EDCs: Interrupting Childhood

If the campaign against endocrine-disrupting chemicals (EDCs) has a public-enemy No. 1, that role probably falls to bisphenol-A (BPA). For more than a decade, the ubiquitous petroleum derivative — used in food packaging, can liners, plastics, and many other consumer products — has swirled at the center of pro- health movements, conflicting scientific studies, and heated political debates. Although evidence continues to accumulate that BPA can be harmful to human health, to this day uncertainties linger about how much and whether the amount that seeps into food reaches the threshold of harm. Expert panels have expressed some concern about BPA’s neurological and behavioral effects on infants and children, but to help settle the outstanding questions, the National Institute of Environmental Health Sciences and other groups are pouring more than $30 million into new scientific studies.

But focusing on BPA — or phthalates and certain pesticides, other commonly mentioned EDCs — may be missing the forest for the trees. The story emerging from the last decade of research paints a much more complicated picture, in which hundreds of different endocrine disruptors may combine minute effects over long periods of time to harm infants and children. Think less poison, more death from a thousand cuts.

The resulting impacts are complex and subtle. They may even make it impossible to prove that any particular endocrine disruptor is causing cardiovascular disease, type 2 diabetes, obesity, thyroid disorders, earlier puberty in girls, male reproductive disorders, or a host of other hormone diseases that scientists suspect are linked to EDCs.

“We humans each have something like a hundred chemicals on board [in measurable quantitities] at any one time,” says R. Thomas Zoeller, a professor of biology at the University of Massachusetts, Amherst. “How do we prove that ‘one’ is ‘the one’?”

An Impossible Task?

This complex mixture poses enormous difficulties for researchers examining how EDCs — which the Endocrine Society defines broadly as chemicals that can interfere with hormone action — might affect fetal and infant health. Low-level exposures can take years before causing any noticeable symptoms, and different EDCs can boost or block each other’s effects.

“The key question is: How do low-level, normal exposures to a fetus or infant cause changes in the endocrine system that play out later in life?” says Andrea C. Gore, a professor of pharmacology and toxicology at University of Texas, Austin. “We can’t make that connection in humans — the time lag is so great, and so much hap- pens in the body during that time.” Researchers face other challenges as well, Gore adds; in many cases, scientists have not yet discovered the normal role of certain hormones, making it even more difficult to track the impact when things go wrong.

Ongoing health trends — particularly the obesity epidemic — create another challenge. EDCs accumulate in body fat, muddying the question of what is causing what. “If you ask me which is the bigger health threat — the food overconsumption or the extremely low levels of EDC in that food — then I would vote unreservedly for the food,” says Richard Sharpe, a professor and male reproductive health researcher at the University of Edinburgh. “We have unequivocal evidence that this causes obesity, so why would you go for the much more speculative option?” The well-established trend toward earlier puberty in girls is similarly complicated, since obesity and stress contribute to precocious puberty but also tend to increase exposure to EDCs.

When it comes to specific links, “probably some of the better data comes from phthalates and male reproductive development and health,” says John Meeker, an associate professor of environmental health sciences at the University of Michigan in Ann Arbor. Researchers have found that phthalates have anti-androgenic effects — meaning they block the effects of male steroids — in multiple species, including humans. Like much EDC research, however, the human studies looked at data from a single date instead of tracking people over time, which is needed to provide stronger evidence that a chemical causes a disease, Meeker says.

The Bigger Picture

The overall case linking fetal and infant disorders to endocrine disruptors, however, is strong and getting stronger, scientists say. “I’m very confident, and that confidence comes with a lot of information,” Gore says. She was one of the co-authors of a 2009 Endocrine Society statement finding that, based on existing evidence, EDCs have demonstrated impacts on reproductive development, cancer rates, metabolism, and other systems. The statement also emphasized that infants and children are particularly vulnerable to EDCs and called for additional research.

According to Gore, at certain critical periods, fetuses possess such small levels of hormones — in some cases none at all — that even small exposures can unbalance the delicate process of development. “This is known as the fetal basis for adult disease,” she adds, “and the concept has woven itself through endocrine research.”

This theory is reflected perhaps most intensely by a body of research suggesting that the effect of EDCs might not depend on their dose. Conventional medical theory holds that a chemical will cause negative effects only once it exceeds a certain level. Some recent findings, however, suggest that EDCs might cause harm at extremely low doses, or might cause opposite effects at low doses and high doses. “There is some evidence that the effect of endocrine disruptors may not be linear or monotonic,” Meeker says. “But it’s not accepted by everyone.” That might be understating the disagreement. A recent International Programme on Chemical Safety report assessing the state of EDC research found that “the issue of dose–response relationships is perhaps the most controversial issue regarding EDCs.”

Regardless, however, researchers warn that while low-level exposures might not seem to affect any given individual, they can still have broad implications. “These effects need to be appreciated in a larger con- text,” says Amir Miodovnik, developmental pediatrician at Boston Children’s Hospital. “Even a small drop in the average IQ of the population could dramatically increase the proportion of people who would be categorized as intellectually disabled.”

A Time for Action

For some researchers, the science remains too uncertain to recommend governmental action. “Any ban should be evidence-driven, not opinion-driven or speculation-driven,” Sharpe says. “For exposures in pregnancy, I would opt for a lower level of proof for precautionary reasons, but I would still want much more convincing evidence than currently available.”

For most others, however, the evidence doesn’t need to be definitive to support taking proactive action on EDCs. Rather, they recommend adopting a philosophical maxim known as the precautionary principle. Often cited in debates about climate change, this principle involves erring on the side of caution when environmental damage or human health is at stake. In the medical realm, this would translate to bans or restrictions on many EDCs unless their manufacturers are able to prove the compounds are not harmful. The Endocrine Society statement also recommends taking a precautionary approach “until such time as conclusive scientific evidence exists to either prove or disprove harmful effects of substances.”

With the exception of a few modest bans on BPA in infant bottles and cups, this vision has yet to come to pass, however. The government is “beyond slow in taking action. Very few chemicals have actually been banned,” Gore says. “Things are not going to get better until we start requiring the groups that make chemicals to start testing for safety.”

Others echo the call for increased government action. “We may not be able to say proof,” Zoeller adds, “but how much information is enough to regulate when our children — and grandchildren — are involved?”

— Mehta is a freelance writer based in Cambridge, Mass. He wrote about the market for kidneys in the February issue.

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