Red No. 3 : Part 2

by Food and Drug Administration (FDA)

(Page 2 of 2)

FD&C Red No. 3

FDA terminated the provisional listings for FD&C Red No. 3 on Jan. 29, 1990, at the conclusion of its review of the 200 straight colors on the 1960 provisional list. Commonly called erythrosine, FD&C Red No. 3 is a tint that imparts a watermelon-red color and was one of the original seven colors on Hesse's list.

The provisionally listed uses that were recently terminated include use of the straight color in cosmetics and externally applied drugs and all uses of the lakes of FD&C Red No. 3.

The case of FD&C Red No. 3, however, presents what one individual familiar with color regulation calls a "regulatory inconsistency." Although the provisional uses (about one-third of its uses) are now banned, FD&C Red No. 3 is still permanently listed for use in ingested drugs and food, such as baked goods, cherries, dairy products, desserts, dietary supplements, food seasonings, jellies, jams, and vegetable products.

This paradox came about because of improvements in scientific methods and the timing of the petitioner's submission for permanently listing the food and ingested drug uses. After the 1960 provisional listings, studies were performed on FD&C Red No. 3. Results did not show any safety concerns, and in response to a petition by the Certified Color Manufacturers Association (CCMA), FD&C Red No. 3 was permanently listed for use in ingested drugs and foods in June 1969.

Cosmetic and externally applied drug uses of the color remained provisionally listed while studies on skin exposure were conducted. Meanwhile, FDA expanded its safety requirements in 1977 to include more extensive studies on provisionally listed color additives. Based upon the results of new studies on FD&C Red No. 3, conducted by the International Research Development Corporation and completed in 1982, the agency concluded that FD&C Red No. 3 causes thyroid cancer in male rats.

The Cosmetic, Toiletry and Fragrance Association and CCMA argued that no direct cancer-causing effect was seen in animals given the color in the low levels used in consumer goods. FDA, however, decided that the evidence of thyroid tumors in rats was clear, and that the additional research cited by industry did not establish that an indirect mechanism — such as a hormonal effect triggered by the dye — caused the tumors, rather than the dye itself. Thus, FDA denied the manufacturers' petition for further permanent listings of the color. Based on data from the studies, the agency estimated that the lifetime risk of thyroid tumors in humans was at most 1 in 100,000.

Like FD&C Red No. 3, FD&C Blue No. 1 and FD&C Yellow No. 5 were also permanently listed for food and ingested drug uses in 1969. When FDA reviewed new, more extensive studies on FD&C Blue No. 1 and FD&C Yellow No. 5, the agency found that these two color additives did not cause cancer in animal studies. (But, since FD&C Yellow No. 5 causes allergic reactions in some people, FDA requires its listing on food labels.)

As experts note, while the provisional listings for straight colors have ended, advances in science will require continual monitoring of the safety of color additives.

Delaney Dilemma

The decision to ban the provisional uses of FD&C Red No. 3 is based on the Delaney Clause of the 1960 Color Additive Amendments. Under that clause, FDA cannot approve color additives shown to induce cancer in humans or animals in any amount.

Many government officials, however, believe that the inflexibility of the Delaney Clause should be replaced by a standard that allows for what may be an insignificant cancer risk. Advances in technology and the ability to detect minute quantities of cancer-causing chemicals in foods may make the risk standard of the Delaney Clause unnecessarily stringent in some cases. In announcing the decision to terminate the provisional uses of FD&C Red No. 3, Health and Human Services Secretary Louis W. Sullivan, M.D., said that the decision to ban the uses of Red No. 3 was not based on risk but on the legal mandate of the Delaney Clause.

In 1986, FDA took a different approach in approving four cosmetic dyes for which cancer risk was trivial. The agency based its approval of D&C Orange No. 17, D&C Red No. 19, and D&C Red Nos. 8 and 9 on the legal maxim "de minimis non curat lex," meaning that the law does not concern itself with trifles. A government review panel had assessed the worst-case risks for externally applied drug and cosmetic uses for D&C Orange No. 17 as 1 in 19 billion (that is, exposure to external cosmetics containing D&C Orange No. 17 may cause at most one additional case of cancer in 19 billion people over a 70-year lifetime of exposure) and for D&C Red No. 19 as 1 in 9 million. The maximum possible cancer risk for D&C Red Nos. 8 and 9 was evaluated as 1 in 60 million.

The next year, however, the U.S. Court of Appeals for the District of Columbia held that the Delaney Clause does not contain an exemption for cancer-causing color additives with only trivial risks. Thus, the court ordered FDA to ban the colors listed under the de minimis principle.

In the past two Congresses, Senator Edward Kennedy of Massachusetts and Congressman Henry Waxman of California have introduced legislation concerning pesticides that others in government would extend to other additives — including colors — as well. The proposed legislation would substitute a "negligible risk" standard for the "zero-risk" standard (such as described in the Delaney Clause) to the regulation of pesticides. The bills define "negligible risk" as causing at most one additional case of cancer in 1 million people over a 70-year lifetime of exposure to the compound.

President Bush endorsed the negligible risk standard for pesticides in his October 1989 Food Safety Plan. A joint press statement issued that same day by HHS Secretary Sullivan, USDA Secretary Yeutter, and EPA Administrator Reilly noted that while the president's plan specifically addresses pesticide residues, the principle of negligible risk is one that naturally applies to other additives to the food supply.

Small Risks

The ban of the provisionally listed uses of FD&C Red No. 3 applies to new manufacture and production of affected products. Because any health risks posed by Red No. 3 are extremely small, FDA concluded that consumers may continue to use existing supplies of products that already contain that color.

Following the mandate of the Delaney Clause, FDA will now reconsider the permanently listed uses of the straight form of FD&C Red No. 3. The procedure for banning a permanently listed dye, however, is more complex than that for terminating the provisional uses and requires time for public comment.

Though in the future, new definitions of acceptable risk spawned by new technologies may replace the Delaney definition, for now FDA must operate under this meaning and say to consumers that because of the risks, certain uses of FD&C Red No. 3 can no longer be allowed.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.