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Mice Harmed by Low Dose of BPA, Not High

Baby mice exposed in the womb to low doses – but not high doses – of bisphenol A were fatter and had metabolic changes linked to obesity and diabetes, according to a new study
little mouse, sleeping



Flickr/Eddy Van 3000

Baby mice exposed in the womb to low doses – but not high doses – of bisphenol A were fatter and had metabolic changes linked to obesity and diabetes, according to a new study published Thursday.

Building on previous studies that link the hormone-altering chemical to changes in body weight and glucose tolerance, the new research fuels an ongoing controversy over whether federal testing of chemicals is adequate to protect people from low doses.

“What’s scary is that we found effects at levels that the government not only says is safe, but that they don’t bother to test,” said Fredrick vom Saal, a University of Missouri, Columbia, professor and senior author of the study published in the journal Reproductive Toxicology.

Many of the effects were reported in the mice fed daily doses – just during pregnancy – that were one-tenth of the amount that the U.S. Environmental Protection Agency says is safe for daily exposure throughout life.

Used in polycarbonate plastics, canned food liners and some thermal receipts, BPA is found in almost everyone’s body. Some earlier studies have linked it to obesity and diabetes in people.

Vom Saal said low doses of BPA caused a “deranged metabolism” in the offspring of the exposed pregnant mice, suggesting that “a component of the obesity epidemic and other metabolic diseases can be due to chemical exposure during development, when your cells are being programmed.”

In the offspring mice, BPA was associated with weight gain, increased abdominal fat and eating, impaired glucose tolerance and increased hormones that regulate glucose and appetite. Those outcomes, however, only happened when mothers were fed daily doses at or below 5,000 micrograms of BPA per kilogram of body weight. That amount is the EPA’s “no effects” level – the daily amount that the agency has concluded would not cause any human effects.

Of the doses fed to the pregnant mice – 5, 50, 500, 5,000 and 50,000 micrograms per kilogram – 500 caused the most metabolic changes, vom Saal said. The number of fat cells doubled at that dose. No effects were seen at doses higher than 5,000.

The study adds to the controversy over a phenomenon called “nonmonotonic dose response,” which means that hormone-like chemicals such as BPA sometimes do not act in a typical way; they can have health effects at low doses but no effects or different effects at high doses.

The EPA frequently evaluates the safety of chemicals with tests that expose lab animals to high doses, then extrapolating to lower doses that people and wildlife encounter.

In a report last year, 12 scientists, including vom Saal, criticized that decades old-strategy, saying it fails to detect health threats from low doses of hormone-like chemicals. Pete Myers, founder of Environmental Health News and chief scientist at Environmental Health Sciences, was the senior author of that report.

Last month, reacting to that report, the EPA defended its testing, concluding that current testing of hormone-altering chemicals is adequate for detecting low-dose effects that may jeopardize health.

In response to vom Saal’s new study, a spokesperson for the American Chemistry Council, which represents chemical companies, said the findings had not been replicated and it “presents conclusions that are not supported by the findings of EPA’s recent extensive review of the state of the science on low dose exposures.”
“The conclusions of EPA’s draft report affirm what most scientists have expressed for years: the scientific evidence for nonmonotonic low dose exposures leading to endocrine disruption and adverse effects is, at best, very weak,” Kathryn St. John said in an email.

But the mouse study offers evidence that “high-dose testing just doesn’t tell us what’s going on at low doses,” said Laura Vandenberg, a Tufts University researcher who did not participate in the new study.

“When you look at the highest dose that regulators say is the no observed adverse effect level [5,000 micrograms per kilogram] we should be finding nothing,” Vandenberg said. “And that’s just not the case.”

The EPA did not respond to requests for comment on vom Saal’s study.

Scientists are increasingly looking at environmental chemicals as a potential contributor to the growing obesity and diabetes problem.

BPA mimics estrogen, which has different effects on different systems and organs in the body, said Thomas Zoeller, a University of Massachusetts, Amherst, professor. Exposure to such chemicals during development can alter metabolism by changing how the body regulates insulin and glucose, he said.

Zoeller said vom Saal’s study adds to the concern about how ubiquitous chemicals are tested. “We’ve created a system where the entire human population is being exposed to chemicals that haven’t been evaluated for safety at relevant levels,” he said.

This article originally ran at Environmental Health News, a news source published by Environmental Health Sciences, a nonprofit media company.

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