FMC Agricultural Solutions, Newark, Delaware, USA.
KJ Scientific, Georgetown, Texas, USA.
Environ Toxicol Chem. 2024 Jun;43(6):1390-1405. doi: 10.1002/etc.5866. Epub 2024 Apr 23.
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.
生物蓄积预测可以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构效关系 (QSAR) 建模方法相结合来大大提高。与体内测试指南经济合作与发展组织 (OECD) 305 和化学品安全和污染预防办公室 (OCSPP；美国环境保护署的一个办公室) 850.1730 相比，最近采用的 OECD 测试指南 319A 和 319B 是体外方法，有可能提供一种省时、高效、人道的解决方案，减少动物使用，同时解决不同物种之间生物蓄积的不确定性。本研究比较了虹鳟鱼、蓝鳃太阳鱼、鲤鱼、黑头呆鱼和大口黑鲈的 S9 亚细胞级分的肝清除率，辨别不同温水和冷水物种之间代谢的潜在差异。通过对高通量分析的体外代谢 S9 测定进行改进，我们测量了七种跨越多种化学和作用模式的化学物质的体外清除率。我们证实，虹鳟鱼肝脏 S9 级分代谢率的数据可用于使用体外到体内外推模型预测虹鳟鱼生物浓缩系数，正如 OECD 319B 生物蓄积预测适用性领域所预期的那样。此外，我们确定 OECD 319B 可适用于其他物种，根据其栖息地、对摄食行为的适应和环境条件（例如温度）进行修改。一旦对每种物种的毒代动力学有了更好的了解并开发出适当的模型，这种方法就可以成为确定跨物种肝清除率和潜在生物蓄积的极好工具。本研究可以在开始体内生物浓缩研究之前或替代体内生物浓缩研究，从而优化选择合适的鱼类物种。环境毒理化学 2024；43:1390-1405。© 2024 SETAC。
