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Neurobehavorial effects of acute exposure to four solvents: meta-abalyses
Citation:
BENIGNUS, V. A., P. Bushnell, W. K. BOYES, C. R. EKLUND, AND E. M. KENYON. Neurobehavorial effects of acute exposure to four solvents: meta-abalyses. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 109(2):295-305, (2009).
Impact/Purpose:
research results
Description:
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. The following hypotheses were proposed: HI: regardless of the solvent tested, the magnitude of the neurobehavioral effect is a function of both the concentration of the solvent in the brain and the motivation to perform the task (as defined by the testing situation); Hz: individual solvents differ in potency at equivalent brain molar concentrations and H3: dose-effect curves do not differ significantly between rats and humans when motivational conditions are comparable. Sufficient data for meta-analyses were found for only four solvents; toluene, trichloroethylene, perchloroethylene and 1,1,I-trichloroethane. The results for these solvents verified HI: 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 electrical shock escape-avoidance, compared to less motivating circumstance. H2 was not verified: the four solvents did not differ significantly in potency on any outcome measure when dose was expressed as molar brain concentration. H3 was weakly supported: when tested in tasks with low motivational contingencies, the dose-effect curves of humans (choice 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.
