Lo Justin C, Campbell David A, Kennedy Christopher J, Gobas Frank A P C
Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Department of Statistics and Actuarial Science, Simon Fraser University, Surrey, British Columbia, Canada.
Environ Toxicol Chem. 2015 Oct;34(10):2282-94. doi: 10.1002/etc.3050. Epub 2015 Aug 17.
To improve current bioaccumulation assessment methods, a methodology is developed, applied, and investigated for measuring in vivo biotransformation rates of hydrophobic organic substances in the body (soma) and gastrointestinal tract of the fish. The method resembles the Organisation for Economic Co-operation and Development (OECD) 305 dietary bioaccumulation test but includes reference chemicals to determine both somatic and gastrointestinal biotransformation rates of test chemicals. Somatic biotransformation rate constants for the test chemicals ranged between 0 d(-1) and 0.38 (standard error [SE] 0.03)/d(-1) . Gastrointestinal biotransformation rate constants varied from 0 d(-1) to 46 (SE 7) d(-1) . Gastrointestinal biotransformation contributed more to the overall biotransformation in fish than somatic biotransformation for all test substances but 1. Results suggest that biomagnification tests can reveal the full extent of biotransformation in fish. The common presumption that the liver is the main site of biotransformation may not apply to many substances exposed through the diet. The results suggest that the application of quantitative structure-activity relationships (QSARs) for somatic biotransformation rates and hepatic in vitro models to assess the effect of biotransformation on bioaccumulation can underestimate biotransformation rates and overestimate the biomagnification potential of chemicals that are biotransformed in the gastrointestinal tract. With some modifications, the OECD 305 test can generate somatic and gastrointestinal biotransformation data to develop biotransformation QSARs and test in vitro-in vivo biotransformation extrapolation methods.
为改进当前的生物累积评估方法，开发、应用并研究了一种用于测量鱼类体内（躯体）和胃肠道中疏水性有机物质体内生物转化速率的方法。该方法类似于经济合作与发展组织（OECD）305号膳食生物累积试验，但包括参考化学品以确定受试化学品的躯体和胃肠道生物转化速率。受试化学品的躯体生物转化速率常数在0 d⁻¹至0.38（标准误差[SE] 0.03）/d⁻¹之间。胃肠道生物转化速率常数从0 d⁻¹到46（SE 7）d⁻¹不等。对于除一种受试物质外的所有受试物质，胃肠道生物转化对鱼类总体生物转化的贡献大于躯体生物转化。结果表明，生物放大试验可以揭示鱼类生物转化的全部程度。肝脏是生物转化主要部位的普遍假设可能不适用于许多通过饮食接触的物质。结果表明，应用定量构效关系（QSARs）来评估躯体生物转化速率以及利用肝脏体外模型来评估生物转化对生物累积的影响，可能会低估生物转化速率，并高估在胃肠道中发生生物转化的化学品的生物放大潜力。通过一些修改，OECD 305试验可以生成躯体和胃肠道生物转化数据，以开发生物转化QSARs并测试体外 - 体内生物转化外推方法。
