You are here:
COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.
Citation:
BUSHNELL, P. J., V. A. BENIGNUS, AND W. K. BOYES. COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published data and by re-analysis of data from our laboratory. Available human data were limited to studies of choice reaction time (CRT). Data from animals included visual evoked potentials (VEPs), signal detection (SD) behavior, and appetitively- and aversively-motivated schedule-controlled behavior. A dose-effect curve was fitted to each set of animal data and compared to the curve for human CRT. The resulting dose-equivalence equations represented doses that produced the same magnitude of effects in humans and animals for each endpoint. The results showed that some kinds of animal experiments were as sensitive to the acute effects of toluene as were human studies, whereas other kinds were less sensitive. The data support the conclusions (a) that if contingencies in animal experiments exert strong control over performance, then performance resists change by toluene and (b) the sensitivity of the test to toluene was not greatly affected by the topology of the task. Thus, CRT in humans and VEPs in rats both lack performance contingencies and were topologically very different, yet the dose-effect curves were virtually identical. Conversely, appetitively-motivated SD behavior in rats was topologically similar to non-contingent CRT in humans, but the rats were less affected than humans. These observations suggest (1) that the task contingencies are more important than response topology in determining the sensitivity to acute toluene and (2) that if the contingencies are similar in human and animal studies, then the two species will show equal sensitivity to acutely-administered toluene, even if the dependent variables differ. (This abstract does not reflect EPA policy.)