Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, United States.
Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, United States; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, 48824, United States.
Toxicology. 2018 Mar 1;396-397:54-67. doi: 10.1016/j.tox.2018.02.004. Epub 2018 Feb 7.
Bisphenol A (BPA) is commonly used in the manufacturing of a wide range of consumer products, including polycarbonate plastics, epoxy resin that lines beverage and food cans, and some dental sealants. Consumption of food and beverages containing BPA represents the primary route of human BPA exposure, which is virtually ubiquitous. An increasing number of studies have evaluated the effects of BPA on immune responses in laboratory animals that have reported a variety of effects some of which have been contradictory. To address the divergent findings surrounding BPA exposure, a comprehensive chronic treatment study of BPA was conducted in Sprague-Dawley rats, termed the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA). As a participant in the CLARITY-BPA project, our studies evaluated the effects of BPA on a broad range of immune function endpoints using spleen cells isolated from BPA or vehicle treated rats. This comprehensive assessment included measurements of lymphoproliferation in response to mitogenic stimuli, immunoglobulin production by B cells, and cellular activation of T cells, NK cells, monocytes, granulocytes, macrophages and dendritic cells. In total, 630 different measurements in BPA treated rats were performed of which 35 measurements were statistically different from vehicle controls. The most substantive alteration associated with BPA treatment was the augmentation of lymphoproliferation in response to pokeweed mitogen stimulations in 1 year old male rats, which was also observed in the reference estrogen ethinyl estradiol treated groups. With the exception of the aforementioned, the statistically significant changes associated with BPA treatment were mostly sporadic and not dose-dependent with only one out of five BPA dose groups showing a statistical difference. In addition, the observed BPA-associated alterations were mostly moderate in magnitude and showed no persistent trend over the one-year time period. Based on these findings, we conclude that the observed BPA-mediated changes observed in this study are unlikely to alter immune competence in adult rats.
双酚 A（BPA）广泛用于制造各种消费品，包括聚碳酸酯塑料、饮料和食品罐内的环氧树脂以及一些牙科密封剂。人类接触 BPA 的主要途径是摄入含 BPA 的食品和饮料，这种接触几乎无处不在。越来越多的研究评估了 BPA 对实验动物免疫反应的影响，这些研究报告了各种影响，其中一些相互矛盾。为了解决围绕 BPA 暴露的分歧发现，对 Sprague-Dawley 大鼠进行了一项 BPA 的综合慢性治疗研究，称为“将学术和监管对 BPA 毒性的见解联系起来的联盟”（CLARITY-BPA）。作为 CLARITY-BPA 项目的参与者，我们的研究使用从 BPA 或载体处理的大鼠中分离的脾细胞，评估了 BPA 对广泛的免疫功能终点的影响。这种全面评估包括测量对有丝分裂原刺激的淋巴细胞增殖、B 细胞产生免疫球蛋白以及 T 细胞、NK 细胞、单核细胞、粒细胞、巨噬细胞和树突状细胞的细胞激活。总共对 BPA 处理的大鼠进行了 630 次不同的测量，其中 35 次测量与载体对照有统计学差异。与 BPA 处理相关的最实质性改变是 1 岁雄性大鼠对 pokeweed 有丝分裂原刺激的淋巴细胞增殖增加，这在参考雌激素乙炔雌二醇处理组中也观察到。除了上述情况外，与 BPA 处理相关的统计学显著变化大多是零星的，没有剂量依赖性，只有五分之一的 BPA 剂量组显示出统计学差异。此外，观察到的与 BPA 相关的改变大多幅度适中，在一年的时间内没有持续趋势。基于这些发现，我们得出结论，在这项研究中观察到的 BPA 介导的变化不太可能改变成年大鼠的免疫能力。
