Abstract:
Bioaccumulation predictions can be substantially improved by combining in vitro metabolic rate measurements derived from rainbow trout hepatocytes and/or hepatic S9 fractions with quantitative structure-activity relationship (QSAR) modeling approaches. Compared with in vivo testing guidelines Organisation for Economic Co-operation and Development (OECD) 305 and Office of Chemical Safety and Pollution Prevention (OCSPP; an office of the US Environmental Protection Agency) 850.1730, the recently adopted OECD test guidelines 319A and 319B are in vitro approaches that have the potential to provide a time- and cost-efficient, humane solution, reducing animal use while addressing uncertainties in bioaccumulation across species. The present study compares the hepatic clearance of the S9 subcellular fraction of rainbow trout, bluegill, common carp, fathead minnow, and largemouth bass, discerning potential differences in metabolism between different warm- and cold-water species. With refinements to the in vitro metabolic S9 assay for high-throughput analysis, we measured in vitro clearance rates of seven chemicals crossing multiple classes of chemistry and modes of action. We confirmed that data from rainbow trout liver S9 fraction metabolic rates can be utilized to predict rainbow trout bioconcentration factors using an in vitro to in vivo extrapolation model, as intended in the OECD 319B applicability domain per the bioaccumulation prediction. Also, we determined that OECD 319B can be applied to other species, modified according to their habitat, adaptations to feeding behavior, and environmental conditions (e.g., temperature). Once toxicokinetics for each species is better understood and appropriate models are developed, this method can be an excellent tool to determine hepatic clearance and potential bioaccumulation across species. The present study could be leveraged prior to or in place of initiating in vivo bioconcentration studies, thus optimizing selection of appropriate fish species. Environ Toxicol Chem 2024;43:1390-1405. © 2024 SETAC.
摘要:
通过将来自虹鳟鱼肝细胞和/或肝S9级分的体外代谢率测量值与定量结构-活性关系(QSAR)建模方法相结合,可以显着改善生物累积预测。与经济合作与发展组织(OECD)305和化学安全与污染预防办公室(OCSPP;美国环境保护局办公室)850.1730相比,最近通过的OECD测试指南319A和319B是体外方法,有可能提供时间和成本效益,人性化的解决方案,减少动物使用,同时解决跨物种生物累积的不确定性。本研究比较了虹鳟鱼S9亚细胞部分的肝清除,bluegill,普通鲤鱼,人头小鱼,还有大嘴鲈鱼,辨别不同温水和冷水物种之间代谢的潜在差异。通过对用于高通量分析的体外代谢S9测定的改进,我们测量了7种化学物质的体外清除率,这些化学物质跨越了多种化学类型和作用方式。我们证实,来自虹鳟鱼肝脏S9部分代谢率的数据可以用来预测虹鳟鱼生物富集因子使用体外到体内外推模型,按照OECD319B适用性领域的预期,根据生物累积预测。此外,我们确定OECD319B可以应用于其他物种,根据它们的栖息地进行了修改,适应喂养行为,和环境条件(例如,temperature).一旦更好地了解了每个物种的毒物动力学并开发了适当的模型,这种方法可以是一个很好的工具,以确定跨物种的肝清除和潜在的生物积累。本研究可以在启动体内生物浓缩研究之前或代替启动体内生物浓缩研究,从而优化选择合适的鱼类种类。环境毒物化学2024;00:1-16。©2024SETAC。