Benignus Vernon A, Bushnell Philip J, Boyes William K
U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Health Effects Laboratory, Human Studies Division, Research Triangle Park, NC 27711, USA.
Risk Anal. 2005 Apr;25(2):447-56. doi: 10.1111/j.1539-6924.2005.00601.x.
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 dose-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.
人们越来越希望能够用货币形式来表达接触潜在有毒化合物的后果,以便评估控制接触的潜在成本效益关系。如果将甲苯的影响与乙醇摄入的影响进行定量比较,急性甲苯暴露的行为影响就可以进行成本效益分析,而乙醇摄入的影响在应用背景下已经货币化。通过对同行评审文献中描述甲苯和乙醇对选择反应时间(在要求受试者在两个或更多选项中做出选择后再做出反应的测试中的反应时间)影响的研究进行荟萃分析,对甲苯和乙醇的行为影响进行了量化。根据报告中提供的接触参数,通过一般生理和毒代动力学(GPAT)模拟估算了这些化合物的内部剂量。将报告的影响转换为一个通用指标(基线比例),并与甲苯和乙醇的估计内部剂量相关联,据此拟合剂量效应方程。通过推导剂量等效方程(DEE),将甲苯的估计影响与乙醇对同一因变量的估计影响进行比较,以便在同等效应大小的基础上,将甲苯的剂量表示为等效乙醇剂量。通过GPAT模拟构建了一个列线图,以将甲苯的环境暴露浓度与一系列乙醇内部剂量的等效效应大小相关联。行为影响及其评估由内部剂量决定,而内部剂量又由多种变量决定。除了通过药代动力学过程决定内部剂量的接触浓度和持续时间外,接触者的活动水平也是一个主要因素。该分析提供了一个在置信区间内以乙醇等效剂量表示的甲苯暴露后果的连续函数。由此产生的函数有可能根据现有的关于乙醇的货币化信息,估算一系列甲苯暴露导致的行为缺陷的货币价值。