≤1 —
TABLE 8
Historical and current uses and use concentrations for Diisopropanolamine, Isopropanolamine, and Triisopropanolamine in
cosmetic products (Continued)
Product category (Elder, 1985) (FDA, 2002) (Elder, 1985) % (CTFA, 2004) %
Suntan
Suntan gels, creams, and lotions 1 1 ≤0.1 —
Total uses/ranges for Isopropanolamine 11 27 ≤1 1
Triisopropanolamine
Baby care
Lotions, oils, powders, and sprays 1 — >0.1–1 —
Conditioners 4 — >0.1–5 —
Sprays 9 9 ≤1 0.4
Wave sets 2 3 >0.1–1 —
Other hair care 2 1 >0.1–1 1*
Skin care
Cleansing creams, lotions, etc. 1 — >1–5 —
Face and neck skin care preparations — —
1*** >0.1–1***
Body and hand skin care preparations — —
Moisturizers 3 — >0.1–1 —
Total uses/ranges for Triisopropanolamine 36 25 ≤5 0.4–1
∗
Nonaerosol pump spray.
∗∗
No longer a cosmetic product category.
∗∗∗
cosmetic products. The most recent information now constitutes REFERENCES

the present practices of use. Bowen, D. 1999. Unpublished information on hair spray particle size provided
The CIR Expert Panel did note that Diisopropanolamine at the September 9, 1999, CIR Expert Panel meeting.9
has a structure that is related to diethanolamine (DEA), which data on sodium lauryl sulfoacetate from industry survey. Unpublished data
has been implicated as an animal carcinogen. Data were pro- submitted by CTFA, 2004 (1 page).9
vided suggesting a mechanism for DEA carcinogenicity in Cooper, S. M., and S. Shaw. 1999. Contact allergy to isopropanolamine in
animals is related to choline metabolism. Data also were
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Traxam gel. Contact Dermatitis 41:233–234.
provided demonstrating that Diisopropanolamine does not act Elder, R. L. 1987. Final report on the safety assessment of diisopropanolamine,
by the same mechanism. It was suggested, therefore, that Di- triisopropanolamine, isopropanolamine, and mixed isopropanolmaine. J. Am.
Coll. Toxicol. 6:53–76.
isopropanolamine is unlikely to present any risk of carcino- Food and Drug Administration (FDA). 2002. Frequency of use of cosmetic
genicity. ingredients. FDA database. Washington DC: FDA.
The Panel acknowledged the use of Diisopropanolamine in Fujimoto, K., S. Hashimoto, T. Kozuka, and K. Yoshikawa. 1989. Contact der-
hair sprays. The effects of inhaled aerosols depend on the spe- matitis due to diisopropanolamine. Contact Dermatitis 21:56.
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ment. Principles Techniques and Applications. ed. K. Willeke, and P. A. Baron,
sure, and site of deposition (Jensen and O’Brien 1993) within New York: John Wiley and Sons, 538–540.
the respiratory system. Particle size is the most important fac- Oisu, N., K. Fukai, and M. Ishii. 2003. Triple allergic contact sensitivities due to
tor affecting the location of depostion. The mean aerodynamic ferbanic, crotamiton, and diisopropanolamine. Contact Dermatitis 49:261–
diameter of pump hair spray particles is approximately 80 μm, 263.
and diameter of anhydrous hair spray particles is 60 to 80 μm. Oakes, D. J., and J. K. Pollak. 1999. Effects of a herbicide formulation, Tordon
R
75D , and its individual components on the oxidative functions of mitochon-
Typically, less than 1% are below 10 μm, which is the upper
dria. Toxicology 136:41–52.
limit for respirable particles (Bowen 1999). Based on the parti-
cle size, Diisoprpanolamine would not be respirable in formu-
lation. Therefore, exposure of the lung by inhalation was not 9
Available for review: Director, Cosmetic Ingredient Review, 1101
considered likely. 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA.
TABLE 9
Historical and current uses and use concentrations for Diethylhexyl Adipate and Diisopropyl Adipate
Diethylhexyl Adipate
Bath
Oils, tablets, salts 4 — >10–25 —
Eye makeup
Lotion — — — 0.6
Other eye makeup — 2 — 0.4-2
Fragrances
Colognes and toilet waters 6 — >1–5 —
Other fragrance — 5 — —
Makeup
Blushers 1 3 ≥ 0.1 13
Foundations 4 2 >0.1–10 16
Makeup bases — 6 — 6
Lipsticks 5 1 >1–5 —
Other makeup 1 2 >1–5 —
Nail care
Nail polish & enamel remover 2 — >1–5 —
Nail creams and lotions — 1 — —
Cuticle softeners — 1 — —
Personal hygiene
Underarm deodorants 1 — >0.1–1 8
Other personal hygiene — 4 — —
Shaving
Aftershave lotions 1 — >1–5 1
Skin care
1* >1–5*
Moisturizers — 4 — —
Other skin care — 5 — —
Suntan
Suntan gels, creams, and liquids — 1 — 38
Other suntan 1 1 — —
Total uses/ranges for Diethylhexyl Adipate 27 49 ≥0.1–25 0.4–38
Diisopropyl Adipate
Bath
Oils, tablets, and salts 7 5 >1–25 5
Bubble baths 1 — >1–5 —
Other bath — 1 — 8
Eye makeup
Eyeliner 1 — >1–5 —
Eye shadow 1 — >10–25 —
Fragrances
Colognes and toilet waters 15 16 >0.1–5 8
Perfumes 20 14 >1–10 8
TABLE 9
Historical and current uses and use concentrations for Diethylhexyl Adipate and Diisopropyl Adipate (Continued)
Sachets 1 — >10–25 —
Other fragrances 9 2 >0.1–25 15
Conditioners 3 — ≥0.1–1 0.1
Sprays 1 1 >1–5 3
Tonics, dressings, etc. 4 2 >1–5 —
Wave sets 2 — >0.1–5 —
Makeup
Blushers 1 — >1–5 —
Face powders 1 — >1–5 —
Foundations 1 — >0.1–1 5
Nail care
Nail polish and enamel removers — 1 — 3
Personal hygiene
Other personal hygiene 1 — >0.1–1 —
Shaving
Aftershave lotions 16 10 >1–5 1
Preshave lotions 1 — >5–10 5
Skin care
Cleansing creams, lotions, etc. 5 1 >0.1–1 —
Face and neck skin care ∗ 1 ∗ —
— —
Foot powders and sprays 1 — >0.1–1 —
Moisturizers 2 5 >0.1–5 0.2
Night skin care 1 — >5–10 —
Skin fresheners 11 2 — —
Other skin care 2 — >1–10 4
Suntan
Suntan gels, creams, and liquids 2 3 >5–10 4
Indoor tanning 2 — >1–5 —
Total uses/ranges for Diisopropyl Adipate 112 66 ≥0.1–25 0.1–15
∗
Stott, W.T. 2004. CIR Board diisopropanolamine review presentation on research and concentrations of use, were considered by the CIR Ex-
by Dow Chemical Company. Dec. 2, 2004.9 pert Panel. The Panel determined to not reopen this safety
Wigfield, Y. Y., M. D. Lacroix, M. Lanouette, and N. P. Gurprasad. 1988.
assessment.
Gas chromatographic determination of N -nitrosodialkanolamines I herbi-
cide di- or trialkanolamine formulations. J. Assoc. Off. Anal. Chem. 71:328– The name of Dioctyl Adipate as listed in the Interna-
333. tional Cosmetic Ingredient Dictionary and Handbook has been
changed to Diethylhexyl Adipate (Pepe et al. 2002).
Diethylhexyl Adipate, according to information provided
DIOCTYL ADIPATE AND DIISOPROPYL ADIPATE by industry to FDA under a voluntary reporting program, was
A safety assessment of Dioctyl Adipate and Diisopropyl Adi- used in 27 cosmetic products in 1981, with the maximum use
pate was published in 1984 with the conclusion that these in- concentration at 25%. Use increased in 2002 to 49 cosmetic
gredients are safe as presently used in cosmetics (Elder 1984). products. As reported in an industry survey, the maximum use
New studies, along with updated information regarding types concentration increased to 38% in 2003.
Diisopropyl Adipate was used in 112 cosmetic products in British Indus. Bio Res Assn. 1985. Rat liver and lipid effects of representative
1981, with the maximum use concentration in the 10% to 25% phthalate esters. NTIS Report No. OTS0509538.
range. Use decreased to 66 reported uses in 2002. The maximum Busser M. T., and W. K. Lutz. 1987. Stimulation of DNA synthesis in
rat and mouse liver by various tumor promoters. Carcinogenesis 8:1433–
use concentration was 15% in 2003, consistent with that reported 1437.
in 1981. Chemical Mfg. Assn. 1989. A study of the hepatic effects of di-(2-ethylhexyl)
Table 9 gives the available use and concentration data for adipate in the mouse and rat with appendices and cover letter dated 11/17/89.
Dioctyl Adipate and Diisopropyl Adipate. The most recent data NTIS Report No. OTS0000731.
Cornu, M. C., Y. Keith, C. R. Elcombe, and J. C. Lhuguenot. 1988. In vivo and
now constitute the present practices of use.
in vitro metabolism of di-(2-ethylhexyl) adipate, a peroxisome proliferator,
The CIR Expert Panel noted that Dioctyl Adipate and Di- in the rat. Arch. Toxicol. Suppl. 12:265–268.
isopropyl Adipate are used in cosmetic products that may be Cornu M. C., J. C. Lhuguenot, A. M. Brady, R. Moore, and C. R. Elcombe. 1992.
incidentally inhaled during use (e.g., hair sprays). The effects Identification of the proximate peroxisome proliferator(s) derived from di (2-
of inhaled aerosols depend on the specific chemical species, the ethylhexyl) adipate and species differences in response. Biochem. Pharmacol.
43:2129–2134.
concentration, the duration of exposure, and site of deposition
Dalgaard, M., H. Ulla, A. M. Vinggaard, et al. 2003. Di(2-ethylhexyl) adipate
(Jensen and O’Brien 1993) within the respiratory system. Par- (DEHA) induced deveopmental toxicity but not antiandrogenic effects in pre-
ticle size is the most important factor affecting the location of and postnatally exposed Wistar rats. Reprod. Toxicol. 17:163–170.
depostion. Divincenzo, G. D., W. H. Donish, K. R. Mueller, M. L. Hamilton, and E. D.
The mean aerodynamic diameter of pump hair spray particles Barber. 1983. Mutagenicity testing of urine from rats dosed with 2-
ethylhexanol derived plasticizers. Environ. Mutagen. 5:471.
is approximately 80 μm, and diameter of anhydrous hair spray
Dirven, H. A., P. H. van den Broek, J. G. Peters, J. Noordhoek, and
particles is 60 to 80 μm. Typically, less than 1% are below F. J. Jongeneelen. 1992. Microsomal lauric acid hydroxylase activities
10 μm, which is the upper limit for respirable particles (Bowen after treatment of rats with three classical cytochrome P450 inducers
1999). Based on the particle size, these ingredients would not and peroxisome proliferating compounds. Biochem. Pharmacol. 43:2621–
be respirable in formulation. Therefore, exposure of the lung by 2629.
Eastman Kodak Co. 1984. Bacterial mutagenicity testing of urine from rats dosed
inhalation was not considered likely.
with 2-ethylhexanol derived plasticizers. NTIS Report No. OTS0206391.
The increase in the maximum concentration of use to 38% (in Eastman Kodak Co. 1992. Submission summary: Synopsis of teratology study
suntan lotion) was considered in the context of newly available in rats (final report) using di(2-ethylhexyl)adipate with cover letter dated
reproductive and developmental toxicity data suggesting that 091391. NTIS Report No. OTS0533689-1.
Diethylhexyl Adipate can be fetotoxic in animal studies. This Elder, R. L. ed. 1984. Final Report on the Safety Assessment of Dioctyl Adipate
and Diisopropyl Adipate. J. Am. Coll. Toxicol. 2:101–130.
was a threshold effect and the systemic dose at which no adverse
effects were seen (NOAEL) was 200 mg/kg day−1 . Using an es- ingredients. FDA database. Washington, DC: FDA.
timated use of 40 g per day of suntan lotion containing Diethyl- Gupta, B. N., and A. K. Mathur. 1985. Effect of dermal application of a skin bar-
hexyl Adipate at 38%, a 60-kg person would receive a dermal rier cream on skin enzymes in rabbits and guinea-pigs. Biol. Membr. 11:157–
dose of 250 mg/kg day−1 . Given that Diethylhexyl Adipate is 160
Gupta, B. N., R. Shanker, P. N. Viswanath, A. K. Mathur, L. Shukla, and A.
soluble in organic solvents, but not in water, dermal penetration
Singh. 1987. Safety evaluation of a barrier cream. Contact Dermatitis 17:10–
of Diethyhexyl Adipate is likely to be less than 1%, yielding a 12.
maximum possible systemic dose of <2.5 mg/kg day−1 , well International Agency for Research on Cancer (IARC). 2000. Di(2-ethylhexyl)
below the level demonstrated to have no fetotoxic effect. adipate entry. IARC Monographs on the Evaluation of Carcinogenic Risks to
Humans 77:149–175.
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at the September 9, 1999 CIR Expert Panel meeting.10
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326.
Kluwe, W. M. 1986. Carcinogenic potential of phthalic acid esters and re-
10
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17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. 65:271–278.
Kluwe, W. M., J. E. Huff, H. B. Matthews, R. Irwin, and J. K. Haseman. Yanagita, T., M. Satoh, H. Nomura, N. Enomot, and M. Sugano. 1987. Alteration
1985. Comparative chronic toxicities and carcinogenic potentials of 2- of hepatic phospholipids in rats and mice by feeding di-(2-ethylhexyl)adipate
ethylhexyl-containing compounds in rats and mice. Carcinogenesis 6:1577– and di-(2-ethylhexyl)phthalate. Lipids. 22:572–577.
1583. Zeiger, E., S. Haworth, K. Mortelmans, and W. Speck. 1985. Mutagenicity test-
Kolmar Res Ctr. 1984. Toxicological examination of di-a-ethyl-hexyl-adipate ing of di(2-ethylhexyl)phthalate and related chemicals in Salmonella. Environ.
(wickenol 158). NTIS Report No. OTS0000286-1. Mutagen. 7:213–232.
Korhonen, A., K. Hemminki, and H. Vainio. 1983. Embryotoxic effects of ph-
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207. FORMALDEHYDE
Lake, B. G., R. J. Price, M. E. Cunninghame, and D. G. Walters. 1997. Compar- A safety assessment of Formaldehyde was published in 1984
ison of the effects of di-(2-ethylhexyl)adipate on hepatic peroxisome pro- (Elder 1984) with the conclusion that this ingredient is safe in
liferation and cell replication in the rat and mouse. Toxicology 123:217– cosmetic products to the great majority of consumers, however,
226.
Litton Bionetics, Inc. 1984. Evaluation of di-2-ethylhexyl-adipate in the in vitro
because of skin sensitivity of some individuals to this agent, the
transformation of balb/3t3 cells assay. NTIS Report No. OTS0000286-0. formulation and manufacture of a cosmetic product should be
Litton Bionetics, Inc. 1989. Mutagenicity evaluation of di-2-ethyl hexyl adipate such as to ensure use at the minimal effective concentration of
in the Ames Salmonella/microsome plate test (final report) with attachments, formaldehyde, not to exceed 0.2% measured as free formalde-
cover sheet and letter dated 06/06/89. NTIS Report No. OTS0520392. hyde. Furthermore, it cannot be concluded that formaldehyde
Litton Bionetics, Inc. 2000. Evaluation of di-2-ethylhexyl-adipate in the in vitro
transformation of balb/3t3 cells assay addendum to the final report of Septem-
is safe in cosmetic products intended to be aerosolized. An ex-
ber 1982. Contract no. Pe-140-mut-lb. NTIS Report No. OTS0508486. tensive number of new studies, along with updated information
Loftus, N. J., W. J. Laird, G. T. Steel, M. F. Wilkd, and B. H. regarding types and concentrations of use, were considered by
Woollen. 1993. Metabolism and pharmacokinetics of deuterium-labelled di- the CIR Expert Panel. The Panel determined to not reopen this
2-(ethylhexyl) adipate (DEHA) in humans. Food Chem. Toxicol. 31:609– safety assessment.
614.
Loftus, N. J., B. H. Woollen, G. T. Steel, M. F. Wilks, and L. Castle. 1994. An
Data reported to the FDA by industry in 1981 indicated that
assessment of the dietary uptake of di-2-(ethylhexyl) adipate (DEHA) in a Formaldehyde was used in a total of 805 cosmetic products, but
limited population study. Food Chem Toxicol. 32:1–5. that figure decreased to 120 reported uses in 2002. The maximum
Microbiological Assc. 1984. Submission of unpublished balb/3t3 cell transfor- use concentration reported to FDA in 1981 was in the ≤0.1% to
mation assays on di-2-ethylhexyl adipate with attached reports. NTIS Report 10% range. Data from an industry use concentration survey in
No. 0000286-0.
National Toxicology Program (NTP) 1984. Carcinogenesis bioassay of di(2-
2003 indicate a maximum use concentration of 0.08%.
ethylhexyl) adipate (CAS no. 103-23-1)F344 rats and B6C3F1 mice (feed Table 10 presents the recent and historical frequency of use
study). NTIS Report No. OTS0000286-0. and concentration of use data as a function of product category.
Pepe, R. C., J. A. Wenninger, and G. N. McEwen, Jr., eds. 2002. International The discussion section in the original safety assessment ac-
Cosmetic Ingredient Dictionary and Handbook, 8th ed., vol. 1. Washington, knowledged that Formaldehyde can be a skin irritant and sensi-
DC: CTFA.
Reisenbichler. H., and P. M. Eckl. 1993. Genotoxic effects of selected peroxi-
tizer in clinical tests, and a developmental toxin, a genotoxin, and
some proliferators. Mutat. Res. 286:135–144. a neoplastic agent in experimental animal studies. The new clin-
Rhodes, C., T. Soames, M. D. Stonard, M. G. Simpson, A. J. Vernall, and C. ical studies confirmed that Formaldehyde can be a skin irritant
R. Elcombe. 1984. The absence of testicular atrophy and in vivo and in vitro and sensitizer, but at levels higher than the 0.2% free Formalde-
effects on hepatocyte morphology and peroxisomal enzyme activities in male hyde upper limit established by the CIR Expert Panel.
rats following the administration of several alkanols. Toxicol. Lett. 21:103–
109
The developmental toxicity, genotoxicity, and carcinogenic-
Takagi, A., K. Sai, T. Umemura, R. Hasegawa, and Y. Kurokawa. 1990. Signif- ity of high doses of Formaldehyde was also confirmed in the
icant increase of 8-hydroxydeoxyguanosine in liver DNA of rats following new studies. These studies demonstrate that there is a threshold
short-term exposure to the peroxisome proliferators di(2-ethylhexyl)phthalate effect; that is, high doses are required before any effect is seen.
and di(2-ethylhexyl)adipate. Jpn. J. Cancer Res. 81:213–215. Again, the limit on the amount of free Formaldehyde established
Takahashi, K., H. Sakano, N. Numata, S. Kuroda, and N. Mizuno. 2002. Effect
of fatty acid diesters on permeation of anti-inflammatory drugs through rat
by the CIR Expert Panel precludes any risk as a result of use of
skin.Drug Dev. Ind. Pharm. 28:1285–1294. cosmetic products containing Formaldehyde.
Takahashi, K., T. Suzuki, H. Sakano, and N. Mizuno. 1995. Effect of vehicles
on diclofenac permeation across excised rat skin. Biol. Pharm. Bull. 18:571–
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TABLE 10
Historical and recent uses and use concentrations of Formaldehyde in cosmetic products
Baby care
Shampoos 7 — ≤ 0.1–1 —
Lotions, oils, powders and creams 1 — >0.1–1 —
Bath
Soaps and detergents 5 5 ≤0.1–1 <0.002–0.08
Oils, tablets and salts 10 6 ≤0.1–1 0.08
Bubble baths 109 4 ≤0.1–1 0.08
Other bath 24 1 ≤0.1–5 0.08
Eye makeup
Mascara 1 — ≤0.1 0.0002
Other eye makeup 3 — ≤0.1–1 —
Fragrance
Sachets 2 — ≤0.1–1 —
Other fragrance — — — 0.02
Conditioners 95 11 ≤0.1–5 —
Permanent waves 11 2 ≤0.1–1 —
Rinses 32 2 ≤0.1–1 —
Shampoos 316 59 ≤0.1–5 <0.005–0.08
Tonics, dressings, etc. 21 9 ≤0.1–10 <0.005
Wave sets 37 8 ≤0.1–10 —
Other hair 13 3 ≤0.1–5 —
Hair coloring
Dyes and colors 5 — ≤0.1 —
Shampoos 3 2 ≤0.1–1 —
Makeup
Face powders 1 — >0.1–1 —
Foundations 2 — ≤0.1–1 —
Leg and body paints — — — 0.02
Makeup bases 3 — ≤0.1–1 —
Nail care
Cuticle softeners 1 — ≤0.1 —
Nail creams and lotions 1 1 ≤0.1 —
Other manicuring — 1 — 2∗
Oral hygiene
Mouthwashes and breath fresheners 2 — ≤0.1–1 —
Personal hygiene
Underarm deodorants 7 — >0.1–1 —
Feminine hygiene deodorants 1 — >1–5 —
Other personal cleanliness 1 1 ≤0.1 0.07–0.08
Shaving
Shaving creams 2 1 ≤0.1 —
Other shaving 1 — >1–5 —
TABLE 10
Historical and recent uses and use concentrations of Formaldehyde in cosmetic products (Continued)
Skin care
Cleansing creams, lotions, etc. 13 1 ≤0.1–1 <0.0001–0.002
Face and neck skin care — —
47∗∗ ≤0.1–1∗∗
Body and hand skin care 2 <0.0001
Foot powders and sprays 1 — >0.1–1 —
Moisturizers 11 1 ≤0.1–1 —
Night skin care 5 — ≤0.1–1 —
Paste masks/mud packs 3 — ≤0.1–1 —
Skin fresheners 1 — >0.1–1 —
Other skin care 4 — >0.1–1 0.06
Suntan
Suntan gels, creams, and liquids 2 — ≤0.1–1 —
Total uses/ranges for Formaldehyde 805 120 ≤0.1–10 <0.0001–0.08
∗
This product was sold only in Europe and no longer marketed
∗∗
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11
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Zimmerman, F. K., and A. Mohr. 1992. Formaldehyde, glyoxal, urethane, methyl A safety assessment of Isostearyl Neopentanoate concluded
carbamate, 2,3-butanedione, 2,3-hexanedione, ethyl acrylate, dibromoace- that this ingredient is safe as a cosmetic ingredient in the present
tonitrile, and 2-hydroxypropionitrile induce chromosome loss in Saccha-
practices of use and concentration (Elder 1985). One new study,
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along with the updated information regarding types and concen-
trations of use, were considered by the CIR Expert Panel. The
HYDROLYZED COLLAGEN Panel determined not to reopen this safety assessment.
A safety assessment of Hydrolyzed Collagen concluded that Data reported to the FDA by industry in 1981 indicated that
this ingredient is safe as a cosmetic ingredient in the present Isostearyl Neopentanoate was used in 208 cosmetic products at
practices of use and concentration (Elder 1985). New studies, concentrations >1% to 50% (Elder 1985). Uses reported to FDA
along with the updated information regarding types and concen- in 2002 decreased to 71 (FDA 2002) and an industry survey of
trations of use, were considered by the CIR Expert Panel. The use concentrations yielded a use concentration range from 0.2%
Panel determined not to reopen this safety assessment. to 14% (CTFA 2003).
Data reported to the FDA by industry in 1981 indicated that Table 12 presents the historical and recent uses of Hydrolyzed
Hydrolyzed Collagen was used in 936 cosmetic products at con- Collagen in cosmetic products. The most current data are now
centrations ranging from ≤0.1% to >50% (Elder 1985). Uses considered the present practices of use.
reported to FDA in 2002 (Hydrolyzed Animal Protein and Hy- The CIR Expert Panel did note a new use in lipsticks at con-
drolyzed Animal Collagen were listed in this FDA database) centrations of use of 9% to 14%. Oral toxicity studies in the
decreased to 569 (FDA 2002) and an industry survey of use con- original report suggest no concerns relating to this new use.
centrations yielded a maximum use concentration of 1% (CTFA
2004).
Table 11 presents the historical and recent uses and concen- REFERENCES
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drolyzed Collagen has been expanded recently to include spe-
cific mention of animal and fish collagen as the source material 12
(Hydrolyzed Collagen is the hydrosylate of animal or fish col- 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA.
lagen derived by acid, enzyme, or other method of hydrolysis) 13
(Gottschalck and McEwen 2004). 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA.
TABLE 11
Historical and recent uses and use concentrations of Hydrolyzed Collagen in cosmetic products
Baby care
Bath
Oils, tablets and salts 2 — >1–5 —
Bubble baths 2 2a >0.1–1 —
Soaps and detergents 3 13a >0.1–5 0.1
Other bath 2 2a >0.1–1 —
Eye makeup
Eyebrow pencils — 1a , 1 — —
Eyeliners 1 1a ≤0.1 1
Eye shadow 6 7a ≤1 —
Eye lotion — — — 3
Eye makeup remover — 1a — —
Mascara 28 9a ≤1 0.02–1
Other eye makeup 5 1a ≤5 0.000004
Noncoloring hair
Hair conditioners 174 126a >50 —
Hair sprays/aerosol fixatives 7 3a ≤1 —
Hair Straighteners 7 7a >0.1–1 —
Permanent waves 70 13a ≤25 0.05
Rinses 34 7a ≤10 —
Shampoos 224 116a ≤10 0.02
Hair tonics, dressings, etc. 35 40a >50 —
Wave sets 39 4a ≤25 —
Other noncoloring hair 18 15a ≤10 0.03–0.2
Hair coloring
Tints 14 2a ≤5 —
Rinses 24 — ≤0.1 —
Shampoos — 2a — —
Bleaches 7 — ≤5 —
Other hair coloring 1 — >0.1–1 —
Makeup
Blushers 5 2a >0.1–1 0.5
Face powders 5 4a ≤1 0.5
Foundations 10 7a ≤1 0.5–4
Lipsticks 15 7a ≤1 1
Makeup bases 15 4a ≤1 —
Nail care
Basecoats — 1a — —
Cuticle softeners 3 2a ≤1 —
Creams and lotions 6 5a ≤50 —
Polishes and enamels 1 — >1–5 —
Polish and enamel removers 2 — ≤0.1 —
Other nail care 6 1a ≤5 —
Personal hygiene
Other personal hygiene — 4a — —
TABLE 11
Historical and recent uses and use concentrations of Hydrolyzed Collagen in cosmetic products (Continued)
Shaving
Aftershave lotions 3 1a >0.1–1 0.007
Other shaving — 1a — 0.007
Skin Care
Cleansing creams, lotions, etc. 27 17a ≤5 —
Face and neck skin care 18a 0.06–6
46c ≤10c
Body and hand skin care 20a 1
Moisturizers 43 36a ≤25 1
Night skin care 11 15a >0.1–25 0.02
Paste masks/mud packs 6 8a ≤5 0.008
Skin fresheners 7 8a ≤5 —
Wrinkle smoothersd 1 —d >1–5 —d
Other skin care preparations 7 27a ≤0.1–5 0.5
Suntan Preparations
Suntan gels, creams and liquids — 7a — 0.000004
Other suntan preparations — 2a — 0.05
Total uses/ranges for Hydrolyzed Collagen 923 569a , 1b ≤0.1− >50 .000004–6
a
Ingredient identified as “Hydrolyzed Animal Protein” in the FDA database.
b
Ingredient identified as “Hydrolyzed Animal Collagen” in the FDA database.
c
d
Food and Drug Administration (FDA). 2002. Frequency of use of cosmetic from a survey of industry practices by the Cosmetic, Toiletry, and
ingredients. FDA database. Washington, DC: FDA. Fragrance Association (CTFA) indicated use at concentrations
Fulton, J. E., S. R. Pay, and J. E. Fulton. 1984. Comedogenicity of current
from 0.1% to 1% in cosmetic products (CTFA 2003).
therapeutic products, cosmetics, and ingredients in the rabbit ear. J. Am. Acad.
Dermatol. 10:96–105. 4-Nitro-o-Phenylenediamine was reported to be used in 26
Pepe, R. C., J. A. Wenninger, and G. N. McEwen, Jr., eds. 2002. International hair dyes and colors in 1981, at concentrations of ≤ 0.1% to 1%
Cosmetic Ingredient Dictionary and Handbook, 8th ed., vol. 1. Washington, (Elder 1985). Industry reports to FDA in 2002 included 22 uses
DC: CTFA. as hair dyes and colors. Use concentration data from an industry
survey in 2003 indicated use at concentrations of 0.1% to 0.2%
(CTFA 2003).
2-NITRO- p-PHENYLENEDIAMINE The available use and concentration as a function of product
AND 4-NITRO-o-PHENYLENEDIAMINE type is given in Table 13. The most recent information now
A safety assessment of 2-Nitro- p-Phenylenediamine and 4- constitutes the current practices of use and concentration.
Nitro-o-Phenylenediamine was published in 1985 with the con- In 2003, an updated review of the available hair dye epi-
clusion “for those persons not sensitized, the Expert Panel demiology literature was prepared (Helzlsouer et al. 2003). The
concludes that 2-Nitro- p-Phenylenediamine and 4-Nitro-o- authors found insufficient evidence to support a causal associa-
Phenylenediamine are safe as hair dye ingredients at the current tion between personal hair dye use and a variety of tumors and
concentration of use” (Elder 1985). Studies available since that cancers. The review highlighted well-designed studies with an
safety assessment was completed, along with updated informa- exposure assessment that included hair dye type, color, and fre-
tion regarding uses and use concentrations, were considered by quency or duration of use, which found associations between
the CIR Expert Panel. The Panel determined to not reopen this personal hair dye use and development of bladder cancer, non-
safety assessment. Hodgkin’s lymphoma, and multiple myeloma. These findings,
2-Nitro-p-Phenylenediamine was reported to be used in 28 however, were not consistently observed across studies.
hair dyes and colors in 1981 at concentrations from ≤0.1% to 1% In considering all these data, the CIR Expert Panel concluded
(Elder 1985). In 2002, voluntary reports provided by industry that the available epidemiology studies are insufficient to con-
to FDA indicated that 2-Nitro- p-Phenylenediamine was used in clude there is a causal relationship between hair dye use and
113 hair dyes and colors (FDA 2002). Use concentration data cancer and other endpoints. The Panel stated that use of direct
TABLE 12
Historical and recent uses and use concentrations of Isostearyl Neopentaoate in cosmetic products
Eye makeup
Eyeliner 5 — >5–10 8–13
Eye shadow 135 5 >1–10 1–13
Eye makeup remover 1 1 >10–25 —
Eye lotion — — — 2
Other eye makeup preparations 3 1 >1–10 13
Fragrances
Perfumes — 1 — —
Makeup
Blushers 20 8 >1–50 2–10
Foundations 10 9 >1–10 —
Face powders — 2 — 3–6
Lipstick — 3 — 9–14
Foundations — — — 1–10
Makeup bases 16 9 >1–50 1–2
Rouges 2 — >1–5 —
Other makeup 1 4 >10–25 0.2–12
Skin care
Cleansing creams, lotions, etc. 1 2 >5–10 3–8
Face and neck skin care ∗ 1 ∗ 4
1 >1–5
Body and hand sprays — — — 6
Moisturizers 8 11 >0.1–10 —
Night skin care 1 1 >1–5 —
Paste masks/mud packs — 1 — 4
Other skin care 1 5 >1–5 1–7
Suntan
Suntan gels, creams, and liquids 2 — >1–5 2–4
Indoor tanning — 1 — —
Other suntan 1 — >1–5 —
Total uses/ranges for Isostearyl Neopentaoate 208 71 >0.1–50 0.2–14
∗
TABLE 13
Historical and current uses and use concentrations for 2-Nitro- p-phenylenediamine and 4-Nitro-o-phenylenediamine
1981 use 2002 use 1981 concentrations 2003 concentrations
2-Nitro- p-phenylenediamine
Hair dyes and colors 28 113 ≤0.1–1 0.1–1
Total uses/ranges for 2-Nitro- p-phenylenediamine 28 113 ≤0.1–1 0.1–1
4-Nitro-o-phenylenediamine
Hair dyes and colors 26 22 ≤0.1–1 0.1–0.2
Total uses/ranges 4-Nitro-o-phenylenediamine 26 22 ≤0.1–1 0.1–0.2
hair dyes, although not the focus in all investigations, appears Food and Drug Administration (FDA). 2002. Frequency of use of cosmetic
to have little evidence of an association with adverse events as ingredients. FDA database. Washington, DC: FDA.
reported in epidemiology studies. However, direct hair dyes are Frosch, P. J., D. Burrows, and J. G. Camarasa. 1993. Allergic reactions to a
hairdressers’ series: Results from 9 European Centers. Contact Dermatitis
a diverse group of chemicals and the determination of safety 28:180–183.
may hinge on other safety test data. Gentile, J. M., G. J. Gentile, S. Townsend, and M. J. Plewa. 1985a. The in vitro
Discussion of the most recent available hair dye epidemiol- enhancement of the mutagenicity of 4-nitro-o-phenylenediamine by plant S-9.
ogy data is available at http://www.cir-safety.org/findings.shtml. Environ. Mutagen. 7:73–85.
Gentile, J. M., G. J. Gentile, S. Townsend, and M. J. Plewa. 1985b. Mutagenicity
of phenylenediamines to Salmonella following plant and mammalian hepatic
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8045, Japan. ACID, AND STEARIC ACID
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A safety assessment of the Oleic Acid group was published in
the bone marrow micronucleus analysis. Cytologia 57:149–154.
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considered by the CIR Expert Panel. The Panel determined to
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compounds. Mutat. Res. 113:33–43. based on industry voluntary reports provided to FDA (Elder
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spermatogonia and intestinal epithelium in Chinese hamsters. Basic Life Sci.
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unscheduled DNA synthesis in rat hepatocytes. Mutat. Res. 271:201–208.
The newly available studies reported findings consistent with
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470.
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tocyte primary culture/DNA repair test in testing in coded carcinogens and be exceeded (lead ≤10 ppm, arsenic ≤3 ppm, mercury ≤1 ppm,
noncarcinogens. Mutat. Res. 97:359–370. total PCB/pesticide ≤40 ppm, with ≤10 ppm for any specific
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models. Chemosphere 30:1275–1296. These fatty acids may also be derived from animal sources,
Wolfram, L. J., and H. I. Maibach. 1985. Percutaneous penetration of hair dyes. including beef. The Panel agrees with the Food and Drug Ad-
Arch. Dermatol. Res. 277:235–241. ministration’s position that tallow derivatives, including these
Yourick, J. J., and R. L. Bronaugh. 2000. Percutaneous absorption and fatty acids, would not present any risk of transmissible en-
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icol. Appl. Pharmacol. 166:13–23.
cephalopathies.
TABLE 14
Historical and current cosmetic product uses and concentrations for Oleic Acid, Lauric Acid, Palmitic Acid,
Myristic Acid, and Stearic Acid
Oleic Acid
Baby care
Shampoos 1 1 >10–25 —
Lotions, oils, powders, and creams 1 1 >1–5 1
Other baby care 2 4 >1–25 2
Bath
Oils, tablets, and salts 1 1 >5–10 —
Soaps and detergents 5 20 >1–10 0.000004–15
Other bath — 10 — —
Eye makeup
Eyeliners 16 10 >0.1–25 0.1–3
Eye shadow 5 — >0.1–5 0.4
Eye makeup remover 2 — >1–5 —
Mascara 41 38 >0.1–10 1–4
Other eye makeup 1 1 >1–5 2–5 a
Fragrances
Sachets 4 2 >0.1–1 —
Other fragrances 8 5 >0.1–5 —
Conditioners 1 — >25–50 —
Permanent waves 1 2 ≤0.1 —
Shampoos 9 5 >1–25 0.000007
Tonics, dressings, etc. 1 1 >0.1–1 0.6
Other noncoloring hair care — — — 20 b
Hair coloring
Dyes and colors 205 946 ≤0.1–25 19
Tints 14 9 >1–25 —
Shampoos 7 — >0.1–5 —
Color sprays — 1 — —
Lighteners with color 1 1 >1–5 —
Bleaches 8 17 >1–50 —
Makeup
Blushers 10 2 >1–5 0.4
Face powders 1 — >0.1–1 0.0001
Foundations 20 9 >0.1–5 0.4–2
Lipsticks 1 5 >5–10 16
Makeup bases 5 3 ≤0.1–5 0.4
Rouges — 1 — 0.00005
Other makeup 4 3 >0.1–25 2
Nail care
Basecoats and undercoats 1 1 >10–25 —
Nail polish and enamels — — — 0.0008
Other nail care — 1 — —
TABLE 14
Myristic Acid, and Stearic Acid (Continued)
Personal hygiene
Underarm deodorants — — — 0.0007–0.6
Other personal hygiene 3 4 >1–10 6e
Shaving
Aftershave lotions 3 — ≤0.1–1 0.00008
Shaving cream 2 3 >1–5 0.7–4
Skin care
Cleansing creams, lotions, etc. 10 5 >0.1–5 0.00002–9
Face and neck skin care — 2
11c >0.1–25c
Moisturizers 14 7 >0.1–5 0.2–0.4
Night skin care — — — 0.5
Other skin care 2 3 >0.1–5 —
Hormone preparationsd 1 NAd >1–5 NAd
Suntan products
Suntan gels, creams, liquids, and sprays 2 5 >1–5 0.02
Indoor tanning preparations — 1 — —
Total uses/ranges for Oleic Acid 424 1131 ≤0.1–50 0.000004–20
Lauric Acid
Bath
Soaps and detergents — 16 — 0.1–8
Other bath — 20 — 2–11
Conditioners — 1 — 0.000004–4
Sprays — — — 0.00002
Shampoos 3 1 >1–25 0.2–0.5
Tonics, dressings, etc. 3 5 >0.1–1 0.00003
Fragrances
Perfumes — — — 0.00002
Hair coloring
Makeup
Foundations — — — 1
Lipsticks — 1 — 0.00003
Personal hygiene
Underarm deodorants 5 3 ≤0.1–1 0.3
Other personal hygiene 4 3 ≤0.1–10 5e
Shaving
Aftershave lotions — — — 0.0003
Shaving cream 3 1 >1–10 0.003
Other shaving — — — 0.2g
Skin care
Cleansing creams, lotions, etc. 3 25 >1–5 —
Face and neck skin care c — c —
— —
Body and hand skin care — 0.00006
Moisturizers 1 2 >0.1–1 —
TABLE 14
Night skin care — — — 0.00003–0.5
Other skin care — — — 2–3
Suntan
Suntan gels, creams and liquids — — — 1
Total uses/ranges for Lauric Acid 22 121 ≤0.1–25 0.000004–11
Palmitic Acid
Bath
Other — 11 — 0.000006–2
Eye makeup
Eyeliners — — — 0.1–0.7
Eye shadow 1 — >5–10 0.006–0.3
Eye lotion — — — 0.05
Mascara — 1 — 0.02–4
Other eye makeup — 2 — 0.003
Fragrance
Colognes and toilet waters — — — 0.01–0.8
Other fragrances — 1 — 3
Conditioners — 1 — 0.00002–0.4
Shampoos 2 26 >1–5 0.001–3
Tonics, dressings, etc. — — — 0.00003–2
Hair coloring
Makeup
Blushers — — — 0.008–0.2
Face powders — 1 — 0.01–1
Foundations 2 10 >0.1–5 0.3–2
Lipsticks — 1 — 0.2–16
Rouges — 1 — 0.00005
Other makeup — — — 0.01–2
Nail care
Nail polishes and enamels — — — 0.02–0.03
Personal hygiene
Underarm deodorants — 1 — 0.09–3
Other personal hygiene — — — 0.3–4
Shaving
Shaving cream 4 11 >0.1–10 2–20
Shaving soap — — — 0.4–8
Other shaving — 17 — 10
Skin care
Cleansing creams, lotions, etc. 8 8 >1–25 0.03–7
TABLE 14
3c >0.1–5c
Foot powders and sprays — 1 — —
Moisturizers 3 8 >0.1–5 0.2–2
Night skin care 3 — >1–25 0.05–1
Paste masks/mud packs — — — 0.02
Skin fresheners — 1 — —
Other skin care 1 4 >1–5 0.2–2
Suntan
Suntan gels, creams, liquids, and sprays 1 5 >10–25 0.0009–3
Indoor tanning — 1 — —
Total uses/ranges for Palmitic Acid 29 132 >0.1–25 0.000006–20
Myristic Acid
Bath
Soaps and detergents 3 7 >5–25 0.005-19
Other bath — 11 — 0.00001–14
Eye makeup
Mascara 2 — >0.1–1 0.005–0.8
Fragrances
Conditioners — 1 — —
Shampoos 2 3 >1–5 0.00006–0.2
Tonics, dressings, etc. — — — 0.00002–0.08
Makeup
Lipsticks — 1 — —
Rouges — — — 0.00005
Oral hygiene
Personal hygiene
Underarm deodorants — 1 — —
Other personal hygiene 2 1 >10–25 1–38 f
Shaving
Beard softeners 2 — >25–50 —
Shaving cream 16 13 >1–10 3–33
Shaving soap — — — 2
Other shaving 1 3 >0.1–1 —
Skin care
Cleansing creams, lotions, etc. 5 26 1–25 0.0005–12
Face and neck skin care — 14
2c >0.1–5c
Moisturizers 1 1 >0.1–1 0.0002–1
TABLE 14
Night skin care — — — 0.0003
Other skin care — 1 — 0.003–15
Total uses/ranges for Myristic Acid 36 73 >0.1–50 0.00001–38
Stearic Acid
Baby care
Shampoos — — — 2
Lotions, oils, powders, and creams 9 11 >0.1–10 2–3
Other baby care 1 7 >10–25 0.1–2
Bath
Bubble baths — 1 — 1–2
Other bath 3 13 >0.1–5 0.000007–7h
Eye makeup
Eyebrow pencils 9 12 >5–25 0.009–15
Eyeliners 55 74 >0.1–50 0.7–22
Eye shadow 128 4 >0.1–5 0.3–16
Eye lotions 1 4 >1–5 0.05–3
Eye makeup remover 1 3 >0.1–1 0.1–0.5
Mascara 139 95 >0.1–50 1–21
Other eye makeup 26 32 >0.1–10 1–14
Fragrances
Colognes and toilet waters 3 — >1–5 1
Perfumes 3 — >0.1–10 —
Sachets 32 4 >0.1–10 —
Other fragrances 34 31 >0.1–10 16
Conditioners 18 7 ≤0.1–5 0.000002–0.5
Sprays/aerosol fixatives 1 — >1–5 —
Straighteners 6 8 >0.1–10 —
Shampoos 17 10 >0.1–25 0.000007–7
Tonics, dressings, etc. 18 4 ≤0.1–>50 0.01–2
Hair coloring
Dyes and colors 76 132 >1–5 —
Tints — 1 — —
Bleaches 4 — >0.1–5 —
Other hair coloring 8 2 >10–25 —
Makeup
Blushers 47 4 >0.1–10 0.8–3
Face powders 2 6 >0.1–1 0.1–1
Foundations 190 119 >0.1–25 1–5
Lipsticks 27 40 >0.1–25 0.02–9
Makeup bases 263 35 >0.1–25 2–3
Rouges 9 — >0.1–10 0.00005–0.1
Makeup fixatives 1 4 >1–5 —
Other makeup 20 22 >0.1–25 0.01–6
TABLE 14
Product category (Elder 1985) (FDA 2002) (Elder 1985)% (CTFA 2005)%
Nail care
Cuticle softeners 10 8 >0.1–25 1–4
Creams and lotions 6 5 >1–5 3–5
Nail polishes and enamels — — — 0.04
Other nail care 2 — >1–10 0.05–4
Personal hygiene
Underarm deodorants 8 21 >1–25 0.2–9
Other personal hygiene 8 6 >1–25 5–6e
Shaving
Aftershave lotions 5 9 >0.1–5 0.5–2
Shaving cream 100 100 >0.1–50 1–43
Shaving soap 1 1 >25–50 0.4–2
Other shaving 6 4 >1–25 0.5–8
Skin care
Cleansing creams, lotions, etc. 173 168 ≤0.1–25 1–25
432c >0.1–50c
Foot powders and sprays — 5 — 4
Moisturizers 327 356 ≤1–50 0.3–10
Night skin care 67 62 ≤0.1–25 0.4–2
Paste masks/mud packs 15 55 >1–25 0.4–8
Skin fresheners 4 4 >10–25 —
Skin lightenersd 11 —d >1–25 —d
Hormone preparationsd 3 —d >1–25 —d
Wrinkle smoothersd 4 —d >1–5 —d
Other skin care 55 133 >0.1–25 0.0005–5
Suntan
Suntan gels, creams, liquids, and sprays 48 42 >0.1–25 —
Indoor tanning 3 9 >0.1–1 0.3–2
Other suntan 13 13 >0.1–5 —
Total uses/ranges for Stearic Acid 2465 2133 ≤0.1–>50 0.000007–43
a
The 5% concentration was for a definer.
b
A hair care protective oil.
c
These categories were combined in 1981, but are now separate.
d
No longer considered as a cosmetic ingredient category.
e
A hand wash product.
f
The highest concentration was for a hand wash product.
g
The 0.2% concentration was specifically reported in a shave lubricant product.
h
The 7% concentration was for a body scrub product.
REFERENCES Cosmetic, Toiletry, and Fragrance Association (CTFA). 2005. Use concentration
Boelsma, E., H. Tanojo, H. E. Bodde, and M. Ponec. 1996. Assessment of the data from industry survey. Unpublished data submitted by CTFA.15
potential irritancy of oleic acid on human skin: Evaluation in vitro and in vivo. De Groot, A. C., H. L. van der Meeren, and J. W. Weyland. 1988. Cosmetic
Toxicol. In Vitro 10:729–742. allergy from stearic acid and glyceryl stearate. Contact Dermatitis 19:77–78.
Cardoso, C. R., M. A. Souza, E. A. Ferro, et al. 2004. Influence of topical
administration of n–3 and n–6 essential and n–9 nonessential fatty acids on 15
the healing of cutaneous wounds. Wound Repair Regen. 12:235–243. 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA.
de Sousa Andrade, L. N., T. M. de Lima, R. Curi, and A. M. de Lauro Castrucci. Siegel, I., A. B. Dudkiewicz, J. Friberg, M. Suarez et al. 1986. Inhibition of
2005. Toxicity of fatty acids on murine and human melanoma cell lines. sperm motility and agglutination of sperm cells by free fatty acids in whole
Toxicol. In Vitro 19:553–560. semen. Fertil. Steril. 45:273–279.
Dobson, C. L., S. S. Davis, S. Chauhan, R. A. Sparrow et al. 1999. Effect of Tholstrup, T., C. Ehnholm, M. Jauhianen, M. Petersen, et al. 2004. Effects of
oleic acid on the human ileal brake and its implications for small intestinal medium-chain fatty acids and oleic acid on blood lipids, lipoproteins, glucose,
transit of tablet formulations. Pharm. Res. 16:92–96. insulin, and lipid transfer protein activities. Am. J. Clin. Nutr. 79:564–569.
Elder, R. L. 1985. Final report on the safety assessment of Oleic Acid, Lauric Tanojo, H., E. Boelsma, H. E. Junginger, M. Ponec, et al. 1999. In vivo hu-
Acid, Palmitic Acid, Myristic Acid, and Stearic Acid. J. Am. Coll. Toxicol. man skin permeability enhancement by oleic acid: Laser Doppler velocimetry
4:161–202. study. J. Controlled Release 58:97–104.
Fermor, B. F., J. R. Masters, C. B. Wood, J. Miller et al. 1992. Fatty acid Tanojo, H., H. E. Junginger, and H. E. Bodde. 1997. In vivo human skin per-
composition of normal and malignant cells and cytotoxicity of stearic, oleic, meability enhancement by oleic acid: Transepidermal water loss and Fourier-
and sterculic acids in vitro. Eur. J. Cancer 28:1143–1147. transform infrared spectroscopy studies. J. Controlled Release 47:31–39.
Garrison, M. D., L. M. Doh, R. O. Potts, and W. Abraham. 1994. Effect of Ulloth, J. E., C. A. Casiano, and M. De Leon. 2003. Palmitic and stearic fatty
oleic acid on human epidermis: Fluorescence spectroscopic investigation. J. acids induce caspase-dependent and independent cell death in nerve growth
Controlled Release 31:263–269. factor differentiated PC12 cells. J. Neurochem. 84:655–668.
Gottschalck, T. E., and G. N. McEwen, Jr. 2004. International cosmetic ingredi- Velasquez, O. R., A. R. Place, P. Tso, and K. D. Crissinger. 1994. Developing
ent dictionary and handbook, 10th ed., p 970, 1106, 1163–1164, 1198, 1822. intestine is injured during absorption of oleic acid but not its ethyl ester. J.
Washington, DC: CTFA. Clin. Invest. 93:479–485.
Gouni-Berthold, I., H. K. Berhold, C. Seul, Y. Ko, et al. 2001. Effects of authentic
and VLDL hydrolysis-derived fatty acids on vascular smooth muscle cell
growth. Br. J. Pharmacol. 132:1725–1734. PANTHENOL AND PANTOTHENIC ACID
Green, P. G., R. H. Guy, and J. Hadgraft. 1988. In vitro and in vivo enhancement A safety assessment of Panthenol and Pantothenic Acid was
of skin permeation with oleic and lauric acids. Int. J. Pharmacol. 48:103– published in 1987 with the conclusion that these ingredients are
111.
Huang, Z. H., D. Gu, and T. Mazzone. 2004. Oleic acid modulates the post-
safe as presently used in cosmetics (Elder 1987). Studies pub-
translational glycosylation of macrophage ApoE to increase its secretion. J. lished since the last assessment, along with updated information
Biol. Chem. 279:29195–29201. concerning frequency of use and use concentrations, were con-
Khalil, M. H., J. F. Marceletti, L. R. Katz, D. H. Katz, et al. 2000. Topical sidered by the CIR Expert Panel. The Panel determined to not
application of docosanol- or stearic acid-containing creams reduces severity reopen the safety assessment.
of phenol burn wounds in mice. Contact Dermatitis 24:79–81.
Khoo, D. E., B. Flaks, H. Oztas, R. C. Williamson, et al. 1991. Effects of dietary
The safety assessment applies to Panthenol in both the D and
fatty acids on the early stages of neoplastic induction in the rat pancreas. the DL form.
Changes in fatty acid composition and development of atypical acinar cell The available use and concentration information is provided
nodules. Int. J. Exp. Pathol. 72:571–580. in Table 15. The most recent information now constitutes the
Kim, H. J., J. H. Lee, C. H. Lee, S. H. Lee, et al. 2002. Experimental cerebral fat present use of these ingredients.
embolism: Embolic effects of triolein and oleic acid depicted by MR Imaging
and electron microscopy. Am. J. Neuroradiol. 23:1516–1623.
Panthenol reported usage increased from 284 in 1981 to 1538
Kinter, M., D. R. Spitz, and R. J. Roberts. 1996. Oleic acid incorporation pro- in 2002, based on industry voluntary reports provided to FDA
tects cultured hamster fibroblasts from oxygen-induced cytotoxicity. J. Nutr. (Elder 1987; FDA 2002). An industry survey in 2004 indicated
126:2952–2959. that use concentrations range from 0.00005% to 6%, which is
Koehler, A. E., M. E. Tobin, and R. T. Sugihara. 1995. Exploration of lauric lower than the maximum use concentration range reported in
acid as a potentiator for enhancing warfarin toxicity to rats. Int. Biodeterior.
Biodegrad. 36:73–87.
1981 (Elder 1987).
Koyama, Y., H. Bando, F. Yamashita, Y. Takakura, et al. 1994. Comparative Pantothenic Acid was not reportedly used in cosmetics in
analysis of percutaneous absorption enhancement by d-limonene and oleic 1981 (Elder 1987), but industry voluntary reports provided to
acid based on a skin diffusion model. Pharm. Res. 11:377–383. FDA in 2002 included three uses in eye makeup and skin care
Kravchenko, I. A., N. Y. Golovenko, V. B. Larionov, A. I. Aleksandrova, et al. products (FDA 2002). An industry survey in 2004 indicated
2003. Effect of lauric acid on transdermal penetration of phenazepam in vivo.
Pharmacol. Toxicol. 136:579–581.
that use concentrations range from 0.00001% to 0.01% in those
Lee, S. P., C. Tasman-Jones, and V. Carlisle. 1986. Oleic acid-induced cholelithi- product categories and in makeup and shaving preparations (cat-
asis in rabbits. Changes in bile composition and gallbladder morphology. Am. egories in which no uses were reported to FDA).
J. Pathol. 124:18–24.
Medvedev, A. V., J. Robidoux, X. Bai, W. Cao, et al. 2002. Regulation of the
uncoupling protien-2 gene in INS-1 β-cells by oleic acid. J. Biol. Chem. REFERENCES
277:42639–42644. Biro, K., D. Thaci, F. R. Ochsendorf, R. Kaufmann, and W. H. Boehncke. 2003.
Müller, D., R. M. Nitsch, R. J. Wurtman, and S. Hoyer. 1998. Streptozotocin Efficiency of dexpanthenol in skin protection against irritation: A double-
increases free fatty acids and decreases phospholipids in rat brain. J. Neural. blind, placebo-controlled study. Contact Dermatitis 49:80–84.
Transm. 105:1271–1281. Cosmetic, Toiletry, and Fragrance Association (CTFA). 2004. Concentration of
Ogiso, T., M. Iwaki, Y. Kashitani, and K. Yamashita. 1991. Enhancement effect use of Panthenol and Pantothenic Acid in cosmetic formulations. Unpublished
of lauric acid on the rectal absorption of propranolol from suppository in rats. data submitted by CTFA. 3 pages.16
Chem. Pharm. Bull. (Tokyo). 39:2657–2661.
Pershing, L. K., G. E. Parry, and L. D. Lambert. 1993. Disparity of in vitro and
16
in vivo oleic acid-enhanced beta-estradiol percutaneous absorption across Available for review: Director, Cosmetic Ingredient Review, 1101
human skin. Pharm. Res. 10:1745–1750. 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA.
TABLE 15
Historical and current cosmetic product uses and concentrations for Panthenol and Pantothenic Acid
Panthenol
Baby care
Bath
Oils, tablets and salts — — — 2
Soaps and detergents — 15 — 0.05–4
Bubble baths — 3 — 0.01–2
Capsules — 1 — —
Other bath — 11 — 0.3–2
Eye makeup
Eyebrow pencils — 3 — 0.01–2
Eyeliners 5 — >0.1–1 0.01–0.05
Eye shadow 23 — >0.1–1 0.5–1
Eye lotions — 5 — 0.01–0.6
Eye makeup remover 2 8 >0.1–1 0.001–1
Mascara 10 70 >0.1–5 0.1–2
Other eye makeup 2 14 >0.1–1 0.3–0.5
Fragrances
Colognes and toilet waters 1 5 >0.1–1 0.003–0.1
Conditioners 33 264 ≤0.1–5 0.09–6
Sprays/aerosol fixatives 17 82 ≤0.1–1 0.01–5
Straighteners — 1 — —
Permanent waves 2 6 >0.1–1 5
Rinses 1 6 >0.1–1 0.1–0.5
Shampoos 25 206 ≤0.1–5 0.01–5
Tonics, dressings, etc. 11 187 ≤0.1–1 0.01–5
Wave sets 31 12 ≤0.1–5 0.9–1
Other noncoloring hair care 6 93 ≤0.1–1 0.01–1∗
Hair coloring
Dyes and colors — 52 — 0.01–0.1
Tints — 1 — —
Bleaches — 1 — 0.5
Other hair coloring — 6 — 0.00005–1
Makeup
Blushers 3 2 >0.1–1 0.2–1
>10–25
Face powders 1 1 >0.1–1 0.02–1
Foundations 8 45 ≤0.1–1 0.2–1
Lipsticks 27 6 ≤0.1–5 0.01–2
Makeup bases 1 8 ≤0.1 0.5
Rouges 1 — >0.1–1 —
Other makeup 2 4 >0.1–1 <1–6
TABLE 15
Historical and current cosmetic product uses and concentrations for Panthenol and Pantothenic Acid (Continued)
Nail care
Basecoats and undercoats — 9 — 0.03–0.2
Cuticle softeners 1 4 >0.1–1 0.1–0.2
Creams and lotions 1 1 >0.1–1 0.05–0.5
Polishes and enamels — 10 — 0.2–1
Polish and enamel removers — 5 — 0.03–0.5
Other nail care — 11 — 0.1–0.2
Personal hygiene
Underarm deodorants 1 3 >0.1–1 0.05–0.5
Douches — — — 0.1–0.8
Other personal hygiene — 8 — 0.1
Shaving
Aftershave lotions 3 14 ≤0.1–1 0.03–3
Shaving cream — 1 — 0.1–0.3
Other shaving 1 2 >0.1–1 0.4–1
Skin care
Cleansing creams, lotions, etc. 5 38 >0.1–1 0.05–3
8∗∗ ≤0.1–1∗∗
Body and hand sprays — — — 2
Foot powders and sprays — — — 0.5
Moisturizers 22 98 ≤0.1–5 0.1–3
Night skin care 14 29 >0.1–1 0.08–2
Paste masks/mud packs 1 24 ≤0.1 0.1–5
Skin fresheners 2 15 >0.1–1 0.01–3
Other skin care 5 46 ≤0.1–1 0.1–5
Suntan
Suntan gels, creams, liquids, and sprays 5 10 >0.1–1 0.1–2
Indoor tanning — 2 — 0.1–2
Other suntan 2 10 >0.1–1 0.5
Total uses/ranges for Panthenol 284 1538 ≤0.1–25 0.00005–6
Pantothenic Acid
Eye makeup
Mascara — — — 0.001–0.01
Makeup
Foundations — — — 0.002
Shaving
Skin Care
Moisturizers — 1 — 0.003
Other skin care — 1 — 0.001
Total uses/ranges for Pantothenic Acid — 3 — 0.00001–0.01
∗
Includes two non-aerosol hair sprays.
∗∗
These categories were combined originally, but are now separate.
Ebner, F., A. Heller, F. Rippke, and I. Tausch. 2002. Topical use dexpanthenol tion regarding uses and use concentrations, were considered by
in skin disorders. Am. J. Clin. Dermatol. 3:427–433. the CIR Expert Panel. The Panel determined to not reopen the
Egger, S. F., V. Huber-Spitzy, E. Alzner, et al. 1999. Corneal wound healing after
safety assessment.
superficial foreign body injury: Vitamin A and dexpanthenol versus a calf
blood extract. A randomized double-blind study. Ophthalmologica 213:246. Although the safety of p-Phenylenediamine as a hair dye in-
Elder, R. L. 1987. Final Report on the Safety Assessment of Panthenol and gredient was reaffirmed, the Panel did agree with FDA that other
Pantothenic Acid. J. Am. Coll. Toxicol. 6:139–162. uses of this dye are unapproved. The Panel expressed particu-
Gehring, W., and M. Gloor. 2000. Effect of topically applied dexpanthenol on lar concern over the practice of combining p-Phenylenediamine
epidermal barrier function and stratum corneum hydration. Results of a human
with henna (so-called dark henna) for use in temporary tattoos—
in vivo study.” Arzneimittelforschung. 50:659–663.
Gottschalck, T. E., and G. N. McEwen, Jr., eds. 2004. International cosmetic p-Phenylenediamine is a known sensitizer, highly inappropriate
ingredient dictionary and handbook. 10th ed., vol. 2. Washington, DC: CTFA. for such use as evidenced by reports of severe adverse skin re-
Hemmer, W., R. Bracun, S. Wolf-Abdolvahab, M. Focke, M. Gotz, and R. actions to dark henna temporary tattoos. The Panel urged users
Jarisch. 1997. Maintenance of hand eczema by oral pantothenic acid in a to report adverse reactions to the FDA (for more information,
patient sensitized to dexpanthenol. Contact Dermatitis 37:51.
see the FDA website at http://www.cfsan.fda.gov/∼dms/cos-
Jeanmougin, M., J. R. Manciet, J. P. Moulin, P. Blanc, A. Pons, and J. Ci-
vatte. 1988. Contact allergy to dexpanthenol in sunscreens. Contact Dermati- tatt.html). The Panel also will work with the Consumer Federa-
tis 18:240. tion of America to help the public understand the need to avoid
Klocker, N., T. Verse, and P. Rudolph. 2003. The protective effect of dexpan- using such unapproved and potentially dangerous products.
thenol in nasal sprays. First results of cytotoxic and ciliary-toxic studies in The CIR Expert Panel also reviewed hair dye epidemiology
vitro. Larynogorhinootologie 82:177–182.
data. In 1993, an International Agency for Research on Cancer
Lokkevik, E., E. Skovlund, J. B. Reitan, E. Hannisdal, and G. Tanum. 1996.
Skin treatment with bepanthen cream versus no cream during radiotherapy— (IARC) working group evaluated 78 epidemiology literature ci-
a randomized controlled trial. Acta Oncol. 35:1021–1026. tations and concluded that “personal use of hair colourants can-
Pugliese, P. T., J. C. Farina, and Y. Chautems. 1995. Efficacy of dexpanthenol not be evaluated as to its carcinogenicity” and that occupation as
in wound healing: A double-blind assessment of excised wound tissue by a hairdresser or barber entails exposures that are probably car-
ultrasound and histologic examination. Nouv. Dermatol. 14:130.
cinogenic” (IARC 1993). The IARC report did not distinguish
Romitti, P., and N. Romitti. 2002. Dexpanthenol cream significantly improves
mucocutaneous side effects associated with isotretinoin therapy. Pediatr. Der- between personal use of oxidative/permanent versus direct hair
matol. 19:368. dyes, or distinguish among the multiple chemical exposures in
Schalock, P. C., F. J. Storrs, and L. Morrison. 2000. Contact urticaria from addition to hair dyes to which a hairdresser or barber might be
panthenol in hair conditioner. Contact Dermatitis 43:223. exposed.
Schepler, H., J. Kessler, and B. Hartmann. 2002. Abuse of silver-nitrate solution
In 2003, an updated review of the available epidemiology lit-
for planing periorbital folds. Burns 28:90–91.
Schmid-Grendelmeier, P., M. Wyss, and P. Elsner. 1995. Contact allergy to erature was prepared (Helzlsouer et al. 2003). This review con-
dexpanthenol. A report of 7 cases and review of the literature. Dermatosen in sidered 83 literature citations available since the IARC review.
Beruf und Umwelt 43:175–178. The authors found insufficient evidence to support a causal as-
Schulze-Dirks, A., and P.J. Frosch. 1988. Contact allergy to dexpanthenol. Hau- sociation between personal hair dye use and a variety of tumors
tarzt 39:375–377.
and cancers.
Slyshenkov, V. S., M. Rakowska, A. G. Moiseenok, et al. 1995. Pantothenic acid
and its derivatives protect tumor cells against lipid peroxidation. Free Radical In considering this information, the CIR Expert Panel agreed
Biol. Med. 19:767–772. that the available epidemiology studies are insufficient to con-
Slyshenkov, V. S., M. Rakowska, and L. Wojtczak. 1996. Protective effect of clude there is a causal relationship between hair dye use and
pantothenic acid and related compounds against permeabilitzation of Ehrlich cancer and other end points described in the Helzlsouer et al.
ascites tumor cells by digitonin. Acta Biochim. Polon. 43:407–410.
(2003) review.
Slyshenkov, V. S., S. N. Omelyanchik, A. G. Moiseenok, R. V. Trebukhina, and
L. Wojtczak. 1998. Pantothenol protects rats against some deleterious effects The Panel also stated that use of direct hair dyes, although
of gamma radiation. Free Radical Biol. Med. 24:894–899. not the focus in all investigations, appear to have little evidence
Stables, G. I., and S. M. Wilkinson. 1998. Allergic contact dermatitis due to of an association with adverse events as reported in epidemi-
panthenol. Contact Dermatitis 38:236–237. ology studies. However, direct hair dyes are a diverse group of
Weiser, H., and G. Erlemann. 1988. Acceleration of superficial wound healing
chemicals and the determination of safety may hinge on other
by panthenol zinc oxide. Cosmet. Toiletries 103:79–81, 84.
safety test data.
p-Phenylenediamine was used in 500 hair-coloring prod-
p-PHENYLENEDIAMINE ucts in 1981, at concentrations of ≤0.1% to 5%. In 2002, p-
A safety assessment on p-Phenylenediamine was published Phenylenediamine was used in 1178 hair-coloring products and
in 1985 in which the CIR Expert Panel acknowledged that in 2 nail care products. Use concentration data provided in 2004
p-Phenylenediamine is a known sensitizer and some persons indicated use at concentrations of ≤0014% to ≤4% in hair col-
may be sensitized under intended conditions of use. For those oring products. The 2004 use concentration data were provided
persons not sensitized, the Expert Panel concluded that p- by CTFA (CTFA 2004).
Phenylenediamine is safe as a hair dye ingredient at the current Available use and concentration information is shown in
concentrations of use (Elder 1985). Studies available since that Table 16. The most recent information now constitutes the
safety assessment was completed, along with updated informa- present practices of use.
TABLE 16
Historical and current cosmetic product uses and concentrations for p-Phenylenediamine
Hair coloring
Dyes and colors 493 1167 ≤0.1–5 ≤4
Tints 7 9 ≤0.1 —
Rinses — — — ≤0.0014
Lighteners with color — 1 — —
Nail care
Total uses/ranges for p-Phenylenediamine 500 1180 ≤0.1–5 ≤0.0014–≤4
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Abdulla, K. A., and N. M. Davidson. 1996. A woman who collapsed after multicenter study of synchronous left-versus right-sided patch tests by the
painting her soles. Lancet 348:658. German contact Dermatitis Research Group. J. Am. Acad. Dermatol. 31:584–
Adams, R. M., and H. I. Maibach. 1985. A five-year study of cosmetic reactions. 591.
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Ahn, H. J., and W. S. Lee. 2002. An ultrastructural study of hair fiber damage intolerance. Contact Dermatitis 16:189–194.
and restoration following treatment with permanent hair dye. Int. J. Dermatol. Bronaugh, R. L., and E. R. Congdon. 1984. Percutaneous absorption of hair dyes:
41:88–92. Correlation with partition coefficients. J. Invest. Dermatol. 83:124–127.
Armstrong, D. K., A. B. Jones, H. R. Smith, J. S. Ross, I. R. White, R. J. Rycroft, Bronaugh, R. L., C. D. Roberts, and J. L. McCoy. 1994. Dose-response relation-
and J. P. McFadden. 1999. Occupational sensitization to p-phenylenediamine: ship in skin sensitization. Food Chem. Toxicol. 32:113–117.
A 17-year review. Contact Dermatitis 41:348–349. Brown, J. H., M. G. McGeown, B. Conway, and C. M. Hill. 1987. Chronic renal
Ashar, A. 2003. Acute angioedema in paraphenylenediamine poisoning. J. Pak. failure associated with topical application of paraphenylenediamine. Br. Med.
Med. Assoc. 53:120–122. J. (Clin. Res. Ed.) 294:155.
Ashraf, W., S. Dawling, and L. J. Farrow. 1994. Systematic paraphenylenedi- Bruckner-Tuderman, L., A. Konig, and U. W. Schnyder. 1992. Patch test results
amine (PPD) poisoning: A case report and review. Hum. Exp. Toxicol. 13:167– of the dermatology clinic Zurich in 1989: Personal computer-aided statistical
170. evaluation. Dermatology 184:29–33.
Averbukh, Z., D. Modai, and Y. Leonov. 1989. Rhabdomyolysis and acute renal Burnett, C. M., and E. I. Goldenthal. 1988. Multigeneration reproduction and
failure induced by paraphenylenediamine. Hum. Toxicol. 8:345–348. carcinogenicity studies in Sprague-Dawley rats exposed topically to oxida-
Bajaj, A. K., S. C. Gupta, A. K. Chatterjee, K. G. Singh, S. Basu, and A. Kant. tive hair-colouring formulations containing p-phenylenediamine and other
1996. Hair dye depigmentation. Contact Dermatitis 35:56–57. aromatic amines. Food Chem. Toxicol. 26:467–474.
Bajaj, A. K., A. Misra, K. Misra, and S. Rastogi. 2000. The azo dye solvent Calzavara-Pinton, P., R. Capezzera, C. Zane, A. Brezzi, G. Pasolini, A. Ubiali,
yellow 3 produces depigmentation. Contact Dermatitis 42:237–238. and F. Tacchetti. 2002. Lymphomatoid allergic contact dermatitis from para-
Bajaj, A. K., R. K. Pandey, K. Misra, A. K. Chatterji, A. Tiwari, and S. Basu. phenylenediaimine. Contact Dermatitis 47:173–174.
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Storrs, F. J., L. E. Rosenthal, R. M. Adams, et al. 1989. Prevalence and relevance Am. J. Epidemiol. 159:148–154.
of allergic reactions in patients patch tested in North America—1984 to 1985. Zhao, B., and W. X. Fan. 1991. Facial contact dermatitis. Pathogenetic factors
J. Am. Acad. Dermatol. 20:1038–1045. in China. Int. J. Dermatol. 30:485–486.
Stransky, L., and M. Krasteva. 1989. Changing patterns of contact sensitivity in Zheng, T., T. R. Holford, B. Leaderer, Y. Zhang, S. H. Zahm, S. Flynn, G. Tallini,
Sofia. Derm. Beruf. Umwelt. 37:214–216. B. Zhang, K. Zhou, P. H. Owens, Q. Lan, N. Rothman, and P. Boyle. 2004.
Sutthipisal, N., J. P. McFadden, and E. Cronin. 1993. Sensitization in atopic and Diet and nutrient intakes and risk of non-hodgkin’s lymphoma in Connecticut
non-atopic hairdressers with hand eczema. Contact Dermatitis 29:206–209. women. Am. J. Epidemiol. 159:454–466.
Taylor, J. S., H. I. Maibach, A. A. Fisher, and W. F. Bergfeld. 1993. Contact
leukoderma associated with the use of hair colors. Cutis 52:273–280.
Temesvari, E. 1984. Contact urticaria from paraphenylenediamine. Contact Der- PHENYL TRIMETHICONE
matitis 11:125.
In 1986, the CIR Expert Panel found that Phenyl Trime-
Thune, P. 1984. Contact and photocontact allergy to sunscreens. Photoderma-
tology 1:5–9. thicone is safe as a cosmetic ingredient in the present practices of
Tosti, A., M. Pazzaglia, and M. Bertazzoni. 2000. Contact allergy from tempo- use and concentration (Elder 1986). A review of the recent liter-
rary tattoos. Arch. Dermatol. 136:1061–1062. ature uncovered no new studies regarding Phenyl Trimethicone,
but the Panel did consider updated information regarding uses REFERENCES
and use concentrations. The Panel determined to not reopen the Barry, B. W., S. M. Harrison, and P. H. Dugard. 1985. Vapour and liquid diffusion
safety assessment. of model penetrants through human skin; correlation with thermodynamic
activity. J. Pharm. Pharmacol. 37:226–236.
Phenyl Trimethicone uses have increased from 169 in 1981
Bushy Run Research Center. 1989. Propylene Carbonate: Nine-Day Aerosol
to 279 in 2002, based on industry voluntary reports provided Inhalation Study on Rats. Unpublished data. Project Report 51–633.19
to FDA (Elder 1986; FDA 2002). An industry survey in 2003 Bushy Run Research Center. 1990. Chronic Dermal Oncogenicity Studies in
indicated that use concentrations range from 0.0075% to 36% C3H/HeJ Mice. Unpublished data. Project Report 52–527.19
(CTFA 2004). The maximum value in that range is higher than Bushy Run Research Center. 1991. Propylene Carbonate: Fourteen-Week
Aerosol Inhalation Study on Rats with Neurotoxicity Evaluation. Unpub-
the maximum use concentration of 5% reported in 1981 (El- lished data. Project Report 52–637.19
der 1986). Table 17 presents the available use and concen- Central Toxicology Laboratory. 2001. Jeffsol Propylene Carbonate-
tration information for Phenyltrimethicone. The most recent NF: Eye Irritation Study in Rabbits. Unpublished data. Report
information now represents the present practice of use and CTL/FB5863/REG/REPT.19
concentration. Chemische Werke Huls Ag. 1979. Mutagenitatsontersuchung von Propylencar-
bonat mit Hilfe des Salmonella typhimurium/ Mirosoman-Mutagentats-Tests
The Panel considered the increased use concentrations in the nach Ames. Unpublished data. Report 41.19
context of the reproductive and developmental toxicity data in Elder, R. L., ed. 1987. Final Report on the Safety Assessment of Propylene
the original safety assessment. Phenyl Trimethicone was not ter- Carbonate. J. Am. Coll. Toxicol. 6(1):23–51.
atogenic at 500 mg/kg/day in rats and rabbits. For a 70-kg person, Gottschalck, T. E., and G. N. McEwen, Jr., eds. 2004. International Cosmetic In-
this dose corresponds to 35 g/day. At the current maximum use gredient Dictionary and Handbook, 10th ed., Vol. 2. Washington, DC: CTFA.
Kawanami, H., A. Sasaki, K. Matsui, and Y. Ikushima. 2003. A rapid and effec-
in lipsticks and the amount of lipstick used in a typical day, a tive synthesis of propylene carbonate using a supercritical CO2 -ionic liquid
dose of Phenyl Trimethicone was estimated to be 10 mg/day. system. Chem. Commun. 7:896–897.
This dose was 3500× lower than the observable effect level. Muzikar, J., T. Van de Goor, B. Gas, and E. Kenndler. 2001. Extension of the ap-
plication range of UV-absorbing organic solvents in capillary electrophoresis
by the use of contactless conductivity detector. J. Chromatogr. A 924:147–154.
REFERENCES Papciak, R. J., and V. T. Mallory. 1990. Acute Toxicological evaluation of propy-
lene carbonate. Acute Toxicity Data 1:15–16.
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2004. Concentration of
Pharmakon Research International, Inc. 1986. Acute Dermal Toxicity Study in
use—phenyl trimethicone. Unpublished data submitted by CTFA on May 10,
Rabbits. Unpublished data. Report PH 422-TX-006-86.19
2004. (2 pages).18
Pharmakon Research International, Inc. 1986. Micronucleus Test OECD. Un-
Elder, R. L. 1986. Final report on the safety assessment of Phenyl Trimethicone.
published data. Report PH 309-TX-004-85.
J. Am. Coll. Toxicol. 5:353–371.
Pharmakon Research International, Inc. 1988. Developmental Toxicity Study in
Rats. Unpublished data. Report PH 328-TX-001-88.19
ingredients. FDA database. Washington, DC: FDA.
Pharmakon Research International, Inc. 1988. Dose-Range-Finding Develop-
mental Toxicity Study in Rats. Unpublished data. Report PH-32DR-TX-001-
87.19
Pharmakon Research Interantional, Inc. 1988. Dose-Range-Finding 28-Day Oral
PROPYLENE CARBONATE Toxicity Study in Rats. Unpublished data. Report PH-436-TX-001-87.19
A safety assessment of Propylene Carbonate was published in Pharmakon Research International, Inc. 1989. Subchronic 90 Day Oral Toxicity
1987 with the conclusion that it is safe as a cosmetic ingredient Study in Rats. Unpublished data. Report PH-470-TX-001-88.19
Sutou, S. 1996. Achievements by CSGMT MMS: The collaborative study group
in the present practices of use and concentration (Elder 1987).
fo rthe micronucleus test in mammalian Mutagenesis Study Group for the
Studies published since the last assessment were reviewed along Environmental Mutagen Society of Japan. Mutat. Res. 340:151–174.
with updated information concerning frequency of use and use Ursin, C., C. M. Hansen, J. W. Van Dyk, P. O. Jensen, I. J. Christensen, and J.
concentrations. The CIR Expert Panel determined to not reopen Ebbehoej. 1995. Permeability of comericial solvents through living human
the safety assessment. skin. Am. Ind. Hyg. Assoc. J. 56:651–660.
Yamada, Y., M. Nakahara, M. Kohno, M. Otsuka, and O. Takaiti. 1989. Metabolic
Based on voluntary reports provided by industry to FDA,
fate of the new anti-ulcer drug enprostil in animals. 4th communication: Effect
there were 295 reported uses in 1981 (Elder 1987) and 178 on hepatic drug metabolizing enzyme system in rats. Arzneimittelforschung
reported uses in 2002 (FDA 2002). Use concentrations from an 39:356–360.
industry survey (CTFA 2003) ranged from 0.003% to 6%, not
very different from the use concentration range reported in 1981 POLYVINYLPYRROLIDONE/VINYL ACETATE
of ≤0.1% to >5% (Elder 1987). COPOLYMER
Table 18 presents the available use and concentration infor-
In 1983, the CIR Expert Panel concluded that this ingredient
mation for Propylene Carbonate. The most recent information
is safe as a cosmetic ingredient under the present practices of
constitutes present practices of use and concentration.
product and concentration use (Elder 1983). New studies avail-
able since that review have been considered by the Expert Panel,
18
Available for review: Director, Cosmetic Ingredient Review, 1101 19
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA.
TABLE 17
Historical and current cosmetic product uses and concentrations for Phenyl Trimethicone
Baby Care 1∗ — >0.1–1∗ —
Bath
Oils, tablets, and salts 1 1 >0.1–1 —
Other bath 2 — >1–5 —
Eye Makeup
Eyeliners — 1 — 2–6
Eye shadow 1 77 ≤0.1–5 4–13
Eye lotions — — — 0.008–1
Mascara 1 1 >0.1–1 0.1–0.4
Other eye makeup 1 4 >0.1–1 6–15
Fragrances
Perfumes — 1 — —
Other fragrances — — — 0.5
Conditioners 10 8 ≤0.1–5 0.3–2
Sprays 25 23 ≤0.1–1 0.1–18
Straighteners 1 — >1–5 —
Rinses 1 — >0.1–1 —
Shampoos — — — 1
Tonics, dressings, etc. 9 31 ≤0.1–5 5–11
Wave sets 2 — >0.1–5 —
Other noncoloring hair care 1 7 >0.1–1 0.5–2
Makeup
Blushers 11 1 >1–5 2–15
Face powders 2 9 >0.1–1 0.1–8
Foundations 2 17 >1–5 2–22
Leg and body paints — — — 2
Lipsticks 2 34 >1–5 0.08–36
Makeup bases 2 8 ≤0.1–5 —
Other makeup — 13 — 0.0075–22
Nail care
Creams and lotions — — — 0.5
Polishes and enamels 7 — >0.1–1 —
Personal hygiene
Other personal hygiene — 1 — —
Shaving
Aftershave lotions — 1 — 0.5–2
Preshave lotions 6 1 >0.1–5 2
Other shaving — — — 0.5
Skin care
Cleansing creams, lotions, etc. — 4 — 2–4
Face and neck skin care ∗∗ 3 ∗∗ 4–6
8 ≤0.1–1
Moisturizers 7 15 ≤0.1–5 0.8–3
Night skin care 1 ≤0.1 2
Other skin care 1 >1–5 2
Suntan
Suntan gels, creams, liquids and sprays 6 2 — 0.5–9
Indoor tanning 1 8 — 0.2–5
Other suntan 1 >1–5 2
Total uses/ranges for Phenyl Trimethicone 113 279 ≤0.1–5 0.0075–36
∗
Product categories within the group not given.
∗∗
TABLE 18
Current and historical uses and concentrations of Propylene Carbonate in cosmetics
Bath
Oils, tablets and salts 1 1 >1–5 —
Eye makeup
Eyebrow pencils 6 6 >1–5 0.3
Eyeliners 17 15 >1–5 0.2–0.6
Eye shadow 42 10 >0.1–5 0.4–1
Eye lotions 1 — >1–5 —
Mascara 34 22 >0.1–5 2–4
Other eye makeup 9 12 >0.1–5 0.5
Fragrances
Colognes and toilet waters 5 — >1–5 —
Perfumes 4 — >1–5 —
Conditioners 1 — >1–5 —
Tonics, dressings, etc. — 1 — —
Hair Coloring
Other hair coloring 3 1 >1–5 —
Makeup
Blushers 13 1 ≤0.1–>5 1–2
Face powders 1 — >1–5 0.4
Foundations 11 3 >0.1–5 0.6–2
Rouges — — — 0.1
Lipsticks 95 35 ≤0.1–>5 0.03–2
Makeup bases 13 4 >0.1–1 —
Makeup fixatives 1 2 >1–5 —
Nail care
Creams and lotions 1 — >1–5 —
Polish and enamel removers — 6 — 1
Personal hygiene
Underarm deodorants — 2 — 0.2–5
Other personal hygiene 4 26 ≤0.1–>5 —
Skin care
Cleansing creams, lotions, etc. 9 1 >1–5 0.1
1∗ >0.1–1∗
Body and hand skin care — —
Moisturizers 2 4 >1–5 0.02–0.2
Paste masks/mud packs — 1 — 0.3–2
Skin fresheners 1 — >0.1–1 —
Suntan preparations
Suntan gels, creams, and liquids 6 1 >1–5 0.08–0.2
Other suntan preparations 1 — >1–5 —
Total uses/ranges for Propylene Carbonate 295 178 ≤0.1–>5 0.003–5
∗
along with the most current information available on use and The Panel acknowledged that inhalation of Vinyl Acetate is
concentration. The Panel noted that most of the newly available associated with nasopharyngeal carcinoma. The mechanism of
data concern Vinyl Acetate. The Panel determined to not reopen action appears to be an irritant-hyperproliferative type which re-
this safety assessment. quires a threshold dose. Two factors suggest that threshold doses
As given in the 9th edition of the International Cosmetic In- could not be achieved from inhalation of cosmetics. First, the
gredient Dictionary and Handbook, the name of this ingredient VP/VA Copolymer is stable, even under adverse environmental
has been changed to VP/VA Copolymer (Pepe et al. 2002). conditions, so that there will be little, if any, Vinyl Acetate ac-
Based on voluntary reports provided by industry to FDA, tually present, especially since the maximum use concentration
there were 114 reported uses of this ingredient in 1976 (Elder is 12%. Second, the effects of inhaled aerosols depend on the
1983) and 210 reported uses in 2002 (FDA 2002). Use concen- specific chemical species, the concentration, the duration of ex-
trations from an industry survey (CTFA 2003) ranged from 0.3% posure, and site of deposition (Jensen and O’Brien 1993) within
to 68%, but these data were clarified to note that the product re- the respiratory system. Particle size is the most important factor
ported to contain 68% is no longer on the market. The actual affecting the location of deposition. The mean aerodynamic di-
current use concentration range is 0.3% to 12%, which is in the ameter of pump hair spray particles is approximately 80 μm, and
range of >0.1% to >50% reported in 1976 (Elder 1983). diameter of anhydrous hair spray particles is 60 to 80 μm. Typ-
Table 19 presents the available use and use concentration ically, less than 1% are below 10 μm, which is the upper limit
information. The most current data now represent the present for respirable particles (Bowen 1999). Based on the particle size,
practices of use. VP/VA Copolymers would not be respirable in formulation.
TABLE 19
Historical and current uses and use concentrations for VP/VA Copolymer
1976 uses 2002 uses 1976 use concentrations 2003 use concentrations
Eye makeup
Eyeliner — — — 0.3
Eye shadow — — — 2
Mascara 2 2 >1–5 6–9
Hair conditioners 17 12 >1–50 0.3
Hair sprays 27 26 >0.1–10 2–4
Permanent waves 1 — >0.1–1 —
Shampoos 2 1 >0.1–50 7
Tonics, dressings, etc. 6 87 >0.1–25 4–12
Wave sets 50 12 >0.1–>50 7
Other noncoloring hair care 4 52 >5–25 8
Hair coloring
Color sprays — 1 — 0.5
Bleaches 1 2 >1–5 —
Makeup
Makeup fixatives 1 — >0.1–1 4
Nail care
Cuticle softeners 1 — >1–5 —
Skin care
Body and hand skin care — 1 — —
Paste masks/mud packs — 2 — 10
Other skin care preparations 1 — >1–5 68∗
Total uses/ranges of VP/VA Copolymer 114 210 >0.1–>50 0.3–12
∗
This product no longer is marketed, so this use concentration is not included in the total range.
REFERENCES SAFFLOWER OIL

Bogdanffy, M. S., H. C. Dreef-Van Der Meulen, R. B. Beems, V. J. Feron, T. In 1985 the CIR Expert Panel concluded that this ingredient
C. Tascieri, T. R. Taylor, M. B. Vinegar, and R. W. Rickard. 1994. Chronic is safe as a cosmetic ingredient in the present practices of use
toxicity and oncogenicity inhalation study with vinyl acetate in the rat and
mouse. Fundam. Appl. Toxicol. 23:215–229.
(Elder 1985). Studies available since that safety assessment was
Bogdanffy, M. S., and M. L. Taylor. 1993. Kinetics of nasal carboxylesterase- completed, along with the updated information regarding uses
mediated metabolism of vinyl acetate. Drug Metab. Dispos. 21:1107–1111. and use concentrations were considered by the CIR Expert Panel.
Bogdanffy, M. S., T. R. Tyler, M. B. Vinegar, R. W. Rickard, F. M. Carpanini The Panel determined not to reopen this safety assessment.
and T. Cascieri. 1994. Chronic toxicity and oncogenicity study with vinyl
The terminology for this ingredient in the International
acetate in the rat: in utero exposure in drinking water. Fundam. Appl. Toxicol.
23:206–214. Cosmetic Ingredient Dictionary and Handbook (Gottshcalck
Bogdanffy, M. S., and R. Valentine. 2003. Differentiating between local cyto- and McEwen 2004) has changed. Safflower Oil is currently
toxicity, mitogenesis, and genotoxicity in carcinogen risk assessments: The Carthamus Tinctorius (Safflower) Seed Oil.
case of vinyl acetate. Toxicol. Lett. 140–141:83–98. Carthamus Tinctorius (Safflower) Seed Oil was used in 94
Bowen, D. 1999. Unpublished information on hair spray particle size provided
products in 1981, based on voluntary reports provided to FDA
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2002. Information re- by industry, and use concentrations ranged from less than 0.1%
garding VA/Crotonates Copolymer. Unpublished data submitted by CTFA on to greater than 50% (Elder 1985). In 2002 there were 142 uses
November 19, 2002. (1 page.)20 (FDA 2002) and according to an industry survey the current
CTFA. 2003. Concentrations of use VA/Crotonates Copolymer. Unpublished range of use concentrations is 0.00005% to 84% (CTFA 2004).
data submitted by CTFA on June 12, 2003. (1 page.)20
Table 20 presents the available use information. The most
Deese, D. E., and R. E. Joyner. 1969. Vinyl acetate: A study of chronic human
exposure. Am. Indust. Hygiene Assoc. J. 30:449–457. recent information is now considered to be the present practices
Elder, R. L. 1983. Final report on the safety assessment of vinyl polyvinylpyrroli- of use and concentration.
done/vinyl acetate copolymer. J. Am. Coll. Toxicol. 2:141–159.
Hurtt, M. E., M. B. Vinegar, R. W. Rickard, T. C. Cascieri and T. R. Tyler. 1995.
Developmental toxicity of oral and inhaled vinyl acetate in the rat. Fundam.
REFERENCES
Appl. Toxicol. 24:198–205. Cheng, J. L., M. Futkuchi, K. Ogawa, et al. 2003. Dose response study of con-
International Agency for Research on Cancer (IARC). 1995. Vinyl acetate. IARC jugated fatty acid derived from safflower oil on mammary and colon car-
Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to cinogenesis pretreated with 7,12-dimethylbenz[a]anthracene (DMBA) and
Humans. 63:443–466. 1,2-dimethylhydrazine (DMH) in female Sprague-Dawley rats. Cancer Lett.
Jensen, P. A., and D. O’Brien. 1993. Industrial Hygiene. In: Aerosol measure- 196:161–168.
ment. Principles techniques and applications, ed. K. Willeke, and P. A. Baron, Chiang T.-A., P.-F. Wu, and Y.-C. Ko. 1999. Identification of carcinogens in
New York: John Wiley and Sons, Inc., 538–540. cooking oil fumes. Environ. Res. 81:18–22.
Kuykendall, J. R., and M. S. Bogdanffy. 1992. Reaction kinetics of DNA-histone Cosmetic, Toiletry, and Fragrance Association (CTFA). 2004. Ingredient Use
crosslinking by vinyl acetate and acetaldehyde. Carcinogenesis. 13(11):2095– Data—Carthamus Tincoriums (Safflower) Seed Oil. Unpublished data sub-
2100. mitted by CTFA.21
Lahdetie, J. 1988. Effects of vinyl acetate and acetaldehyde on sperm morphol- Elder, R. L. Final Report on the Safety Assessment of Safflower Oil. J. Am. Coll.
ogy and meiotic micronuclei in mice. Mutat. Res. 202:171–178. Toxicol. 4:171–197.
Lijinsky, W., and M. D. Reuber. 1983. Chronic toxicity studies of vinyl acetate Food and Drug Administration (FDA). 2002. Frequency of use of cosmetic
in Fischer rats. Toxicol. Appl. Pharm. 68:43–53. ingredients. FDA database. Washington, DC: FDA.
Maki-Paakkanen, J., and H. Norppa. 1987. Induction of micronuclei by vinyl Gottschalk,T. E., and G. N. McEwen, Jr., eds. 2004. International Cosmetic
acetate in mouse bone marrow cells and cultured human lymphocytes. Mutat. Ingredient Dictionary and Handbook, 10th ed. Washington, DC: CTFA.
Res. 190:41–45. National Toxicology Program (NTP). 1994. Comparative Toxicology Studies
Maltoni, C., A. Ciliberti, G. Lefemine, and M. Soffritti. 1997. Results of a long- of Corn Oil, Safflower Oil, and Tricaprylin (CAS Nos. 8001-30-7, 800-23-8,
term experimental study on the carcinogenicity of vinyl acetate monomer in and 538-23-8) in male F344/N rats as vehicles for gavage. Final study report.
mice. Ann. N.Y. Acad. Sci. 837:209–238. PB 95103958.
Mebus, C. A., F. M. Carpanini, R. W. Rickard, T. C. Cascieri, T. R. Tyler, and Okuno M., T. Tanaka, C. Komaki, et al. 1998. Suppressive effect of low amounts
M. B. Vinegar. 1995. A two-generation reproduction study in rats receiving of safflower and perilla oils on diethylnitrosamine-induced hepatocarcinogen-
drinking water containing vinyl acetate. Fundam. Appl. Toxicol. 24:206–216. esis in male F344 rats. Nutr. Cancer 30:186–193.
Minardi, F., F. Belpoggi, M. Soffritti, A. Ciliberti, M. Lauriola, E. Cattin, and C.
Maltoni. 2002. Results of long-term carcinogenicity bioassay on vinyl acetate
monomer in Sprague-Dawley rats. Ann. N.Y. Acad. Sci. 982:106–122. SODIUM BORATE AND BORIC ACID
Norppa, H., F. Tursi, P. Pfaffli, J. Maki-Paakkanen, and H. Jarventaus. 1985.
Chromosome damage induced by vinyl acetate through formation of acetalde-
In 1983, the CIR Expert Panel concluded that Sodium Borate
hyde in human lymphocytes and Chinese ovary cells. Cancer Res. 45:4816– and Boric Acid, at concentrations ≤5%, are safe as cosmetic
4821. ingredients when used as currently recommended, but that cos-
Pepe, R. C., J. A. Wenninger, and G. N. McEwen. 2002. International Cosmetic metic formulations containing free Sodium Borate or Boric Acid
Ingredient Dictionary and Handbook, 9th ed. Washington, DC: CTFA. should not be used on infant or injured skin (Elder 1983). Stud-
Simon, P., J. G. Filser, and H. M. Bolt. 1985. Metabolism and pharmacokinetics
of vinyl acetate. Arch. Toxicol. 57(3):191–195.
ies available since that safety assessment was completed, along
20 21
Available for review: Director, Cosmetic Ingredient Review, 1101 Available for review: Director, Cosmetic Ingredient Review, 1101
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA.
TABLE 20
Historical and current cosmetic product uses and concentrations for Carthamus Tinctorius (Safflower) Seed Oil
Baby care
Lotions, oils, powders, and creams — — — 10
Bath
Oils, tablets, and salts 1 — >0.1–1 7
Other bath 2 1 >0.1–1 —
Eye makeup
Eye makeup remover 1 — >10–25 2
Mascara — — — 1
Other eye makeup 1 5 >0.1–1 6
Fragrances
Conditioners — 15 — —
Sprays/aerosol fixatives 1 2 >5–10 —
Shampoos — 5 — —
Tonics, dressings, etc. — 5 — 0.00005–27
Hair coloring
Other hair coloring — — — 1
Makeup
Blushers — — — 2
Foundations 6 2 >0.1–5 0.02–27
Lipsticks 4 18 ≤0.1–5 0.1–60
Makeup bases 5 3 — —
Nail care
Creams and lotions — 1 — —
Shaving
Skin Care
Face and neck skin care ∗ 4 ∗ 0.5–8
15 ≤0.1–50
Foot powders and sprays — — — —
Moisturizers 28 17 ≤0.1– >50 0.2–20
Paste masks/mud packs 1 3 >5–10 72
Skin fresheners 1 1 >0.1–1 —
Wrinkle smoothers∗∗ 1 — >25–50 —
Other 7 16 ≤0.1– >50 0.03
Suntan products
Suntan gels, creams, liquids and sprays 7 16 >0.1–>50 0.1
Indoor tanning preparations — 1 — —
Total uses/ranges for Carthamus Tinctorius 94 142 ≤0.1–>50 0.00005–84
(Safflower) Oil
∗
These categories were combined in 1981, but since have been separated.
∗∗
with the updated information regarding uses and use concen- tivity to boric acid treatment in CD-1 mice in utero. Reprod. Toxicol. 16:237–
trations were considered by the CIR Expert Panel. The Panel 243.
determined to not reopen this safety assessment. Cosmetic, Toiletry, and Fragrance Association (CTFA). 2002. Use concentra-
tions of Boric Acid and Sodium Borate as a function of product category–
Sodium Borate was used in 488 products in 1981, based on results of industry survey. Unpublished data submitted by CTFA.22
voluntary reports provided to FDA by industry; use concentra- Dieter, M. P. 1994. Toxicity and Carcinogenicity Studies of Boric Acid in Male
tions ranged from less than 0.1% to greater than 50% (Elder and Female B6C3F1 Mice. Environ. Health Perspect., 102:93–97.
1983). In 2002 there were 280 uses (FDA 2002) and according Fail, P. A., J. D. George, J. C. Seely, T. B. Grizzle, and J. J. Heindel. 1991.
to an industry survey the current range of use concentrations is Reproductive toxicity of boric acid in Swiss (CD-1) mice: Assessment
using the continuous breeding protocol. Fundam. Appl. Toxicol. 17:225–
0.1% to 3% (CTFA 2002). 239.
Boric Acid was used in 142 ingredients in 1981, based on Fisher, R. S., and J. C. Middleton. 1984. Dermatitis following ingestion of
voluntary reports provided to FDA by industry, and use concen- diuretics and boric acid. J. Am. Acad. Dermatol. 11:146–147.
trations ranged from less than 0.1% to greater than 50% (Elder Fukuda, R., M. Hirode, I. Mori, F. Chatani, H. Morishima, and H. Mayahara.
2000. Collaborative work to evaluate toxicity on male reproductive organs by
1985). In 2002 there were 77 uses (FDA 2002) and according
repeated dose studies in rats 24). Testicular toxicity of boric acid after 2- and
to an industry survey the current range of use concentrations is 4-week administration periods. J. Toxicol. Sci. 25(special issue):233–239.
0.1% to 2% (CTFA 2002). Garabrant, D. H., L. Bernstein, J. M. Peters, and T. J. Smith. 1984. Respiratory
Table 21 presents the available usage and use concentration and eye irritation from boron oxide and boric acid dusts. J. Occup. Med.
information as a function of cosmetic product category for both 26:584–586.
Garabrant, D. H., L. Bernstein, J. M. Peters, T. J. Smith, and W. E. Wright. 1985.
ingredients.
Respiratory effects of borax dust. Br. J. Ind. Med. 42:831–837.
Significant among the new studies considered by the CIR Heindel, J. J., C. J. Price, and B. A. Schwetz. 1994. Developmental toxicity
Expert Panel are those on the reproductive and developmen- of boric acid in mice, rats, and rabbits. Environ. Health Perspect. 102(suppl.
tal toxicity of Boric Acid. Under the auspices of the National 7):107–112.
Toxicology Program, Fail et al. (1991) reported results of a re- Hu, X., D. H. Wegman, E. A. Eisen, and S. R. Woskie. 1993. Application of
an event marker in the occupational epidemiologic study of acute irritant
productive assessment by continuous breeding protocol in which
symptoms. Epidemiology 4:266–270.
Boric Acid administered to rats in their feed was determined to Hu, X., D. H. Wegman, E. A. Eisen, S. R. Woskie, and R. G. Smith. 1992. Dose
be a reproductive toxicant. The NOAEL was suggested to be related acute irritant symptom responses to occupational exposure to sodium
110 mg/kg day−1 and the LOAEL was 598 mg/kg day−1 . Price borate dusts. Br. J. Ind. Med. 49:706–713.
et al. (1997) reported results of another rat feeding study with a Ishii, Y., N. Fujizuka, T. Takahashi, K. Shimizu, A. Tuchida, S. Yano, T. Naruse,
NOEAL of 10 mg/kg day−1 and a LOEAL of 13 mg/kg day−1 and T. Chishiro. 1993. A fatal case of acute boric acid poisoning. J. Toxicol.
Clin. Toxicol. 31:345–352.
for decreased fetal body weight per litter. Yoshizaki et al. (1999) Ku, W. W., R. E. Chapin, R. F. Moseman, R. E. Brink, K. D. Pierce, and K. Y.
reported that an oral study using rats resulted in a NOAEL of Adams. 1991. Tissue disposition of boron in male Fischer rats. Toxicol. Appl.
50 mg/kg day−1 and a LOAEL of 150 mg/kg day−1 for reduced Pharmacol. 111:145–151.
sperm counts and the same NOAEL and LOAEL values for re- Ku, W. W., R. E. Chapin, R. N. Wine, and B. C. Gladen. 1993a. Testicular
toxicity of boric acid (BA): Relationship of dose to lesion development and
duced implants and viable embryos.
recovery in the F344 rat. Reprod. Toxicol. 7:305–319.
The CIR Expert Panel considered that these findings do not Ku, W. W., L. M. Shih, and R. E. Chapin. 1993. The effects of boric acid (BA)
suggest any reason for concern in the context of current use on testicular cells in culture. Reprod. Toxicol. 7:321–331.
concentrations and the low dermal absorption through intact Kudo, S., H. Tanase, M. Yamasaki, M. Nakao, Y. Miyata, K. Tsuru, and S. Imai.
skin. These findings reinforce the Panel’s prior determination 2000. Collaborative work to evaluate toxicity on male reproductive organs
by repeated dose studies in rats 23). A comparative 2- and 4-week repeated
that these ingredients should not be used on damaged skin, i.e.,
oral dose testicular toxicity study of boric acid in rats. J. Toxicol. Sciences 25
skin in which the barrier function has been compromised by (special issue):223–232.
disease or injury. Landolph, J. R. 1985. Cytotoxicity and negligible genotoxicity of borax and
borax ores to cultured mammalian cells. Am. J. Indust. Med. 7:31-44.
Linden, C. H., A. H. Hall, K. W. Kulig, and B. H. Rumack. 1986. Acute ingestions
REFERENCES of boric-acid. J. Toxicol. Clin. Toxicol. 24:269–280.
Astier, A., F. Baud, and A. Fournier. 1988. Toxicokinetics of boron after an Linder, R. E., L. F. Strader, and G. L. Rehnberg. 1990. Effect of acute exposure
acute poisoning (translated from the French). J. Pharm. Clin. 7(special issue to boric acid on the male reproductive system of the rat. J. Toxicol. Environ.
II):57–62. Health. 31:133–146.
Ban, Y., M. Naya, T. Nishimura, M. Kaneto, K. Kishi, T. Inoue, H. Yoshizaki, Linder, R. E., L. F. Strader, V. L. Slott, and J. D. Suarez. 1992. Endpoints of sper-
and Y. Ooshima. 2001. Collaborative study on rat sperm motion analysis using matotoxicity in the rat after short duration exposures to fourteen reproductive
CellSoft Series 4000 semen analyzer. J. Toxicol. Sci. 26:9–24. toxicants. Reprod. Toxicol. 6:491–505.
Benson, W. H., W. J. Birge, and H. W. Dorough. 1984. Absence of mutagenic Miyazaki, T., M. Yashiki, Y. Iwasaki, T. Kojima, H. Ito, and A. Yoshida. 1992.
activity of sodium borate (borax) and boric acid in the Salmonella typhimurium A case of death from boric acid poisoning (translated from Japanese). Res.
preincubation test. Environ. Toxicol. Chem. 3:209–214. Pract. Forensic Med. 35:173–176.
Chapin, R. E., and W. W. Ku. 1994. The reproductive toxicity of boric acid.
Environ. Health Perspect. 102:87–91.
Chapin, R. E., W. W. Ku, M. A. Kenney, and H. McCoy. 1998. The effects of
22
dietary boric acid on bone strength in rats. Biol. Trace Elem. Res. 66:395–399. Available for review: Director, Cosmetic Ingredient Review, 1101
Cherrington, J. W., and N. Chernoff. 2002. Periods of vertebral column sensi- 17th Street, NW, Suite 412, Washington, DC 20036-4702, USA.
TABLE 21
Historical and current uses and use concentrations for Sodium Borate and Boric Acid
Sodium Borate
Baby care
Lotions, oils, powders, creams 1 — 0.1–1 —
Bath
Soaps and detergents 1 1 >0–0.1 20a
Bath oils, tablets, salts 3 — 1–50 —
Bubble baths 10 — 10–50 —
Eye makeup
Eyeliner 14 1 0.1–5 —
Eye shadow — — — 0.2
Eye lotion 2 — 0.1–1 —
Eye makeup remover 5 2 >0–5 —
Mascara 24 12 0.1–10 0.6
Other eye makeup 4 1 0.1–1 2
Fragrances
Other fragrances 4 1 >0–1 —
Noncoloring Hair Care
Conditioners 3 2 0.1–1 0.6
Sprays 1 — 1–5 —
Straighteners 2 — 1–5 —
Permanent waves 16 5 0.1–10 —
Shampoos 2 1 0.1–1 —
Wave sets 3 — >0–1 —
Other hair care 3 1 0.1–10 —
Hair coloring
Other hair coloring 3 — 0.1–1 —
Makeup
Blushers 2 2 0.1–1 0.2
Face powders — 1 — —
Foundations 4 3 0.1–1 0.2–0.5
Lipstick 1 — 0.1–1 —
Makeup bases 19 15 0.1–5 —
Other makeup 1 — 0.1–1 1
Nail care
Nail creams and lotions 2 — 0.1–1 —
Oral hygiene
Dentifrices — 3 — —
Mouthwashes and breath fresheners — 1 — —
Personal hygiene
Underarm deodorants 2 — >0–1 —
Other personal hygiene 8 6 5–>50 0.1
Shaving
Aftershave lotions 2 — >0–0.1 —
Shaving cream 4 8 0.1–5 —
Other shaving 1 1 0.1–1 —
TABLE 21
Historical and current uses and use concentrations for Sodium Borate and Boric Acid (Continued)
Skin care
Cleansing creams, lotions, etc. 144 68 >0–5 0.4–1
Depilatories 1 — 0.1–1 —
71b >0–5b
Moisturizers 47 31 >0–5 0.3–1
Night skin care 37 22 >0–1 0.4–0.9
Paste masks/mud packs 3 6 1–5 0.2–3
Fresheners 12 4 >0–1 0.3
Other skin care 1 23 >0–>50 0.6–0.8
Skin lightenersc 1 NAc 0.1–1 NAc
Hormone productsc 2 NAc 0.1–5 NAc
Wrinkle smoothingc 4 NAc 0.1–5 NAc
Suntan
Suntan gels, creams, liquids 5 5 0.1–1 0.4
Total uses/ranges for Sodium Borate 488 280 >0–>50 0.1–3
Boric Acid
Baby Care
Baby shampoos 1 — 0.1–1 —
Bath
Soaps and detergents 1 — 1–5
Oils, tablets, and salts 1 1 0.1–1 —
Bubble baths — 1 — —
Eye makeup
Eye lotion 1 — 1–5 —
Eye makeup remover 3 4 0.1–5 —
Fragrances
Powders 13 7 0.1–5 —
Other fragrances 1 — 0.1–1 —
Conditioners — 1 — 2
Permanent waves 13 5 0.1–5 —
Rinses 1 — 1–5 —
Shampoos 13 8 0.1–5 —
Wave sets 2 3 >0–5 —
Other hair care 3 — 0.1–5 —
Hair coloring
Coloring rinses 14 — 1–10 —
Bleaches — 3 — —
Other hair coloring 3 — 0.1–5 —
Makeup
Blushers 2 — 0.1–1 —
Face powders 1 1 0.1–1 —
Rouges 1 — 0.1–1 —
Makeup fixatives 2 2 1–5 —
TABLE 21
Historical and current uses and use concentrations for Sodium Borate and Boric Acid (Continued)
Oral hygiene
Mouthwashes and breath fresheners 5 — >0–5 —
Personal hygiene
Underarm deodorants 5 2 1–10 —
Douches 5 1 >50 10c
Other personal hygiene 1 2 0.1–1 —
Shaving
Aftershave lotions 5 5 >0–5 0.4
Preshave lotions 1 — >0–0.1 —
Shaving cream 6 4 0.1–5 0.1–1
Other shaving 1 1 0.1–1 —
Skin care
Cleansing creams, lotions, etc. 4 2 0.1–5 —
5b 0.1–5b
Foot powders and sprays — 1 — —
Moisturizers 4 2 0.1–5 0.5
Night skin care 1 1 0.1–1 —
Paste masks/mud packs 3 3 0.1–5 —
Skin fresheners 17 6 >0–5 —
Other skin care — 1 — —
Total uses/ranges of Boric Acid 142 77 >0–>50 0.1–2
a
Diluted to about 0.3% Sodium Borate during use.
b
These categories were combined in 1981 but are now separate.
c
No longer considered as cosmetic product categories.
d
Powder dissolved in water to produce a solution of about 0.1% Boric Acid before use.
Moore, J. A., and an Expert Scientific Committee. 1997. An assessment of boric Schillinger, B. M., M. Berstein, L. A. Goldberg, and A. R. Shalita. 1982. Boric
acid and borax using the IEHR (Institute for Evaluating Health Risks) eval- acid poisoning. J. Am. Acad. Dermatol. 7:667–673.
uative process for assessing human developmental and reproductive toxicity Schou, J. S., J. A. Jansen, and B. Aggerbeck. 1984. Human pharmacokinetics
of agents. Reprod. Toxicol. 11:123–160. and safety of boric acid. Arch. Toxicol. Suppl. 7:232–235.
Murray, F. J. 1998. A comparative review of the pharmacokinetics of boric acid Siegel, E. 1986. Boric-acid toxicity. Pediatr. Clin. N. Am. 33:363–368.
in rodents and humans. Biol. Trace Elem. Res. 66:331–341. Siegel, E., and S. Wason. 1986. Boric acid toxicity. Pediatr. Clin. N. Am. 33:363–
Nartosky, M. G., J. E. Schmid, J. E., Andrews, and R. J. Kavlock. 1998. Effects 367.
of boric acid on axial skeletal development in rats. Biol. Trace Elem. Res. Stüttgen, G., T. Siebel, and B. Aggerbeck. 1982. Absorption of boric acid through
66:373–394. human skin depending on the type of vehicle. Arch. Dermatol. Res. 272:21–
O’Sullivan, K., and M. Taylor. 1983. Chronic boric acid poisoning in infants. 29.
Arch. Dis. Child. 58:737–739. Sylvain, I. C., J. P. Berry, and P. Galle. 1998. Ultrastructural apoptotic lesions
Pahl, M. V., B. D. Culver, P. L. Strong, F. J. Murray, and N. D. Vaziri. 2001. The induced in rat thymocytes after borax ingestion. Anticancer Res. 18:2455–
effect of pregnancy on renal clearance of boron in humans: A study based on 2461.
normal dietary intake of boron. Toxicol. Sci. 60:252–256. Treinen, K. A., and R. E. Chapin. 1991. Development of testicular lesions in
Price, C. J., M. C. Marr, C. B. Myers, J. J. Heindel, and B. A. Schwetz. 1996. De- F344 rats after treatment with boric acid. Toxicol. Appl. Pharmacol. 107:325–
velopmental toxicity of boric acid (BORA) in rabbits. Fundam. Appl. Toxicol. 335.
34:176–187. Vaziri, N. D., F. Oveisi, B. D. Culver, M. V. Pahl, M. E., Andersen, P. L. Strong,
Price, C. J., P. L. Strong, M. C. Marr, C. B. Myers, and F. J. Murray. 1996. and F. J. Murray. 2001. The effect of pregnancy on renal clearance of boron
Developmental toxicity NOAEL and postnatal recovery in rats fed boric acid in rats given boric acid orally. Toxicol. Sci. 60:257–263.
during gestation. J. Am. Coll. Toxicol. 14:179–193. Wester, R. C., X. Hui, H. I. Maibach, K. Bell, M. J. Schell, D. J. Northington, P.
Price, C. J., P. L. Strong, F. J. Murray, and M. M. Goldberg. 1997. Blood boron Strong, and B. D. Culver. 1998. In vivo percutaneous absorption of boron as
concentrations in pregnant rats fed boric acid throughout gestation. Reprod. boric acid, borax, and disodium octaborate tetrahydrate in humans: A sum-
Toxicol. 11:833–842. mary. Biol. Trace Elem. Res. 66:101–109.
Restuccio, A., M. E. Mortensen, and M. T. Kelley. 1992. Fatal ingestion of boric Wester, R. C., T. Hartway, H. I. Maibach, M. J. Schell, D. J. Northington, B.
acid in an adult. Am. J. Emerg. Med.10:545–547. D. Culver, and P. L. Strong. 1998. In vitro percutaneous absorption of boron
as boric acid, borax, and disodium octaborate tetrahydrate in human skin: A Hayashi, M. M. Kishi, T. Sofuni, and M. Ishidate. 1988. Micronucleus tests in
summary. Biol. Trace Elem. Res. 66:111–120. mice on 39 food additives and eight miscellaneous chemicals. Food Chem.
Yoshizaki, H., Y. Izumi, C. Hirayama, A. Fujimoto, H. Kandori, T. Sugitani, and Toxicol. 26:487–500.
Y. Ooshima. 1999. Availability of sperm examination for male reproductive Ishidata, M., T. Sofuni, W. A. Yoshika, M. Hayashi, T. Nohmi, M. Sawada,
toxicities in rats treated with boric acid. J. Toxicol. Sci. 24:199–208. and A. Matsuoka. 1984. Primary mutagenicity screening of food additives
currently used in Japan. Food Chem. Toxicol. 22:623–636.
Registry of Toxic Effects of Chemical Substances (RTECS). 1997. Dehy-
SODIUM DEHYDROACETATE AND DEHYDROACETIC droacetic Acid entry. RTECS database. Bethesda, MD: National Library of
ACID Medicine.
Sugihara, N., K. Shimomichi, and K. Furuno. 1997. Cytotoxicity of food preser-
A safety assessment of Sodium Dehydroacetate and Dehy- vatives in cultured rat hepatocytes loaded with linolenic acid. Toxicology.
droacetic Acid was published in 1985 with the conclusion that 120(1):29–36.
these ingredients are safe as cosmetic ingredients in the present Tanaka, S., K. Kawashima, S. Nakaura, S. Djajalaksana, and A. Takanaka. 1988.
practices of use and concentration (Elder 1985). Studies avail- Studies on the teratogenic potential of sodium dehydroacetate in rats. Bull.
able since that safety assessment was completed, along with up- Natl. Inst. Hyg. Sci. (Tokyo). 0(106):54–61.
Tomei, F., S. Iavicoli, A. Iavicoli, B. Papaleo, and T.P. Baccolo. 1995. Liver
dated information regarding uses and use concentrations were damage in pharmaceutical industry workers. Arch. Environ. Health. 50:293–
considered by the CIR Expert Panel. The Panel determined to 297.
not reopen this safety assessment. Uchida, O., K. Naito, K. Yasuhara, et al. 1985. Studies on the acute oral toxicity
Sodium Dehydroacetate was used in 260 products in 1981, of dehydroacetic-acid sorbic-acid and their combination compound in rats.
based on voluntary reports provided to FDA by industry; use con- Bull. Natl. Inst. Hyg. Sci. (Tokyo). 0(103):166–171.
Uchida, O., T. Ochiai, K. Naito, K. Yasuhara, K. Takada, T. Furuya, K.
centrations ranged from less than 0.1% to 1% (Elder 1985). In Kobayashi, Y. Ikeda, and M. J. Tobe. 1986. Study on the inhibitory effect of
2002 there were 325 uses (FDA 2002) and according to an indus- sodium dehydroacetate on the hepatocarcinogenicity of 4 dimethylaminoa-
try survey the current range of use concentrations is 0.00003% zobenzene in the rat. Food Hyg. Soc. Jpn. 27:466–473.
to 0.5% (CTFA 2002). Yamaguchi, T. 1987. Mutagen formation on photolysis of dehydroacetic acid.
Dehydroacetic Acid was used in 139 products in 1981, based Agric. Biol. Chem. 51:167–172.
Zeiger, E., B. Anderson, S. Haworth, T. Lawlor, K. Mortelmans, and W. Speck.
on voluntary reports provided to FDA by industry; use concen- 1987. Salmonella mutagenicity tests. 3. Results from the testing of 255 chem-
trations ranged from less than 0.1% to 1% (Elder 1985). In 2002 icals. Environ. Mutagen. 9:1–110.
there were 88 uses (FDA 2002) and according to an industry sur-
vey the current range of use concentrations is 0.007% to 0.7%
(CTFA 2002). SODIUM LAURYL SULFOACETATE
Table 22 presents the available use and concentration infor- A safety assessment on Sodium Lauryl Sulfoacetate was pub-
mation. The most recent information now constitutes the present lished in 1987 with the conclusion “On the basis of the available
practices of use. data presented in this report, the Expert Panel concludes that
Sodium Lauryl Sulfoacetate is safe as a cosmetic ingredient in
the present practices of use and concentration” (Elder 1987).
REFERENCES
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2003. Use concentra-
Studies available since that safety assessment was completed,
tion data on Sodium Dehydroacetate and Dehydroacetic Acid from industry along with updated information regarding uses and use con-
survey. Unpublished data submitted by CTFA, October, 2003. (1 page.)23 centrations, were considered by the CIR Expert Panel. After
De Groot, A. C., J. W. Weyland, J. D. Bos, and B. A. Jagtman. 1986. Contact reviewing the available data, the Panel determined to not reopen
allergy to preservatives I. Contact Dermatitis 14:120–122. this safety assessment.
Elder, R. L., ed. 1985. Final report on the safety assessment of Sodium Dehy-
droacetate and Dehydroacetic Acid. J. Am. Coll. Toxicol. 4:123–159.
Sodium Lauryl Sulfoacetate was used in 93 products in 1981,
Food and Drug Administration (FDA). 2002. Food additives permitted for di- based on voluntary reports provided to FDA by industry; use
rect addition to food for human consumption. Code of Federal Regulations concentrations ranged from >0.1% to >50% (Elder 1985). In
21CFR172.130:30–31. 2002 there were 68 uses (FDA 2002) and according to an in-
Fujita, H., and M. Sasaki. 1986. Mutagenicity test of food additives with dustry survey in 2004 the current range of use concentrations is
Salmonella Typhimurium TA97a and TA102. Kenkyu Nenpo-Tokyo-Toritsu
Eisei Kenkyusho 37:447–452.
0.6% to 21% (CTFA 2004).
Gazzaniga, A., M. E. Sangalli, F. Giordano, U. Conte, A. Semenzato, and A. Table 23 presents the available use and concentration infor-
Bettero. 1994. Controlled release of dehydroacetic acid sodium salt for the mation. The most recent information now constitutes the present
stability improvement of cosmetic formulations. Int. J. Cosmet. Sci. 16:105– practices of use.
112. The CIR Expert Panel did note that Stepan Company had
Hasegawa, R., Y. Nakaji, Y. Kurokawa, and M. Tobe. 1989. Acute toxicity tests
on 113 environmental chemicals. Sci. Rep. Res. Inst. Tohoku Univ. Ser. C Med.
submitted robust summaries and test plans on Sodium Lauryl
36:10–16. Sulfoacetate as part of EPA’s high production volume chemical
testing program. This submission argued that the only miss-
ing data were reproductive and developmental toxicity data.
23
Available for review: Director, Cosmetic Ingredient Review, 1101 The company proposed conducting such a study. Though the
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. Panel noted that there are no data in the published literature,
TABLE 22
Historical and current uses and use concentrations for Sodium Dehydroacetate and Dehydroacetic Acid
Sodium Dehydroacetate
Baby care
Lotions, oils, powders & creams — — — 0.6
Bath
Oils, tablets, and salts 1 — ≤0.1 —
Eye makeup
Eyebrow Pencil — — — 0.2–0.3
Eyeliner 2 4 ≤0.1–1 0.05–0.5
Eye shadow 56 74 ≤0.1–1 0.05–0.3
Eye lotion — 3 — —
Eye makeup remover — 1 — 0.05
Mascara 13 16 ≤0.1–1 0.001–0.4
Other eye makeup 4 12 >0.1–1 0.0006–0.4
Fragrances
Powders 1 3 >0.1–1 —
Colognes and toilet waters — — — 0.001–0.5
Conditioners — — — 0.2
Shampoos — 2 — 0.2
Hair coloring
Tints — 1 — —
Makeup
Blushers 22 15 ≤0.1–1 0.1–0.4
Face powders 23 31 ≤0.1–1 0.05–0.4
Makeup foundations 8 10 ≤0.1–1 0.0001–0.4
Makeup bases 14 6 >0.1–1 0.1
Leg and body paints — — — 0.1
Lipstick — 1 — 0.3
Rouges 2 — ≤0.1–1 —
Other makeup 2 4 >0.1–1 0.0003–0.2
Nail care
Basecoats and undercoats — — — 0.02
Nail creams and lotions — 3 — —
Cuticle Softeners 4 2 >0.1–1 —
Creams and lotions 2 — ≤0.1–1 —
Other nail care 1 — >0.1–1 0.2
Personal hygiene
Shaving
Shaving cream 1 4 >0.1–1 —
Other shaving 1 1 >0.1–1 —
Aftershave lotions 1 1 ≤0.1 0.0003
TABLE 22
Historical and current uses and use concentrations for Sodium Dehydroacetate and Dehydroacetic Acid (Continued)
Product category (Elder 1985) (FDA 2002) (Elder 1985) (%) (CTFA 2003) (%)
Skin care
Skin-cleansing preparations 23 13 ≤0.1–1 0.0003–0.3
Face and neck skin care ∗ 4 ∗ 0.008–0.2
24 ≤0.1–1
Moisturizers 27 39 ≤0.1–1 0.001–0.3
Night skin care 7 5 ≤0.1 0.003–0.2
Paste masks/mud packs 4 6 ≤0.1–1 0.03–0.2
Fresheners 2 2 >0.1–1 —
Other skin care — 25 — 0.00003–0.1
Skin lighteners∗∗ 2 —∗∗ ≤0.1–1 —∗∗
Wrinkle smoothers∗∗ 1 —∗∗ >0.1–1 —∗∗
Suntan
Suntan gels, creams, and liquids 5 1 >0.1–1 0.2
Indoor tanning preparations 3 2 ≤0.1–1 0.4
Other suntan preparations 3 2 >0.1–1 0.1
Total uses/ranges for Sodium Dehydroacetate 260 325 ≤0.1–1 0.00003–0.6
Dehydroacetic Acid
Bath
Soaps and detergents — — — 0.03
Oils, tablets and salts 1 — ≤0.1 —
Bubble baths 2 1 ≤0.1 —
Eye makeup
Eyeliner 1 — >0.1–1 0.1
Eye shadow 11 4 ≤0.1–1 0.3
Eye lotion — — — 0.2
Eye makeup remover 8 5 ≤0.1–1 0.1
Mascara 1 — >0.1–1 0.2
Other eye makeup 9 — ≤0.1–1 —
Fragrances
Colognes and toilet waters 4 — ≤0.1 —
Perfumes 4 — ≤0.1 —
Shampoos 2 — ≤0.1 0.02–0.03
Tonics, dressings, etc. 2 1 ≤0.1–1 —
Makeup
Blushers 5 1 ≤0.1–1 0.05–0.2
Face powders 6 3 ≤0.1–1 0.7
Makeup foundations 13 3 ≤0.1–1 0.1
Makeup bases 1 — ≤0.1 —
Rouges 1 1 >0.1–1 —
Lipstick 1 — ≤0.1 —
Other makeup 1 — ≤0.1 0.07
Nail care
Polish and enamel — 1 — —
Personal hygiene
Other personal hygiene — — — 0.03
TABLE 22
Historical and current uses and use concentrations for Sodium Dehydroacetate and Dehydroacetic Acid (Continued)
Skin care
Cleansing creams, lotions, etc. 15 8 ≤0.1–1 0.007–0.02
Face and neck skin care 11 0.01–0.08
16* ≤0.1–1∗
Moisturizers 10 10 ≤0.1–1 —
Night skin care 5 2 ≤0.1–1 0.03
Paste masks/mud packs 3 6 ≤0.1–1 —
Other skin care 9 16 ≤0.1–1 0.03
Wrinkle smoothers∗∗ 2 —∗∗ ≤0.1 —∗∗
Suntan
Suntan gels, creams, and liquids 3 — >0.1–1 0.2
Indoor tanning preparation — 5 — —
Other suntan preparations 1 — >0.1–1 —
Total Uses/Ranges for Dehydroacetic Acid Totals 139 88 ≤0.1–1 0.007–0.7
∗
These categories were combined in 1981 but are now separate.
∗∗
No longer considered as cosmetic product categories.
which suggest that the reproductive and developmental tox- SODIUM SESQUICARBONATE, SODIUM
icity potential of Sodium Lauryl Sulfoacetate is an issue, BICARBONATE, AND SODIUM CARBONATE
it was agreed that the results of the proposed reproductive A safety assessment of Sodium Sesquicarbonate, Sodium Bi-
and developmental toxicity study would be considered when carbonate, and Sodium Carbonate was published in 1987 with
available. the conclusion that these ingredients are safe as presently used
in cosmetic products (Elder 1987). Studies available since that
safety assessment was completed, along with updated informa-
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Cosmetic, Toiletry, and Fragrance Association (CTFA). 2004. Use concentration the CIR Expert Panel. After reviewing the available data, the
data on sodium lauryl sulfoacetate from industry survey. Unpublished data
Panel determined to not reopen this safety assessment.
submitted by CTFA, 2004 (1 page.)24
Elder, R. L. 1987. Final report on the safety assessment of sodium lauryl sul- Sodium Sesquicarbonate was used in 111 products in 1981,
foacetate. J. Am. Coll. Toxicol. 6:261–277. based on voluntary reports provided to FDA by industry; use
Environmental Protection Agency (EPA). 2004. High Production Volume concentrations ranged from >1% to 50% (Elder 1985). In 2002
(HPV) Challenge Program. Robust summaries & test plans: sodium lau- there were 24 uses (FDA 2002) and according to an industry
ryl sulfoacetate (acetic acid, sulfo-, 1-dodecyl ester sodium salt). Internet
survey in 2004 the current range of use concentrations is 2.0%
site accessed August, 2004. http://www.epa.gov/chemrtk/sdmlaurl/c14936tc.
html. to 90% (CTFA 2004).
Food and Drug Administration (FDA). 2002. Frequency of use of cosmetic Sodium Bicarbonate was used in 45 products in 1981, based
ingredients. FDA database. Washington, DC: FDA. on voluntary reports provided to FDA by industry; use concen-
Gottschalck, T. E., and G. N. McEwen, Jr., eds. 2004. International Cosmetic In- trations ranged from less than 0.1% to 50% (Elder 1985). In
gredient Dictionary and Handbook, 10th ed., Washington, DC: CTFA. 1743.
2002 there were 70 uses (FDA 2002) and according to an in-
Nikitakis, J. M., and G. N. McEwen, Jr., eds. 1990. CTFA Compendium of
Cosmetic Ingredient Composition—Descriptions I and II. Washington, DC: dustry survey in 2004 the current range of use concentrations is
CTFA. 0.006% to 95% (CTFA 2004).
NOTOX Safety and Environmental Research BV. 2003. HPV assessment re- Sodium Carbonate was used in 25 products in 1981, based
port and test plan for sodium lauryl sulfoacetate (acetic acid, sulfo-, 1- on voluntary reports provided to FDA by industry; use concen-
dodecyl ester sodium salt) CAS 1847-58-1. Prepared for: Stepan Com-
trations ranged from less than 0.1% to 25% (Elder 1985). In
pany, Northfield, IL. Appendix A. Hambakenwetering: NOTOX, 1–
24.24 2002 there were 21 uses (FDA 2002) and according to an in-
dustry survey in 2004 the current range of use concentrations is
0.000002% to 51% (CTFA 2004).
Table 24 presents the available use and concentration infor-
24
Available for review: Director, Cosmetic Ingredient Review, 1101 mation. The most recent information now constitutes the present
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. practices of use.
TABLE 23
Historical and current cosmetic product uses and concentrations for Sodium Lauryl Sulfoacetate
Baby care
Lotions, oils, powders, and creams — — — 1
Bath
Oils, tablets and salts 1 13 >1–5 5–21
Soaps and detergents — — — 0.6–4
Bubble baths 85 21 >1–>50 6–10
Fragrances
Shampoos — 1 — 1–5
Hair coloring
Bleaches — 2 — —
Nail care
Oral hygiene
Dentifrices 3 1 >0.1–5 —
Other oral hygiene — — — 0.7*
Personal hygiene
Douches — — — 2
Other personal hygiene 1 — >0.1–1 2
Shaving
Shaving cream — — — 2
Skin care products
Cleansing creams, lotions, etc. 2 2 >1–25 4
Body and hand skin care — — — 2
Foot powders and sprays — — — 3
Other skin care 1 — >5–10 —
Total uses/ranges for Sodium Lauryl Sulfoacetate 93 68 >0.1–>50 0.6–21
∗
A denture cleanser.
REFERENCES Depasquale, D. A., A. El-Nanarawy, D. Rosen, and T. J. Montville. 1990. Am-

Akpaffiong, M. J. 1987. Natriuretic and Blood Pressure Effects of Trona in the monium bicarbonate inhibition of mycotoxigenic fungi and spoliage yeasts.
Rat. West Afr. J. Pharmacol. Drug Res. 7:9–14. J. Food Prot. 53:324–328.
Canadian Centre for Occupational Health and Safety. 2004. Sodium Carbonate Einhorn, A., L. Horton, L. Altieri, M. Ochsenschlager, and B. Klein. 1989. Se-
Chemical Profile. http://www.intox.org Accessed on 11/8/2004. rious respiratory consequences of detergent ingestions in children. Pediatrics
Clayton, G. D., and F. E. Clayton, eds. 1994. Patty’s Industrial Hygiene and 84(3):472–474.
Toxicology. Vol. 2A, 2B, 2C, 2D, 2E, and 2F. 4th ed., 770. Emebiri, L. C., and M. I. Nwufo. 1990. Effect of Trona (urao) on the survival
Cooper, D. J., K. R. Walley, B. R. Wiggs, and J. A. Russell. 1990. Clinical study and reproduction of Sitophilus zeamais and Tribolium castaneum on stored
on bicarbonate. Ann. Intern. Med. 112:492–498. maize. Agric. Ecosyst Environ. 32:69–76.
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2004. Concentration of Gosselin, R. E., H. C. Hodge, R. P. Smith, and M. N. Gleason. 1976. Clinical
Use–Sodium Sesquicarbonate, Sodium Carbonate, and Sodium Bicarbonate. toxicology of commercial products. 4th, ed., II-72. Baltimore: Williams and
Unpublished data submitted by CTFA 3 pages.25 Wilkins.
Dean, B. S., and E. P. Krenzeloc. 1987. In vivo effectiveness of oral complexation Gosselin, R. E., R. P. Smith, and H. C. Hodge. 1984. Clinical Toxicology of
agents in the management of iron poisoning. J. Toxicol. Clin. Toxicol. 25:221– Commercial Products, 5th ed, 194, II-103. Baltimore: Williams and Wilkins.
230. Gottschalck, T. E., and G. N. McEwen, Jr., eds. 2004. International Cosmetic
Ingredient Dictionary and Handbook, 10th ed. 151. Washington, DC: CTFA.
International Programme on Chemical Safety. 2004. Sodium Bicarbonate. Un-
published data submitted by CTFA. 2 pages.25
25 Jackson, E. M. 1996. Familiarity with oral care products: must for the derma-
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. tologist. Cosmet. Dermatol. 9:43–44.
TABLE 24
Historical and current uses and use concentrations for Sodium Sesquicarbonate, Sodium Bicarbonate, and Sodium Carbonate
Sodium Sesquicarbonate
Bath
Oils, tablets, and salts 24 16 >1–50 2–90
Soaps and detergents — 2 — —
Bubble baths 68 2 >5–50 18
Capsules 2 — >10–25 —
Other bath 11 2 >5–50 10–35
Fragrances
Straighteners 1 — >50 —
Permanent waves 2 — >1–10 —
Personal hygiene
Other personal hygiene 2 1 >5–10 —
Skin care
Foot powders and sprays — — — 35–59
Total uses/ranges for Sodium Sesquicarbonate 111 24 >1–50 2–90
Sodium Bicarbonate
Baby care
Lotions, oils, powders, and creams — 1 — 5
Bath
Oils, tablets, and salts 1 7 <5–10 30–64
Soaps and detergents — 2 — 25–54
Bubble baths 4 — >10–25 5–52
Capsules — — — 49
Other bath — — — 1–64
Eye makeup
Eyebrow pencils — — — 0.2
Eyeliners 2 1 ≤0.1–1 0.04–0.1
Mascara — 6 — 0.2
Other eye makeup 1
Fragrance
Powders 5 9 >0.1–10 20
Conditioners — — — 5
Straighteners 1 — >0.1–1 —
Permanent waves 5 3 ≤0.1–1 10
Shampoos — — — 0.09
Other noncoloring hair care 1 — >1–5 —
Hair-coloring products
Bleaches 1 — >25–50 0.1–10
Makeup
Lipsticks — — — 0.03–1
Nail care
Other — — — 39
TABLE 24
(Continued)
Oral hygiene
Dentifrices 5 10 >1–50 3–95
Mouthwashes and breath fresheners — 2 — 0.1
Other oral hygiene — 1 — 0.5
Personal hygiene
Underarm deodorants 2 — >1–5 0.01–15
Douches 4 2 ≤0.1–25 —
Feminine deodorants — 2 — —
Other personal hygiene 4 3 ≤0.1–25 0.07–56
Shaving
Other shaving 1 1 ≤0.1 —
Skin care
Cleansing creams, lotions, etc. — — — 0.04–26
Face and neck skin care —∗ — —∗ 0.01–7
Body and hand skin care — 10
Foot powders and sprays — 4 — 25–56
Moisturizers — — — 0.4
Paste masks/mud packs 3 1 ≤0.1–50 61
Skin fresheners 2 2 ≤0.1–10 —
Other skin care 4 4 >10–25 2–5∗∗∗
Suntan products
Suntan gels, creams, liquids, and sprays — — — 0.2
Total uses/ranges for Sodium Bicarbonate 45 70 ≤0.1–50 0.006–95
Sodium Carbonate
Bath
Oils, tablets, and salts — 4 — 40–51
Soaps and detergents 2 1 >0.1–1 3–32
Bubble baths 4 — >10–25 7–39
Other — — — 0.009–39
Eye makeup
Eyebrow pencils — — — 0.2
Eye shadow — — — 0.3
Eye lotions — — — 0.004
Mascara — — — 0.2
Fragrances
Conditioners 1 2 >0.1–1 0.01
Straighteners 1 — >1–5 —
Permanent waves 1 1 >1–5 —
Shampoos 2 1 >0.1–1 0.08
Tonics, dressings, etc. — — — 0.000002–0.01
Wave sets — — — 1
TABLE 24
(Continued)
Hair coloring
Dyes and colors 1 2 >1–5 0.1–0.6
Rinses — — — 0.02
Bleaches 2 — >0.1–10 25
Other hair coloring — — — 1
Makeup
Blushers — — — 0.03
Foundations 1 1 ≤0.1 0.3
Lipsticks — 3 — —
Nail care
Other nail care — — — 0.6
Oral hygiene
Dentifrices — — — 2
Other oral hygiene — — — 22∗∗∗
Personal hygiene
Douches 1 >5–10 —
Other 3 2 >1–5 —
Skin care
Cleansing creams, lotions, etc. 2 1 ≤0.1 0.02–0.2
Face and neck skin care —∗ — —∗ 0.008
Moisturizers 2 2 ≤0.1 —
Hormone preparations∗∗ 1 N/A∗∗ ≤0.1 N/A∗∗
Total uses/ranges for Sodium Carbonate 25 21 ≤0.1–25 0.000002–51
∗
∗∗
∗∗∗
Denture cleanser.
JEFO. 2004a. Sodium Bicarbonate Powder “Cow Brand”. http://www.jefo.ca Orica. 2004. Chemical Fact Sheet–Sodium Carbonate. http://www.orica.com.
Accessed on 11/8/2004. Accessed on 11/8/2004.
JEFO. 2004b. Sodium Sesquicarbonate (Arm & Hammer). http://www.jefo.ca. Sander, J. E., S. I. Savage, and G. N. Rowland. 1998. Sodium
Accessed on 11/8/2004. sesquicarbonate toxicity in broiler chickens. Avian Dis. 42:215–
Kuu, W. Y., R. Chilamkurti, and C. Chen. 1998. Effect of relative humidity and 218.
temperature on moisture sorption and stability of sodium bicarbonate powder. Sodipo, O. A. 1993. How safe is the consumption of Trona? Am. J. Public Health
Int. J. Pharmacol. 166:167–175. 83:1181.
Lewis, R. J. ed. 1996. Sax’s Dangerous Properties of Industrial Materials, 9th Solvay Chemicals. 2004a. Dense Soda Ash—Properties. http://www.sodaash.
ed., 2952. New York: John Wiley and Sons. com. Accessed on 11/8/2004.
Mallinkrodt Baker, Inc. 2004. Sodium bicarbonate. http://www.chem.tamu.edu Solvay Chemicals. 2004b. Trona—Sodium Sesquicarbonate. http://www.
Access 11/8/2004. solvaychemicals.us. Accessed on 11/8/2004.
Mallinkrodt Baker, Inc. 2004. Sodium carbonate anhydrous. http://www. United States Department of Energy. 2004. Soda Ash. http://www.oit.doe.gov.
jtbaker.com 11/8/2004. 6 pages.
Marvola, M., Nykanen, S., and M. Nokelainen. 1991. Bioavailability of ery- Uzogara, S. G., Morton, I. D., Daniel, J. W., and Emery, J. M. 1990. Use
thromcin acistrate from hard gelatin capsules containing sodium bicarbonate. of kanwa-cooked cowpea (Vigna unguiculata) in infant food formulation:
Pharm. Res. 8:1056–1058. effect on protein utilization and digestibility. J. Trop. Pediatr. 36:207–
Miller, H. C. 1993. Cardiac arrest after intravenous pentamidine in an infant. 208.
Pediatr. Infect. Dis. J. 12:694–696. Walker, J. A., Sherman, R. A., and R. P. Cody. 1990. Effect of oral
National Institute for Occupational Safety and Health (NIOSH). 2004. Sodium base on enteral aluminum absorption. Arch. Intern. Med. 150:2037–
sesquicarbonate dihydrate. http://www.cdc.gov. Accessed on 11/8/2004. 2039.
STEARYL ALCOHOL, OLEYL ALCOHOL, AND de Berker, D., P. Marren, S. M. Powell, and T. J. Ryan. 1992. Contact sensitivity
OCTYLDODECANOL to the stearyl alcohol in Efudix cream (5-fluorouracil). Contact Dermatitis
26:138.
A safety assessment of Stearyl Alcohol, Oleyl Alcohol, and
Elder, R. L. 1985. Final report on the Safety Assessment of Stearyl Alcohol,
Octyldodecanol was published in 1985 with the conclusion “safe Oleyl Alcohol and Octyl Dodecanol. J. Am. Coll. Toxicol. 4:1–29.
as currently used in cosmetic products” (Elder 1985). New stud- Filippi, U., M. Gibellini, G. Guasoni, et al. 1982. Proposal for the pharmacopeia;
ies, along with the updated information in Table 25 regarding octyl dodecanol. Boll. Chim. Farm. 121:425–427.
uses and used concentrations, were considered by the CIR Ex- Food and Drug Administration. 2002. Frequency of use of cosmetic ingredients.
FDA database. Washington, DC: FDA.
pert Panel. The Panel determined not to reopen this safety as- Guidetti, M. S., C. Vincenzi, L. Guerra, and A. Tosti. 1994. Contact dermatitis
sessment. due to oleyl alcohol. Contact Dermatitis 31:260–261.
Stearyl Alcohol was used in 425 cosmetic products in 1981, Hannuksela, M. 1988. Skin contact allergy to emulsifiers. Int. J. Cosmet. Sci.
based on voluntary reports provided to FDA by industry with 10:9–14.
concentrations ranging from ≤0.1% to 50% (Elder 1985). In Koch, P. 1995. Occupational allergic contact dermatitis from oleyl alcohol and
monoethanolamine in a metalworking fluid. Contact Dermatitis 33:273.
2002, Stearyl Alcohol was reportedly used in 1063 cosmetic Komamura, H., T. Doi, S. Inui, and K. Yoshikawa. 1997. A case of contact
products (FDA 2002). Concentration of use data from an indus- dermatitis due to impurities of cetyl alcohol. Contact Dermatitis 36:44–
try survey in 2003 indicated that Stearyl Alcohol was used in a 46.
range from 0.002% to 56% (CTFA 2003). Lashmar, U. T., J. Hadgraft, and N. Thomas. 1989. Topical application of pen-
The Panel noted that the Hannuksela (1988) report reviewed etration enhancers to the skin of nude mice: A histopathological study. J.
Pharm. Pharmacol. 41:118–122.
the previous literature which included a report of positive patch Lee, B. J., J. S. Choe, and C. K. Kim. 1998. Preparation and characterization
test reactions to Stearyl Alcohol as high as 44%. Although this of melatonin-loaded stearyl alcohol microspheres. J. Microencapsul. 15:775–
information raised some concern, Hannuksela (1988) did report 787.
current data with a frequency of 11 positive tests out of over 1000 McNeil, J. D., M. W. Whitehouse, M. A. Quin, L. G. Cleland, and B. Vernon-
patch tests performed; a low frequency consistent with current Roberts. 1985. Oleyl alcohol is a potent inflammogen in both the rat paw and
the rabbit knee. Aust. N. Z. J. Med. 15:191.
experience. Murota, K., T. Kawada, N. Matsui, M. Sakakibara, N. Takahashi, and T. Fushiki.
Oleyl Alcohol was used in 1018 cosmetic products in 1981, 2000. Oleyl alcohol inhibits intestinal long-chain fatty acid absorption in rats.
with concentrations ranging from ≤0.1% to >50% (Elder 1985). J. Nutr. Sci. Vitaminol. 46:302–308.
In 2002, Oleyl Alcohol was used in 343 cosmetic products (FDA Niven, R. W., and P. R. Byron. 1990. Solute absorption from the airways of the
2002). Concentration of use data from a 2003 survey indicated isolated rat lung. II. Effect of surfactants on absorption of fluorescein. Pharm.
Res. 7:8–13.
that Oleyl Alcohol was used in a range from 0.0002% to 18% Olsen, O., M. Ainsworth, O. B. Schaffalitzky de Muckadell, and P. Cantor.
(CTFA 2003). 1989. Effects of oleic acid and oleyl alcohol on cholecystokinin and se-
Although Tosti et al. (1996) reported a high proportion of 34 cretin in plasma pancreatobiliary secretion. Scand. J. Gastroenterol. 24:529–
patients as positive to Oleyl Alcohol in a patch test, the Panel 532.
indicated that such reactions are not seen in their experience. Petersen, F., O. Olsen, L.V. Jepsen, and J. Christiansen. 1992. Fat and gastric
acid secretion. Digestion 52:43–46.
Octyldodecanol was used in 371 cosmetic products in 1981, Sato, A., K. Obata, Y. Ikeda, et al. 1996. Evaluation of human skin irritation by
with concentrations ranging from ≤0.1% to >50% (Elder 1985). carboxylic acids, alcohols, esters, and aldehydes, with nitrocellulose-replica
In 2002, Octyldodecanol was used in 814 cosmetic products method and closed patch testing. Contact Dermatitis 34:12–16.
(FDA 2002). Concentration use data from 2003 indicted that Takada Y., K. Kageyama, R. Yamada, Y. Onoyama, T. Nakajima, M. Hosono,
Octyldodecanol was used in a range from 0.006% to 85% (CTFA and N. Miwa. 2001. Correlation of DNA synthesis-inhibiting activity and the
extent of alcohols of graded chain-length upon hyperthermia. Oncol. Rep.
2003). 8:547–551.
Table 25 presents the available use information for Stearyl Tan, B. B., A. L. Noble, M. E. Roberts, J. T. Lear, and J. S. English. 1997.
Alcohol, Oleyl Alcohol, and Octyldodecanol. The most current Allergic contact dermatitis from oleyl alcohol in lipstick cross-reacting with
information now represents the present practices of use. ricinoleic acid in castor oil and lanolin. Contact Dermatitis 37:41–42.
Tosti, A., C. Vincenzi, L. Guerra, and E. Andrisano. 1996. Contact dermatitis
from fatty alcohols. Contact Dermatitis 35:287–289.
REFERENCES Wakabayashi, T., M. Horiuchi, K. Adachi, and T. Koyama. 1984. Induction of
Abdullah, A., S. Walker, C. Y. Tan, and I. S. Foulds. 1997. Sensitization to megamitochondria in rat hepatocytes by 1-octadecanol. J. Electron Microsc.
oleth-3-phosphate and oleth-5 in hair wax. Contact Dermatitis 37:188. (Tokyo) 33:236–238.
Blevins, R. D., and D. E. Taylor. 1982. Mutagenicity screening of twenty-five Yesudian, P. D., and C. M. King. 2001. Allergic contact dermatitis from stearyl
cosmetic ingredients with the salmonella/microsome test. J. Environ. Sci. alcohol in Efudix cream. Contact Dermatitis 45:313–314.
Health, Part A 17:217–239.
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2003. Ingredient Use
Data. Unpublished data submitted by CTFA.26
Dawn, G., and A. Forsyth. 2003. Genital swelling caused by octyldodecanol TOLUENE
contact dermatitis. Clin. Exp. Dermatol. 28:228–229. A safety assessment of Toluene was published in 1987 with
the conclusion that Toluene “is safe for cosmetic use at the
26
Available for review: Director, Cosmetic Ingredient Review, 1101 present practices of use and concentration” despite limited skin
17th Street, NW, Suite 412, Washington, DC 20036–4702, USA. exposure data (Elder 1987). Since then a large number of studies
TABLE 25
Historical and current cosmetic product uses and concentrations for Stearyl Alcohol, Oleyl Alcohol, and Octyldodecanol
Stearyl Alcohol
Baby care
Lotions, oils, powders, and creams 2 9 >0.1–1 0.6–2
Other baby care — 1 — 2
Bath
Bubble baths — — — 2
Eye makeup
Eyebrow pencils 1 — >1–5 3
Eyeliners — 3 — —
Eye shadow 24 6 ≤0.1–1 8
Eye lotions — 5 — 0.4–0.5
Mascara 2 5 >0.1–1 0.2 - 2
Other eye makeup 2 9 ≤0.1–1 5
Fragrances
Sachets 26 1 >0.1–25 1
Conditioners 46 174 ≤0.1–10 0.02–8
Straighteners 2 7 >0.1–1, >5–10 2
Permanent waves 5 4 ≤0.1–1 3
Rinses 21 4 ≤0.1–5 3–5
Shampoos 1 23 >0.1–1 0.1–5
Tonics, dressings, etc. — 9 — 1–5
Other noncoloring hair care — 3 — 1–5
Hair coloring
Dyes and colors 1 259 >0.1–1 —
Tints — — — 4
Rinses — — — 2–5
Lighteners with color — 1 — —
Bleaches 5 25 >0.1–5 —
Other hair coloring 2 1 >1–5 2
Makeup
Blushers 15 — ≤0.1–1 2
Foundations 8 32 >0.1–1 0.8–3
Leg and body paints 3 — >0.1–1 —
Lipsticks 3 2 ≤0.1–1 0.2–3
Makeup bases 63 12 ≤0.1–5 0.6
Rouges 1 1 ≤0.1 —
Makeup fixatives 1 2 ≤0.1 —
Other makeup 2 6 ≤0.1–1 0.5–5
Nail care
Cuticle softeners 2 1 >0.1–1 2
TABLE 25
(Continued)
Creams and lotions 1 2 >1–5 1
Other nail care — 1 — 6
Personal hygiene
Underarm deodorants 3 8 >25–50 13–25
Other personal hygiene 10 66 >1–5, >10–25 —
Shaving
Aftershave lotions — 5 — 0.2–3
Beard softeners 1 — >5–10 —
Preshave lotions — — — 1
Shaving cream 6 7 >0.1–5 0.2–3
Other shaving 2 — ≤0.1–1 2
Skin care
Depilatories 6 1 >1–5 1
36∗ ≤0.1–10∗
Foot powders and sprays — 3 — 2–17
Moisturizers 50 106 ≤0.1–10 0.002–56
Night skin care 12 14 ≤0.1–5 0.002–3
Paste masks/mud packs 2 11 >0.1–5 0.8–6
Skin fresheners 1 2 >0.1–1 —
Other skin care 9 31 ≤0.1–10 0.02–12
Skin lighteners∗∗ 6 NA∗∗ >0.1–10 NA∗∗
Suntan products
Suntan gels, creams, liquids, and sprays 2 3 >0.1–1, >5–10 1–4
Indoor tanning preparations 1 19 >1–5 2–3
Other — 1 — 0.3
Total uses/ranges for Stearyl Alcohol 425 1063 ≤0.1–50 0.002–56
Oleyl Alcohol
Bath
Oils, tablets, and salts 17 1 ≤0.1–25 —
Bubble baths 1 — >1–5 —
Capsules 1 — >5–10 1–5
Other bath 3 — >1–5 —
Eye makeup
Eyebrow pencils 1 — >5–10 —
Eyeliners 15 5 >1–25 0.4–0.5
Eye shadow 124 5 ≤0.1–25 1
Mascara 26 2 >1–5 —
Other eye makeup 8 2 >0.1–25 —
Fragrances
Colognes and toilet waters 2 — >0.1–1 —
Perfumes 5 1 ≤0.1, >1–5, >10–25 5
Sachets 2 1 >1–5 —
Other fragrances 9 1 >0.1–5 1–5
TABLE 25
(Continued)
Conditioners 9 26 >0.1–5 0.3–3
Sprays/aerosol fixatives — 3 — —
Straighteners 4 9 >1–5 1
Permanent waves — — — 3
Rinses — — — 18
Tonics, dressings, etc. 4 6 >0.1–5 0.3–4
Other noncoloring hair care 1 2 >1–5 —
Hair coloring
Dyes and colors 63 143 >1–5, >10–25 6–8
Tints 13 — >10–25 —
Bleaches 2 2 >1–5 —
Makeup
Blushers 13 2 >1–>50 1–10
Face powders 1 — >1–5 —
Foundations 5 5 >0.1–5 0.5–5
Lipsticks 633 82 ≤0.1–> 50 —
Makeup bases 2 — >1–5, >10–25 —
Rouges 3 — >1–5, >10–25 —
Nail care
Nail polish and enamel removers 1 — >1–5 —
Personal hygiene
Underarm deodorants 2 — >1–5 0.0005
Feminine deodorants 1 1 >25–50 0.1
Other personal hygiene 2 2 >0.1–5 —
Shaving products
Aftershave lotions 2 2 >1–5 0.05
Preshave lotions 1 1 >0.1–1 —
Skin care
Cleansing creams, lotions, etc. 2 1 >1–5 —
6∗ ≤0.1–10∗
Body and hand skin care 6 0.05
Foot powders and sprays — — — 2
Moisturizers 8 9 ≤0.1–25 4
Night skin care 2 1 >1–25 3
Paste masks/mud packs 2 2 ≤0.1–5 —
Skin fresheners 2 6 ≤0.1–1 —
Other skin care 4 — ≤0.1–25 3
Hormone preparations∗∗ 1 NA∗∗ >10–25 NA∗∗
Suntan products
Suntan gels, creams, liquids and sprays 5 3 >0.1–10 —
Total uses/ranges for Oleyl Alcohol 1018 343 ≤0.1–>50 0.0002–18
TABLE 25
(Continued)
Octyldodecanol
Bath
Oils, tablets, and salts 4 8 >5–10 1–30
Soaps and detergents 1 — ≤0.1 —
Eye makeup
Eyebrow pencils 1 10 >5–10 4
Eyeliners 14 202 >0.1–10 3–7
Eye shadow 82 17 >1–25 0.1–15
Eye lotions 1 — >25–50 —
Eye makeup remover 3 3 >1–5, >10–25 5
Mascara 1 — >1–5 1–3
Other eye makeup 4 20 >5–25 0.1
Fragrances
Perfumes 3 — >25–50 —
Powders 4 — >0.1–1 0.3
Sachets 6 — >25–50 —
Conditioners 3 11 >0.1–5 3–15
Sprays/aerosol fixatives 2 2 >0.1–5 —
Straighteners — — — 0.5
Rinses 2 3 >0.1–1 4–6
Tonics, dressings, etc. — — — 0.5–20
Other noncoloring hair care — — — 3
Hair coloring
Dyes and colors 41 84 >5–25 10
Rinses — — — 1
Makeup
Blushers 6 9 >1–25 15–23
Face powders 6 6 >0.1–10 8
Foundations — 20 — 5–16
Lipsticks 112 182 >0.1–>50 3–82
Makeup bases 1 1 >0.1–1 —
Rouges 1 2 >10–25 10–20
Makeup fixatives 1 — >5–10 —
Other 2 23 >1–10 3–17
Nail care
Polishes and enamels — — — 2
Other nail care — — — 0.06
Personal hygiene
Underarm deodorants 1 3 >10–25 2–17
Other personal hygiene 1 2 >1–5 1
Continued on next page
TABLE 25
(Continued)
Shaving products
Aftershave lotions — 2 — 0.03–0.07
Preshave lotions 1 3 >0.1–1 —
Shaving cream 1 1 >0.1–1 0.4
Other — 3 — —
Skin care
Cleansing creams, lotions, etc. 9 22 ≤0.1, >1–10 0.03–17
23∗ >0.1–50*
Moisturizers 14 35 ≤0.1–25 2–3
Night skin care 3 15 >1–5, >10–25 1
Paste masks/mud packs — 7 —
Other skin care 7 24 >1–25 0.03–14
Wrinkle smoothers∗∗ 1 NA∗∗ >1–5 NA∗∗
Skin lighteners∗∗ 4 NA∗∗ >0.1–5 NA∗∗
Suntan
Suntan gels, creams, liquids, and sprays 3 9 >5–25 3–59
Other suntan 1 4 >1–5
Total uses/ranges for Octyldodecanol 371 814 ≤ 0.1–>50 0.006–85
∗
∗∗
have appeared in the scientific literature. These studies, along Table 26 provides the available data on usage and use con-
with updated information regarding uses and use concentrations, centration as a function of cosmetic product category. The most
were considered by the CIR Expert Panel. Based on its consid- current information now represents the present practices of use.
eration of the available data, the Panel decided to not reopen this Many of the newly available studies reported findings con-
safety assessment. sistent with the data in the original safety assessment.
Toluene was used in 555 cosmetic products in 1981, based New findings of adverse effects included the following ef-
on voluntary reports provided to FDA by industry with con- fects: Toluene was ototoxic for guinea pigs; interferes with per-
centrations ranging from >10%–50% (Elder 1987). In 2002, formance and learning in neurotoxicity and behavior studies in
toluene was reportedly used in 59 cosmetic products (FDA animals; increased numbers of litters with low birth weights pups
2002). Concentration of use data from an industry survey in 2003 and adversely affected brain development; in cultured embryos
indicated that Toluene was used in a range from 20% to 26% exposed to Toluene, yolk sac diameter, crown-rump length,
(CTFA 2004). somite number, and protein concentration were significantly
TABLE 26
Historical and current cosmetic product uses and concentrations for Toluene
Nail care
Basecoats and undercoats 32 21 >10–50 —
Polishes and enamels 501 23 >10-50 20–25
Polish and enamel removers — 2 — —
Other nail care 22 13 >10–50 26
Total uses/ranges for Toluene 555 59 >10–50 20–26
reduced. A National Toxicology Program study concluded that Brugnone, F., M. Gubbi, K. Ayyad, and C. Giuliari. 1995. Blood toluene as a
there was no evidence of carcinogenic activity for Toluene in biological index of environmental toluene exposure in the “normal” popula-
tion and in occupationally exposed workers immediately after exposure and
F344/N rats and B6C3F1 mice.
16 hours later. Int. Arch. Occup. Environ. Health 66:421–425.
The new adverse effects noted above appeared only at high Bushnell, P. J., K. L. Kelly, and K. M. Crofton. 1994. Effects of toluene inhalation
exposures. They were found only when animals were exposed on detection of auditory signals in rats. Neurotoxicol. Teratol. 16:149–160.
to Toluene vapor at a level of 102 to 103 ppm. Such exposures, Cambell, L., D. M. Marsh, and H. K. Wilson. 1987. Towards a biological mon-
however, were not attainable in an exposure study of human itoring strategy for toluene. Ann. Occup. Hyg. 31:121–133.
Campo, P., R. Lataye, B. Cossec, and V. Placidi. 1997. Toluene-induced hearing
subjects using nail polish—those values ranged from 1–4 ppm.
loss: A mid-frequency location of the cochlear lesions. Neurotoxicol. and
The Panel recognized that other data indicate adverse effects Teratol. 19:129–140.
in the brain of Toluene abusers and in children born to mothers Cavalleri, A., F. Gobba, E. Nicali, and V. Fiocchi. 2000. Dose-related color vision
who inhaled Toluene during pregnancy. Again, the nature of impairment in toluene-exposed workers. Arch. Environ. Health 6:399–404.
these studies suggests high exposures and are not relevant to the Chan, M. H., and H. H. Chen. 2003. Toluene exposure increases aminophylline-
induced seizure susceptibility in mice. Toxicol. Appl. Pharmacol. 193:303–
use of Toluene in cosmetic products.
308.
Chao, T. C., D. S. Lo, J. Koh, and T. C. Ting. 1993. Glue sniffing deaths
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A safety assessment of Toluenesulfonamide/Formaldehyde
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of subchronic toluene exposure on spatial learning and memory, dopamine- was published in 1986 with the conclusion that these ingredients
mediated locomotor activity and dopamine D2 agonist binding in the rat. were safe as cosmetic ingredients in the present practices of
Toxicology 77:223–232. use and concentration (Elder 1986). Studies available since that
Von Euler, M., T. M. Pham, M. Hillefors, and B. Bjelke. 2000. Inhalation of low
concentrations of toluene induces persistent effects on a learning retention
time, along with updated information regarding uses and use
task, beam-walk performance, and cerebrocortical size in the rat. Exp. Neurol. concentrations, were considered by the CIR Expert Panel. Based
163:1–8. on its consideration of the available data, the Panel decided to
Vrca, A., D. Bozicevic, V. Karacic, and R. Fuchs. 1995. Visual evoked poten- not reopen this safety assessment.
tials in individuals exposed to long-term low concentrations of toluene. Arch. The terminology for this ingredient in the International
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Cosmetic Ingredient Dictionary and Handbook has changed—
evoked potentials in individuals exposed to long-term low concentrations of Tosylamide/Formaldehyde Resin is the current terminology
toluene. Am. J. Ind. Med. 30:62–66. (Gottschalck and McEwen 2004).
TABLE 27
Historical and current cosmetic product uses and concentrations for Tosylamide/Formaldehyde Resin
Tosylamide/Formaldehyde Resin
Nail care products
Basecoats and undercoats 31 — 1–10 8–11
Nail polishes and enamels 172 29 ≤0.1–25 7–13
Other 8 — 1–10 7–8
Total uses/ranges for 211 29 ≤0.1–25 7–13
Tosylamide/Formaldehyde Resin
Tosylamide/Formaldehyde Resin-80
Nail care products
Basecoats and undercoats (44) 5 — 1–10 —
Nail polishes and enamels (767) 344 — ≤0.1–25 —
Other (50) 7 — ≤0.1–25 —
Total uses/ranges for 356 29 ≤0.1–25 —
Tosylamide/Formaldehyde Resin-80
Tosylamide/Formaldehyde Resin was used in 211 cosmetic De Wit, F. S., A. C. de Groot, J. W. Weyland, and J. D. Bos 1988. An outbreak
products in 1981, based on voluntary reports provided to FDA by of contact dermatitis from toluenesulfnamide Formaldehyde resin in a nail
industry with concentrations ranging from ≤0.1%–25% (Elder hardener. Contact Dermatitis. 18:280–283.
Duarte, I., R. Lazzarinin, and C. M. Kobata 2003. Contact dermatitis in adoles-
1986). In 2002, stearyl alcohol was reportedly used in 29 cos- cents. Am. J. Contact Dermatitis 14:200–204.
metic products (FDA 2002). Concentration of use data from an Elder, R. L. 1986. Final report on the safety assessment of Toluenesulfon-
industry survey in 2003 indicated that Toluene was used in a amide/Formaldehyde Resin. J. Am. Coll. Toxicol. 5:471–490.
range from 7%–13% (CTFA 2004). Giorgini, S., C. Brusi, S. Francalanci, et al. 1994. Prevention of allergic contact
dermatitis from nail vanishes and hardeners. Contact Dermatitis 31:325–
Tosylamide/Formaldehyde Resin-80 was used in 356 cos-
326.
metic products in 1981, based on voluntary reports provided to Gottschalck, T., and G. N. McEwen, Jr. 2004.International cosmetic ingredient
FDA by industry with concentrations ranging from ≤0.1%–25% dictionary and handbook. Washington, DC: CTFA.
(Elder 1986). In 2002, there were no reports of use (FDA 2002), Guin, J. D., K. Baas, and P. Nelson-Adesokan. 1998. Contact sensitization to
nor did an industry survey in 2003 indicated any current use cyanoacrylate adhesive as a cause of severe onychodystorphy. Int. J. Dermatol.
37:31–36.
concentrations (CTFA 2004).
Hausen, B. M., M. Milbrodt, and W. A. Koenig. 1995. The aller-
Table 27 provides the available data on usage and use con- gens of nail polish. (I). Allergenic constituents of common nail polish
centration as a function of cosmetic product category. The most and toluenesulfonamide-Formaldehyde resin (TS-F-R). Contact Dermatitis
current information now represents the present practices of use 33:157–164.
and concentration. Lazarov, A. 1999. Perianal contact dermatitis caused by nail lacquer allergy. Am.
J. Contact Dermatitis 10:43–44.
Case reports of allergic reaction to nail care products con-
Staines, K. S., D. H. Felix and A. Forsyth. 1998. Desquamative gingivitis, sole
taining Tosylamide/Formaldehyde Resin were consistent with manifestation of tosylamide/formaldehyde resin allergy. Contact Dermatitis
the data in the original safety assessment. 39:90.
Vilaplana, J., and C. Romaguera. 2000. Contact dermatitis from tosy-
lamide/formaldehyde resin with photosensitivity. Contact Dermatitis 42:311–
REFERENCES 312.
Berne, B., A. Boström, A. F. Grahfén, and M. Tammela. 1996. Adverse effects
of cosmetics and toiletries reported to the Swedish Medical Products Agency
1989–1994. Contact Dermatitis 34:359–362. TRAGACANTH GUM
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2004. Survey of A safety assessment of Tragacanth Gum was published in
Tosylamide/Formaldehyde Resin usage. Unpublished data submitted by 1987 with the conclusion that these ingredients were safe as
CTFA.28 1 page.
cosmetic ingredients in the present practices of use and con-
de Groot, A., D. P. Bruynzeel, J. D. Bos, et al. 1988. The allergens in cosmetics.
Arch Dermatol. 124:1525–1529. centration (Elder 1987). Studies available since that time, along
with updated information regarding uses and use concentrations,
were considered by the CIR Expert Panel. Based on its consid-
28
Available for review: Director, Cosmetic Ingredient Review, 1101 eration of the available data, the Panel decided to not reopen this
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. safety assessment.
TABLE 28
Historical and current cosmetic product uses and concentrations for Astragalus Gummifer Gum
Eye makeup
Eye shadow 3 — ≤0.1 —
Conditioners — 1 ≤0.1 —
Tonics, dressings, etc. 1 2 >0.1–1 ≤0.01
Wave Sets — 1 —
Hair coloring
Hair Bleaches 2 1 >1–5 ≤3
Makeup
Blushers 2 — >1–5 —
Face Powders 6 — ≤0.1–1 —
Foundations 1 — >0.1–1 —
Rouges 1 — >0.1–1 —
Oral hygiene
Dentrifices 2 2 >0.1–5 —
Shaving
Skin care
Cleansing creams, lotions, etc. 1 >0.1–1 —
Body and hand skin care 2∗ — >0.1–1∗ —
Moisturizers 1 — >0.1–1 —
Paste masks/mud packs 5 1 >0.1–10 —
Total uses/ranges for Astragalus Gummifer Gum 29 8 ≤0.1–10 ≤0.01%–≤3
∗
The terminology for this ingredient in the Interna- mention of Astragalus Microcephalus Gum, and a new name
tional Cosmetic Ingredient Dictionary and Handbook has adopted, if needed.
changed—Astragalus Gummifer Gum is the current terminol- The Panel noted that pesticide impurities may form part of
ogy (Gottschalck and McEwen 2004). the composition of this plant-derived ingredient and has advised
Astragalus Gummifer Gum was used in 29 cosmetic products industry that the total (polychlorinated biphenyl) PCB/pesticide
in 1981, based on voluntary reports provided to FDA by industry contamination should be limited to not more than 40 ppm, with
with concentrations ranging from ≤0.1% to 10% (Elder 1987). not more than 10 ppm for any specific residue. The following
In 2002, stearyl alcohol was reportedly used in 8 cosmetic prod- limitations for other impurities were also recommended: arsenic
ucts (FDA 2002). Concentration of use data from an industry (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg
survey in 2004 indicated that Astragalus Gummifer Gum was max).
used at concentrations from ≤0.01% to ≤3% (CTFA 2004).
Table 28 provides the available data on usage and use con-
centration as a function of cosmetic product category. The most REFERENCES
current information now represents the present practices of use Anderson, D. M. W., and M. M. E. Bridgeman. 1985. The composition of the
proteinaceous polysaccharides exuded by Astragalus microcephalus, A. Gum-
and concentration. mifer and A. Kurdicus—the sources of Turkish gum tragacanth. Phytochem-
In the original safety assessment, this ingredient was de- istry 24:2301–2304.
scribed as derived from various Astragalus species, principally Anderson, D. M., P. Ashby, A. Busuttil, S. A. Kempson, and M. E. Lawson.
Astragalus gummifer. More recent information suggests that As- 1984. Transmission electron microscopy of heart and liver tissues from rats
tragalus microcephalus may be another source of this gum. The fed with gums arabic and tragacanth. Toxicol. Lett. 21:83–89.
Anderson, D. M., A. Busuttil, S. A. Kempson, and D. W. Penman. 1986. Trans-
Panel suggested that the International Cosmetic Ingredient Dic- mission electron microscopy of jejunum, ileum, and caecum tissues from rats
tionary and Handbook should be updated to include specific fed with gums arabic, karaya and tragacanth. Toxicology 41:75–82.
Anderson, D. M., J. F. Howlett, and C. G. McNab. 1985. The amino acid compo- Lagier, F., A. Cartier, J. Somer, J. Dolovich, and J.-L. Malo. 1990. Occupational
sition of the proteinaceous component of gum tragacanth (Asiatic Astragalus asthma caused by guar gum. J. Allergy Clin. Immunol. 85:785–790.
spp.). Food Addit. Contam. 2:231–235. Lammers, J. H. C. M., and B. M. Kulig. 1997. Multivariate time of peak effects
Andrikopoulos, N. K., A. C. Kaliora, A. N. Assimopoulou, and V. P. Papapeor- assessment for use in selecting time of testing in acute neurotoxicity studies.
giou. 2003. Biological activity of some naturally occurring resins, gums and Neurotoxicology 18:1079–1084.
pigments against in vitro LDL oxidation. Phytother. Res. 17:501–507. Manson, J. M., F. J. Guerriero, T. Brown, and J. San Sebastian. 1986. Lack of
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2004. Use concentration in vivo mutagenicity and testicular toxicity of triamterene in mice. Fundam.
data on Astragalus Gummifer Gum from industry survey. Unpublished data Appl. Toxicol. 7:533–546.
submitted by CTFA, 2004 (1 page).29 National Academy of Sciences (NAS). (1996) Food chemicals codex, 4th ed.,
De la Rosa, M. C., M. R. Medina, and C. Vivar. 1995. Microbiological quality 424. Washington, DC: National Academy Press.
of pharmaceutical raw materials. Pharm. Acta Helv. 70:227–232. Paulson, J. D., J. W. Oldham, R. F. Preston, and D. Newman. 1985.
De Paermentier, F., P. Heuschling, B. Knoops, P. Janssens De Varebeke, G. Lack of genotoxicity of the cancer chemopreventive agent N -(4-
Pauwels, C. Laszlo de Kaszon-Jakabfalva, and P. Vanden Bosch De Aguilar. hydroxyphenyl)retinamide. Fundam. Appl. Toxicol. 5:144–150.
1989. Suloctidil increases the rat brain cortex microvascular regeneration after Strobel, S., A. Ferguson, and D. M. Anderson. 1986. Immunogenicity, immuno-
a lesion. Life Sci. 44:41–47. logical cross reactivity and non-specific irritant properties of the exudate
Eastwood, M. A., W. G. Brydon, and D. M. Anderson. 1984. The effects of gums, arabic, karaya and tragacanth. Food Addit. Contam. 3:47–56.
dietary gum tragacanth in man. Toxicol. Lett. 21:73–82. Taylor, S. L., and S. L. Hefle. 2001. Ingredient and labeling issues associated
Elder, R. L. 1987. Final report on the safety assessment of tragacanth gum. J. with allergenic foods. Allergy. 56:64–69.
Am. Coll. Toxicol. 6:1–22. Verbeken, D., S. Dierckx, and K. Dewettinck. 2003. Exudate gums: Occurrence,
Food and Drug Administration (FDA). 2002. Frequency of use of cosmetic production, and applications. Appl. Microbiol. Biotechnol. 63:10–21.
ingredients. FDA database. Washington, DC: FDA. Yamaguchi, T. 1992. Inhibitory activity of heat treated vegetables and indi-
Gottschalck, T. E., and G. N. McEwen, Jr., eds. 2004. International Cosmetic gestible polysaccharides on mutagenicity. Mutat. Res. 284:205–213.
Ingredient Dictionary and Handbook, 10th ed., 151. Washington, DC: CTFA.
Hagiwara, A., P. Boonyaphiphat, M. Kawabe, H. Naito, T. Shirai, and N. Ito.
1992. Lack of carcinogenicity of tragacanth gum in B6C3F1 mice. Food VINYL ACETATE/CROTONIC ACID COPOLYMER
Chem. Toxicol. 30:673–679. A safety assessment of the Vinyl Acetate/Crotonic Acid
Hagiwara, A., H. Tanaka, D. Tiwawech, T. Shirai, and N. Ito. 1991. Oral toxicity
Copolymer in 1983 concluded that this ingredient is considered
study of tragacanth gum in B6C3F1 mice: Development of squamous-cell
hyperplasia in the forestomach and its reversibility. J. Toxicol. Environ. Health. safe as a cosmetic ingredient under present practices of product
34:207–218. and concentration use (Elder 1983). New studies, along with
Hashimoto, R., M. Inouye, and Y. Murata. 1999. Hypoplastic lung observed in updated information regarding types and concentrations of use,
rat with chemical-induced congenital diaphragmatic hernia: A preliminary were considered by the CIR Expert Panel. The Panel determined
report. Environ. Med. 43:66–68.
to not reopen this safety assessment.
Johnston, D., M. R. Gray, C. S. Reed, F. W. Bonner, and N. H. Anderson. 1990.
Comparative evaluation of five common suspending agents used in drug safety The terminology for this ingredient in the Interna-
studies. Drug Dev. Ind. Pharm. 16:1893–1909. tional Cosmetic Ingredient Dictionary and Handbook has
Joint FAO/WHO Expert Committee on Food Additives (JECFA). 1986a. Eval- changed—VA/Crotonates Copolymer is the current terminology
uation of certain food additives: Twenty-ninth report of the Joint FAO/WHO (Gottschalck and McEwen 2004).
Expert Committee on Food Additives, 37–38. WHO technical report series
VA/Crotonates Copolymer was used in 55 cosmetic products
733. Geneva: WHO.
JECFA. 1986b. Toxicological monograph on tragacanth gum, 1–21, WHO food in 1976, based on voluntary reports provided to FDA by indus-
additive series 20. Geneva: WHO. try with concentrations ranging from >0.01% to 25% (Elder
JECFA. 2004. Compendium of Food Additive Specifications. Spec- 1986). In 2002, VA/Crotonates Copolymer was used in 38 cos-
ifications for food additives. Internet site accessed July, 2004. metic products (FDA 2002). Concentration of use data from an
http://apps3.fao.org/jecfa/additive specs/docs/0/additive-0453.htm.
industry survey in 2003 indicated that this ingredient was used
Kitchin, K. T., and J. L. Brown. 1987. Biochemical effects of two promoters of
hepatocarcinogenesis in rats. Food Chem. Toxicol. 25:603–607. at concentrations from 0.05% to 11% (CTFA 2003).
Kitchin, K. T., and J. L. Brown. 1989. Biochemical studies of promoters of Table 29 presents the available use information for
carcinogenesis in rat liver. Teratog. Carcinog. Mutagen. 9:273–285. VA/Crotonates Copolymer. The most recent information now
Kitchin, K. T., J. L. Brown, and A. P. Kulkarni. 1991. Ornithine decarboxylase constitutes the present practice of use and concentration.
induction and DNA damage as a predictive assay for potential carcinogenicity.
The CIR Expert Panel acknowledged the use of Vinyl
Prog. Clin. Biol. Res. 369:137–144.
Kitchin, K. T., J. L. Brown, and A. P. Kulkarni. 1993. Predicting rodent car- Acetate/Crotonic Acid Copolymer in aerosol hair sprays. The ef-
cinogenicity of Ames test false positives by in vivo biochemical parameters. fects of inhaled aerosols depend on the specific chemical species,
Mutat. Res. 290:155–164. the concentration, the duration of exposure, and site of deposi-
Kitchin, K. T., J. L. Brown, and A. P. Kulkarni. 1994. Complementarity of tion within the respiratory system. Particle size is the most im-
genotoxic and nongenotoxic predictors of rodent carcinogenicity. Teratogen.
portant factor affecting the location of deposition (Jensen and
Carcinogen. Mutagen. 13:83–100.
Kuroda, K., Y. S. Yoo, and T. Ishibashi. 1989. Rec-assay of natural food additives. O’Brien 1993). The mean aerodynamic diameter of pump hair
Part 2. Seikatsu Eisei 33:15–23. spray particles is ≥80 μ, and the diameter of anhydrous hair
spray particles is 60 to 80 μ. Typically less than 1% are below
10 μ, which is the upper limit for respirable particles (Bower
29
Available for review: Director, Cosmetic Ingredient Review, 1101 1999). Based on the particle size, Vinyl Acetate/Crotonic Acid
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. Copolymer would not be respirable in formulation. Therefore,
TABLE 29
Historical and current cosmetic product uses and concentrations for VA/Crotonates Copolymer
Product category (Elder 1983) (FDA 2002) (Elder 1983, 1976) (%) (CTFA 2002b) (%)
Bath capsules — — — 9
Eye makeup remover — — — 9
Mascara — 5 — —
Hair conditioners 4 1 >1–10 —
Hair sprays (aerosol fixatives) 30 9 >.01–25 2–11
Hair straighteners — 1 — —
Tonics, dressings, and other hair-grooming aids 2 10 >1–5 0.05–4
Wave sets 9 3 >1–5 2
Other hair preparations (noncoloring) 10 9 >1–10 2–3
Hair dyes and colors (all types — — — 5
requiring caution statement and patch testing)
Moisturizing creams, lotions, and powders — — — 2
Total uses/ranges for VA/Crotonates Copolymer 55 38 >0.01–25 0.05–11
the Panel was not concerned about inhalation as a route of Deese, D. E., and R. E. Joyner. 1969. Vinyl acetate: A study of chronic human
absorption. exposure. Am. Ind. Hyg. Assoc. J. 30:449–457.
Elder, R. L. 1983. Final report on the safety assessment of vinyl acetate/crotonic
Although there were reports associating vinyl acetate with
acid copolymer. J. Am. Coll. Toxicol. 2:125–140.
nasopharyngeal carcinoma in rat inhalation studies, the amount Food and Drug Administration (FDA). 2002. Frequency of use of cosmetic
of residual vinyl acetate monomer in VA/Crotonates Copolymer ingredients. FDA database. Washington, DC: FDA.
was below the no observed effect level. Additionally, studies Fromming, K. H., K. P. Krahl, and F. Fischer. 1983. Enteric coated film tablets
show that the reported carcinogenicity of vinyl acetate in rats from an aqueous solution of a copolymer of vinyl acetate and crotonic acid.
Part 3. Roentgenographical experiments. Pharm. Ind. 45:199–202.
is through a nongenotoxic mechanism. Occupational studies in
Gottschalck, T., and G. N. McEwen. 2004. International Cosmetic Ingredient
which workers were exposure to vinyl acetate ranging from 5 to Dictionary and Handbook, 10th ed. Washington, DC: CTFA.
10 ppm, with intermittent exposures near 50 ppm and acute ex- Hurtt, M. E., M. B. Vinegar, R. W. Rickard, T. C. Cascieri, and T. R. Tyler. 1995.
posures to 300 ppm, showed no long-term chronic effects. These Developmental toxicity of oral and inhaled vinyl acetate in the rat. Fundam.
data support the CIR Expert Panel’s confidence that vinyl acetate Appl. Toxicol. 24:198–205.
International Agency on Risk of Cancer (IARC). 1995. Vinyl acetate. IARC
is not a concern in the safety of VA/Crotonates Copolymer.
Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans. 63:443–466.
Jensen, P. A. and D. O’Brien. 1993. Industrial hygiene. In: Aerosol measurement.
REFERENCES
Principles techniques and applications, ed. K. Willeke, and P. A. Baron, 538–
Bogdanffy, M. S., and M. L. Taylor. 1993. Kinetics of nasal carboxylesterase-
540. New York: John Wiley and Sons.
mediated metabolism of vinyl acetate. Drug Metab. Dispos. 21:1107–1111.
Krahl, K. P., and K. H. Fromming. 1982. Enteric coated film tablets from an
Bogdanffy, M. S., H. C. Dreef-Van Der Meulen, R. B. Beems, V. J. Feron,
aqueous of a copolymer of vinylacetate and crotonic acid. Part 2. In vivo
T. C. Tascieri, T. R. Taylor, M. B. Vinegar and R. W. Rickard. 1994a. Chronic
drug release from enteric coated tablets with methylene blue. Pharm. Ind.
toxicity and oncogenicity inhalation study with vinyl acetate in the rat and
44:1084–1087.
mouse. Fundam. Appl. Toxicol. 23:215–229.
Kuykendall, J. R., and M. S. Bogdanffy. 1992. Reaction kinetics of DNA-histone
Bogdanffy, M. S., T. R. Tyler, M. B. Vinegar, R. W. Rickard, F. M. Carpanini
crosslinking by vinyl acetate and acetaldehyde. Carcinogenesis. 13:2095–
and T. Cascieri. 1994b. Chronic toxicity and oncogenicity study with vinyl
2100.
acetate in the rat: In utero exposure in drinking water. Fundam. Appl. Toxicol.
Lahdetie, J. 1988. Effects of vinyl acetate and acetaldehyde on sperm morphol-
23:206–214.
ogy and meiotic micronuclei in mice. Mutat. Res. 202:171–178.
Bower, D. 1999. Unpublished information on hair spray particle size provided
Lijinsky, W., and M. D. Reuber. 1983. Chronic toxicity studies of vinyl acetate
in Fischer rats. Toxicol. Appl. Pharm. 68:43–53.
Cosmetic, Toiletry, and Fragrance Association (CTFA). 2002a. Information re-
Maki-Paakkanen, J., and H. Norppa. 1987. Induction of micronuclei by vinyl
garding VA/Crotonates Copolymer. Unpublished data submitted by CTFA on
acetate in mouse bone marrow cells and cultured human lymphocytes. Mutat.
October 31, 2002. (1 page.)30
Res. 190:41–45.
CTFA. 2002b. Concentrations of use VA/Crotonates Copolymer. Unpublished
Maltoni, C., A. Ciliberti, G. Lefemine, and M. Soffritti. 1997. Results of a long-
data submitted by CTFA on November 1, 2002. (1 page.)30
term experimental study on the carcinogenicity of vinyl acetate monomer in
mice. Ann. N.Y. Acad. Sci. 837:209–238.
Mebus, C. A., F. M. Carpanini, R. W. Rickard, T. C. Cascieri, T. R. Tyler, and
30
Available for review: Director, Cosmetic Ingredient Review, 1101 M. B. Vinegar. 1995. A two-generation reproduction study in rats receiving
17th Street, NW, Suite 412, Washington, DC 20036-4702, USA. drinking water containing vinyl acetate. Fundam. Appl. Toxicol. 24:206–216.
TABLE 30
Historical and current cosmetic product uses and concentrations for Zinc Phenolsulfonate
Product category (CIR 1986) (FDA 2002) (CIR 1986) (%) (CTFA 2004) (%)
Fragrances
Powders 5 1 >0.1–5 —
Personal hygiene
Underarm deodorants 40 15 >0.1–5 4
Shaving
Aftershave lotions 4 2 >0.1–5 —
Shaving cream 3 — — —
Skin care
Skin cleansing creams, lotions, liquids, and pads 2 >0.1–5 —
Body and hand skin care preparations — 2 — —
Foot powders and sprays — 1 — 3
Moisturizers 1 1 ≤0.1 —
Paste masks/mud packs 1 — >1–5 —
Skin fresheners 9 — ≤0.1–5 —
Other 2 1 1–5 —
Total uses/ranges for Zinc Phenolsulfonate 67 23 ≤0.1–5 3–4
Minardi, F., F. Belpoggi, M. Soffritti, A. Ciliberti, M. Lauriola, E. Cattin, and with concentrations ranging from ≤0.1 to 5% (Elder 1986). In
C. Maltoni. 2002. Results of long-term carcinogenicity bioassay on vinyl 2002, Zinc Phenolsulfonate was used in 23 cosmetic products
acetate monomer in Sprague-Dawley rats. Ann. N. Y. Acad. Sci. 982:106–
(FDA 2002). Concentration of use data from an industry survey
122.
Norppa, H., F. Tursi, P. Pfaffli, J. Maki-Paakkanen, and H. Jarventaus. 1985. in 2004 indicated that this ingredient was used at concentrations
Chromosome damage induced by vinyl acetate through formation of acetalde- from 3 to 4% (CTFA 2004).
hyde in human lymphocytes and Chinese ovary cells. Cancer Res. 45:4816– Table 30 presents the available use information for Zinc Phe-
4821. nolsulfonate. The most recent information now constitutes the
Simon, P., J. G. Filser, and H. M. Bolt. 1985. Metabolism and pharmacokinetics
present practice of use and concentration.
of vinyl acetate. Arch. Toxicol. 57:191–195.
Sipi, P., H. Jarventaus, and H. Norppa. 1992. Sister-chromatid exchanges in-
duced by vinyl esters and respective carboxylic acids in cultured human lym-
phocytes. Mutat. Res. 279:75–82.
REFERENCES
Cosmetic, Toiletry, and Fragrance Assocation (CTFA). 2004. Concentration of
ZINC PHENOLSULFONATE use data for Zinc Phenolsulfonate. Unpublished data submitted by CTFA. 1
A safety assessment of Zinc Phenolsulfonate published in page.31
Elder, R. L. 1986. Final report on the safety assessment of Zinc Phenolsulfonate.
1986 concluded that this ingredient is considered safe as a cos- J. Am. Coll. Toxicol. 5:373–390.
metic ingredient under present practices of product and con- Food and Drug Administration (FDA). 2002. Frequency of use of Zinc Phenol-
centration use (Elder 1986). New studies, along with updated sulfonate. FDA database. Washington, DC: FDA.
information regarding types and concentrations of use, were Gottschalck, T. E., and G. N. McEwen, Jr., eds. 2004. International Cosmetic
considered by the CIR Expert Panel. The Panel determined to Ingredient Dictionary and Handbook, 10th ed., vol. 3. Washington, DC:
CTFA.
not reopen this safety assessment. Stern, M., M. Klausner, R. Alvarado, K. Renskers, and M. Dickens. 1998. Evalu-
Zinc Phenolsulfonate was used in 67 cosmetic products in ation of the EpiOcular tissue model as an alternative to the Draize eye irritation
1981, based on voluntary reports provided to FDA by industry test. Toxicol. In Vitro 12:455–461.
31
Available from the Director, Cosmetic Ingredient Review, 1101
17th Street, NW, Suite 412, Washington, DC 20036, USA.

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International Journal of Toxicology, 25(Suppl.

Annual Review of Cosmetic Ingredient Safety

The Cosmetic Ingredient Review (CIR) program Expert Chloroxylenol

Foot powders and sprays — 1 — 0.004

Skin fresheners 6 2 ≤0.1 —

Other skin care 42 30 ≤1 0.03

2003 found concentrations of use ranging from 0.00007% to REFERENCES

cosmetic products. The most recent information now constitutes REFERENCES

REFERENCES SAFFLOWER OIL

REFERENCES Depasquale, D. A., A. El-Nanarawy, D. Rosen, and T. J. Montville. 1990. Am-

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