Cantu Mark A, Chee Beatrice, Cole Talia R, Lee Yung-Shan, Gobas Frank A P C
School of Resource and Environmental Management, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Department of Biology, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Environ Sci Technol. 2025 Apr 29;59(16):8119-8129. doi: 10.1021/acs.est.4c11277. Epub 2025 Apr 15.
In vitro hepatic biotransformation assays have been proposed as methods for expediting and improving bioaccumulation assessment for substances that are difficult to test in conventional in vivo bioaccumulation assays and to reduce animal testing. However, to date, there has been no convincing evidence to demonstrate the ability and limitations of in vitro assays to estimate in vivo biotransformation rates and corresponding bioconcentration and biomagnification factors of difficult-to-test substances in fish. The present study presents the first measurements of in vitro biotransformation rates of superhydrophobic and highly volatile linear and cyclic siloxanes in rainbow trout liver S9 subcellular fractions and the extrapolation of in vitro rates to whole body in vivo biotransformation rates, bioconcentration factors (BCFs), and biomagnification factors (BMFs). In vitro results are tested against measured in vivo biotransformation rates, BCFs, and BMFs in rainbow trout. The study shows the degree of agreement between in vitro and in vivo derived biotransformation rates, BCFs, and BMFs; points to the importance of dosing concentrations on biotransformation rates and corresponding bioaccumulation metrics; highlights the role of nonhepatic biotransformation; and contributes an in-depth analysis of the performance of in vitro hepatic biotransformation assays and in vitro to in vivo extrapolation (IVIVE) methods. The study aims to advance and expedite bioaccumulation assessment and meet the objectives of the UN Stockholm Convention on Persistent Organic Pollutants to reduce risks in indigenous communities from the biomagnification of pollutants in traditional foods.
体外肝脏生物转化试验已被提议作为一种方法，用于加速和改进对难以在传统体内生物累积试验中进行测试的物质的生物累积评估，并减少动物试验。然而，迄今为止，尚无令人信服的证据证明体外试验在估计鱼类体内难测物质的生物转化率以及相应的生物浓缩和生物放大因子方面的能力和局限性。本研究首次测量了虹鳟鱼肝S9亚细胞组分中超疏水和高挥发性线性及环状硅氧烷的体外生物转化率，并将体外转化率外推至体内全身生物转化率、生物浓缩因子（BCF）和生物放大因子（BMF）。将体外结果与虹鳟鱼体内测得的生物转化率、BCF和BMF进行对比。该研究显示了体外和体内得出的生物转化率、BCF和BMF之间的一致程度；指出了给药浓度对生物转化率和相应生物累积指标的重要性；强调了非肝脏生物转化的作用；并对体外肝脏生物转化试验和体外到体内外推（IVIVE）方法的性能进行了深入分析。该研究旨在推进和加速生物累积评估，并实现联合国《关于持久性有机污染物的斯德哥尔摩公约》的目标，即降低传统食物中污染物生物放大给土著社区带来的风险。
