"It's not a question of whether it can occur," says Michael K. Skinner, director of Washington State University's Center for Reproductive Biology. "We know that it can occur. The question is whether there's a sufficient amount of those endocrine disruptors in the environment to do the same in humans."

The crucial issue is how much of these substances is in the environment and what quantity would have an effect on humans. If 1 milligram of a compound has an effect in the lab, what will 1 milligram do in the wild? Is one-thousandth of a miligram likely to have an impact? How much is enough to cause premature puberty in girls?

Environmental estrogens in Washington state's Columbia River were found to have dramatic effects on salmon. James J. Nagler, an assistant professor at the University of Idaho, and his colleagues found that 80 percent of female salmon studied were born as males. These females had an XY chromosome instead of an XX. Skinner says that humans have too many biological checks and balances for exposure to environmental estrogens to have so dramatic an effect. But if fish are sensitive to this type of compound, it will most likely have some effect on a mammalian species.

One important obstacle to understanding how environmental estrogens affect humans and how much of the compound will trigger early puberty is an ethical one. Scientists cannot expose healthy children to strong and potentially dangerous compounds. Instead they have to study industrial accidents like the one in Michigan or focus on animal populations, waiting impatiently to see what kind of deformities the chemical tide washes ashore.

The existing evidence about the effect of environmental estrogens already has provoked a call for controls. Since chemicals often travel thousands of miles on transpacific air currents from Asia to the United States, many environmentalists believe the only way to control them here is to invoke international bans.

In December, representatives from 122 countries met in South Africa and signed the Global POPs Elimination Treaty (POPs stands for "persistent organic pollutants"). The agreement calls for 12 contaminants to be banned, including dioxin, aldrin, endrin, chlordane, DDT, dieldrin and heptachlor, all of which are environmental estrogens. The treaty must be ratified by at least 50 countries before taking effect. Once that happens, participants can then begin identifying the next batch of chemicals to be eliminated.

"We need to shift the burden of proof," says Peter Myers, coauthor of "Our Stolen Future," a book about how contaminants affect human hormones. "Right now the public-health authorities have to prove that [a contaminant] causes harm to people. But when you have strong animal evidence, that burden should shift -- it should be the responsibility of the people who want to use [the contaminant] in a consumer product."

Even if you start eliminating chemicals one compound at a time, researchers say, there is no guarantee that the threat of environmental estrogens can be diminished. "We can regulate on individual compounds, but it's the combination of compounds that might sneak up and bite us from behind," says Ralph Cooper, Ph.D., chief of the Environmental Protection Agency's endocrinology branch. "My mind is open that we eventually might find something that is capable of influencing reproductive development in humans."

Michele Marcus does not know whether the Michigan women exposed to PBBs are at greater risk of ovarian cancer or other diseases. She is still analyzing that part of the study. But as horrific as the accident was, it could be the red flag scientists have been waiting for, the evidence that at least one environmental estrogen sped up sexual maturity for some girls. That, along with compelling animal evidence, some researchers say, should be enough to justify the use of preventive medicine to stop a potential environmental disaster before it's too late.

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