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Toward Cost-Benefit Analysis of Acute Behavioral Effects of Toluene in Humans

机译:甲苯对人类急性行为影响的成本效益分析

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There is increasing interest in being able to express the consequences of exposure to potentially toxic compounds in monetary terms in order to evaluate potential cost-benefit relationships of controlling exposure. Behavioral effects of acute toluene exposure could be subjected to cost-benefit analysis if the effects of toluene were quantitatively compared to those of ethanol ingestion, which has been monetized for applied contexts. Behavioral effects of toluene and ethanol were quantified by meta-analysis of studies from the peer-reviewed literature describing their effects on choice reaction time (reaction time in a test requiring a subject to choose among two or more alternatives before responding). The internal doses of these compounds were estimated by a general physiological and toxicokinetic (GPAT) simulation from exposure parameters provided in the reports. The reported effects were converted to a common metric (proportion of baseline) and related to the estimated internal doses of toluene and ethanol, from which dose-effect equations were fitted. The estimated effect of toluene was compared to the estimated effect of ethanol on the same dependent variable by deriving a close-equivalence equation (DEE) to express the dose of toluene as an equivalent dose of ethanol on the basis of equal effect magnitude. A nomogram was constructed by GPAT simulation to relate the environmental exposure concentration of toluene to the equivalent effect magnitude of a range of ethanol internal doses. Behavioral effects and their evaluation are determined by internal doses, which in turn are determined by a variety of variables. In addition to concentration and duration of exposure, which determine internal dose by pharmacokinetic processes, the activity level of exposed persons is a major factor. This analysis provides a continuous function of the consequences of toluene exposure expressed as ethanol-equivalent doses within confidence limits. The resulting function has the potential to estimate the monetary values of behavioral deficits caused by a range of exposures to toluene from existing monetized information on ethanol.
机译:为了评估控制暴露的潜在成本效益关系,人们越来越有兴趣以货币形式表示暴露于潜在有毒化合物的后果。如果将甲苯的影响与乙醇摄入的影响进行定量比较(已针对应用环境货币化),则可以对急性甲苯接触的行为影响进行成本效益分析。甲苯和乙醇的行为影响通过对同行评审文献的研究进行荟萃分析进行量化,描述了其对选择反应时间的影响(测试中的反应时间要求受试者在做出反应之前必须在两种或多种替代物中进行选择)。这些化合物的内部剂量是根据报告中提供的暴露参数通过一般生理和毒代动力学(GPAT)模拟估算的。将报告的效应转换为通用度量(基线比例),并与估计的甲苯和乙醇内部剂量相关,由此拟合了剂量效应方程式。通过推导近似等式(DEE),将甲苯的剂量估算值与乙醇对相同因变量的估算效果进行比较,以等效作用量为基础将甲苯的剂量表示为乙醇的等效剂量。通过GPAT模拟构建了诺模图,以将甲苯的环境暴露浓度与一系列乙醇内部剂量的等效作用量相关联。行为影响及其评估由内部剂量决定,内部剂量又由各种变量决定。除了通过药代动力学过程确定内部剂量的浓度和持续时间外,接触者的活动水平也是一个主要因素。该分析提供了在置信范围内以乙醇当量表示的甲苯暴露后果的连续功能。由此产生的功能有可能根据现有的关于乙醇的货币化信息来估算由一系列甲苯暴露引起的行为缺陷的货币价值。

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