School of Resource and Environmental Management, Simon Fraser University, Burnaby, British Columbia, Canada.
Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Environ Toxicol Chem. 2022 Oct;41(10):2565-2579. doi: 10.1002/etc.5439. Epub 2022 Sep 6.
To advance methods for bioaccumulation assessment of organic substances in air-breathing organisms, the present study developed an in vitro approach for screening neutral hydrophobic organic substances for their bioaccumulation potential in air-breathing organisms consisting of (1) depletion assays for chemicals in rat liver S9 subcellular fractions, (2) in vitro-in vivo extrapolation, and (3) whole-organism bioaccumulation modeling to assess the biomagnification potential of neutral organic substances in the rat. Testing of the in vitro method on 14 test chemicals of potentially biomagnifying substances showed that the bioassays could be conducted with a high level of reproducibility and that in vitro-derived elimination rate constants were in good agreement with in vivo-determined elimination rate constants in the rat. Exploring the potential of the in vitro approach for screening organic chemicals for bioaccumulation in air-breathing organisms indicated that chemical substances that exhibit a depletion rate constant in the S9 in vitro bioassay ≥0.3 h are not expected to biomagnify in rats independent of their octanol-water partitioning coefficient (K ) or octanol-air partitioning coefficient (K ). The high level of reproducibility achieved in the test, combined with the good agreement between in vitro-derived and in vivo-determined depuration rates, suggests that the in vitro approach in combination with a K - and K -based screening approach has good potential for screening chemicals in commerce for their bioaccumulation potential in air-breathing organisms in a cost-effective and expedient manner, especially if the bioassay can be automated. Environ Toxicol Chem 2022;41:2565-2579. © 2022 SETAC.
为了推进呼吸生物体内有机物质生物累积评估方法的发展，本研究开发了一种体外方法，用于筛选具有呼吸生物体内生物累积潜力的中性疏水性有机物质，该方法包括（1）大鼠肝 S9 亚细胞部分中化学物质的耗尽测定，（2）体外-体内外推，以及（3）整体生物累积建模，以评估中性有机物质在大鼠体内的生物放大潜力。用 14 种具有潜在生物放大物质的测试化学品对该体外方法进行测试表明，生物测定可以具有很高的重现性，并且体外衍生的消除速率常数与大鼠体内确定的消除速率常数非常吻合。探索该体外方法筛选呼吸生物体内有机化学物质生物累积的潜力表明，在 S9 体外生物测定中表现出的耗尽率常数≥0.3 h 的化学物质，无论其辛醇-水分配系数（K ）或辛醇-空气分配系数（K ）如何，都不会在大鼠体内生物放大。该测试中实现的高重现性水平，结合体外衍生和体内确定的净化率之间的良好一致性，表明该体外方法与基于 K 和 K 的筛选方法相结合，具有以具有成本效益和便捷的方式筛选商业化学品在呼吸生物体内的生物累积潜力的良好潜力，特别是如果可以使生物测定自动化。Environ Toxicol Chem 2022;41:2565-2579. © 2022 SETAC.
