A two-year toxicology study of bisphenol A (BPA) in Sprague-Dawley rats: CLARITY-BPA core study results
A two-year toxicology study of bisphenol A (BPA) in Sprague-Dawley rats: CLARITY-BPA core study results
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DOI：
10.1016/j.fct.2019.110728
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发表时间：
2019-10-01
影响因子：
4.3
通讯作者：
Delclos, K. B.
中科院分区：
文献类型：
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作者：
Camacho, L.;Lewis, S. M.;Delclos, K. B.
我们报告了符合指南的为期两年的毒理学研究的数据，该研究是双酚A毒性学术和监管见解联盟(Clarity-BPA)的一部分。BPA(0、2.5、25、250、2500和25000微克/千克体重/天)每天以0.3%羧甲基纤维素剂灌胃给NCTR SD大鼠，从妊娠第6天到分娩开始，然后从出生次日到出生后第21天(停药组)直接给仔鼠灌胃，或连续灌胃，直到1~2年终止。包括停止剂量的ARM是为了评估由于发育暴露而产生的任何SPA影响的可能性。在活体和非组织病理学数据中没有明显的BPA相关影响。在女性和男性中诊断的肿瘤性和非肿瘤性病变是常见的与年龄相关的病变，在对照组和双酚A治疗组中是不同的。在组织内和组织间的连续和停止剂量臂内缺乏一致的反应，这使人们对这些病变中的大多数与双酚A治疗的可信关系产生了疑问。女性生殖道和男性垂体病变发生率的增加可能与暴露于25000微克双酚A/千克体重/天剂量水平有关。
We report the data from the guideline-compliant two-year toxicology study conducted as part of the Consortium Linking Academic and Regulatory Insights on Bisphenol A Toxicity (CLARITY-BPA). BPA (0, 2.5, 25, 250, 2,500, and 25,000 mu g/kg body weight (bw)/day) was administered daily by gavage in 0.3% carboxymethylcellulose vehicle to NCTR Sprague-Dawley rats from gestation day 6 through the start of parturition and then directly to pups from the day after birth until postnatal day 21 (stop-dose arm) or continuously until termination at one or two years. The stop-dose arm was included to assess the potential for any SPA effects that were due to developmental exposure. No BPA-related effects were evident in the in-life and non-histopathology data. Neoplastic and nonneoplastic lesions diagnosed in both females and males were common age-associated lesions that were variable across control and BPA-treated groups. The lack of consistent responses within the continuous- and stopdose arms within and across tissues brought into question the plausible relationship of most of these lesions to BPA treatment. There was a possible relationship between the increased incidences of lesions in the female reproductive tract and the male pituitary and exposure to the 25,000 mu g BPA/kg bw/day dose level.