by revere, cross-posted at Effect Measure

We’ve discussed the component of plastics bisphenol A (BPA) here before (here, here) but yesterday the Journal of the American Medical Association published a significant paper with an accompanying editorial that deserves mention. A panel of the FDA was scheduled to meet the same day to review FDA’s draft assessment that BPA was not a safety problem in the US food supply and environment. As a result of the JAMA article, the ranking member of the Committee on Finance, Chuck Grassley (R-Iowa) has written to the Commissioner of the FDA asking for a clarification of the FDA’s position on the science underlying a recent NIH review of BPA’s safety together with the names, titles, internal communications and communications with the chemical industry trade association and manufacturers of BPA. Clearly Grassley smells a rat. The precincts of the FDA are already so odorous it’s a wonder a new stink can even be detected. So this one must really reek. Here’s some of the background from the Editorial:

In this issue of JAMA, Lang and colleagues report the results of the first major epidemiologic study to examine the health effects associated with the ubiquitous estrogenic chemical bisphenol A (BPA). This compound is the base chemical (monomer) used to make polycarbonate plastic food and beverage containers, the resin lining of cans, and dental sealants; it also is found in “carbonless” paper used for receipts as well as a wide range of other common household products. Based on their analysis of data from the National Health and Nutrition Examination Survey 2003-2004, Lang et al report a significant relationship between urine concentrations of BPA and cardiovascular disease, type 2 diabetes, and liver-enzyme abnormalities in a representative sample of the adult US population. (vom Saal, F, Myers P in JAMA)

BPA is one of the highest volume chemicals in production worldwide. It has become ubiquitous in the environment, including food and drink, and BPA levels can now be detected in 90% of Americans. BPA also acts like a mimic of the major female sex hormone family, the estrogens. A very large body of animal literature has showed two things: that BPA has biological effects at levels relevant to environmental exposure and similar to natural estrogens (nanomole range); and that in animals it acts through response mechanisms also present in humans. The Lang et al. paper therefore is not surprising. It is pretty much what we would expect to see. On the other hand, the paper is surprising, because looking a representative sample of the US population for common diseases usually involves so much noise you can only see the strongest signals through the static.

The study involved 1455 participants in one of the two year random samples of the US population (NHANES, the National Health and Nutrition Examination Survey) done by the National Center for Health Statistics. Each was asked if a doctor had ever told them whether they had one of a series of conditions, including various kinds of heart conditions, asthma, diabetes, etc. A spot urine sample was taken and a blood draw and further questions about age, etc. This is the dataset used by the researchers based at the University of Exeter (UK) and published yesterday.

This was a very carefully done study but the results are best characterized as preliminary. The adult onset diabetes (Type II) and the liver function results are consistent with existing animal data.

The cardiovascular results (angina, heart attack, coronary artery disease) were new. They have not been looked for in animal models. Considerable pains were taken to evaluate and if possible eliminate alternative explanations but no single study can cover all possibilities. The cross-sectional nature of the design (meaning that the putative cause, BPA exposure, and the disease outcomes, were measured simultaneously, so the temporal sequence that is one hallmark of causal associations could not be evaluated. This will require some well designed prospective studies which should include pregnant women, infants, children and adults. The NHANES data in this study only included adults.

One of the important features of the existing science as underlined in this paper is that the FDA and EPA still base their safety assessments on old, high dose laboratory studies. One thing abundantly clear about hormones is that their effects are not necessarily increasing with dose. Higher doses often have lower effects than lower doses, that is the dose – response curve is U-shaped. Unfortunately the Bush FDA and EPA approved methods only look at the right hand branch of the U and take the bottom as the acceptable exposure. This isn’t 21st century biology, as the accompanying Editorial notes. Canada has already called BPA a toxic chemical, not a safe one. It isn’t that the Canadians are ahead of the curve. It is that the Bush FDA is behind the curve.

Way behind.