Researchers Exploring Faster Alternatives to 2-Year Test for Carcinogenicity

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For nearly 40 years, scientists have relied on a costly, time-consuming test called the 2-year bioassay to screen chemicals for carcinogenicity. This assay exposes mice and rats of both sexes to a given substance at the maximum tolerated dose (and one or two lower doses) for the animal's lifetime—about 2 years. Chemicals that produce more tumors in test animals than control subjects are flagged as carcinogens, and this designation triggers regulatory measures to set human exposure limits with the goal of protecting the public's health.

Health agencies in the United States and abroad view the 2-year bioassay as a “gold standard” for carcinogen identification. Most human carcinogens listed by the Environmental Protection Agency in its Integrated Risk Information System were first identified with the assay, and the U.S. Food and Drug Administration requires it in premarket studies of drugs destined for long-term clinical use.

But despite its entrenched regulatory role, the assay's costs and time requirements have long been a source of contention. Each assay requires millions of dollars, years of planning, and extensive preliminary dosing studies. Bruce Ames, Ph.D., professor of biochemistry and molecular biology at the University of California at Berkeley, has found that more than half of all chemicals evaluated test positive in the 2-year bioassay. He attributes this to the maximum tolerated dose, which he claims overwhelms the body's natural detoxification mechanisms independently of a substance's carcinogenicity.