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低剂量双酚A生殖与发育效应的证据权重评估

Weight-of-evidence evaluation of reproductive and developmental effects of low doses of bisphenol A.

作者信息

Goodman Julie E, Witorsch Raphael J, McConnell Ernest E, Sipes I Glenn, Slayton Tracey M, Yu Carrie J, Franz Amber M, Rhomberg Lorenz R

机构信息

Gradient Corporation, Cambridge, Massachusetts 02138, USA.

出版信息

Crit Rev Toxicol. 2009;39(1):1-75. doi: 10.3109/10408440903279946.

Abstract

Recent public concern has focused on potential reproductive and developmental effects from exposure to low levels of bisphenol A (BPA, CAS number 80-05-7). Two previous published reviews (Gray et al., 2004a; Goodman et al., 2006) conducted weight-of-evidence evaluations of in vivo reproductive/developmental toxicity from BPA exposure < or = 5 mg/kg-d based on studies published through February 2006. Here, an update of those analyses presents additional relevant studies that were published through July 25, 2008, and a weight-of-evidence analysis of the studies evaluated in all three reviews. As with the earlier literature, positive findings: (1) are countered by null findings in more numerous studies; (2) have not been replicated; (3) do not exhibit coherence and plausibility; (4) do not show consistency across species, doses, and time points; and/or (5) were from studies using non-oral exposure routes. Owing to the lack of first-pass metabolism, results from non-oral studies are of limited relevance to human exposure. Exposure levels in most of the low-dose oral and non-oral animal studies are generally much higher than those experienced by even the most exposed people in the general population. The weight of evidence does not support the hypothesis that low oral doses of BPA adversely affect human reproductive and developmental health.

摘要

近期公众关注的焦点集中在低剂量双酚A(BPA,化学物质登记号80 - 05 - 7)暴露对生殖和发育的潜在影响上。之前发表的两篇综述(Gray等人,2004a;Goodman等人,2006)基于截至2006年2月发表的研究,对暴露于≤5 mg/kg - d的双酚A的体内生殖/发育毒性进行了证据权重评估。在此,对这些分析进行更新,纳入了截至2008年7月25日发表的更多相关研究,并对这三篇综述中评估的研究进行了证据权重分析。与早期文献一样,阳性研究结果存在以下情况:(1)在更多研究中的阴性结果与之相矛盾;(2)未得到重复验证;(3)缺乏连贯性和合理性;(4)在不同物种、剂量和时间点上缺乏一致性;和/或(5)来自使用非口服暴露途径的研究。由于缺乏首过代谢,非口服研究的结果与人类暴露的相关性有限。大多数低剂量口服和非口服动物研究中的暴露水平通常远高于一般人群中暴露程度最高的人所经历的水平。证据权重不支持低剂量口服双酚A会对人类生殖和发育健康产生不利影响这一假设。

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