Food, Drug and Cosmetic Additives

Excerpted from "The Safety and Regulatory Status of Food, Drug, and Cosmetic Color Additives" by Joseph F. Borzelleca, Ph. D., Medical College of Virginia and John B. Hallagen, J.D./Daniel R. Thompson, P.C. Washington, D.C. To be published in Food Safety Evaluation, Finley & Armstron, Editors, American Chemical Society.
Lifeline, Winter 1992, Vol X, No 1, pp 1-2

Color additives for use in foods, drugs, and cosmetics are regulated by the Food and Drug Administration (FDA) under its authority derived from the 1960 Color Additive Amendments to the Federal Food, Drug, and Cosmetic Act (FFDCA). The amendments shifted the burden to industry to prove that the FD&C color additives are safe. Section 706 of the Act established how a color additive can be "permanently listed." Permanent listing means that the FDA has completed its scientific review and concluded that the color additive is safe under Section 706(b) (4) of the Act.

A variety of factors may be considered in FDA's safety evaluation including total anticipated exposure to the color additive, safety factors, and analytical methods (FFDCA Sec 706(b)(5)(A)). The Delaney Clause prohibits the listing of color additives found by FDA to induce cancer in laboratory animals or man (FFDCA Sec 706(b)(5)(B)). The FDA defines safe as "convincing evidence that established with reasonable certainty that no harm will result from the intended use of the color additive" (21 CFR Sec 70.3(i)(1989)).

The Color Additive Amendments of 1960 also included the "Transitional Provisions" which established the "provisional listing" of commercially established colors (Pub L.86-618, Sec 203, Title II). Provisional listing permitted color additives approved when the amendments were enacted to continue to be marketed while FDA determined whether they could be permanently listed. All approved color additives were placed on the provisional list in 1960 (25 Fed Reg 9759 (12 October 1960)) and were subsequently removed either because they were eventually permanently listed upon agency approval of a color additive petition, or they were delisted for various reasons.

There are two forms of the FD&C color additives, the dye and the lake. The dye is the color additive itself and is water soluble. The lake is the dye form attached to an aluminum or calcium substrate to make it insoluble.

All FD&C dyes are now permanently listed for use in foods, drugs, and cosmetics; the lakes of these color additives remain provisionally listed for all uses with two exceptions: 1) the dye and lake form of FD&C Red No 40 are permanently listed for all uses; and, 2) the dye form of FD&C Red No 3 is permanently listed for food and ingested drug use only; provisionally listed lakes were terminated in 1990 because of FDA concerns that the color additive caused thyroid tumors in rats (55 Fed Reg 3516 (1 February 1990)). At some point the agency plans to propose termination of the permanently listed uses of FD&C Red No 3 dye.

The lakes of the FD&C color additives, except for FD&C Red No 40 and FD&C Red No 3, remain provisionally listed because FDA has kept their approval separate from the dye form of the color additive for regulatory purposes. The agency first proposed to permanently list the FD&C lakes as a group in 1965 (30 Fed Reg 6490 (11 May 1965)). This proposal was subsequently withdrawn and a new proposal was published in 1979 also to permanently list the lakes as a group (44 Fed Reg 36411 (22 June 1979)). FDA is working toward published in 1990 or 1991 a final proposal to permanently list the lakes.

There are few restrictions on the use of FD&C color additives. All are permitted for use at levels consistent with good manufacturing practice. The FD&C color additives generally need not be specifically identified on food labels and may be declared by stating "colored," "color added" or another generic term (21 CFR Sec 101.22(c)(1989)). The one exception is FD&C Yellow No 5 which must be specifically declared in a product's ingredient statement because of concerns about allergenicity (21 CFR Sec 74.705(d)(1989)). Whether FD&C Yellow No 5 causes sensitivity reactions remains an open question but it appears that it does not cross-react with aspirin, precipitate asthma or induce hyperactivity as once reported. It appears that the color additive may cause urticaria is a very small population (Robinson, 1988).

(Urticaria: a vascular reaction of the skin characterized by the eruption of pale evanescent wheals, which are associated with severe itching. Commonly seen as hives or nettle rash. There typically has been contact with an external irritant such as the nettle weed, some physical agent or food, and insect bite, serum sickness, pollens, drugs, or neurogenic factors. Common symptoms: sudden general eruption of papules or wheals associated with intense itching.)


(general measures) Because the skin manifestation is an allergic reaction, identify and remove the antigenic offender if possible. Check diet for common offenders such as wheat, milk, eggs, chocolate, and other common food allergenics. Avoid unnecessary medications as drugs are often causative factors.

(specific measure) Antihistaminic drugs often give quick relief. Injection of epinephrine (subcutaneous). Ephedrine may be used. In severe cases ACTH or cortisone used with caution has proved effective. Locally, antipruritic lotions and baths are frequently beneficial. (Tabor's Cyclopedic Medical Dictionary, F.A. Davis Company, Philadelphia, 1982, U-20).

It is likely that many of the skin manifestations reported by celiacs may fall into the above category. From the many patient reports by letter and telephone, it would appear that the reaction may be caused both by foods ingested or by creams, shampoos, and products applied to the skin. Patient reports without physician or research documentation still include consideration for the lakes. The celiac with concerns for urticaria should consult a physician who understands his/her primary diagnosis of non-tropical sprue.

The Nutrition Labeling and Education Act of 1990 amended Sec 403(i) of the Food, Drug, and Cosmetic Act to require the specific declaration of FD&C color additives as individual ingredients on the ingredient label of foods. However, color additives exempt from certification can still be declared generically. The effective date for this change was published as 8 November 1991, one year after the enactment, as specified in the amendments.



CSA Library Series
CSA Library Series is a collection of articles that pertain to celiac disease and dermatitis herpetiformis. Most of these articles have appeared in CSA’s quarterly newsletter, Lifeline, which all CSA members receive. Historic articles included in these resources may or may not include updated notes. Updated information indicated in red type. Articles represent the work of the author.