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A QUANTITATIVE COMPARISON OF THE EFFECTS OF ACUTE INHALED TOLUENE IN HUMAN RATS
Citation:
BENIGNUS, V. A., P. J. BUSHNELL, AND W. K. BOYES. A QUANTITATIVE COMPARISON OF THE EFFECTS OF ACUTE INHALED TOLUENE IN HUMAN RATS. Presented at Intl Neurotoxicology Association 11th Biannual Meeting, Pacific Gove, CA, June 10 - 15, 2007.
Impact/Purpose:
research results
Description:
The effects of acute exposure to toluene have been explored more thoroughly than other hydrocarbon solvents. These effects have been experimentally studied in humans and other species, e.g., rats, as well as in a number of in vitro preparations. The existence ofdosimetric and effects data from both rats and humans offers the opportunity to quantitatively compare the relative sensitivities of humans and rats to effects ofacute toluene exposure. The purpose of this work was to fit dose-effect curves and estimate dose-equivalence equations (DEEs) between rats and humans from the peer-reviewed literature. The DEE gives the values ofdoses that produce the same magnitude of effect in both species. Doses were estimates ofbrain concentrations of toluene from PBPK models. Human experimental studies of toluene effects on choice reaction time (CRT) were meta-analyzed. Rat studies employed various dependent variables including visual function from visual evoked potentials (VEPs), sustained attention from signal detection behavior (SIGDET) and escape/avoidance behaviors (ES-AV). Human and rat sensitivity was nearly the same for the two assessments that lacked explicit reinforcement contingencies (YEP in rats and CRT in humans). Rats performing with food reinforcement were less affected by similar brain concentrations oftoluene. Finally, rats performing electric shock escape/avoidance were least affected by brain toluene. These findings strongly suggested that the sensitivity ofrats to toluene impairment depended on the coerciveness ofthe contingencies which were used to control behavior such that the potency oftoluene decreased with increasing coerciveness. It was hypothesized that if humans and rats perform under the same contingencies, they will be equally sensitive to the effects of toluene. Because of the broad range of effects produced by toluene (both behavioral and in vitro), human effects may also be estimated from rat effects in tasks controlled by various contingencies. (This abstract does not reflect EPA policy