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How much Bisphenol A is okay?

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A new study came out this week that happened to remind me of one of my pet peeves about certain biomedical studies — choosing an “outcome” measure that doesn’t tell you what you really want to know. The study, which was led by Stanford postdoctoral fellow Jennifer Hartle, DrPH, and estimated the amount of BPA a child is exposed to in the course of a normal school day, was great. But her description of EPA safety tests on the plastics component Bisphenol A, or BPA — done back in the 1980s — made me think back to earlier work by University of California, Berkeley biologist Tyrone Hayes, PhD.

In the 1990s, the agricultural herbicide atrazine was safety tested by exposing frogs to low doses of atrazine as they developed from eggs to tadpoles to frogs. The adult frogs didn’t die or show obvious deformities such as extra legs, so the pesticide was deemed safe. But Hayes took a closer look and, in 2002, found that even at very low levels of atrazine exposure, male frogs were producing eggs instead of sperm.

So no gross deformities if you just looked at the frogs for 30 seconds. But in fact the animals had experienced a dramatic change in their health and biology. The lesson is that, in biology, sometimes the right outcome measure is something you have to really look for. There is a lot more to the Hayes-atrazine story.

But back to the current study: Hartle and her colleagues turned their attention to national school breakfast and lunch programs, which provide nutritious meals to 30 million kids every year but also deliver small amounts of BPA, an estrogen mimic that messes with hormones. Children’s meals are disproportionately packaged in tiny one-meal containers. Those tiny packages of apple sauce and juice have a greater BPA-emitting surface area than a big carton or can for the amount of food. And school kids often eat meals off plastic trays with plastic forks and spoons. For children who eat a lot of meals at school, it can add up.

According to Hartle’s paper, appearing today in the Journal of Exposure Science and Environmental Epidemiology, the question isn’t whether the kids are getting BPA in their meals — they are — but whether any of them are getting doses of BPA that could affect their long-term health. Based on those 1980s studies, the EPA estimates that BPA is safe at chronic exposure levels below 50 μg per kilogram of body weight per day. Happily, Hartle and her colleagues found that children are getting far less than that — as little as 0.0021 μg for a low-BPA breakfast to 0.17 μg for a high-BPA lunch. Everything should be hunky-dory, right?

Not,” say some researchers who question the EPA’s 50-μg limit. According to Hartle, research done in the last decade suggests that much lower doses than 50 μg produce health effects in lab animals, including changes in brain structure, behavior, immune function and growth. In humans, BPA exposure is associated with neural and behavioral changes, early puberty, and weight gain. The European Food Safety Authority has set the upper limit at four μg per kilogram of bodyweight per day— less than a tenth the EPA’s limit.

Where did the EPA’s much higher number come from? In the 1980s, researchers fed high does of BPA to rats and then weighed them. The thinking was that if the rats lost weight, the BPA was bad for them and if they didn’t, the BPA was harmless. “The rats were fed either 0 ppm, 1000 ppm (50 mg/kg/day) or 2000 ppm. No one looked at exposures between 0 and 1000 ppm — the exposure that humans experience in real life,” Hartle told me. At the lowest levels of exposure, the rats didn’t lose weight. Which brings me back to outcome measures. It’s 20:20 hindsight, but weight loss is a pretty crude outcome measure of overall health — especially for a compound that causes weight gain.

Hartle and colleagues note in their paper of the EPA’s reference dose, “…we are concerned that the current RfD may not be protective enough for the human population.” “At the least,” she said, “EPA should re-explore low-dose toxicity testing of BPA.”

For now, the FDA, hewing to EPA guidelines, says that current levels of BPA in food are safe. But the agency has meanwhile disallowed BPA’s use in infant formula packaging, baby bottles and sippy cups; the EPA is reevaluating BPA; and a Health and Human Services web page suggests ways for parents to reduce their kids’ exposure to BPA.

Previously: Packard Children's physicians discuss new research linking higher urine BPA levels and child obesity, California bans BPA in baby bottles and cups and Cutting out canned, packaged foods can reduce exposure to BPA
Photo by Lance Cheung for the U.S. Department of Agriculture

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