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カナダ ビスフェノールAを毒物指定 by 農業情報研究所

カナダ ビスフェノールA[bisphenol A]を毒物指定 含有哺乳瓶禁止や環境放出規制を提案 農業情報研究所(WAPIC) 08.10.22

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 Proposed Risk Management Approach for Phenol, 4,4'-(1-methylethylidene) bis (Bisphenol A) Chemical Abstract Service Registry Number (CAS RN): 80-05-7,Environment Canada,08.10

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 1)Iain A. Lang et al,Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults,Journal of the American Medical Association, Vol. 300 No. 11, September 17, 2008

2)University of Cincinnati:Bisphenol A Linked to Chemotherapy Resistance,08.10.8

 カナダ ビスフェノールA入り哺乳瓶禁止へ 米国でも癌等との関連を認める報告書,08.4.21

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エストロゲン関連受容体γ型(ERRγ):ビスフェノールA が非常に強く結合する自発活性化型核内受容体の発見 下東 康幸 (九州大学大学院理学研究院化学部門)


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Environ Health Perspect. 2003 Jun;111(8):994-1006.
Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Welshons WV, Thayer KA, Judy BM, Taylor JA, Curran EM, vom Saal FS.
Department of Veterinary Biomedical Sciences, Columbia, MO, USA. welshonsw@missouri.edu

Information concerning the fundamental mechanisms of action of both natural and environmental hormones, combined with information concerning endogenous hormone concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity (EEDCs) can be active at concentrations far below those currently being tested in toxicological studies. Using only very high doses in toxicological studies of EEDCs thus can dramatically underestimate bioactivity. Specifically: a) The hormonal action mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose ranges of biological activity, which have been missed by traditional toxicological testing. b) Toxicology assumes that it is valid to extrapolate linearly from high doses over a very wide dose range to predict responses at doses within the physiological range of receptor occupancy for an EEDC; however, because receptor-mediated responses saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses can first increase and then decrease as dose increases, contradicting the assumption that dose-response relationships are monotonic. d) Exogenous estrogens modulate a system that is physiologically active and thus is already above threshold, contradicting the traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses. These doses are within the range of current exposures to numerous chemicals in wildlife and humans. These problems are exacerbated by the fact that the type of positive and negative controls appropriate to the study of endocrine responses are not part of traditional toxicological testing and are frequently omitted, or when present, have been misinterpreted.

PMID: 12826473 [PubMed - indexed for MEDLINE]

Environ Res. 2006 Jan;100(1):50-76. Epub 2005 Oct 27.
Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A. vom Saal FS, Welshons WV.
Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA. vomsaalf@missouri.edu

Over six-billion pounds per year of the monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, resins lining cans, dental sealants, and polyvinyl chloride plastic products. There are 109 published studies as of July 2005 that report significant effects of low doses of BPA in experimental animals, with many adverse effects occurring at blood levels in animals within and below average blood levels in humans; 40 studies report effects below the current reference dose of 50 microg/kg/day that is still assumed to be safe by the US-FDA and US-EPA in complete disregard of the published findings. The extensive list of significant findings from government-funded studies is compared to the 11 published studies that were funded by the chemical industry, 100% of which conclude that BPA causes no significant effects. We discuss the importance of appropriate controls in toxicological research and that positive controls are required to determine whether conclusions from experiments that report no significant effects are valid or false.

PMID: 16256977 [PubMed - indexed for MEDLINE]

Endocrinology. 2006 Jun;147(6 Suppl):S56-69. Epub 2006 May 11.
Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Welshons WV, Nagel SC, vom Saal FS.
Department of Biomedical Sciences, E102 Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri 65211-5120, USA. WelshonsW@missouri.edu

Over 6 billion pounds per year of the estrogenic monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, in resins lining metal cans, in dental sealants, and in blends with other types of plastic products. The ester bond linking BPA molecules in polycarbonate and resins undergoes hydrolysis, resulting in the release of free BPA into food, beverages, and the environment, and numerous monitoring studies now show almost ubiquitous human exposure to biologically active levels of this chemical. BPA exerts estrogenic effects through the classical nuclear estrogen receptors, and BPA acts as a selective estrogen receptor modulator. However, BPA also initiates rapid responses via estrogen receptors presumably associated with the plasma membrane. Similar to estradiol, BPA causes changes in some cell functions at concentrations between 1 pM and 1 nM, and the mean and median range of unconjugated BPA measured by multiple techniques in human pregnant maternal, fetal, and adult blood and other tissues exceeds these levels. In contrast to these published findings, BPA manufacturers persist in describing BPA as a weak estrogen and insist there is little concern with human exposure levels. Our concern with human exposure to BPA derives from 1) identification of molecular mechanisms mediating effects in human and animal tissues at very low doses, 2) in vivo effects in experimental animals caused by low doses within the range of human exposure, and 3) widespread human exposure to levels of BPA that cause adverse effects in animals.

PMID: 16690810 [PubMed - indexed for MEDLINE]

by oninomae | 2008-10-24 00:45 | 有毒化学物質  

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