FDA Cosmetics Handbook

This page handbook contains valuable information on FDA's requirements and policies for safe production and accurate labeling of cosmetics. The material in it has been carefully selected for use in the production and distribution of cosmetic products.

The handbook is composed of five sections:

1. Regulatory Requirements for Marketing Cosmetics in the United States
2. Cosmetic Good Manufacturing Practice Guidelines - Cosmetic Establishments Self-Inspection Guidelines as Excerpted from FDA's Inspection Operations Manual
3. Cosmetic Product-Related Regulatory Requirements and Health Hazard Issues as Excerpted from FDA's Inspection Operations Manual
4. Permanently & Provisionally Listed Color Additives
5. How to Obtain FDA Cosmetic Regulations

Regulatory Requirements for Marketing Cosmetics in the United States

Cosmetics marketed in the United States, whether manufactured here or imported from abroad, must be in compliance with the provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the Fair Packaging and Labeling Act (FPLA), and the regulations published under the authority of these laws.

The regulations published by the Food and Drug Administration (FDA) are all codified in Title 21, Code of Federal Regulations (21 CFR). The regulations applicable to cosmetics are stated at 21 CFR, parts 700 to 740 (21 CFR 700 to 740). The color additive regulations applicable to cosmetics are found at 21 CFR 73, 74 and 82. Copies of the 21 CFR volumes containing these regulations may be obtained at current cost from the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402, telephone (202) 783-3238.

The FD&C Act defines cosmetics as articles intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance without affecting the body's structure or functions. Included in this definition are products such as skin creams, lotions, perfumes, lipsticks, fingernail polishes, eye and facial make-up preparations, shampoos, permanent waves, hair colors, toothpastes, deodorants, and any material intended for use as a component of a cosmetic product. Soap products consisting primarily of an alkali salt of fatty acid and making no label claim other than cleansing of the human body are not considered cosmetics under the law.

Cosmetics that are also Drugs

Products that are cosmetics but are also intended to treat or prevent disease, or otherwise affect the structure or functions of the human body, are considered also drugs and must comply with both the drug and cosmetic provisions of the law. Examples of products which are drugs as well as cosmetics are anticaries toothpastes (e.g., "fluoride" toothpastes), hormone creams, suntanning preparations intended to protect against sunburn, antiperspirants that are also deodorants, and antidandruff shampoos.

Most currently marketed cosmetics which are also drugs are over-the-counter drugs. Several are new drugs for which safety and effectiveness had to be proved to the agency before they could be marketed. A new drug is a drug which is not generally recognized by experts as safe and effective under the conditions of intended use or which has become so recognized but has not been used to a material extent or for a material time under such conditions.

The regulatory requirements for drugs are more extensive than the requirements applicable to cosmetics. For example, the FD&C Act requires that drug manufacturers register every year with the FDA and update their lists of all manufactured drugs twice annually. See 21 CFR 207. Additionally, drugs must be manufactured in accordance with current good manufacturing practice regulations as codified at 21 CFR 210 and 211.

Adulterated or Misbranded Cosmetics

The FD&C Act prohibits the distribution of cosmetics which are adulterated or misbranded. A cosmetic is considered adulterated if it contains a substance which may make the product harmful to consumers under customary conditions of use; if it contains a filthy, putrid, or decomposed substance; if its container is composed of a harmful substance; if it is manufactured or held under insanitary conditions whereby it may have become contaminated with filth, or may have become harmful to consumers; or if it is not a hair dye that contains a non-permitted color additive.

Coal-tar hair dyes bearing on the label the caution statement prescribed by law and give "patch-test" instructions are exempted from the adulteration provision even if they are irritating to the skin or are otherwise harmful to the human body. Eyelash and eyebrow dyes are not included in this exemption. All dyes used in eyelash and eyebrow dye products must be approved by the FDA for such use.

A cosmetic is misbranded if its labeling is false or misleading, if it does not bear the required labeling information, or if the container is made or filled in a deceptive manner.

Cosmetic Safety

Although the FD&C Act does not require that cosmetic manufacturers or marketers test their products for safety, the FDA strongly urges cosmetic manufacturers to conduct whatever toxicological or other tests are appropriate to substantiate the safety of their cosmetics. If the safety of a cosmetic is not adequately substantiated, the product may be considered misbranded and may be subject to regulatory action unless the label bears the following statement: "Warning - The safety of this product has not been determined." See 21 CFR 740.10.

With the exception of color additives and a few prohibited ingredients, a cosmetic manufacturer may, on his own responsibility, use essentially any raw material as a cosmetic ingredient and market the product without approval. The law requires that color additives used in food, drugs and cosmetics must be tested for safety and approved by the FDA for their intended uses. A cosmetic containing an unlisted color additive; i.e., a color additive which has not been approved by the FDA for its intended use, is considered adulterated and subject to regulatory action. The color additives approved for use in cosmetics are listed at 21 CFR 73, 74 and 82.

The use of the following ingredients is either restricted or prohibited in cosmetics: bithionol, mercury compounds, vinyl chloride, halogenated salicylanilides, zirconium complexes in aerosol cosmetics, chloroform, methylene chloride, chlorofluorocarbon propellants, and hexachlorophene. See 21 CFR 700.11 to 700.23 and 250.250. The agency also considers as adulterated cosmetic nail products containing methyl methacrylate monomer or those containing more than 5% formaldehyde. Although not prohibited by law or regulation, in addition, the manufacturers of cosmetic fragrance products have voluntarily agreed to not use or to limit maximum use levels of certain selected ingredients which have been found to cause depigmentation, irritant, neurotoxic, or phototoxic or other allergic reactions.

Voluntary Registration

Although the FD&C Act does not require cosmetic firms to register manufacturing establishments or formulations with the FDA or make available safety data or other information before a product is marketed in the United States, manufacturers or distributors of cosmetics may submit this information to the agency voluntarily. Voluntary registration and assignment of a registration number by the agency does not denote approval of a firm or product by the FDA. Any use of a registration number in labeling must be accompanied by a conspicuous disclaimer phrase as prescribed by regulation. See 21 CFR 710, 720 and 730.

Cosmetic Labeling

The cosmetics distributed in the United States must comply with the labeling regulations published by the FDA under the authority of the FD&C Act and the FPLA. Labeling means all labels and other written, printed or graphic matter on or accompanying a product. The label statements required under the authority of the FD&C Act must appear on the inside as well as any outside container or wrapper. FPLA requirements, e.g., ingredient labeling and statement of the net quantity of contents on the principal display panel, only apply to the label of the outer container. The labeling requirements are codified at 21 CFR 701 and 740. Cosmetics bearing false or misleading label statements or otherwise not labeled in accordance with the codified requirements may be considered misbranded and may be subject to regulatory action.

The principal display panel, i.e., the part of the label most likely displayed or examined under customary conditions of display for sale (21 CFR 701.10) and generally bearing the name of the product. It must identify by descriptive name or illustration the nature or use of the product and bear an accurate statement of the net quantity of contents of the cosmetic in the package in terms of weight, measure, numerical count, or a combination of numerical count and weight or measure. The declaration must be distinct, placed in the bottom area of the panel in line generally parallel to the base on which the package rests, and in a type size commensurate with the size of the container as prescribed by regulation.

The net quantity of contents statement of a solid, semi-solid or viscous cosmetic must be in terms of the avoirdupois pound and ounce, and a statement of liquid measure must be in terms of the U.S. gallon of 231 cubic inches and the quart, pint, and fluid ounce subdivisions thereof. If the net quantity of contents exceeds one pound or one pint, it must be expressed in ounces, followed in parenthesis ( ) by a declaration of the largest whole units (i.e., pounds and ounces or quarts and pints and ounces). The net quantity of contents may additionally be stated in terms of the metric system of weights or measures.

The name and place of business of the firm marketing the product must be stated on an information panel of the label (21 CFR 701.12). The address must state the street address, city, state, and zip code. If a firm is listed in a current city or telephone directory, the street address may be omitted. If the distributor is not the manufacturer or packer, this fact must be stated on the label by the qualifying phrase "Manufactured for ..." or "Distributed by ..." or similar, appropriate wording.

The Tariff Act of 1930 (19 U.S.C. 1304) requires that all imported articles state on the label the English name of the country of origin. See also 19 CFR 134.

All label statements required by regulation must be in the English language and must be placed on the label or labeling with such prominence and conspicuousness that they are readily noticed and understood by consumers under customary conditions of purchase (21 CFR 701.2).

Declaration of Ingredients

Cosmetics produced or distributed for retail sale to consumers for their personal care are required to bear an ingredient declaration (21 CFR 701.3). Cosmetics not customarily distributed for retail sale, e.g., hair preparations or makeup products used by professionals on customers at their establishments or skin cleansers made available to persons at their place of work, are exempt from this requirement provided these products are not also sold to consumers at professional establishments or workplaces for their consumption at home.

The ingredient declaration must be conspicuous so that it is likely to be read at the time of purchase. It may appear on any information panel of the outer container, i.e., an information panel of the folding carton, box or wrapping if the immediate container is so pack-aged or, if not packaged in an outer container, an information panel of the jar, tube or bottle containing the product. The ingredient declaration may also appear on a tag, tape or card that is firmly affixed to the outer container. The letters must not be less than 1/16 of an inch in height (21 CFR 701.3(b)). If the total package surface available to bear labeling is less than 12 square inches, the letters must not be less than 1/32 of an inch in height (21 CFR 701.3(p)). Off-package ingredient labeling is permitted if the cosmetic is held in tightly compartmented trays or racks, it is not enclosed in a folding carton, and the package surface area is less than 12 square inches (21 CFR 701.3(i)).

The ingredients must be declared in descending order of predominance. Color additives (21 CFR 701.3(f)(3)) and ingredients present at one percent or less (21 CFR 701.3(f)(2)) may be declared after the ingredients present at concentrations exceeding one percent without regard for predominance. The ingredients must be identified by the names established or adopted by regulation (21 CFR 701.3(c)); those accepted by the FDA as exempt from public disclosure may be stated as "and other ingredients" (21 CFR 701.3(a)).

Cosmetics which are also drugs must first identify the drug ingredient(s) as "active ingredients(s)" before listing the cosmetic ingredients (21 CFR 701.3(d)).

Label Warnings

Cosmetics which may be hazardous to consumers when misused must bear appropriate label warnings and adequate directions for safe use. The statements must be prominent and conspicuous. Some cosmetics must bear label warnings or cautions prescribed by regulation (21 CFR 740). Cosmetics in self-pressurized containers (aerosol products), feminine deodorant sprays and, children's bubble bath products are examples of products requiring such statements.

Tamper-Resistant Packaging

Liquid oral hygiene products (e.g., mouthwashes, fresheners) and all cosmetic vaginal products (e.g., douches, tablets) must be packaged in tamper-resistant packages when sold at retail. A package is considered tamper-resistant if it has an indicator or barrier to entry (e.g., shrink or tape seal, sealed carton, tube or pouch, aerosol container) which, if breached or missing, alerts a consumer that tampering has occurred. The indicator must be distinctive by design (breakable cap, blister) or appearance (logo, vignette, other illustration) to preclude substitution. The tamper-resistant feature may involve the immediate or outer container or both. The package must also bear a prominently placed statement alerting the consumer to the tamper-resistant feature. This statement must remain unaffected if the tamper-resistant feature is breached or missing. See 21 CFR 700.25.

Law Enforcement Authority

For enforcement of the law, the FDA may conduct examinations and investigations of products, inspect establishments in which products are manufactured or held, and seize adulterated (harmful) or misbranded (incorrectly or deceptively labeled or filled) cosmetics. Adulterated or misbranded foreign products may be refused entry into the United States. To pre-vent further shipment of an adulterated or misbranded product, the agency may request a federal district court to issue a restraining order against the manufacturer or distributor of the violative cosmetic. The FDA may also initiate criminal action against a per-son violating the law. Examples of products seized are nail preparations containing methyl methacrylate or formaldehyde, various eyebrow and eyelash dye products containing prohibited coal-tar dyes, and products contaminated with harmful microorganisms.

Further questions regarding regulatory requirements for marketing cosmetics should be directed to the Food and Drug Administration, Division of Colors and Cosmetics (HFF-440), 200 C Street, SW, Washington, DC 20204. Questions regarding requirements for marketing products which are cosmetic and drugs should also be addressed to the Division of Drug Labeling, OTC Compliance Branch (HFN-312), 5600 Fishers Lane, Rockville, MD 208567.

Cosmetic Good Manufacturing Practice Guidelines

The Federal Food, Drug, and Cosmetic Act prohibits the introduction or delivery for introduction into interstate commerce of cosmetics that are adulterated or misbranded (Sec. 301).

A cosmetic may be deemed adulterated (Sec. 601) for essentially four reasons, namely:

1. It may be injurious to users under conditions of customary use because it contains, or its container is composed of, a potentially harmful substance.
2. It contains filth.
3. It contains a non-permitted, or in some instance non-certified, color additive.
4. It is manufactured or held under insanitary conditions whereby it may have become injurious to users or contaminated with filth.

A cosmetic may be deemed misbranded (Sec. 602) for reasons of:

1. False or misleading labeling.
2. Failure to state prominently and conspicuously any information required by or under authority of this act.
3. Misleading container presentation or fill.

To determine whether cosmetic firms manufacture, hold or deliver for introduction into interstate commerce cosmetics that are adulterated or misbranded, and to prevent these and other practices violating Sec. 301 of the FD&C Act, the law gives the agency the authority to enter the establishments of such firms and inspect their facilities as well as all pertinent equipment, finished and unfinished materials, containers and labeling therein. See Sec. 704(a) of the FD&C Act.

Rigorous adherence to good manufacturing practice minimizes the risk of adulteration or misbranding of cosmetics. The following cosmetic establishment instructions, excerpted from FDA's Inspection Operations Manual, may serve as guidelines for effective self-inspection. A good inspection score means that an establishment follows good manufacturing practice.

Guidelines

1. Building and Facilities. Check whether:

a. Buildings used in the manufacture or storage of cosmetics are of suitable size, design and construction to permit unobstructed placement of equipment, orderly storage of materials, sanitary operation, and proper cleaning and maintenance.

b. Floors, walls and ceilings are constructed of smooth, easily cleanable surfaces and are kept clean and in good repair.

c. Fixtures, ducts and pipes are installed in such a manner that drip or condensate does not contaminate cosmetic materials, utensils, cosmetic contact surfaces of equipment, or finished products in bulk.

d. Lighting and ventilation are sufficient for the intended operation and comfort of personnel.

e. Water supply, washing and toilet facilities, floor drainage and sewage system are adequate for sanitary operation and cleaning of facilities, equipment and utensils, as well as to satisfy employee needs and facilitate personal cleanliness.

2. Equipment. Check whether:

a. Equipment and utensils used in processing, holding, transferring and filling are of appropriate design, material and workmanship to prevent corrosion, buildup of material, or adulteration with lubricants, dirt or sanitizing agent.

b. Utensils, transfer piping and cosmetic contact surfaces of equipment are well-maintained and clean and are sanitized at appropriate intervals.

c. Cleaned and sanitized portable equipment and utensils are stored and located, and cosmetic contact surfaces of equipment are covered, in a manner that protects them from splash, dust or other contamination.

3. Personnel. Check whether:

a. The personnel supervising or performing the manufacture or control of cosmetics has the education, training and/or experience to perform the assigned functions.

b. Persons coming into direct contact with cosmetic materials, finished products in bulk or cosmetic contact surfaces, to the extent necessary to prevent adulteration of cosmetic products, wear appropriate outer garments, gloves, hair restraints etc., and maintain adequate personal cleanliness.

c. Consumption of food or drink, or use of tobacco is restricted to appropriately designated areas.

4. Raw Materials. Check whether:

a. Raw materials and primary packaging materials are stored and handled in a manner which prevents their mix-up, contamination with microorganisms or other chemicals, or decomposition from exposure to excessive heat, cold, sunlight or moisture.

b. Containers of materials are closed, and bagged or boxed materials are stored off the floor.

c. Containers of materials are labeled with respect to identity, lot identification and control status.

d. Materials are sampled and tested or examined in conformance with procedures assuring the absence of contamination with filth, microorganisms or other extraneous substances to the extent necessary to prevent adulteration of finished products. Pay particular attention to materials of animal or vegetable origin and those used in the manufacture of cosmetics by cold processing methods with respect to contamination with filth or microorganisms.

e. Materials not meeting acceptance specifications are properly identified and controlled to prevent their use in cosmetics.

5. Production. Check whether manufacturing and control have been established and written instructions, i.e., formulations, processing, transfer and filling instructions, in-process control methods etc., are being maintained. Determine whether such procedures require that:

a. The equipment for processing, transfer and filling the utensils, and the containers for holding raw and bulk materials are clean, in good repair and in sanitary condition.

b. Only approved materials are used.

c. Samples are taken, as appropriate, during and/or after processing, transfer or filling for testing for adequacy of mixing or other forms of processing, absence of hazardous microorganisms or chemical contaminants, and compliance with any other acceptance specification.

d. Weighing and measuring of raw materials is checked by a second person, and containers holding the materials are properly identified.

e. Major equipment, transfer lines, containers and tanks used for processing, filling or holding cosmetics are identified to indicate contents, batch designation, control status and other pertinent information.

f. Labels are examined for identity before labeling operations to avoid mix-up.

g. The equipment for processing, holding, transferring and filling of batch is labeled regarding identity, batch identification and control status.

h. Packages of finished products bear permanent code marks.

i. Returned cosmetics are examined for deterioration or contamination.

6. Laboratory Controls. Check whether:

a. Raw materials, in-process samples and finished products are tested or examined to verify their identity and determine their compliance with specifications for physical and chemical properties, microbial contamination, and hazardous or other unwanted chemical contaminants.

b. Reserve samples of approved lots or batches of raw materials and finished products are retained for the specified time period, are stored under conditions that protect them from contamination or deterioration, and are retested for continued compliance with established acceptance specifications.

c. The water supply, particularly the water used as a cosmetic ingredient, is tested regularly for conformance with chemical-analytical and microbiological specifications.

d. Fresh as well as retained samples of finished products are tested for adequacy of preservation against microbial contamination which may occur under reasonably foreseeable conditions of storage and consumer use.

7. Records. Check whether control records are maintained of:

a. Raw materials and primary packaging materials, documenting disposition of rejected material.

b. Manufacturing of batches, documenting the:

(i) Kinds, lots and quantities of materials used.

(ii) Processing, handling, transferring, holding and filling.

(iii) Sampling, controlling, adjusting and reworking.

(iv) Code marks of batches and finished products.

c. Finished products, documenting sampling, individual laboratory controls, test results and control status.

d. Distribution, documenting initial interstate shipment, code marks and consignees.

8. Labeling. Check whether the labels of the immediate and outer containers bear:

a. On the principal display panel:

(i) In addition to the name of the product, the statements of identity and net contents,

(ii) The statement "Warning - The safety of this product has not been determined" if the safety of the respective product has not adequately been substantiated. Determine whether and what toxicological and/or other testing the firm has conducted to substantiate the safety of its products. See 21 CFR 740.10.

b. On an information panel:

(i) The name and address of the firm manufacturing the product or introducing it into interstate commerce.

(ii) The list of ingredients (only on outer container) if intended for sale or customarily sold to consumers for consumption at home.

(iii) The warning statement(s) required at 21 CFR 740.11, 740.12 and 740.17.

(iv) Any other warning statement necessary or appropriate to prevent a health hazard. Determine the health hazard or other basis for a warning statement.

(v) Any direction for safe use of product.

(vi) In the case of a hair dye product, the caution statement of sec. 601(a) of the Act and appropriate directions for preliminary patch testing. This warning only applies to coal-tar hair dyes which, if so labeled, are then exempted from the adulteration provision of the Act.

9. Complaints. Check whether the firm maintains a consumer complaint file and determine:

a. The kind and severity of each reported injury and the body part involved.

b. The product associated with each injury, including the manufacturer and code number.

c. The medical treatment involved, if any, including the name of the attending physician.

d. The name(s) and location(s) of any poison control center, government agency, physician's group etc., to whom formula information and/or toxicity data are provided.

e. Whether the firm voluntarily files Cosmetic Product Experience Reports (21 CFR 730).

10. Other. Check whether the firm is:

a. Participating in the program of voluntary registration of:

(i) Cosmetic manufacturing establishments (21 CFR 710).

(ii) Cosmetic product ingredient and cosmetic raw material composition statements (21 CFR 720).

(iii) Cosmetic product experiences (21 CFR 730).

b. Using a color additive which is not listed for use in cosmetics (21 CFR 73, 74 and 82) or which is not certified (21 CFR 80).

c. Using a prohibited cosmetic ingredient (21 CFR 700).

Cosmetic Product-Related Regulatory Requirements and Health Hazard Issues

Ingredient Labeling

Cosmetics produced or distributed for retail sale to consumers for their personal care are required to bear an ingredient declaration (21 CFR 701.3). Cosmetics not customarily distributed for retail sale, e.g., hair preparations or make-up products used by professionals at their establishments and skin cleansing or emollient creams used at places of work, are exempt from this requirement provided these products are not also sold to consumers.

The ingredient declaration must be conspicuous so that it is likely to be read at the time of purchase. It may appear on any information panel of the package, i.e., the folding carton, box or wrapping if the immediate container is so packaged, and may also appear on a firmly affixed tag, tape or card. The letters must not be less than 1/16 of an inch in height (701.3(b)). If the total package surface available to bear labeling is less than 12 square inches, the letters must not be less than 1/32 of an inch in height (701.3(p)). Off-package ingredient labeling is permitted if the cosmetic is held in tightly compartmented trays or racks, it is not enclosed in a folding carton, and the package surface area is less than 12 square inches (701.3(i)).

The ingredients must be declared in descending order of predominance. Color additives (701.3(f)(3)) and ingredients present at one percent or less (701.3(f)(2)) may be declared without regard for predominance. The ingredients must be identified by the names established or adopted by regulation (701.3(c)); those accepted by the FDA as exempt from public disclosure may be stated as "and other ingredients" (701.3(a)).

Cosmetics which are also drugs must first identify the drug ingredient(s) as "active ingredient(s)" before listing the cosmetic ingredients (701.3(d)).

Prohibited Ingredients and other Hazardous Substances

1. Hexachlorophene (21 CFR 250.250).

Because of its neurotoxic effect and ability to penetrate human skin, hexachlorophene (HCP) may be used only when an alternative preservative has not been shown to be as effective. The HCP concentration of the cosmetic may not exceed 0.1%, and it may not be used in cosmetics which in normal use may be applied to mucous membrane.

2. Mercury compounds (21 CFR 700.13).

The use of mercury compounds as cosmetic ingredients is limited to eye area cosmetics at concentrations not exceeding 65 parts per million (0.0065%) of mercury calculated as the metal (about 100 ppm or 0.01% phenylmercuric acetate or nitrate) and provided no other effective and safe preservative is available for use.

Mercury compounds are readily absorbed through the skin on topical application and have the tendency to accumulate in the body. They may cause allergic reactions, skin irritation or neurotoxic manifestations.

3. Chlorofluorocarbon propellants (21 CFR 700.23 and 2.125).

The use of chlorofluorocarbon propellants (fully halogenated chlorofluoroalkanes) in cosmetic aerosol products intended for domestic consumption is prohibited.

Chlorofluorocarbon-containing cosmetic aerosol products may continue to be manufactured for export provided they are not in conflict with the laws of the country to which they are to be exported and the following control system is being followed to ensure that there is no likelihood, by mistake or otherwise, of diversion of such products into domestic commerce:

(a) The manufacturer has an order from the foreign purchaser stating the exact amount desired, that a chlorofluorocarbon be used as propellant, and that he is aware of its illegality in the United States. The manufacturer must also have in his possession a current letter from a responsible official of the country to which the product is to be shipped stating that the use of chlorofluorocarbon propellants is legal in the respective country.

(b) The stock of chlorofluorocarbon propellants intended for export production is kept under adequate security at all times.

(c) During all stages of manufacture and storage the chlorofluorocarbon-containing aerosol product is kept segregated from all other products and is clearly marked "for export only."

(d) Complete records are kept accounting for all chlorofluorocarbon propellant use as well as for all manufacture, storage, shipment and exportation of aerosol products containing these propellants. These records must be retained for at least 3 years and made available to any FDA official upon oral or written request.

4. Other prohibited ingredients.

The following additional substances are prohibited as cosmetic ingredients, (but not as unintentional contaminants of cosmetics manufactured in accordance with current good manufacturing practices):

(a) Bithionol because of its likelihood of causing photo-contact sensitization (21 CFR 700.11).

(b) Halogenated salicylanilides (di-, tri-, metabromsalan and tetrachlorosalicylanilide) because of their potential of causing photocontact sensitization (21 CFR 700.15).

(c) Chloroform because of its animal carcinogenicity and likely hazard to human health (21 CFR 700.18).

(d) Vinyl chloride as an ingredient of aerosol products because of its carcinogenic effect in humans and animals (21 CFR 700.14).

(e) Zirconium-containing complexes in aerosol cosmetic products because of their toxic effect on lungs, including granulomas (21 CFR 700.16).

(f) Methylene chloride because of its animal carcinogenicity and likely hazard to human health (21 CFR 700.18).

5. Acetylethyltetramethyltetralin (AETT).

AETT should not be used in fragrance formulations and finished cosmetic products (usually in products claiming to be fragrance-free). In a subchronic toxicity study in rats conducted in 1977, AETT was found to cause serious neurotoxic disorders and discoloration of internal organs. It was also determined to penetrate human skin. The fragrance industry voluntarily discontinued use of AETT in 1978.

6. Musk ambrette.

Various tests and clinical experience have demonstrated that musk ambrette may cause photocontact sensitization, i.e., allergic reactions of the skin on exposure to musk ambrette and sunlight. Other studies have indicated that musk ambrette may also cause neurotoxic effects. The International Fragrance Association has recommended that musk ambrette should not be used in products applied to the skin, particularly those products used on skin that is customarily also exposed to sunlight.

7. 6-Methylcoumarin (6-MC).

The fragrance ingredient 6-MC is a potent photo-contact sensitizer which may cause serious skin and systemic disorders in some consumers on contact in the presence of sunlight. Between 1976 and 1978, the FDA received many reports of adverse reactions associated with the use of 6-MC-containing suntan preparations. The photocontact allergenicity of 6-MC was subsequently confirmed in clinical studies. In 1978, the FDA asked the manufacturers of suntan and sunscreen products to discontinue the use of 6-MC. Two firms voluntarily recalled products containing 6-MC from the market.

8. Nitrosamines.

Cosmetics containing as ingredients amines or amino derivatives, particularly di- or triethanolamine, may form nitrosamines if they also contain an ingredient which acts as a nitrosating agent as, for example, 2-bromo-2-nitropropane-1,3-diol (Bronopol, Onyx-ide 500), 5-bromo-5-nitro-1,3-dioxane (Bronidox C) or tris (hydroxymethyl) nitromethane (Tris Nitro), or if they are contaminated with a nitrosating agent, e.g., sodium nitrite. Amines and their derivatives are mostly present in creams, cream lotions, hair shampoos and cream hair conditioners. The nitrosation may occur during manufacture or during product storage.

Many nitrosamines have been determined to cause cancer in laboratory animals. They have also been shown to penetrate the skin. Nitrosamine contamination of cosmetics became an issue in early 1977. In a study of 29 cosmetic creams and lotions, N-Nitrosodiethanolamine (NDELA) was determined in 27. The levels of NDELA contamination ranged from less than 10 parts per billion (ppb) to 50 parts per million (ppm). Of the more than 300 cosmetic samples analyzed in 1978, 1979 and early 1980 in FDA's laboratories, 7% contained less than 30 ppb NDELA, 26% contained 30 ppb to 2 ppm and 7% contained between 2 ppm and 150 ppm.

The FDA expressed its concern about the contamination of cosmetics with nitrosamines in a notice published in the Federal Register of April 10, 1979 (44 FR 21365). It stated that cosmetics containing nitrosamines may be considered adulterated and subject to enforcement action. In surveys of cosmetic products conducted in 1991-92, NDELA was found in 65% of the samples at levels up to 3 ppm.

9. Dioxane.

Cosmetics containing as ingredients ethoxylated surface active agents, i.e., detergents, foaming agents, emulsifiers and certain solvents identifiable by the prefix, word or syllable "PEG," "Polyethylene," "Polyethylene glycol," "Polyoxyethylene," "-eth-," or "-oxynol-," may be contaminated with 1,4-dioxane. It may be removed from ethoxylated compounds by means of vacuum stripping at the end of the polymerization process without an unreasonable increase in raw material cost.

In rodent feeding studies conducted for the National Cancer Institute, 1,4-dioxane was found to produce cancer of the liver and the nasal turbinates. It also caused systemic cancer in a skin painting study. Skin absorption studies demonstrated that dioxane readily penetrates animal and human skin from various types of vehicles. However, it was also determined that most of the dioxane applied to the skin in a vehicle evaporates into the environment and may not be available for skin absorption.

The contamination of ethoxylated surface-active agents with dioxane was first reported in 1978. Many of the raw materials analyzed since then have been found to contain dioxane; some contained as much as, or more than, 100 ppm. In finished cosmetic products containing ethoxylated surface-active agents, the incidence and level of dioxane contamination was significantly lower.

Adequacy of Preservation

Cosmetics need not be sterile, however, they must not be contaminated with microorganisms which may be pathogenic, and the density of non-pathogenic microorganisms should be low. In addition, cosmetics should remain in this condition when used by consumers. Some cosmetics, i.e., those containing more than about 10% ethanol, propylene glycol, glycerol, etc., and cosmetics in self-pressurized containers, are usually self-preserving and are not likely to become contaminated with microorganisms.

The hazard of inadequately preserved cosmetics to human health has been amply demonstrated by reports of staphylococcal infections in hospitals from use of contaminated hand creams and hand lotions and in studies conducted on eye area cosmetics. Regardless of whether a cosmetic becomes contaminated during manufacture or during consumer use, the hazard is twofold, namely, (1) the direct effect of microorganisms on human health and (2) the circuitous effect on human health due to product contamination and spoilage, product separation, or formation of harmful microbial metabolites.

Microbial contamination of cosmetics during manufacture was a major issue during the 1960's and early 1970's. Since then, significant progress has been made by the cosmetic industry towards implementation of sanitary manufacturing practices, more rigorous microbiological control, and the development of better-preserved cosmetic products. However, the problem of adequacy of preservation of cosmetics to prevent contamination during consumer use continues to be of concern to the agency, particularly with respect to cosmetics coming into contact with the eye.

The studies conducted to determine the hazard associated with inadequately preserved eye area cosmetics revealed that microbial contamination of new mascaras was rare but that many became readily contaminated with the microorganisms found on the eyelids and fingers of consumers. If an inadequately preserved mascara becomes contaminated with Pseudomonas aeruginosa and the delicate cornea of the eye is scratched with the applicator, the eye may become infected. P. aeruginosa is an ubiquitous microorganism which may also occasionally be present on the skin. Corneal ulceration may lead to partial or total blindness in the injured eye. Several cases of corneal ulceration and blindness associated with Pseudomonas-contaminated mascaras have been identified. Eye area cosmetics contaminated with Staphylococcus epidermidis or other cocci may cause conjunctivitis or blepharitis.

The issue of adequacy of preservation of eye area cosmetics was addressed in the Federal Register notice of October 11, 1977 (42 FR 54837). The agency announced its intention to propose regulations and invited interested persons to submit information on microbial testing methods and standards of performance suitable to ensure that such cosmetics do not become contaminated with microorganisms during manufacture and use by consumers. Since no useful information was received about such methods, the agency decided to have standards for determining adequacy of preservation developed under contract, and this work is currently underway. The notice also stated that "FDA does not intend to await the completion of the rulemaking pronounced in this notice of intent before taking needed regulatory action."

In addition to sanitary storage and handling of raw materials and sanitary manufacture of finished products, it is recommended that:

(a) Each batch of a cosmetic which is not self-preserving be tested for microbial contamination before it is released for interstate shipment, and

(b) Each cosmetic, particularly each eye area cosmetic, be tested during product development for adequacy of preservation against microbial contamination which may occur under reasonably foreseeable conditions of consumer use.

Aerosol Products

Chlorofluorocarbon propellants, vinyl chloride, and zirconium compounds are prohibited as ingredients of cosmetic aerosol products (21 CFR 700.23, 700.14 and 700.16).

Cosmetic aerosol products must bear the following label statement (21 CFR 740.11(a)(1)):

Warning - Avoid spraying in eyes. Contents under pressure. Do not puncture or incinerate. Do not store at temperature above

120 degrees F. Keep out of reach of children.

Hydrocarbon propellant-containing products must also bear the statement (21 CFR 740.11(b)(1)).

Warning - Use only as directed. Intentional misuse by deliberately concentrating and inhaling the contents can be harmful or fatal.

Exempt from the second warning requirement are:

(a) Foam or cream products containing less than 10% propellant.

(b) Products in a container with a physical barrier that prevents escape of the propellant at the time of use.

(c) Products with a net quantity of contents of less than 2 ounces and equipped with a metering valve.

(d) Products with a net quantity of contents of less than ½ ounce.

Feminine Deodorant Sprays

Products whose labeling states or suggests that the product is for use in the female genital area or for use all over the body must bear the following label statement (21 CFR 740.12):

Caution - For external use only. Spray at least 8 inches from skin. Do not apply to broken, or irritated, or itching skin. Persistent, unusual odor or discharge may indicate conditions for which a physician should be consulted. Discontinue use immediately if rash, irritation, or discomfort develops.

Feminine deodorant sprays which are not packaged in self-pressurized containers, need not bear the sentence "Spray at least 8 inches from skin." If they are aerosol products, they must also bear the warning required at 21 CFR 740.11(a)(1). Additionally, if the propellant is a hydrocarbon, the label must bear the warning required at 740.11(b)(1).

Bubble Bath Products

The risk associated with certain conditions of use of foaming detergent bath products, i.e., bubble bath products, particularly excessive or prolonged exposure, has been known for some time. Over the years, the agency has received numerous complaints from consumers and physicians about itching, rashes and urinary tract disorders. Reports in the medical literature have mentioned that the adverse reactions either subsided or disappeared when the use of bubble bath products was discontinued. Most adverse reactions appeared to have been caused by inadvertent product misuse which may not have occurred if consumers had been given proper directions for safe use of these products and had been cautioned about the possible adverse effects by means of a mandatory label warning.

In 1980, the FDA published a regulation requiring that the labels of bubble bath products bear adequate directions for safe use and the prescribed caution statement. The effective date was subsequently stayed to permit reconsideration of the regulation. The new effective date of the revised regulation (it does not apply to foaming detergent bath products clearly labeled that they are intended for use exclusively by adults) is June 5, 1987 (51 FR 20471).

The regulation (21 CFR 740.17) requires that children's foaming detergent bath products, i.e., children's bubble bath products, and all foaming detergent bath products not labeled as intended for use exclusively by adults, bear adequate directions for safe use and this caution:

Caution - Use only as directed. Excessive use or prolonged exposure may cause irritation to skin and urinary tract. Discontinue use if rash, redness, or itching occur. Consult your physician if irritation persists. Keep out of reach of children.

For the purpose of this regulation, a foaming deter-gent bath product (bubble bath product) is defined as any product intended to be added to the bath for the purpose of producing foam and containing a surface-active agent serving as a detergent or foaming agent. Examples of label statements properly identifying a product as being intended for use exclusively by adults are: "Keep out of reach of children" or "For adult use only."

Hair Dye Products

Hair dye products may be divided into three categories, i.e., permanent, semi-permanent and temporary hair colors. Permanent hair colors are the most popular hair dye products. They may be further divided into oxidation hair dyes and progressive hair dyes. Oxidation hair dye products consist of (1) a solution of dye intermediates, e.g., p-phenylene-diamine, which form hair dyes on chemical reaction, and preformed dyes, e.g., 2-nitro-p-phenylene-diamine, which already are dyes and are added to achieve the intended shades, in an aqueous, ammoniacal vehicle containing soap, detergents and conditioning agents; and, (2) a solution of hydrogen peroxide, usually 6%, in water or a cream lotion.

The ammoniacal dye solution and the hydrogen peroxide solution, often called the developer, are mixed shortly before application to the hair. The applied mixture causes the hair to swell and the dye intermediates (and preformed dyes) penetrate the hair shaft to some extent before they have fully reacted with each other and the hydrogen peroxide and formed the hair dye.

Progressive hair dye products contain lead acetate as the active ingredient. Lead acetate is approved as a color additive for coloring hair on the scalp at concentrations not exceeding 0.6% w/v, calculated as metallic lead (21 CFR 73.2396). Bismuth citrate, the other approved color additive (21 CFR 73.2110), is used to a much lesser extent. Progressive hair dyes change the color of hair gradually from light straw color to almost black by reacting with the sulfur of hair keratin as well as oxidizing on the hair surface.

Semi-permanent and temporary hair coloring products are solutions (on rare occasions dry powders) of various coal-tar, i.e., synthetic organic, dyes which deposit and adhere to the hair shaft to a greater or lesser extent. Temporary hair colors must be re-applied after each shampooing. The vehicle may consist of water, organic solvents, gums, surfactants and conditioning agents. The coal-tar dyes are either listed and certified color additives or dyes for which approval has not been sought. The dyes may not be non-permitted metallic salts or vegetable substances.

A hair dye product containing a non-approved coal-tar color (but not a non-approved metallic or vegetable dye) which is known to cause adverse reactions under conditions of use cannot be considered adulterated if the label bears the caution statement provided in section 601(a) of the FD&C Act and offers adequate directions for preliminary patch testing by consumers for skin sensitivity. The caution statement reads as follows:

Caution - This product contains ingredients which may cause skin irritation on certain individuals and a preliminary test according to accompanying directions should first be made. This product must not be used for dyeing the eyelashes or eyebrows; to do so may cause blindness.

If the label of a coal-tar color-containing hair dye product does not bear the caution statement of section 601(a) and the patch testing directions, it may be subject to regulatory action if it is determined to be harmful under customary conditions of use.

Several coal-tar hair dye ingredients have been found to cause cancer in laboratory animals. In the case of 4-methoxy-m-phenylenediamine (4-MMPD, 2,4-diaminoanisole) which had also been demonstrated in human and animal studies to penetrate the skin, the agency considered the risk associated with its use in hair dyes a "material fact" which should be made known to consumers. The regulation requiring a label warning on hair dye products containing 4-MMPD published in October 1979 was to become effective April 16, 1980. The regulation required that hair dyes containing 4-MMPD bear the following warning:

Warning - Contains an ingredient that can penetrate your skin and has been determined to cause cancer in laboratory animals.

Some hair dye manufacturers held that the potential risk was too small to be considered "material" and challenged the validity of the regulation in court. The agency decided to reconsider its earlier position, entered into a consent agreement with the hair dye manufacturers, and stayed the effectiveness of the regulation until completion of an assessment of the carcinogenic risk of 4-MMPD in accordance with scientifically accepted procedures.

In addition to 4-MMPD, the following other hair dye ingredients have been reported to cause cancer in at least one animal species in lifetime feeding studies: 4-chloro-m-phenylenediamine, 2,4-toluenediamine, 2-nitro-p-phenylenediamine and 4-amino-2-nitro-phenol. They also were found to penetrate human and animal skin.

Depilatories and Hair Straighteners

Chemical depilatories are highly alkaline pastes, creams or cream lotions containing either alkali or alkali-earth sulfides (usually up to 35% barium or strontium sulfide) or mixtures of alkali-earth hydroxides (usually 5-10% calcium hydroxide) and salts of aliphatic mercapto acids (usually 2-5% calcium thioglycolate). These ingredients cause degradation of hair keratin and deterioration of hair fibers to a jelly-like mass that can easily be removed by wiping or scraping. The pH of chemical depilatories usually falls between 10 and 12.5.

Hair straighteners are mostly creams or cream lotions containing about 3% sodium hydroxide or, as a kit, a lotion containing about 5% calcium hydroxide and a solution of up to about 30% guanidine carbonate. The pH is around 12. Some straighteners contain about 4% ammonium thioglycolate as the active ingredient.

Because improperly formulated or incorrectly used depilatories or hair straighteners may cause serious skin irritation, they should be thoroughly tested for safety, be subjected to careful quality control during manufacture, and provide explicit warnings and directions for safe use.

Hair Shampoos, Rinses, Conditioners

Hair shampoos contain anionic or ampholytic detergents serving as cleansing and foaming agents; rinses and conditioners may contain cationics (quaternary ammonium compounds) serving as antistatic agents. When inadvertently introduced into the eye, these surface active agents may cause stinging, mucosal irritation or even corneal damage; and products contaminated with microorganisms may cause infection.

If the cornea has been scratched or otherwise damaged, pathogenic microorganisms, particularly Pseudomonas aeruginosa, may cause corneal ulceration and blindness. Cosmetic hair products may be adequately preserved with, for example, formaldehyde or formaldehyde releasing preservatives to prevent microbial contamination. See section on "Adequacy Of Preservation" above.

Hair care products, like all other cosmetics, should be tested thoroughly to determine the type and degree of irritation that may occur when coming into contact with the eye and to assure that marketed products are not contaminated and will not become contaminated during normal use. The labels of these products should bear appropriate warnings and directions for safe use.

Products Containing Estrogenic Hormones, Placental Extract or Vitamins

Products containing estrogen, estrone, estradiol, progesterone, placental extract or vitamins may be considered drugs, misbranded drugs, or misbranded cosmetics, particularly if the label declaration is supplemented with standards implying prevention or treatment of disease or effect on the structure or any function of the human body. See Federal Register notice of the proposed rule of October 28, 1977 (42 FR 56757) and 21 CFR 201.300.

The estrogen content of an OTC product, be it a drug or a drug as well as cosmetic, may not exceed 10,000 IU per ounce. Users must be directed to limit the amount of product applied daily so that no more than 20,000 IU of estrogen or equivalent be used per month. Some estrogen-containing products have been claiming to prevent or reduce wrinkles, treat seborrhea, or stimulate hair growth. The Advisory Review Panel on OTC Miscellaneous External Drug Products has concluded that there are inadequate data to establish the safety of these products and that they are ineffective and may therefore be misbranded, even if marketed as cosmetics without making medicinal claims. See Advance notice of proposed rulemaking, Federal Register of January 5, 1982 (47 FR 430). It should be noted, however, that this panel's recommendation has not yet been accepted by the FDA as a basis for regulatory decisions.

In addition to being considered misbranded drugs, products claiming to contain placental extract may also be deemed to be misbranded cosmetics if the extract has been prepared from placentas from which the hormones and other biologically active substances have been removed and the extracted substance consists principally of protein. The FDA recommends that this substance be identified by a name other than "placental extract" which describes its composition more accurately because consumers associate the name "placental extract" with a therapeutic use or some biological activity.

Cosmetics declaring ingredients as vitamins as, for example, tocopherol as vitamin E, convey the misleading impression that these ingredients and products offer a nutrient or health benefit and may therefore be deemed misbranded. The second edition of the CTFA Cosmetic Ingredient Dictionary, the currently recognized source of cosmetic ingredient names, lists "vitamin" ingredients by their respective chemical names.

Nail Builders, Hardeners, Enamels

Nail builders (elongators, extenders) have been involved in numerous reports of irritation, inflammation and infection of the nail bed and nail fold as well as in complaints of discoloration, splitting and loss of fingernails. The products are marketed as kits consisting of a powder (a mixture of methyl methacrylate polymer and peroxide catalyst) and a liquid (a mixture of methacrylate ester monomer and promoter). Ultraviolet light-cured products consist of a single unit containing methacrylate ester monomers, polyurethane and a curing agent (e.g., hydroxylcyclohexyl phenyl ketone).

The methacrylate monomers currently used in nail builders are mostly ethyl, hydroxyethyl, butyl, iso-butyl, hydroxypropyl or other esters of methacrylic acid. Methyl methacrylate is now rarely used because of a court ruling in an injunction proceeding against a former manufacturer of nail builders and numerous seizures and recalls of methyl methacrylate-containing products. The currently used esters of methacrylic acid may be as harmful as methyl methacrylate.

Nail hardeners often contain formaldehyde as the active ingredient. Although formaldehyde may be irritating to the skin or cause allergic reactions, the FDA does not object to its use as an ingredient of nail hardeners provided the product:

1. Contains no more than 5% formaldehyde,
2. Provides the user with nail shields which restrict application to the tip (and not the nail bed or fold),
3. Furnishes adequate directions for safe use, and
4. Warns consumers about the consequences of misuse and potential for causing adverse reactions in sensitized users.

The safety of formaldehyde as a cosmetic ingredient was reviewed in 1984 by a panel of scientific experts appointed by the Cosmetic, Toiletry and Fragrance Association, a trade association representing a major portion of the cosmetic industry. The panel reported that available toxicological data and other information were insufficient to conclude that cosmetics containing formaldehyde in excess of 0.2% are safe. (J. American Coll. Tox., 3, 3, 157-184, 1984).

Nail enamels usually consist of nitrocellulose and arylsulfonamide-formaldehyde resin as film formers, toluene or ethyl or butyl acetate as solvents, and phthalate, citrate or phosphate esters as plasticizers. Adverse reactions associated with nail enamels are not uncommon. The formaldehyde resin or residual formaldehyde may elicit allergic reactions in already sensitized consumers, the solvents or plasticizers may be irritating, and the deposited film may cause irritation and inflammation because of its occlusiveness or lack of flexibility. Nail enamels marketed as hardeners have had a particularly high rate of adverse reactions. Their high resin content or low concentration of plasticizer causes them to be particularly occlusive and inflexible. Another frequent complaint is flammability during and shortly after application.

Soap

Products that are "soap" are exempt from the provisions of the FD&C Act because soap is excluded from the definition of the term "cosmetic" in Section 201(i) of the Act. The FDA interprets the term "soap" to apply to products:

1. Intended for cleansing the human body,
2. Labeled, sold and represented solely as soap, and,
3. Consisting primarily (i.e., the bulk of its non-volatile matter serving as the detergent) of alkali salts of fatty acids (21 CFR 701.20).

Products consisting of detergents, or products consisting primarily of alkali salts of fatty acids and intended not only for cleansing but also for other cosmetic uses, i.e., products intended also for beautifying, promoting attractiveness or altering the appearance, must comply with the regulatory requirements applicable to cosmetics and must, for example, bear ingredient declarations as required at 21 CFR 701.3. They may also be regulated as drugs if intended to cure, treat or prevent disease or if intended to affect the structure or any function of the human body.

Products intended solely for cleansing of the human body and having characteristics consumers generally associate with soap may be identified in labeling as soap even though they do not consist predominantly of alkali salts of fatty acids. However, these products are regulated as cosmetics.

Suntan Products

Suntan products generally are sunscreening preparations which permit penetration of sufficient erythemal ultraviolet radiation to produce a perceptible erythema for best tanning results. When used as directed, consumers may remain in the sun for a predetermined time period without risking a sun-burn. The sunburn protection is provided by sun-screen active ingredients, e.g., cinoxate, homosalate, padimate O (octyl dimethyl PABA).

Suntan products claiming to prevent sunburn are also regulated as drugs if:

1. The labeling bears any direct or implied statement that the product screens out ultraviolet sunlight, prevents or treats sunburn, helps prevent wrinkles, or prevents premature aging of the skin,
2. The label bears a number representing the sun protection factor (SPF) value, or
3. The sunscreen ingredient is declared as an active drug ingredient and is listed before the listing of the cosmetic ingredients (Section 502(c)(1) of the FD&C Act and 21 CFR 702.3(d)).

Products regulated as cosmetics should, and those regulated as drugs must, bear adequate directions for safe use (Sec. 502(f)(1) of the Act and 21 CFR 201.5). As an example, the label should state the maximum safe sun exposure period under conditions of prescribed use. Suntan and sunscreen products also must bear warning statements as necessary or appropriate to prevent health hazards (21 CFR 740.1 and Section 502(f)(2) of the Act). The need for an appropriate warning applies particularly to suntan products not containing a sunscreen ingredient or providing only marginal sunburn protection (those with SPF values of less than 4).

Other "suntan" products of interest are capsules intended for ingestion and containing mostly beta carotene and canthaxanthin. These color additives enter the blood stream and are partially deposited in skin tissue, giving the skin a tan-like color. Neither color additive is approved for this particular use, and products containing them are considered adulterated. Some reports of adverse reactions associated with "tanning pills" have mentioned stomach cramps, hepatitis, nausea, diarrhea, and deposition of the color in the retina of the eye.

In recent years, "suntan accelerators" have appeared on the market. They claim to enhance tanning by stimulating and increasing melanin formation. Because their intended purpose is to affect a function of the human body, they may be considered drugs. One type of suntan accelerator is based on bergapten (5-methoxypsoralen) which is found in bergamot oil and is a well-known phototoxic substance (responsible for Berloque dermatitis). Bergapten increases the skin's sensitivity to ultraviolet light, intensifies erythema formation, and stimulates melanocytes to produce melanin. It has also been reported to be photo-carcinogenic in animals.

The other kind of suntan accelerator contains tyro-sine, alone or in combination with other amino acids, as the "active" principle. Tyrosine is the starting compound of the melanin synthesis in the skin. Its use is based on the assumption that it penetrates the skin, increases the tyrosine content of the melanocytes, and thus enhances melanin formation. This effect has not been documented in the scientific literature. In fact, an animal study reported a few years ago demonstrated that ingestion or topical application of tyrosine has no effect on melanogenesis. The Agency has recently concluded that "suntan accelerators" are unapproved new drugs within the meaning of Section 201(p) of the FD&C Act, and has issued warning letters to several major manufacturers of these products.

Permanently Listed Cosmetic Color Additives Subject To Certification (August 10, 1994)

Color Additive Cosmetic Use* 21 CFR

FD&C Blue No. 1 Generally, including cosmetics74.2101

(including the intended for use in the areas of Aluminum Lake) the eye

FD&C Green No. 3Except eye area74.2203

FD&C Red No. 4 Externally except eye area74.2304

FD&C Red No. 40 Generally, including cosmetics74.2340

(including the intended for use in the area of Aluminum Lake) the eye

FD&C Yellow No. 5 Except eye area74.2705

FD&C Yellow No. 6 Except eye area74.2706

D&C Blue No. 4 Externally except eye area74.2104

D&C Brown No. 1 Externally except eye area74.2151

D&C Green No. 5 Generally, including cosmetics intended for use in the area of the eye

D&C Green No. 6 Externally except eye area74.2206

D&C Green No. 8 Externally except eye area(0.01%maximum)74.2208

D&C Orange No. 4Externally except eye area74.2254

D&C Orange No. 5Externally except eye area74.2255

Lip products (5% maximum) Mouthwashes/dentifrices (GMP)

D&C Orange No. 10 Externally except eye area74.2260

D&C Orange No. 11 Externally except eye area74.2261

D&C Red No. 6 Except eye area74.2306

D&C Red No. 7 Except eye area74.2307

D&C Red No. 17 Externally except eye area74.2317

D&C Red No. 21 Except eye area74.2321

D&C Red No. 22 Except eye area74.2322

D&C Red No. 27 Except eye area74.2327

D&C Red No. 28 Except eye area74.2328

D&C Red No. 30 Except eye area74.2330

D&C Red No. 31 Externally except eye area74.2331

D&C Red No. 33 Externally except eye area74.2333

Lip products (3% maximum) Mouthwashes/dentifrices (GMP)

D&C Red No. 34 Externally except eye area74.2334

D&C Red No. 36 Externally except eye area74.2336

D&C Violet No. 2 Externally except eye area74.2602

D&C Yellow No. 7 Externally except eye area74.2707

D&C Yellow No. 8 Externally except eye area74.2708

D&C Yellow No. 10 Except eye area74.2710

D&C Yellow No. 11 Externally except eye area74.2711

Ext.D&C Violet no.2 Externally except eye area74.2602a

Ext.D&C Yellow no.7 Externally except eye area74.2707a

* As a general rule, color additives should not be exposed to oxidizing or reducing agents that may affect the integrity of the color additives. Amounts of color additives used in cosmetic products are restricted to levels consistent with good manufacturing practice (unless the regulation specifies a maximum level).

Provisionally Listed Cosmetic Color Additives

Subject to Certification

(March, 1992)

Color Additive Cosmetic Use21 CFR

Lakes of As specified in listing of82.1051

FD&C Blue No. 1straight color in Part 74

FD&C Green No. 3

FD&C Red No. 4

FD&C Yellow No. 5

FD&C Yellow No. 6

D&C Blue No.4

D&C Green No. 5

D&C Green No. 6

D&C Orange No. 4

D&C Orange No. 5

D&C Orange No. 10

D&C Orange No. 11

D&C Red No. 6

D&C Red No. 7

D&C Red No. 17

D&C Red No. 21

D&C Red No. 22

D&C Red No. 27

D&C Red No. 28

D&C Red No. 30

D&C Red No. 31

D&C Red No. 33

D&C Red No. 34

D&C Red No. 36

D&C Violet No. 2

D&C Yellow No. 7

D&C Yellow No. 8

D&C Yellow No. 10

Lakes of

Ext. D&C Yellow No. 7Externally except82.2051

in eye area

Permanently Listed Cosmetic Color Additives

Exempt From Certification

(March, 1992)

Color Additive Cosmetic Use21 CFR

Aluminum powderExternally including eye area 73.2645

Annatto No restrictions73.2030

Bismuth citrateScalp hair dye only

(0.5% w/v maximum)73.2110

Bismuth oxychloride No restrictions73.2162

Bronze powder No restrictions73.2646

Caramel No restrictions73.2085

Carmine No restrictions73.2087

Carotene, Beta-No restrictions73.2095

Chromium hydroxide green Externally including eye area 73.2326

Chromium oxide greensExternally including eye area 73.2327

Copper powder No restrictions73.2647

DihydroxyacetoneExternally except eye area

(only for imparting color to

human body)73.2150

Disodium EDTA-copperCosmetic shampoo only73.2120

Ferric ammonium

ferrocyanideExternally including eye area 73.2298

Ferric ferrocyanide Externally including eye area 73.2299

Guanine No restrictions73.2329

GuaiazuleneExternally except eye area73.2180

HennaScalp hair dye only 73.2190

Iron oxidesNo restrictions73.2250

Lead acetateScalp hair dye only73.2396

(0.6% Pb w/v maximum)

Manganese violetNo restrictions73.2775

Mica No restrictions73.2496

Potassium sodiumCosmetic dentifrices73.2125

copper chlorophyllin(0.1% maximum)

(chlorophyllin-copper(required combination with

complex) specified substances

PyrophylliteExternally except eye area73.2400

SilverNail polish only (1% maximum) 73.2500

Titanium dioxideNo restrictions73.2575

Ultramarines (blue, green, Externally including eye area 73.2725 pink, red, violet)

Zinc oxideNo restrictions73.2991

How to Obtain FDA Regulations

Regulations published by the Food and Drug Administration are codified under Title 21 Code of Federal Regulations. Before codification, regulations are published in the Federal Register, first as proposed regulations and then as final rules. Both, the Code of Federal Regulations and the Federal Register, may be purchased with VISA copyrighted or MasterCard copyrighted or by submitting a check or money order to the Superintendent of Documents, Government Printing Office, Washington, DC 20402, telephone 202-783-3238. Contact the Government Printing Office directly for current costs.

Title 21, Code of Federal Regulations

Title 21 of the Code of Federal Regulations is updated each year in April. It consists of eight volumes which may be purchased singly or as a set. The individual volumes consist of:

Parts 1 to 99. General regulations for the enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the Fair Packaging and Labeling ACT (FPLA). Color additive Regulations

Parts 100 to 169. Food standards, good manufacturing practice regulation for food, infant formula regulations, food labeling regulations.

Parts 170 to 199. Food additive regulations

Parts 200 to 299. Drug labeling regulations, good manufacturing practice regulations for drugs.

Parts 300 to 499. Regulations covering drugs for human use.

Parts 500 to 599. Regulations concerning animal drugs, feeds and related products.

Parts 600 to 799. Regulations concerning biological products and cosmetics.

Parts 800 to 1299. Regulations concerning medical devices and radiological health. Regulations published under the authority of laws other than the FD&C Act and the FPLA.

Federal Register

The Federal Register is published daily, Monday through Friday. It is mailed, postage paid, to subscribers. There is a 25% surcharge for foreign mailing. It is also available on microfiche.