Brunel University London, Centre for Pollution Research and Policy, College of Health, Medicine and Life Sciences, Kingston Lane, Uxbridge, UB8 3PH, United Kingdom.
Brunel University London, Centre for Pollution Research and Policy, College of Health, Medicine and Life Sciences, Kingston Lane, Uxbridge, UB8 3PH, United Kingdom.
Int J Hyg Environ Health. 2022 May;242:113953. doi: 10.1016/j.ijheh.2022.113953. Epub 2022 Mar 22.
To support a mixture risk assessment for chemicals that interfere with male reproductive health, we reviewed the literature to identify studies of polybrominated diphenyl ethers (PBDEs) and poor semen quality. Several epidemiological studies have shown associations of PBDE exposures with declining semen quality, non-descending testes and penile malformations. In rodent studies, poor semen quality, changes in testosterone levels and reproductive tissues have been observed. In vitro studies with reporter gene constructs show PBDE congeners as androgen receptor antagonists, and mixture studies in these systems have demonstrated that PBDE congeners act together with other androgen receptor antagonists. These observations led us to attempt the estimation of reference doses for specific PBDE congeners that can be used in a future mixture risk assessment for deteriorations of semen quality. While epidemiological studies provide support for such associations, they were uninformative for derivations of reference doses, due to the incompatibility of dose metrics used in exposure assessments. We therefore based our estimates on animal studies. Using a rigorous confidence rating approach, we found robust evidence that BDE-47 produced reductions in semen quality. We identified only one high confidence study of BDE-99 and accordingly evaluated the strength of evidence as moderate. One high confidence, and several medium confidence experimental studies observed declines in semen quality after BDE-209 exposure. Using established risk assessment procedures, we estimated that BDE-47 exposures below 0.15 μg/kg/d are unlikely to lead to reductions in semen quality. The corresponding exposures for BDE-99 and BDE-209 are 0.003 μg/kg/d and 1000 μg/kg/d. It is planned to use these estimates as reference doses in a mixture risk assessment of deteriorations in semen quality, involving multiple other chemicals also contributing to poor semen quality.
为了支持对干扰男性生殖健康的化学物质进行混合风险评估，我们回顾了文献，以确定多溴二苯醚 (PBDEs) 和精液质量差的研究。一些流行病学研究表明，PBDE 暴露与精液质量下降、睾丸未下降和阴茎畸形有关。在啮齿动物研究中，观察到精液质量差、睾酮水平和生殖组织变化。体外研究使用报告基因构建体表明 PBDE 同系物为雄激素受体拮抗剂，并且在这些系统中的混合物研究表明 PBDE 同系物与其他雄激素受体拮抗剂一起起作用。这些观察结果促使我们尝试估计特定 PBDE 同系物的参考剂量，这些剂量可用于未来对精液质量恶化的混合风险评估。虽然流行病学研究为这些关联提供了支持，但由于暴露评估中使用的剂量指标不兼容，因此它们对参考剂量的推导没有信息。因此，我们的估计基于动物研究。使用严格的置信度评分方法，我们发现了强有力的证据表明 BDE-47 导致精液质量下降。我们只发现了一项关于 BDE-99 的高置信度研究，因此评估证据强度为中度。一项高置信度和几项中置信度实验研究观察到 BDE-209 暴露后精液质量下降。使用既定的风险评估程序，我们估计 BDE-47 暴露低于 0.15μg/kg/d 不太可能导致精液质量下降。BDE-99 和 BDE-209 的相应暴露量分别为 0.003μg/kg/d 和 1000μg/kg/d。计划在涉及其他多种也导致精液质量差的化学物质的精液质量恶化的混合风险评估中使用这些估计值作为参考剂量。
