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A Toxicokinetic Framework and Analysis Tool for Interpreting Organisation for Economic Co-operation and Development Guideline 305 Dietary Bioaccumulation Tests.
Environmental Toxicology and Chemistry ( IF 3.6 ) Pub Date : 2019-11-30 , DOI: 10.1002/etc.4599
Frank A P C Gobas 1 , Yung-Shan Lee 1 , Justin C Lo 2 , Thomas F Parkerton 3 , Daniel J Letinski 4
Affiliation  

The Organisation for Economic Co-operation and Development guideline 305 for bioaccumulation testing in fish includes the option to conduct a dietary test for assessing a chemical's bioaccumulation behavior. However, the one-compartment toxicokinetic model that is used in the guidelines to analyze the results from dietary bioaccumulation tests is not consistent with the current state of the science, experimental practices, and information needs for bioaccumulation and risk assessment. The present study presents 1) a 2-compartment toxicokinetic modeling framework for describing the bioaccumulation of neutral hydrophobic organic chemicals in fish and 2) an associated toxicokinetic analysis tool (absorption, distribution, metabolism, and excretion [ADME] B calculator) for the analysis and interpretation of dietary bioaccumulation test data from OECD-305 dietary tests. The model framework and ADME-B calculator are illustrated by analysis of fish dietary bioaccumulation test data for 238 substances representing different structural classes and susceptibilities to biotransformation. The ADME of the chemicals is determined from dietary bioaccumulation tests and bioconcentration factors, biomagnification factors, and somatic and intestinal biotransformation rates. The 2-compartment fish toxicokinetic model can account for the effect of the exposure pathway on bioaccumulation, which the one-compartment model cannot. This insight is important for applying a weight-of-evidence approach to bioaccumulation assessment where information from aqueous and dietary test endpoints can be integrated to improve the evaluation of a chemical's bioaccumulation potential. Environ Toxicol Chem 2019;39:171-188. © 2019 SETAC.

中文翻译:

解释经济合作与发展指南305饮食生物蓄积测试组织的毒物动力学框架和分析工具。

经济合作与发展组织关于鱼类中生物蓄积性测试的指南305包括进行膳食测试以评估化学品的生物蓄积行为的选项。但是,指南中用于分析饮食生物蓄积测试结果的单室毒物动力学模型与当前的科学状况,实验实践以及生物蓄积和风险评估的信息需求不符。本研究提出1)两室毒性动力学模型框架,用于描述鱼类中性疏水性有机化学物质的生物蓄积; 2)相关的毒性动力学分析工具(吸收,分布,代谢,和排泄物[ADME] B计算器),以分析和解释来自OECD-305饮食测试的饮食生物蓄积测试数据。通过分析代表不同结构类别和生物转化敏感性的238种物质的鱼类饮食生物蓄积测试数据,说明了模型框架和ADME-B计算器。化学品的ADME由饮食中的生物蓄积性测试和生物浓缩系数,生物放大系数以及体细胞和肠道的生物转化率确定。2室鱼的毒物动力学模型可以解释暴露途径对生物蓄积的影响,而1室模型则不能。这种见解对于将证据权重方法应用于生物蓄积性评估非常重要,其中可以整合来自水和饮食测试终点的信息,以改善对化学物质生物蓄积性的评估。Environ Toxicol Chem 2019; 39:171-188。©2019 SETAC。
更新日期:2019-12-27
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