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vom Saal, F and W Welshons. 2006. Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A. Environmental Research 100: 50-76. Part 1 of this series More on bisphenol A Contents A review of BPA's history, basic chemistry and current uses A review of the prediction that BPA would have biological impacts at low exposures Low
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   vom Saal, F and W Welshons. 2006. Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A . Environmental Research 100: 50-76.  Part 1 of this series More on bisphenol A Contents A review of BPA's history, basic chemistry and current uses A review of the prediction that BPA would have biological impacts at low exposures Low-dose BPA results challenge the assumptions used in chemical risk assessment Evidence of bias in industry-funded research on BPA Conclusions    Latest news about bisphenol A Search 6 September  Plastic debris clogs   our oceans and hurts wildlife.  Recycling and the proper disposal of waste are necessary to help reduce the amount of plastic trash. Salisbury Daily Times, Maryland.   2 September  Commentary:   Twenty-five years of endocrine   disruption science:   Remembering Theo Colborn.  Theo Colborn was a visionary leader who excelled at synthesizing scientific findings across disciplines. Using her unique insights and strong moral convictions, she changed the face of toxicological research, influenced chemical regulatory policy, and educated the public. Environmental Health Perspectives.  While chemical manufacturers claim in public statements that high-quality repeat studies in independent laboratories have not been able to replicate claims that bisphenol A causes adverse effects at low levels (for example on industry's NoAB319  website), a careful analysis of the 'high quality' studies they reference reveals deep flaws , and that industry-financed research on the health effects of bisphenol A is strongly biased against finding adverse effects . These flaws result from the way the studies have been designed and executed. Read about industry's AB319 claims According to vom Saal and Welshon's analysis in this paper, of  30 August  10 things you need to   know about the new U.S. chemicals law.  The updated Toxic Substances Control Act brings new hope for protecting American s’ health and environment. Here's what it does —   and doesn’t —  do. Ensia.   27 August  FLASHBACK: That time when Maine's controversial Governor talked about BPA.  The political debate over bisphenol A is heating up in Maine after Gov. Paul LePage’s recent comments questioning whether the controversial chemical is as dangerous as many scientists claim. Bangor Daily News, Maine.     27 August  FLASHBACK: That time back in 2011 when Maine's controversial Governor talked about BPA.  Today, the Bangor Daily News reports on Maine governor Paul LePage's weird comments on the chemical bisphenol A. Bangor Daily News,  Maine.  More news about  bisphenol A the 130 studies of low dose effects  of BPA published as of summer 2005, 119 have been funded by governments and 11 by industry. 92% of the government funded studies report adverse effects. None of the industry studies do . In this  paper, vom Saal and Welshons examine in detail the government and industry funded studies that found no effects, and show several reasons why poor study design destined them to failure.  Not only is industry's own research flawed, but they have repeatedly chosen to ignore all but a handful of the studies on low level effects of  bisphenol A that have been  published in the peer-reviewed scientific literature. This is a classic  ploy, perfected by representatives of tobacco companies, to undermine  progress toward better health standards. They focus on a small  piece of the overall picture, focus on creating the impression that that  piece is flawed, and then argue that  because of that flaw the entire body of literature is invalid. For bisphenol, this tactic requires them to ignore over 100 studies that have been published in the peer reviewed literature by independent scientists and to rely instead upon a small number of demonstrable flawed studies conducted by industry labs. What did vom Saal and Welshons do?  Section 1: A review of BPA's history, basic chemistry and current uses.       The ester bond that links BPA molecules into  polycarbonate and resins is subject to hydrolysis, which results in leaching of BPA into water  even from new polycarbonate at room temperature. The leaching rate increases over 1000-fold as it begins to show signs of wear. Older studies that reported no leaching used very insensitive methods. Hence the FDA's assertion that with baby bottles, we haven't been able to detect BPA is outdated.    Until recently, BPA has been considered to be a weak estrogen because in some assays it can be 10,000 to 100,000-fold weaker than estradiol,  based on binding affinity to the nuclear estrogen receptor. New research contradicts, this however. BPA can be  just as powerful as estradiol, with detectable effects at the lowest doses tested, approximately 0.23 parts per trillion. Section 2: A review of the srcinal prediction that BPA would have  biological impacts at very low levels of exposure,  published in 1997.     Previous studies had used only high doses, and in light of the relative low binding affinity to the nuclear hormone receptor, this seemed reasonable. But then  Nagel et al  . discovered that while serum  binding proteins bind with most of the estradiol in serum, rendering it biologically inactive, they bind with little of the BPA. This led them to calculate a correction factor for the relative potency of BPA compared to estradiol, and to calculate, based on known effects of estradiol, that 20 µg/kg/day of BPA fed to a pregnant female should stimulate an increase in the prostate size, decrease sperm count and alter other reproductive organs in male offspring. This is in fact what they found.    These findings have been replicated by an independent laboratory and by vom Saal's lab.    In this section vom Saal and Welshons also introduce the first criticism of one of the failed attempts by industry labs to replicate their findings. This study, by Tyl et al  . used a strain of rats known to be insensitive to any exogenous estrogen, including potent estrogenic drugs. Tyl et al  . used this strain because it was their standard experimental animal in their laboratory. In reviewing the work, the National Toxicology Program concluded: animal selection should be   based on responsiveness to endocrine active agents of concern, not on convenience and familiarity. Unfortunately, Tyl et al  . did not include a  positive control in their work. Based on the overall insensitivity of the strain they used, it is likely that the positive control would have shown no reaction, proving the lack of validity of the study. Without data on a positive control, Tyl et al. cannot conclude that bisphenol A does not have low dose activity. Section 3: Low-dose BPA results challenge the assumptions used in chemical risk assessment.
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