Mixed response to BPA study

A journal article claiming that bisphenol A (BPA) exposure during pregnancy in mice can affect brain function and behaviour has drawn mixed responses from experts.

The article, which was published in the peer-reviewed journal Proceedings of the National Academy of Sciences (PNAS), describes a study in which mice were exposed to “environmentally relevant” doses of BPA.

According to the authors, “BPA exposure induced persistent, largely sex-specific effects on social and anxiety-like behaviour, leading to disruption of sexually dimorphic behaviours.” They found that the effects of in utero BPA exposure were not found to be mediated by maternal care.

Experts who responded to the study disagreed on whether the levels of BPA the mice were exposed to were similar to human exposure levels.

“This is a well-designed study that uses concentrations of BPA that cover the upper levels of permitted exposure for BPA in humans, as well as very high doses,” said Dr Ian Musgrave, Senior Lecturer in the Faculty of Health Sciences at the University of Adelaide. “The doses are given in a way which mimics human exposure.”

“Whilst these findings raise the possibility that comparable effects of bisphenol A could occur in humans, several factors suggest this is unlikely,” said Professor Richard Sharpe from the MRC Centre for Reproductive Health, University of Edinburgh.

“First, the lowest dose use is still 10-20 times higher than normal human bisphenol A exposure. Second, the endpoints measured showed huge between-animal variation and considering that there were low numbers per group for some endpoints, the likelihood of false positive results is high, and no information on reproducibility of the results is provided. Third, if the effects described work through an oestrogen mechanism, they are unlikely to be human relevant because pregnancy levels of oestrogens in humans are far higher than in mice and would swamp any weak oestrogenic effects of bisphenol A.”

“The doses of BPA in the study are in an appropriate concentration range, spanning the suggested recommended tolerable limit for BSA in humans of 50 micrograms/kg body weight/day,” said Professor Tamara Galloway, Professor of Ecotoxicology, University of Exeter.

“As the authors quite rightly point out, there are differences in metabolism of BPA between humans and rodents, and they have taken account of this as far as they can in their planning. The doses have been administered orally, which is in line with current thinking on appropriate route of exposure. Earlier experiments by other groups have been criticised for administering BPA intravenously, which would bypass normal routes of metabolism in the gut,” she said.

“This publication is in line with other reports suggesting that in pregnant experimental animals, bisphenol A may influence the methylation of genes, controlling their action and leading to subtle differences in physiology of offspring,” said Professor Andrew Smith, MRC Toxicology Unit, University of Leicester, and Royal Society of Chemistry’s Toxicology Group.

“The work is well organised but its findings emphasise the need for more fundamental research in this area. Although administered by the authors at relatively low doses possibly compatible with human experience, there are important issues of the degree of exposure to bisphenol A versus the direction of methylation and behavioural/brain changes.

“These must be confirmed, clarified and mechanisms resolved before any extrapolation can be made to the human context especially in relation to mental and cognitive disorders. Indeed, it is unclear how understanding consequences of low bisphenol A exposure fit in the landscape of human exposure to other chemicals.”

The PNAS article, Sex-specific epigenetic disruption and behavioural changes following low-dose in utero bisphenol A exposure, is available here.