New research from the US has linked foetal exposure to bisphenol A (BPA) in monkeys with an increased risk of cancer in primates. But scientists have questioned the validity of the study’s methodology and the relevance of its findings to humans.
Researchers from the School of Molecular Biosciences at Washington State University (WSU) concluded that exposing female rhesus macque monkeys to BPA altered the structure of newborn mammary glands and boosted the chances of developing cancers later in life.
Breast cancer concerns
The group, led by Andrew Tarp, said the findings added to evidence that “the chemical can cause health problems in humans and bolsters concerns about it contributing to breast cancer”.
Pregnant monkeys were fed a piece of fruit containing what the scientists described as a “small amount of BPA each day” during the gestational period corresponding to the human third trimester of pregnancy. This level of exposure resulted in BPA blood levels comparable to those of many Americans today, said the team.
They found that, at birth, the density of mammary buds was significantly increased in BPA-exposed monkeys, and the overall development of the mammary gland was more advanced compared to unexposed monkeys.
The study was co-designed by three scientists with an established track record on BPA research; Ana Soto and Carlos Sonnenschein, from Hunt and Tufts University, along with Catherine VandeVoort at the University of California at Davis, School of Medicine.
The research was published in the latest Proceedings of the National Academies of Sciences (PNAS).
The WSU team said previous studies by Soto and Sonnenschein had demonstrated that exposing rodents in-utero to small amounts of BPA could alter mammary gland development, leading to pre-cancerous and cancerous lesions when the animals reach adult age.
They added they were confident the rodent mammary gland was a reliable model to study developmental exposures to chemicals like BPA that disrupt a mammal’s estrogen activity and showed that foetal exposure could lead to mammary cancer later in life.
"Because BPA is chemically related to diethylstilbestrol, an estrogen that increased the risk of breast cancer in both rodents and women exposed in the womb, the sum of all these findings strongly suggests that BPA is a breast carcinogen in humans and human exposure to BPA should be curtailed,” said Soto.
WSU geneticist Patricia Hunt said that showing a link between the effects of foetal exposure to BPA in primates “really hits uncomfortably close to home.”
Study flawed, say scientists
But scientific experts in Australia and Canada have expressed serious doubts over the study’s methodology and the conclusions drawn regarding the possible human health hazard they represent.
Dr Ian Musgrave, senior lecturer in the Discipline of Pharmacology at the University of Adelaide, Australia, said the doses used and plasma concentrations reached in the study were unrepresentative of most human exposure.
“The dosage used was eight times higher than the upper limit of permitted human exposures,” he added. “It was also administered as a single, large dose which would have produced a much larger concentration in the blood than was seen when the plasma levels were measured four hours later. The serum level of total BPA measured at this time were around 50 times higher than is seen in several human studies, but as this plasma level was measured several hours after dosing, the actual exposures would be much higher.”
Dr Musgrave questioned whether the study highlighted legitimate concerns as he said long term studies with rats at high levels of exposure had shown no adverse effects.
Canada-based Professor Warren Foster, of McMaster University, said major strengths of the study were employing oral exposure routes in non-human primates and appropriate analytical methods of the data.
Sample size too small
However, he too raised questions over the very high dose level administered in one go. Human exposure occurs in repeated lower levels, which meant the WSU method “may not necessarily be reflective of how people and tissues are exposed”
Prof Foster also raised concerns that the sample size was far too small to draw statistically relevant conclusions.
“It is appreciated that non-human primate studies are expensive and difficult to run, yet four and five animals/group is not robust and it is difficult to extrapolate the findings to the larger population,” he said.
While acknowledging the study was scientifically sound in general, he said: “The results do not however suggest that BPA is a carcinogen or that it is implicated in breast cancer. Furthermore, the dosing paradigm is not representative of human exposure which makes generalization of the study results to humans difficult.”
Bisphenol A alters the development of the rhesus monkey mammary gland Andrew P. Tharp, Maricel V. Maffini, Patricia A. Hunt, Catherine A. VandeVoort, Carlos Sonnenscheina, and Ana M. Soto published in Proceedings of the National Academies of Sciences; doi: 10.1073/pnas.1120488109