Kortenkamp Andreas, Martin Olwenn, Ermler Sibylle, Baig Asma, Scholze Martin
Brunel University London, Centre for Pollution Research and Policy, College of Health, Medicine and Life Sciences, Kingston Lane, Uxbridge, UB8 3PH, UK.
Brunel University London, Centre for Pollution Research and Policy, College of Health, Medicine and Life Sciences, Kingston Lane, Uxbridge, UB8 3PH, UK.
Int J Hyg Environ Health. 2022 Apr;241:113942. doi: 10.1016/j.ijheh.2022.113942. Epub 2022 Feb 12.
To support a mixture risk assessment with a focus on male reproductive health, we conducted a systematic review of associations between bisphenol A (BPA) exposures and declines in semen quality, based on animal and epidemiological studies. Contrary to a widely held view that there is "conflicting" evidence of such associations, our review and confidence rating approach reveals that animal studies provide convincing evidence of declines of semen quality after gestational BPA exposures. Many of the reported negative findings can be attributed to deficiencies in study sensitivity, insufficient control of background contamination and probable confounding through hormonal interference due to the use of soy-containing diets. We did not evaluate animal studies of adult BPA exposures. Divergent findings in "medium to high" and "medium" confidence epidemiological studies can be explained in terms of differences in exposure conditions. We attempted the estimation of a BPA reference dose based on animal studies. Due to variations in the no-observed adverse effect levels (NOAELs) in high confidence studies, possible reference doses ranged from 0.0001 to 0.0099 μg/kg/d. In choosing 0.003 μg/kg/d we struck a balance between caution suggested by studies at the lower end of the doses and the weight of evidence from studies with higher NOAELs. This weighting was motivated by the intended use of the value in a mixture risk assessment which meant arriving at a reasonable estimate of BPA exposures likely without effects on semen quality. We realise that our approach does not conform with the standards necessary for deriving tolerable daily intakes (TDIs) for single chemical exposures, which is not our interest here. BPA exposures currently experienced by European populations and beyond are in excess of 0.003 μg/kg/d and even fall in the range where some epidemiological studies observed effects on semen quality as a result of BPA exposures in adulthood.
为支持以男性生殖健康为重点的混合风险评估，我们基于动物研究和流行病学研究，对双酚A（BPA）暴露与精液质量下降之间的关联进行了系统综述。与普遍认为此类关联存在“相互矛盾”证据的观点相反，我们的综述和置信度评级方法表明，动物研究提供了令人信服的证据，证明孕期暴露于BPA后精液质量会下降。许多报告的负面结果可归因于研究敏感性不足、背景污染控制不力以及由于使用含大豆饮食导致激素干扰可能造成的混杂因素。我们未评估成年期BPA暴露的动物研究。“中高”和“中等”置信度的流行病学研究中存在不同结果，可以根据暴露条件的差异来解释。我们尝试根据动物研究估算BPA参考剂量。由于高置信度研究中未观察到不良影响水平（NOAELs）存在差异，可能的参考剂量范围为0.0001至0.0099μg/kg/d。在选择0.003μg/kg/d时，我们在低剂量端研究建议的谨慎性与较高NOAELs研究的证据权重之间取得了平衡。这种加权是由该值在混合风险评估中的预期用途推动的，这意味着要对可能不会影响精液质量的BPA暴露进行合理估计。我们认识到我们的方法不符合推导单一化学物质暴露的每日可耐受摄入量（TDIs）所需的标准，而这并非我们此处的关注点。欧洲及其他地区人群目前经历的BPA暴露超过0.003μg/kg/d，甚至处于一些流行病学研究观察到成年期BPA暴露对精液质量有影响的范围内。
