By GAYATHRI VAIDYANATHAN
U.S. EPA regulators convened with scientists last month to discuss how to design regulations for chemicals based on emerging science that connects exposures during pregnancy with disease much later in life.
A mother exchanges with her child in the womb chemicals that have remained constant for much of human evolution. They dictate which genes will be turned on and off in the child, which proteins the child will make in his body and how much of them.
New research, in a field called epigenetics, now suggests that these changes, made during the earliest part of gestation, could spell out the child’s longer-term medical record. It could determine his propensity for mood swings, his tendency to gain weight into the realms of obesity, his risk of developing cardiovascular disease or cancer when he hits 50, and his propensity of passing on his genes to his children.
The idea is that the child adapts to environmental cues in the womb that will reflect the chemical composition of the world, thus conferring a Darwinian fitness advantage.
The mix of chemicals a fetus is exposed to has exploded in the past 200 years, heralded by the Industrial Revolution. Technology has outstripped evolution, said Robert Chapin, senior research fellow in drug safety research and development at Pfizer Inc. People were suddenly surrounded by particulate matter from cars, coal-plant emissions, metals, organic molecules from hand sanitizers, body lotions and other chemicals, some of which could cross into the placenta and merge into the child’s aqueous world.
Some, such as folic acid, were intentionally given to moms as beneficial; others such as bisphenol A became common in the modern environment and had the ability to mimic hormones that are naturally present in humans. Yet others, such as arsenic and tin, are naturally present in some places.
Scientists now suspect that the altered chemical cues during the critical windows of pregnancy — at stages when gender is still developing and the human is little more than a collection of cells — could trigger pathways that manifest as disease well into adulthood.
The science is still developing and has more holes than cheese at this point, cautioned Chapin of Pfizer. But links can be drawn to late-life events such as hypertension, insulin resistance (a hallmark of the diabetes epidemic), high blood cholesterol levels and cancer, he said.
“It’s like building a bunch of windows into the south face of a house,” he said. “Now you’ve got all those windows so you are going to be dealing with increased solar gain every month that house is in existence.”
Some follow-on things, such as higher summer cooling bills but lower winter heating bills, will happen inexorably as you add widows to your house. The same thing is true of the body, he said.
Chemicals as ‘obesogens’
EPA risk assessors, who are federal scientists that study chemicals for toxic effects in populations, got together in Washington, D.C., last month at a workshop by the National Academies to hear the latest research. The field, still in its initial stages, buzzed with proof of late-life effects in mice, rats with genetic dispositions similar to humans.
The researchers talked of chemicals that may be triggering the rise in obesity in the country; agents that promote cancer; and the need to quickly go through a list of about 200,000 chemicals in a European library of commercial compounds called REACH, to determine their toxicity.
The agency is already struggling to assess the environmental health impact for a backlog of 478 chemicals, according to the Center for Progressive Reform, or CPR. The process of studying a new chemical can take years and generate a thousand-page risk assessment document called IRIS (Greenwire, Nov. 9).
The chemical is carefully reviewed within and outside of EPA, with the aim that any new restrictions by the agency on industry would be able to stand up to legal challenges in court and to political scrutiny.
During the George W. Bush administration, the agency managed to go through two chemicals a year; the number has increased to nine under the Obama administration, according to CPR.
Given such a backlog for toxins that are harmful as demonstrated using traditional science, regulating based on epigenetic research is perhaps many years away. And more importantly, the science is not yet ready for such an effort in most cases, according to scientists and EPA regulators.
Bruce Blumberg, a developmental biologist at the University of California, Irvine, has some of the most compelling evidence to show the fetal origins of obesity, said Chapin.
Blumberg’s research suggests that a child exposed to tin (“tributyltin”) during the earliest part of life will throughout his life have a propensity to become fat. At a vital step where a cell decides to become specialized as either a bone or fat cell, ones that were exposed to tin during pregnancy are twice as likely to become fat cells, said Blumberg.
He called such chemicals “obesogens,” or chemicals that are thought to promote obesity.
“I’d say obesogens are a factor we hadn’t previously thought about, and it is a fact we are starting to think more about,” Blumberg said. “Diet and exercise are insufficient to explain the obesity epidemic, particularly the epidemic of obese six-month-old babies.”
But he stressed that the science is not ready enough to say how much of an effect prenatal exposure to tin actually has. Obesity is a multicausal factor.
Ila Cote, a senior science adviser at EPA’s National Center for Environmental Assessment, speaking for herself, said the epigenetic data should be considered seriously but is not yet ready for risk assessment. It could be used in very preliminary stages to identify problematic chemicals but cannot be used in a quantitative manner, she said.
“I think in very selected cases, it is coming close to being used, but we are a long ways away from being able to broadly use it,” she said. “There are beginning to be selective examples that could be explored further.”
Stan Barone, senior scientist and assistant director for Human Health Risk Assessment at the National Center for Environmental Assessment, said not making a decision about chemicals is also a decision.
“A zero value is right now evaluated at the context of no risk for many chemicals and many mixtures of chemicals,” Barone said. “That is not a real satisfactory place to be as a risk assessor, as a public health policymaker or as a person in the public or in the community.”
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