U.S. FDA, National Center for Toxicological Research, Jefferson, AR, 72079, USA.
Toxicologic Pathology Associates, Jefferson, AR, 72079, USA.
Food Chem Toxicol. 2019 Oct;132:110728. doi: 10.1016/j.fct.2019.110728. Epub 2019 Jul 28.
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 μg/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 BPA 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 stop-dose 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 μg BPA/kg bw/day dose level.
我们报告了作为 BPA 毒性学术和监管洞察联盟 (CLARITY-BPA) 一部分进行的符合指南的为期两年的毒理学研究的数据。BPA（0、2.5、25、250、2500 和 25000μg/kg 体重（bw）/天）以 0.3%羧甲基纤维素载体通过灌胃每日给予 NCTR 斯普拉格-道利大鼠，从妊娠第 6 天到分娩开始，然后直接给予新生仔鼠，从出生后第 1 天到第 21 天（停药组）或连续给药直至 1 或 2 年结束。停药组包括评估任何因发育暴露而导致的 BPA 作用的可能性。在体内和非组织病理学数据中没有发现与 BPA 相关的作用。在雌性和雄性中诊断出的肿瘤和非肿瘤病变是常见的与年龄相关的病变，在对照组和 BPA 处理组之间存在差异。在连续和停药组内和跨组织中没有一致的反应，这使得这些病变与 BPA 治疗的合理关系受到质疑。在雌性生殖道和雄性垂体中的病变发生率增加与暴露于 25000μg BPA/kg bw/天剂量水平之间可能存在关系。
