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首页> 外文期刊>Journal of applied toxicology >Consideration of dosimetry in evaluation of ToxCast data.
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Consideration of dosimetry in evaluation of ToxCast data.

机译：在评估ToxCast数据时要考虑剂量法。

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The US Environmental Protection Agency (US EPA) Toxcast program has the stated goal of predicting hazard, characterizing toxicity pathways and prioritizing the toxicity testing of environmental chemicals through the use of in vitro high-throughput screening (HTS) assays. This analysis integrates data from biomonitoring and from in vivo toxicity and pharmacokinetic studies to examine the physiological relevance of the tested and responding in vitro concentrations for five case study chemicals: triclosan, 2,4-dichlorophenoxyacetic acid, perfluorooctanoic acid, monobutyl phthalate and mono-2(ethylhexyl)phthalate. This analysis also examines the ToxCast phase 1 data set for approximately 50 chemicals belonging to four 'common mechanism groups' which have been the subject of cumulative risk assessments by the US EPA for both the pattern of key responses and the relative potencies of included chemicals compared with the in vivo relative potencies. Responding concentrations in vitro were generally in the range of serum or plasma concentrations associated with no-observed to lowest-observed effect levels for the case study chemicals, while available biomonitoring data demonstrating actual exposures were generally lower. ToxCast assay endpoints related to acetylcholinesterase (AChE) inhibition had low sensitivity for detecting organophosphate pesticides but good sensitivity for detecting N-methyl carbamates. However, in vitro relative potencies did not correlate with in vivo potency. Both qualitative and quantitative predictive power is probably affected by the lack of comprehensive metabolic activity in most current in vitro systems explored in the ToxCast program, and this remains a fundamental challenge for high-throughput toxicity screening efforts. Copyright (c) 2011 John Wiley & Sons, Ltd.
机译：美国环境保护局（US EPA）的Toxcast计划具有明确的目标，即通过使用体外高通量筛选（HTS）分析来预测危害，表征毒性途径并优先进行环境化学品的毒性测试。该分析整合了来自生物监测，体内毒性和药代动力学研究的数据，以检验五种案例研究化学品：三氯生，2,4-二氯苯氧乙酸，全氟辛酸，邻苯二甲酸单丁酯和邻苯二甲酸2-（乙基己基）酯。该分析还检查了属于四个“共同机制”组的大约50种化学品的ToxCast第一阶段数据集，这些数据已被美国EPA进行了累积风险评估，涉及的主要响应方式和所含化学品的相对效力具有体内相对效力。体外反应浓度通常在与案例研究用化学物质的未观察到的最低观察到的效应水平相关的血清或血浆浓度范围内，而可用的生物监测数据表明实际暴露通常较低。与乙酰胆碱酯酶（AChE）抑制有关的ToxCast分析终点对检测有机磷酸酯农药的灵敏度较低，但对N-甲基氨基甲酸酯的灵敏度较高。但是，体外相对效价与体内效价不相关。在ToxCast程序中探索的大多数当前体外系统中，缺乏全面的代谢活性可能会影响定性和定量预测能力，这仍然是高通量毒性筛选工作的一项基本挑战。版权所有（c）2011 John Wiley＆Sons，Ltd.

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