title: Toward cost-benefit analysis of acute behavioral effects of toluene in humans.
abstract: 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.
authors.affiliation: 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. benignus.vernon@epa.gov
authors.forename: Vernon A
authors.initials: VA
authors.lastname: Benignus
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bushnell
authors.forename: William K
authors.initials: WK
authors.lastname: Boyes
mesh_terms: D000280:Administration, Inhalation; D001519:Behavior / Q000187:drug effects*; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects / Q000097:blood; D006801:Humans; D015201:Meta-Analysis as Topic; D015233:Models, Statistical; D009010:Monte Carlo Method; D018570:Risk Assessment / Q000379:methods; D012984:Software; D013810:Therapeutic Equivalency; D013997:Time Factors; D014050:Toluene / Q000009:adverse effects* / Q000097:blood
chemical_list: D014050:Toluene; D000431:Ethanol