Final Report on the Safety Asssment of Benzyl Alcohol,Benzoic Acid,and Sodium Benzoate1
Benzyl Alcohol is an aromatic alcohol ud in a wide variety of cosmetic formulations as a fragrance component,prervative,sol-vent,and viscosity-decreasing agent.Benzoic Acid is an aromatic acid ud in a wide variety of cosmetics as a pH adjuster and prer-vative.Sodium Benzoate is the sodium salt of Benzoic Acid ud as a prervative,also in a wide range of cosmetic product types. Benzyl Alcohol is metabolized to Benzoic Acid,which reacts with glycine and excreted as hippuric acid in the human body.Accept-able daily intakes were established by the World Health Organiza-tion at5mg/kg for Benzyl Alcohol,Benzoic Acid,and Sodium Ben-zoate.Benzoic Acid and Sodium Benzoate are generally recognized as safe in foods according to the U.S.Food and Drug Administra-tion.No adver effects of Benzyl Alcohol were en in chronic expo-sure animal studies using rats and mice.Effects of Benzoic Acid and Sodium Benzoate in chronic exposure animal studies were limited to reduced feed intake and reduced growth.Some differences be-tween control and Benzyl Alcohol–treated populations were noted in one reproductive toxicity study using mice,but the were limited to lower maternal body weights and decread mean litter weights. Another study also noted that fetal weight was decread compared to controls,but a third study showed no differences between control and Benzyl Alcohol–treated groups.Benzoic Acid was associated with an incread number of resorptions and malformatio
ns in hamsters,but there were no reproductive or developmental toxicty ndings in studies using mice and rats expod to Sodium Benzoate, and,likewi,Benzoic Acid was negative in two rat studies.Geno-toxicity tests for the ingredients were mostly negative,but there were some assays that were positive.Carcinogenicity studies,how-ever,were negative.Clinical data indicated that the ingredients can produce nonimmunologic contact urticaria and nonimmuno-logic immediate contact reactions,characterized by the appearance of wheals,erythema,and pruritis.In one study,5%Benzyl Alcohol elicited a reaction,and in another study,2%Benzoic Acid did like-wi.Benzyl Alcohol,however,was not a nsitizer at10%,nor was Benzoic Acid a nsitizer at2%.Recognizing that the nonimmuno-logic reactions are strictly cutaneous,likely involving a cholinergic mechanism,it was concluded that the ingredients could be ud safely at concentrations up to5%,but that manufacturers should consider the nonimmunologic phenomena when using the ingre-dients in cosmetic formulations designed for infants and children. Additionally,Benzyl Alcohol was considered safe up to10%for u in hair dyes.The limited body exposure,the duration of u,and the frequency of u were considered in concluding that the nonim-
Received15May2001;accepted12July2001.
1Reviewed by the Cosmetic Ingredient Review Expert Panel.Bindu Nair,former CIR Scienti c Analyst
and Writer,prepared this report. Address correspondence to Director,Cosmetic Ingredient Review,1101 17th Street,NW,Suite310,Washington,DC20036,USA.munologic reactions would not be a concern.Becau of the wide variety of product types in which the ingredients may be ud,it is likely that inhalation may be a route of exposure.The available safety tests are not considered suf cient to support the safety of the ingredients in formulations where inhalation is a route of ex-posure.Inhalation toxicity data are needed to complete the safety asssment of the ingredients where inhalation can occur.
INTRODUCTION
This report is a compilation of data concerning Benzyl Alco-hol(CAS No.100-51-6),Benzoic Acid(CAS No.65-85-0),and Sodium Benzoate(CAS No.532-32-1).Reviews of early litera-ture(1920–1977)were prepared for the Food and Drug Adminis-tration(FDA)on Benzyl Alcohol and Benzoic Acid(Flavor and Extract Manufacturers’Association1984)and on Benzoic Acid and Sodium Benzoate(Informatics,Inc.1972;Federation of American Societies for Experimental Biology[FASEB]1973). This Cosmetic Ingredient Review(CIR)report includes relevant studies cited in the earlier reviews as well as recent animal and clinical studies.
CHEMISTRY
De nition and Structure
Benzyl Alcohol is an aromatic alcohol that conforms to the following formula(Wenninger,Canterbery,and McEwen2000)
:
Synonyms for Benzyl Alcohol include Benzenemethanol (Wenninger,Canterbery,and McEwen2000),Phenyl-methanol, Phenylcarbinol,Phenylmethyl Alcohol(Food and Agricultural Organization of the United Nations/World Health Organiza-tion[FAO/WHO]1994);Hydroxytoluene,®-Hydroxytoluene, (Lewis1993).
articlea
Benzoic Acid is an aromatic acid that conforms to the fol-lowing formula(Wenninger,Canterbery,and McEwen2000)
pcu:
International Journal of Toxicology,20(Suppl.3):23–50,2001 Copyright c°2001Cosmetic Ingredient Review
24
COSMETIC INGREDIENT REVIEW
Synonyms for Benzoic Acid include Benzeneformic acid,Benzenemethanoic Acid,Benzoate,Carboxybenzene,Dracylic Acid,Phenylformic Acid,Benzenecarboxylic Acid,Phenylcar-boxylic Acid (Budavari 1989;Lewis 1993).
The sodium salt of Benzoic Acid,Sodium Benzoate conforms to the following formula (Wenninger,Canterbery,and McEwen 2000):Synonyms for Sodium Benzoate include sodium salt of ben-zenecarboxylic acid,sodium salt of phenylcarboxylic acid (FAO/WHO 1994).
Physical and Chemical Properties
Table 1lists physical properties of Benzyl Alcohol and Benzoic Acid.
Benzyl Alcohol is a combustible liquid.When heated to de-composition it emits acrid smoke and fumes (Lewis 1993).Benzoic Acid burns rapidly in oxygen and is combustible when expod to heat or ame.It can react with oxidizing ma-terials.When heated to decomposition it emits acrid smoke and fumes (Lewis 1993).
When Sodium Benzoate is heated to decomposition it emits toxic fumes of Na 2O.It is cautioned that oral dos of 8to 10g can cau naua and vomiting;small dos have little or no effect (Lewis 1993).
Method of Manufacture
Benzyl Alcohol is found naturally in many foods such as apricots,snap beans,cocoa,cranberries,mushrooms,and honey (Flavor and Extract Manufacturers’Association 1984).Ben-zyl Alcohol is also found in the esntial oil of many plants
TABLE 1
Physical properties of Benzyl Alcohol and Benzoic Acid
Property Benzyl alcohol Benzoic acid Reference
Appearance Liquid
Budavari 1989—
White crystalline powder
Lewis 1993Odor/taste Faint aromatic odor,—Budavari 1989sharp burning taste Molecular weight 108.14Da 122.12Da Lide 1993Boiling point (±C )205.3249Lide 1993Melting point (±C )¡15.3122.13
Lide 1993Density 1.0419
1.0749,1.2659
Lide 1993Solubility Water;alcohol;ether;Alcohol;ether;acetone;Lide 1993
acetone;benzene chloroform;benzene Flash point (±F )213(CC )250(CC )
Lewis 1993
Refractive index
¡0.002
—
Nikitakis and McEwen 1990
including jasmine,hyacinth,and ylang-ylang (Lewis 1993).Large scale production of Benzyl Alcohol is achieved by the action of sodium or potassium carbonate on benzyl chloride (Budavari 1989).
Benzoic Acid is also found naturally in many foods such as apricots,snap beans,cocoa,cranberries,mushrooms,and honey (Flavor and Extract Manufacturers’Association 1984).Analytical Methods
The Benzoic Acid content of cosmetic formulations can be determined by high-performance liquid chromatography (Gagliardi et al.1984).
Impurities
The Cosmetic,Toiletry,and Fragrance Association (CTFA )lists the following speci cations for Benzyl Alcohol,0.2%max-imum aldehyde (as benzaldehyde )and 0.005%maximum sul-fated ash.Other characteristics such as chlorinated compounds,speci c gravity,refractive index,and distilling range must match the standards of the National Formulary (NF )or United States Pharmacopeia (USP )(Nikitakis and McEwen 1990).
CTFA speci cations for Benzoic Acid and Sodium Benzoate with regard to congealing range,equivale
nt weight,water con-tent,and alkalinity follow standards t by the USP and NF (Nikitakis and McEwen 1990).USE
Cosmetic
Benzyl Alcohol
Benzyl Alcohol is ud in cosmetics as a fragrance com-ponent,prervative,solvent,and viscosity-decreasing agent (Wenninger,Canterbery,and McEwen 2000).In January 1998,Benzyl Alcohol was reported to be ud in 322cosmetic for-mulations (FDA 1998).(See Table 2.)Concentration of u data
BENZYL ALCOHOL,BENZOIC ACID,AND SODIUM BENZOATE25
英语在线翻译句子TABLE2
Frequency of u of Benzyl Alcohol(FDA1998)
No.of aining
Product category in category ingredient
Baby shampoos215
Baby lotions,oils,powders,creams533
Other baby products292
Bath oils,tablets,and salts1242
Other bath preparations1593
Eyeliner5143
Eye shadow5064
Eye makeup remover8410
Mascara1675
大学英语六级词汇
Other eye makeup preparations1204
Colognes and toilet waters6561
Other fragrance preparations1482
Hair conditioners6367
启德留学Hair sprays(aerosol xatives)2614
Rins(noncoloring)401
Shampoos(noncoloring)8607
Tonics,dressings,and other hair grooming aids54914
Hair dyes and colors1572130
Hair rins(coloring)3318
Hair color sprays(aerosol)41
Other hair-coloring preparations592
Face powders2501
Foundations2872
Lipstick7901
Makeup bas1321
Other makeup preparations1352
Deodorants(underarm)2501
Feminine hygiene deodorants42
Other personal cleanliness products2911
Aftershave lotion2164ghk
Preshave lotions(all types)141
Shaving cream1393
Cleansing65310
Face and neck skin care(excluding shaving)26312
Body and hand skin care(excluding shaving)79616
Foot powders and sprays352
Moisturizing7698
Night skin care1883
Paste masks(mud packs)2554
Skin fresheners1844
Other skin care preparations69211
Suntan gels,creams,and liquids1362
Other suntan preparations383
1998total for Benzyl Alcohol322
26COSMETIC INGREDIENT REVIEW
are no longer reported to the FDA(FDA1992).Data from FDA (1984)indicated that Benzyl Alcohol was ud at concentrations ·25%.Studies cited in the Clinical Asssment of Safety c-tion of this report tested mascara formulations containing0.65%
Benzyl Alcohol(Hill Top Rearch1997a,1997b).
Benzoic Acid and Sodium Benzoate
Benzoic Acid is ud as a pH adjustor and prervative and
Sodium Benzoate is ud as a prervative(Wenninger,
Canterbery,and McEwen2000).In January1998,Benzoic Acid
and Sodium Benzoate were reported to be ud in223and156
cosmetic formulations,respectively(FDA1998)(See Table3).造价员考试科目
Data from1984indicated that although Benzoic Acid and Sodium Benzoate were ud at up to5%and
25%,respectively, the majority of u of both ingredients was at·1%(FDA1984).
Studies cited in the Clinical Asssment of Safety ction
of this report tested eye shadow formulations containing0.1%
Benzoic Acid(Bioarch Inc.1991;TKL Rearch1991)and liquid/powder foundation formulations containing0.2%Ben-zoic Acid(Bioarch Inc.1992a,1992b,1992c,1992d;Educa-tion and Rearch Foundation1992).
International
Benzyl Alcohol
The European Union(EU)has stipulated that when ud as a prervative,Benzyl Alcohol is restricted to a maximum con-centration of1%(EU1995).
Benzyl Alcohol is listed in the Japane Comprehensive Li-censing Standards of Cosmetics by Category(CLS).Benzyl Alcohol,which conforms to the speci cations of the Japane Standards of Cosmetic Ingredients,has precedent for u without restriction in the following CLS categories:soaps,
face cleansing products,shampoos,hair rins,hair coloring preparations,and eye creams,eyeshadows,and mascaras.There has been prece-dent for u of Benzyl Alcohol at concentrations up to5%in the following categories:hair care products,creams and milky lo-tions,shaving creams and lotions,suntan and sun cream,lotion and oil formulations,shaving lotions,cosmetic oils,powders, foundations,perfumes,packs,nail creams,nail enamels,nail makeup removers,cheek color products,eyebrow products,and bath preparations.There has been no precedent regarding its u in eyeliners,lipsticks,lip creams,and dentifrices(Santucci 1999).
According to Noti cation990of the Pharmaceutical and Medical Safety Bureau of the Japan Ministry of Health and Welfare,issued September29,2000,Benzyl Alcohol is not pro-hibited or restricted(beyond the limits in the CLS discusd above)in its u beyond a basic obligation of manufacturers to u all ingredients in a manner which guarantees safety(Japan Ministry of Health and Welfare2000).
Benzoic Acid and Sodium Benzoate
The EU has stipulated that when ud as prervatives,Ben-zoic Acid,its salts and esters are restricted to a maximum con-centration of0.5%(acid)(EU1995).
Benzoic Acid and Sodium Benzoate are listed in the CLS and must conform to the speci cations of the Japane Stan-dards of Cosmetic Ingredients.Precedent to u Benzoic Acid at concentrations up to0.2%has been established in all CLS cosmetic categories except eyeliners.Precedent to u Sodium Benzoate at concentrations up to1%has been established in all CLS categories(Santucci1999).
According to Noti cation990of the Pharmaceutical and Medical Safety Bureau of the Japan Ministry of Health and Welfare,issued September29,2000,u of Benzoic Acid is restricted to0.2g per100g of any cosmetic formulation(Japan Ministry of Health and Welfare2000).
Noncosmetic
Benzyl Alcohol
Benzyl Alcohol is approved for u as a food additive (Rothschild1990).In1979,the Joint Expert Committee on Food Additives(JECFA)of the World Health Organization(WHO)es-tablished an acceptable daily intake(ADI)level of0to5mg/kg body weight.This ADI concerned Benzyl Alcohol and benzyl benzoate and“applies to the benzyl/benzoic moiety related to benzoic acid reprenting total benzoate from all food additive sources”(FAO/WHO1994).
Benzyl Alcohol can be ud as an active ingredient in over-the-counter(OTC)drug preparations(Wenninger,Canterbery, and McEwen2000).In1982,the FDA Panel on OTC Dentifrices and Dental Care Products recommended that Benzyl Alcohol not be ud in the treatment of dental pain in children younger than 2years of age(Grad and Grushka1986).
In human pain studies,Benzyl Alcohol was an effective lo-cal anesthetic.Subjects complained of less pain after receiving intramuscular(IM)injections of various medications that con-tained Benzyl Alcohol(Wightman and Vaughan1976;Gouyette et al.1982;Rasmusn,Zachmann,and Nilsson1989;Frenken, van Lier,and Koene1994;Jørgenn1994;Williams and Howe 1994).
Benzoic Acid and Sodium Benzoate
Benzoic Acid and Sodium Benzoate both have the status “generally recognized as safe”(GRAS)(Rothschild1990).In 1983,the JECFA established an ADI of0to5mg/kg body weight for Benzoic Acid,its salts,benzyl acetate,alcohol and benzoate(FAO/WHO1994).
Benzoic Acid(USP)is a component of benzoic and salicylic acid ointments(USP),a topical antifungal agent(Taylor1988).
Since the late1970s,Sodium Benzoate has been ud in the treatment of hyperammonemia in patients with inborn errors of the urea cycle.The treatment is bad on the synthesis and excretion of hippurate as an alternative pathway to eliminate nitrogen versus urea synthesis(Brusilow et al.1979,1980).
An extensive review of this therapeutic u of benzoates by Tremblay and Qureshi(1993)noted that laboratory models have yet to corroborate clinical ndings.Further,animal studies demonstrated that Sodium Benzoate,at some dos,potentiated
BENZYL ALCOHOL,BENZOIC ACID,AND SODIUM BENZOATE27
TABLE3
Frequency of u of Benzoic Acid and Sodium Benzoate(FDA1998)
No.of aining
Product category in category ingredient
Benzoic Acid
Other baby products291
青岛英语家教Bath oils,tablets,and salts1242
Bubble baths20026
Other bath preparations15932
Eye shadow5065
Eye makeup remover843
Mascara1671
Other eye makeup preparations1201
Other fragrance preparations1482
Hair conditioners6362
Hair straighteners631
Shampoos(noncoloring)8603
Tonics,dressings,and other hair grooming aids5495
Other hair preparations2762
Blushers(all types)2381
Face powders2503
Foundations2877
Lipstick79037
Makeup bas1321
Other makeup preparations1351
Cuticle softeners191
项目负责人 翻译Other manicuring preparations611
Mouthwashes and breath fresheners4912
Other oral hygiene products62
Bath soaps and detergents3858
Aftershave lotion2164
Shaving cream1392
Cleansing65312
cover girlFace and neck skin care(excluding shaving)2632
Body and hand skin care(excluding shaving)7968
Moisturizing7698
Night skin care1881
Paste masks(mud packs)2553
Skin fresheners1849
Other skin care preparations6929
Suntan gels,creams and liquids1362
Indoor tanning preparations623
1998total for Benzoic Acid223
Sodium Benzoate
Bath oils,tablets and salts1241
Other bath preparations1591
Eyeliner5143
Eye shadow5064
Eye makeup remover845
Other eye makeup preparations1202
Hair conditioners6365
Hair sprays(aerosol xatives)26124
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