ToxSci Advance Access published online on April 1, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp063
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NEUROBEHAVIORAL EFFECTS OF ACUTE EXPOSURE TO FOUR SOLVENTS: META-ANALYSES
1 Human Studies Division, Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. and University of North Carolina, Chapel Hill, Department of Psychology 2 Neurotoxicology Division 3 Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Correspondence concerning this article should be addressed to: Vernon A. Benignus, Ph.D., Human Studies Division, Mail Code B105-06, US Environmental Protection Agency, Research Triangle Park, NC 27711, Tel: 919-541-1522, FAX: 919-541-4849, Email: benignus.vernon{at}epa.gov
Received February 2, 2009; revision received March 20, 2009; accepted March 20, 2009
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Abstract |
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Meta- and re-analyses of the available data for the neurobehavioral effects of acute inhalation exposure to toluene were reported by Benignus et al. (2007). The present study was designed to test the generality of the toluene results in as many other solvents as possible by further meta- and re-analyses. Sufficient data for meta-analyses were found for only four solvents; toluene, trichloroethylene, perchloroethylene and 1,1,1-trichloroethane. The results for these solvents showed that rats were less affected by each of the solvents when they were tested in highly-motivating situations, e.g., rewarded for rapid or correct responding or escape from electrical shock, compared to less motivating circumstance. The four solvents did not differ significantly in potency on any outcome measure when dose was expressed as molar brain concentration. When tested in tasks with low motivational contingencies, the dose-effect curves of humans (reaction times) and rats (electrophysiological responses to visual stimuli) were not significantly different. However, on an exploratory follow-up analysis, humans were less sensitive than rats. No human data were found to test whether species differed under strong motivation. Dose-equivalence curves were derived for extrapolating to human effects from rat data.
Key Words: toxicity; acute; Safety Evaluation, nervous system; Neurotoxicology, volatile organic compounds; Agents.