vened the Committee on Toxicity Testing and Assessment of Environmental Agents, which prepared this report.


To gain an appreciation of current toxicity-testing strategies, it is helpful to examine how they evolved, why differences arose among and within federal agencies, and who contributed to the process. The current strategies have their foundation in the response to a tragedy that occurred in 1937 (Gad and Chengelis 2001). At that time, few laws prevented the sale of unsafe food or drugs. A labeling law prohibited the sale of “misbranded” food or drugs, but the law could be enforced only on the basis of criminal charges that arose after sale of a product. During fall 1937, the Massengil Company marketed a drug labeled “Elixir of Sulfanilamide,” which was a solution of sulfanilamide in diethylene glycol. From the recognition of the drug’s toxicity to its removal from the market by the Food and Drug Administration (FDA), it had caused at least 73 deaths. The tragedy revealed the inadequacy of the existing law. FDA was able to act only because the drug had been mislabeled; at that time, an elixir was defined as a product that contained alcohol. If the company had labeled the drug “Solution of Sulfanilamide,” FDA would not have been able to act.

As a result of the sulfanilamide tragedy, Congress passed the Food, Drug, and Cosmetic Act (FDCA) of 1938, which required evidence (that is, from toxicity studies in animals) of drug safety before marketing (Gad and Chengelis 2001). Major amendments to the FDCA in 1962, known as the Kefauver-Harris Amendments, strengthened the original law and required proof not only of drug safety but of drug efficacy. More extensive clinical trials were required, and FDA had to indicate affirmative approval of a drug

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