Department of Veterinary and Biomedical Sciences, Penn State University, University Park, PA, USA; INDIGO Biosciences, Inc., 3006 Research Drive, State College, PA 16801, USA; Institute for Sustainable Agricultural, Food, and Environmental Science, The Pennsylvania State Univ., University Park, PA 16802, USA.
Department of Veterinary and Biomedical Sciences, Penn State University, University Park, PA, USA.
Sci Total Environ. 2024 Nov 25;953:176115. doi: 10.1016/j.scitotenv.2024.176115. Epub 2024 Sep 10.
In this study, we compared a wide range of cell-based bioassays to the use of chemical analysis followed by exposure-activity ratio (EAR) and Toxicological Prioritization index (ToxPi) for prioritizing chemicals, sites, and hazard concerns in water samples. Surface water samples were collected from nine sites in three Central Pennsylvania streams and analyzed for a forty-six contaminants of emerging concern (CECs), including pesticides, personal care products, and pharmaceuticals. Cell-based reporter assays evaluated human and zebrafish molecular initiating events (MIEs) in endocrine and metabolic disruption, altered lipid metabolism, and oxidative stress. Bioassays showed that 12 out of 40 assays had at least one site with activity over the effect-based trigger (EBT) values. The receptors that exhibited the highest number of samples above the EBT that would be expected to cause toxicity were Aryl hydrocarbon receptor (AhR, human and zebrafish), Pregnane X Receptor (PXR), Estrogen Receptor-beta (ERB), and Androgen Receptor (AR). Characterizing the collection sites by their bioactivity aligned closely with the stream in which samples were collected. The sum of all EARs for each chemical indicated that the pharmaceutical Carbamazepine and the pesticides Carbaryl and Atrazine posed the greatest concern. However, predicted activity and site prioritization based on individual chemical analysis and calculated EAR were different than those measured by bioassay, indicating that biologically active chemicals are present in the samples that were not included in the targeted analytes. Taken together, these data show that chemical analysis and EAR analysis are beneficial for prioritization of chemicals, whereas mechanism-based bioassays are more inclusive of known as well as unknown chemical contaminants and thus of more use for overall water quality analysis and site prioritization.
在这项研究中，我们将广泛的基于细胞的生物测定法与化学分析后使用暴露-活性比 (EAR) 和毒性优先指数 (ToxPi) 进行比较，以优先考虑水样中的化学物质、地点和危害关注点。采集了宾夕法尼亚州中部三条溪流的九个地点的地表水样本，并对包括农药、个人护理产品和药品在内的 46 种新兴关注污染物 (CEC) 进行了分析。基于细胞的报告基因检测评估了内分泌和代谢紊乱、脂质代谢改变和氧化应激中的人类和斑马鱼分子起始事件 (MIE)。生物测定表明，40 项测定中有 12 项至少有一个地点的活性超过基于效应的触发值 (EBT) 值。表现出高于 EBT 值的样本数量最多的受体预计会引起毒性的是芳香烃受体 (AhR，人类和斑马鱼)、孕烷 X 受体 (PXR)、雌激素受体-β (ERβ) 和雄激素受体 (AR)。根据生物活性对采集地点进行分类，与采集样本的溪流密切相关。每种化学物质的所有 EAR 总和表明，药物卡马西平和农药 Carbaryl 和 Atrazine 构成最大的关注。然而，基于个别化学分析和计算的 EAR 进行的预测活性和地点优先排序与生物测定测量的结果不同，这表明在未包括在目标分析物中的样本中存在具有生物活性的化学物质。综上所述，这些数据表明，化学分析和 EAR 分析有助于优先考虑化学物质，而基于机制的生物测定则更全面地包括已知和未知的化学污染物，因此更有助于全面水质分析和地点优先排序。
