Exposure to low doses of Bisphenol A (BPA) during gestation had immediate and long-lasting, trans-generational effects on the brain and social behaviors in mice, according to a recent study accepted for publication in the journal Endocrinology, a publication of The Endocrine Society.
BPA is a man-made chemical present in a variety of products including food containers, receipt paper and dental sealants and is now widely detected in human urine and blood. Public health concerns have been fueled by findings that BPA exposure can influence brain development. In mice, prenatal exposure to BPA is associated with increased anxiety, aggression and cognitive impairments.
BPA is a man-made chemical present in a variety of products including food containers, receipt paper and dental sealants and is now widely detected in human urine and blood. Public health concerns have been fueled by findings that BPA exposure can influence brain development. In mice, prenatal exposure to BPA is associated with increased anxiety, aggression and cognitive impairments.
BPA molecule
Credit: Wikipedia
"We have demonstrated for the first time to our knowledge that BPA has trans-generational actions on social behavior and neural expression," said Emilie Rissman, PhD, of the University of Virginia School of Medicine and lead author of the study. "Since exposure to BPA changes social interactions in mice at a dose within the reported human levels, it is possible that this compound has trans-generational actions on human behavior. If we banned BPA tomorrow, pulled all products with BPA in them, and cleaned up all landfills tomorrow it is possible, if the mice data generalize to humans, that we will still have effects of this compound for many generations."
In this study, female mice received chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented female mice were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice. The changes in genes were most dramatic in the first generation (the offspring of the mice that were exposed to BPA in utero), but some of these gene changes persisted into the fourth generation.
"BPA is a ubiquitous chemical, it is in the air, water, our food, and our bodies," said Rissman. "It is a man-made chemical, and is not naturally occurring in any plant or animal. The fact that it can change gene expression in mice, and that these changes are heritable, is cause for us to be concerned about what this may mean for human health."
In its March 30, 2012 response to a Citizen Petition from 2008, the FDA denied the petitioners’ request to ban BPA from food and food packaging, stating that they had failed to provide sufficient data to persuade the FDA to begin a rulemaking. In its response, the FDA again called into question the relevance of small, academic studies on the effects of EDCs, despite the advice of its own scientific advisory board in November 2008 to include such studies in the assessment of BPA.
The FDA’s approach to discounting studies in the regulatory process does not allow for a thorough examination of the data and hinders the agency’s ability to ensure appropriate regulation of EDCs. A recent Endocrine Reviews article outlines a Weight-of-Evidence approach to evaluating low-dose studies from an endocrine perspective, focusing on criteria different from those used by the FDA.
“We encourage the FDA to consider low-dose studies examining important endocrinological endpoints when making policies regarding BPA or other endocrine-disrupting chemicals,” said Hall. “Many of the neglected studies of low-dose effects are well designed, heavily reviewed, NIH-funded work. The results of this research show significant health effects at exposures substantially lower than those deemed safe by the FDA."
Endocrinologists have a valuable and unique insight into the impact of EDCs, and modern endocrinology has greatly advanced the body of scientific knowledge in this field in the past decade. The Endocrine Society published its Scientific Statement on endocrine-disrupting chemicals in 2009. The Scientific Statement, available at www.endo-society.org/journals/scientificstatements, presents evidence on the health effects of endocrine-disrupting chemicals as well as recommendations for increasing understanding and raising awareness of these effects.
Contacts and sources:
"We have demonstrated for the first time to our knowledge that BPA has trans-generational actions on social behavior and neural expression," said Emilie Rissman, PhD, of the University of Virginia School of Medicine and lead author of the study. "Since exposure to BPA changes social interactions in mice at a dose within the reported human levels, it is possible that this compound has trans-generational actions on human behavior. If we banned BPA tomorrow, pulled all products with BPA in them, and cleaned up all landfills tomorrow it is possible, if the mice data generalize to humans, that we will still have effects of this compound for many generations."
In this study, female mice received chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented female mice were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice. The changes in genes were most dramatic in the first generation (the offspring of the mice that were exposed to BPA in utero), but some of these gene changes persisted into the fourth generation.
"BPA is a ubiquitous chemical, it is in the air, water, our food, and our bodies," said Rissman. "It is a man-made chemical, and is not naturally occurring in any plant or animal. The fact that it can change gene expression in mice, and that these changes are heritable, is cause for us to be concerned about what this may mean for human health."
BPA is a known endocrine-disrupting chemical (EDC). EDCs are substances in the environment that interfere with hormone action resulting in adverse developmental, reproductive, neurological and immune effects in both humans and wildlife. Many of these chemicals are designed, produced and marketed largely for specific industrial purposes, but they are also found in some natural foods and may become further concentrated as foods are processed.
“ The Society supports the FDA's continuing efforts to evaluate the safety of BPA, but it remains concerned that policy on BPA and other endocrine disrupting chemicals is ignoring the entirety of available scientific data,” said Janet E. Hall, MD, president of The Endocrine Society in a statement earlier this year.
“ The Society supports the FDA's continuing efforts to evaluate the safety of BPA, but it remains concerned that policy on BPA and other endocrine disrupting chemicals is ignoring the entirety of available scientific data,” said Janet E. Hall, MD, president of The Endocrine Society in a statement earlier this year.
The FDA’s approach to discounting studies in the regulatory process does not allow for a thorough examination of the data and hinders the agency’s ability to ensure appropriate regulation of EDCs. A recent Endocrine Reviews article outlines a Weight-of-Evidence approach to evaluating low-dose studies from an endocrine perspective, focusing on criteria different from those used by the FDA.
“We encourage the FDA to consider low-dose studies examining important endocrinological endpoints when making policies regarding BPA or other endocrine-disrupting chemicals,” said Hall. “Many of the neglected studies of low-dose effects are well designed, heavily reviewed, NIH-funded work. The results of this research show significant health effects at exposures substantially lower than those deemed safe by the FDA."
Endocrinologists have a valuable and unique insight into the impact of EDCs, and modern endocrinology has greatly advanced the body of scientific knowledge in this field in the past decade. The Endocrine Society published its Scientific Statement on endocrine-disrupting chemicals in 2009. The Scientific Statement, available at www.endo-society.org/journals/scientificstatements, presents evidence on the health effects of endocrine-disrupting chemicals as well as recommendations for increasing understanding and raising awareness of these effects.
Health studies and the ill affects of BPA are listed here: http://en.wikipedia.org/wiki/Bisphenol_A
Contacts and sources:
Aaron Lohr
The Endocrine Society
The article, "Gestational exposure to Bisphenol A produces trans-generational changes in behaviors and gene expression," appears in the XX 2012 issue of Endocrinology.
Other researchers working on the study include: Jennifer Wolstenholme, Michelle Edwards, Savera Shetty, Jessica Gatewood and Jessica Connelly of the University of Virginia; and Julia Taylor of the University of Missouri.
The Endocrine Society
The article, "Gestational exposure to Bisphenol A produces trans-generational changes in behaviors and gene expression," appears in the XX 2012 issue of Endocrinology.
Other researchers working on the study include: Jennifer Wolstenholme, Michelle Edwards, Savera Shetty, Jessica Gatewood and Jessica Connelly of the University of Virginia; and Julia Taylor of the University of Missouri.
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