PDF(Pubmed)
Abstract：
Many persistent organic pollutants (POPs) are suspected endocrine disruptors and it is important to investigate their effects at low concentrations relevant to human exposure. Here, the OECD test guideline #456 steroidogenesis assay was downscaled to a 96-well microplate format to screen 24 POPs for their effects on viability, and testosterone and estradiol synthesis using the human adrenocortical cell line H295R. The compounds (six polyfluoroalkyl substances, five organochlorine pesticides, ten polychlorinated biphenyls and three polybrominated diphenyl ethers) were tested at human-relevant levels (1 nM to 10 µM). Increased estradiol synthesis, above the OECD guideline threshold of 1.5-fold solvent control, was shown after exposure to 10 µM PCB-156 (153%) and PCB-180 (196%). Interestingly, the base hormone synthesis varied depending on the cell batch. An alternative data analysis using a linear mixed-effects model that include multiple independent experiments and considers batch-dependent variation was therefore applied. This approach revealed small but statistically significant effects on estradiol or testosterone synthesis for 17 compounds. Increased testosterone levels were demonstrated even at 1 nM for PCB-74 (18%), PCB-99 (29%), PCB-118 (16%), PCB-138 (19%), PCB-180 (22%), and PBDE-153 (21%). The MTT assay revealed significant effects on cell viability after exposure to 1 nM of perfluoroundecanoic acid (12%), 3 nM PBDE-153 (9%), and 10 µM of PCB-156 (6%). This shows that some POPs can interfere with endocrine signaling at concentrations found in human blood, highlighting the need for further investigation into the toxicological mechanisms of POPs and their mixtures at low concentrations relevant to human exposure.
摘要：
许多持久性有机污染物（POPs）被怀疑是内分泌干扰物，重要的是研究其在低浓度下与人类接触有关的影响。这里,OECD测试指南#456类固醇生成试验被缩减为96孔微孔板格式，以筛选24种POPs对生存力的影响，以及使用人肾上腺皮质细胞系H295R合成睾酮和雌二醇。化合物(六种多氟烷基物质，五种有机氯农药,在人类相关水平（1nM至10µM）下测试了十种多氯联苯和三种多溴联苯醚）。雌二醇合成增加，高于经合组织规定的1.5倍溶剂控制阈值，在暴露于10µMPCB-156（153%）和PCB-180（196%）后显示。有趣的是,基础激素合成根据细胞批次而变化。因此,应用了使用线性混合效应模型的替代数据分析,该线性混合效应模型包括多个独立实验并考虑批次依赖性变化。该方法揭示了17种化合物对雌二醇或睾酮合成的小但统计学上显著的影响。甚至在1nM时，PCB-74（18％）的睾酮水平也增加。PCB-99(29%),PCB-118（16%），PCB-138（19%），PCB-180（22%），和PBDE-153(21%)。MTT分析显示暴露于1nM全氟十一烷酸（12％）后对细胞活力有显著影响，3nMPBDE-153(9%),和10µM的PCB-156（6%）。这表明，某些POPs可以干扰人体血液中发现的浓度的内分泌信号，强调需要进一步研究低浓度持久性有机污染物及其混合物与人类接触相关的毒理学机制。
