BPA, in turn, is becoming this year’s poster child for all our doubts and fears about the safety of plastic. New research highlighting the possible dangers of BPA has received tremendous media coverage. In mice, at least, BPA exposure at crucial stages of development induces observable changes (such as breast or prostate abnormalities) that last a lifetime. The research may be confusing to a layperson, yet some consensus has been reached: Last November a panel sponsored by the National Institutes of Health (NIH) determined that there was at least “some concern” about BPA’s effect on the fetal and infant brain. Around the same time, the Centers for Disease Control reported that researchers there had found BPA—the United States produces 6 billion pounds of it yearly—in 93 percent of urine samples from 2,500 Americans aged 6 to 85. Children under age 12 had the highest concentrations.

What is not known is whether infants and children under 6 are even more heavily exposed, since they have not yet been studied (for phthalates, Swan says, levels are definitely higher in children than in adults). This, at least, has been measured: Infants fed canned formula heated in a polycarbonate bottle—one source of BPA—can consume more than 20 micrograms of the chemical a day. Animal studies show effects of BPA at much lower concentrations.

To shift public understanding on this issue is staggeringly difficult, especially given that exposure to plastic is not a matter of individual lifestyle. Unlike tobacco and lead paint, plastics are so useful we can hardly manage a day without them. Biologist Frederick vom Saal of the University of Missouri likens the issue to another colossal environmental threat. “This is the global warming of biology and human health,” he says.

Last summer, a panel of 38 researchers headed by vom Saal published a report in Reproductive Toxicology warning that BPA (much like the synthetic estrogen diethylstilbestrol, or DES) is a potential chemical time bomb that may lead to multiple problems, including a higher risk of cancer, especially if exposure occurs in the womb or an infant’s early life and on an unrelenting daily basis.

Two weeks after the report came out, an NIH panel came to a different conclusion: Although public exposure to BPA could pose some risk to the brain development of babies and children, there was “negligible concern” about reproductive effects in adults. This was the first official federal report on BPA, and the chemical industry took it as good news: An August 2007 statement by the American Chemistry Council claims that “BPA is not a risk to human health at the extremely low levels to which consumers might be exposed.” Criticism of the report began even before its publication and has dogged it ever since. In January the NIH agreed to a thorough review of the report. This NIH decision came in response to claims from scientists and public health advocates that members of the panel worked for the chemical industry and cherry-picked the data in favor of industry-funded studies, which did not test low-dose exposure to BPA. A new panel has been convened, and its findings are expected in June.

Chemicals like BPA pose a challenge for conventional toxicology, vom Saal says. To determine what level of a toxin is safe, researchers take a dose that has no observed toxicological effect in an animal and divide it by 10 once (to account for the differences between species) and then again (to account for variations among humans’ ability to handle toxins); for pesticides, the dose is then divided by 10 a third time (to allow for the extraordinary sensitivity of babies and children). Although this is somewhat arbitrary, it generally gives enough room to provide protection. The first studies of BPA toxicity in the 1980s tested rats at high levels of exposure (50 milligrams of BPA per kilogram of body weight per day). Lower levels were not tested; BPA was deemed safe.

But the modus operandi of hormone-mimicking chemicals is different from that of typical toxins. In fact, they are not toxins in the strict sense of the word because they behave like ordinary hormonal signals. “It turns out we are, to a very intriguing degree, programmed by phenomenally small amounts of hormones in terms of our behavior, our core physiology, our neuroendocrine system, and our ability to metabolize drugs,” vom Saal says. “The brain along with the reproductive system and every other cell in your body is exquisitely sensitive to exceedingly small changes in estrogen and other sex hormones, and the fact that the environment is full of chemicals that can activate estrogen receptors means this phenomenally sensitive system is being perturbed constantly by environmental factors.”

At key stages of development, a seemingly infinitesimal dose of an estrogenic chemical such as BPA or phthalates may be life-altering. This is most evident in fetuses. When BPA hits cell receptors, it is as powerful as estradiol, the most potent estrogen in humans. “Our cells are built to take a single molecular-binding event,” vom Saal says, “and turn that into a huge, highly amplified outcome. We’ve studied doses of BPA between 2 and 20 micrograms per kilogram of body weight—the lowest dose ever tested before was 2,500 times higher—and it scrambles the male reproductive system in mice.”

In other research, by reproductive biologist Patricia Hunt of Washington State University, female mice exposed to low amounts of BPA in the womb—amounts deemed “environmentally relevant”—had high levels of genetic errors in the eggs they produced. Worse still, the genetic errors in those eggs led to chromosome abnormalities in 40 percent of the next generation’s eggs. That is 20 times the incidence of such abnormalities in unexposed mice. How might this relate to human risk? According to commentators reviewing Hunt’s work in PLoS Genetics, the answers will be hard to tease out: Nearly one in five human pregnancies ends in miscarriage, half of which are due to chromosomal abnormalities. Abnormalities in a woman’s eggs increase as she ages, and more women are having children at a later age. “A proper study of this problem,” they wrote, “would require assessing the woman’s level of chemical exposure now and maintaining those data for two to three decades,” tracking the abnormalities in her children and grandchildren.

Another troubling animal study comes from Randy Jirtle, a Duke University geneticist, who found that BPA permanently reprogrammed a gene in pups of mice fed BPA-laced food. Jirtle is well known for his work on mice that carry the agouti gene, which is highly vulnerable to environmental influences. In this study, he exposed lean, brown-furred female mice to 50 milligrams of BPA per kilogram of body weight daily, and the next generation was transformed: More of them were fat, with blond fur. “If I were a pregnant woman, I would try hard to avoid exposure to BPA,” Jirtle says.

Phthalate studies show similarly dramatic effects. When pregnant rats are exposed to high doses of phthalates, their male offspring are born with deformed genitalia. In 2005 Shanna Swan published the first study that looked for evidence of an obvious effect among boys. In 134 boys aged 2 months to 30 months, she found that sons whose mothers had higher levels of certain phthalates in their urine had a shorter distance between the anus and the penis. These boys were also likelier to have smaller penises and incompletely descended testicles. About one-quarter of American women have the higher phthalate levels she found in her study. This was particularly evident among women working in poorly ventilated nail salons, where one especially harmful phthalate, DBP, is released.

Chemicals leaching out of plastics may reshape not only your children but your children’s children.

In a recent study, Swan found that “we could predict the anogenital distance in babies just by knowing which phthalates a mother was exposed to and how much.” Those with the highest exposure to phthalates gave birth to boys with the shortest anogenital distance.

Phthalate exposure does not come just from moms. A new study gives evidence that infants and toddlers exposed to lotions, shampoos, and powders with phthalates may have up to four times as much of it in their urine as those whose parents do not use the products. The study, just published in Pediatrics by Sheela Sathyanarayana of the University of Washington, looked at 163 children between the ages of 2 months and 28 months between the years 2000 and 2005. The results were alarming, not least because manufacturers are not required to list phthalates as ingredients on labels.

So what are the long-term consequences of exposure to plastics? Teasing out the answers is difficult, in part because early exposure can have effects observed only much later in life. One of the scientists at work on the problem is Danish researcher Niels Skakkebaek of Copenhagen University Hospital, who has been documenting reproductive problems in men for more than two decades. His research in the 1970s showed links between testicular cancer in adults and abnormalities in genital development. He suspected that clues to the disorder lay in early life, when the reproductive organs are still developing. An especially crucial time is around 3 months or earlier, when boy babies experience a surge of testosterone. To see if phthalate exposure might influence this developmental period, Skakkebaek and his colleagues investigated how the amount of phthalates in breast milk correlated with a baby’s hormonal profile. In a study of 65 infants published in 2006, they discovered that the higher the level of phthalates, the greater the evidence of anti-androgenic hormonal activity.

Whatever the impact of plastics exposure, the effects are not easy to isolate. There are no babies rendered obviously deformed, as with thalidomide. There are no children robbed of mental agility, as with lead exposure. There is no clear-cut evidence of lung cancer, as with tobacco. As Swan admits: “The baby boys in our study were not freaks. They did not look abnormal. We’re talking about small changes you won’t find unless you look carefully.”

“Nobody knows what to do with the information,” says Tufts University environmentalist Sheldon Krimsky, author of Hormonal Chaos: The Scientific and Social Origins of the Environmental Endo­crine Hypothesis. “This is a highly contested arena with no standards for consensus. And because, for instance, BPA is not put into food but leaches into food from containers, it doesn’t qualify for the Delaney clause, which mandates that if an additive causes cancer in any amount in two species, we can’t put it in the food supply.”

Back in the 1940s when plastics were being developed, no one suspected that chemicals leaching out of these marvelous materials could have insidious biological effects. What industrial chemists did know was that by tinkering with a highly reactive molecule called a phenol they were able to devise countless synthetic chemicals for use in new materials. Only through subsequent studies has it been shown that the estrogen receptor has a particular affinity for a characteristic molecular component of phenols. “I’d say 99.9 percent of what turn out to be chemical estrogens have a phenolic hydroxyl group on the molecule, and any of those can bind to the estrogen receptor, ” says Wade Welshons, a University of Missouri cell biologist and endocrinologist who has spent his career studying estrogen. Moreover, “almost everything that binds to the estrogen receptor turns it on in some way. I’ve run across only two chemicals that fully antagonize, or switch off, the receptor.”

Despite this new insight, regulation of synthetic estrogens as a class seems far off. BPA alone is “worth at least a million dollars every hour,” Welshons says. “And that figure is conservative. I’m surprised the chemical industry hasn’t tried to blow up our labs.”

In 1989 little was known about synthetic chemicals in everyday plastics and how they mimicked estrogens. Ana Soto, professor of cellular biology at Tufts University School of Medicine, and her colleagues were studying the effects of estrogen on a breast cancer cell line. “Suddenly all the cancer cells were proliferating maximally, whether they were being grown in a medium with estrogen or not,” Soto recalls. “We thought that somebody must have opened a bottle of the female hormone estradiol in the wrong place. We scrubbed the whole room, we bought new batches of everything, and the cells kept proliferating. So we began one by one to replace and substitute our equipment, and we finally found the contamination in tubes storing a component of the medium. The tube manufacturer had changed its formula, with the best intention of rendering the tubes more impact resistant. They said the new chemical was a trade secret. So we analyzed it ourselves, and it turned out to be nonylphenol. We injected the chemical into rats and demonstrated that it makes the epithelial lining of the uterus proliferate—a sign of its being an estrogen.” Nonylphenol is also a component in some detergents and other products, and its presence in British streams has been linked to the feminization of fish.

In 1998 another synthetic estrogen leached from animal cages and bottles in a different lab—this was the now-infamous BPA. Patricia Hunt (then working at Case Western Reserve University) was studying the endocrine environment of the aging ovary in mice. Suddenly, as in Soto’s lab, “our control data went nuts,” Hunt says. “We saw chromosomal abnormalities that would lead to pregnancy loss and birth defects. It turned out that all of our cages and water bottles were contaminated by the BPA in the polycarbonate plastic, which was being sterilized at high temperatures. We set about proving this contamination was coming from the water bottles and cages.” They published that work in 2003. In 2007 Hunt and her colleagues published a paper in PLoS Genetics demonstrating that BPA exposure in utero disrupts the earliest stages of egg development. The fetuses of pregnant mice exposed to low doses of BPA, Hunt says, had “gross aberrations. We were stunned to see the effects of this estrogenic substance.”

For Hunt, this accident was particularly poignant: She calls it the second of two “lightning strikes” in her life. She is a DES daughter who had multiple abnormal Pap smears in her youth and is also a breast cancer survivor (cancer runs in her family, but there is also evidence that DES daughters get more breast cancer). “It’s very ironic,” Hunt explains. “BPA was studied as a synthetic estrogen in the 1930s and abandoned in favor of DES, which was more potent. Yet both of them found their way into my life. A lot of the abnormalities turning up in DES sons and daughters can be reproduced in mouse experiments. And that’s one reason I’m concerned about BPA. The effects we see in our mice are pretty significant,” Hunt says.

Hunt’s research on BPA and the fetal ovary shows that “one exposure can hit three different generations. It hits the mom, crosses the placenta, and affects the fetus, but it also affects that fetal ovary that is busy producing the eggs that will make the next generation. So the mom’s exposure is impacting the genetic quality of her grandchildren. We’re dealing here with multigenerational changes.”

Through studies like these, Jirtle says, “we’re beginning to understand how a molecule present at the very earliest stages after fertilization can in effect be remembered into your twenties and thirties and maybe give rise to diseases. You can’t do toxicology anymore without that insight.”

While chemists, biologists, geneticists, and toxicologists are piecing together the puzzle, some consumers have concluded they should simply try to limit exposure to plastics in their own lives. “But how do you do that?” asks Soto, who herself uses glass containers at home. “For instance, the milk you’re drinking was pumped through plastic tubes. And you can’t store milk in permeable paper cartons—they have plastic linings. Even if you try, you don’t know whether you’re limiting your exposure by 5 percent or 95 percent.” BPA has been found in drinking water, in 41.2 percent of 139 streams sampled in 30 states, even in house dust. Even if we could regulate BPA to levels that were safe, Soto cautions, “zero plus zero plus zero is actually not zero. By that I mean you can take 10 estrogenic chemicals at doses that on their own don’t have an effect, but if you add them together, you end up with problems. BPA is only one of many estrogenic chemicals in our environment.”

Krimsky favors legislation based on an entirely new way of thinking. “We should base legislation on two rules,” he explains. “One, if a synthetic chemical accumulates in your body and is not metabolized, let’s ban it unless we need it for survival. Why? On the precautionary notion that it can’t be good for the body to be a storage site for junk chemicals with no known physiological purpose. Two, if a chemical is biologically active and interacts with our receptors, it’s probably not good. Ban it. Maybe it’s OK in very small doses, but it’s going to take you 50 or 100 years to figure out those doses, if you can even do it. We put a human being in prison for life based on circumstantial evidence. Yet we’re looking for more than circumstantial evidence in order to ban these chemicals.”

Hunt and other scientists hope their research will catch the attention of the public even more so than industry or policymakers. “I’m struck by how fast companies respond to consumer demand,” Hunt says. “When our study broke in 2003 and the media came calling, I kept saying that what concerns me the most are baby bottles. They’re polycarbonate, and it doesn’t stand up well. I got a call from a baby bottle manufacturer one day, and he said, ‘What’s going on? We’re getting all these calls from consumers.’ And I was amazed to see how rapidly new polymers came on the market for baby bottles.” Indeed, sales of glass and non-polycarbonate baby bottles are rising. In turn, when consumers are charged for plastic bags at the supermarket, they tend to bring their own. Ireland’s “plastax,” launched in 2002, has resulted in a 90 percent voluntary reduction in plastic bag use. Finally, corn-based, biodegradable plastics are beginning to surface, and though these polymers are not yet as durable as current plastics, the technology is advancing.

“We have no choice,” Soto says. “If reproduction is being affected, the survival of the species is compromised. Sooner or later we have to regulate it. And what constitutes proof? In the 1950s a woman’s lifetime risk of breast cancer was 1 in 22; today it’s 1 in 7. A threefold increase cannot be genetic, it is most likely environmental, and many of us believe it is due to endocrine disrupters. To know whether fetal exposure to BPA is producing breast cancer in humans, you have to collect blood from the mother and the newborn, bank it, and follow that cohort for many, many decades. One generation of researchers can’t do it. This is painful, and the public should know about it.”