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TOLUENE DOSE-EFFECT META ANALYSIS AND IMPORTANCE OF EFFECTS
Citation:
Benignus, V A., W K. Boyes, AND P J. Bushnell. TOLUENE DOSE-EFFECT META ANALYSIS AND IMPORTANCE OF EFFECTS. Presented at EPA Science Forum 2003, Washington, DC, May 5-7, 2003.
Description:
TOLUENE DOSE-EFFECT META ANALYSES AND IMPORTANCE OF EFFECTS
Benignus, V.A., Research Psychologist, ORD, NHEERL, Human Studies Division,
919-966-6242, benignus.vernon@epa.gov
Boyes, W.K., Supervisory Health Scientist, ORD, NHEERL, Neurotoxicology Division
919-541-7538, boyes.william@epa.gov
Bushnell, P.J. Toxicologist, ORD, NHEERL, Neurotoxicology Division
919-541-7747, bushnell.philip@epa.gov
Science Forum Theme Area - Emerging Technologies (ORD)
Key Words: Health effects, toluene, quantification of importance, acute, behavior
Environmental Issue: Acute exposure to most solvents has an effect on the central nervous system and thereby on ability to perform various tasks. Peer-reviewed reports of laboratory studies involving human exposures are available for a few solvents (e.g., toluene, styrene, acetone). For some of these solvents, the acute neurotoxic effects are proportional to the concurrent blood concentration, and to ameliorate as the substance is eliminated. As environmental policy decisions are being evaluated more closely for cost-benefit relationships, it becomes important to estimate the costs associated with temporary deficits in performance due to environmental solvents.
Scientific Approach: Meta analyses of the literature for behavioral effects of toluene in humans have been conducted to estimate the magnitude of its effects on choice reaction time (CRT), using pharmocokinetic models to estimate internal dose. The resulting dose-effect equation can be used to predict the magnitude of an acute effect on CRT. The importance of the magnitude of this sort of acute behavioral effect is, however, difficult to assess. This problem was addressed by quantitatively comparing the internal dose of toluene with equally potent internal doses of ethanol, a much more extensively studied substance. This was done by constructing a dose-equivalence curve for toluene and ethanol. Because the effects of acute ethanol intoxication have been monetized, a cost-benefit analysis is made possible for toluene exposure via this comparison.
Toluene exposures were simulated for various conditions of exposure both at rest and at various work loads. Results indicate that toluene effects are comparable to those produced by intoxication with ethanol in the vicinity of (and sometimes exceeding) legally-impaired levels.
These methods could be applicable to other toxicants and exposure scenarios for which there exist well-studied "standard" toxicants with a common mode of action. Given common mode of action, dose-equivalence equations can be used to estimate dose-additive exposures to combinations of toxicants, and the effects of single or combined doses can be monetized for cost-benefits analyses.
Partnerships: This work was conducted by scientists from ORD/NHEERL Human Studies Division and Neurotoxicology Division, cooperating to solve a regulatory problem for Office of Transportation and Air Quality.
Impact: The method has been used to assist rule-making for snowmobile emission standards. Because of its quantitative approach to monetization, it can contribute to other rule-making efforts and health effect assessments.
This presentation does not necessarily reflect EPA policy.