RAT AND HUMAN SENSORY EVOKED-POTENTIALS AND THE PREDICTABILITY OF HUMAN NEUROTOXICITY FROM RAT DATA

The development of comprehensive quantitative models as alternatives t o risk assessment based on uncertainty factors will require many steps , among them consideration of the relationships between the health end points which are measured in laboratory animals and humans. Sensory ev oked potentials are measures of sensory function which can be recorded from many species, including humans, and as such provide an opportuni ty for examining the extrapolation of neurotoxicity data from laborato ry animals to humans. Our research strategy for investigating how well laboratory rat data predict human neurotoxic risk involves comparing parametric stimulus manipulations and drug treatments in both species. Finally, we are comparing results in humans with neurodegenerative co nditions, including those induced by neurotoxicant exposure, with anim al models, fo date, we have focused on pattern-elicited visual evoked potentials (VEPs) recorded from pigmented rats and humans. Parametric manipulations of spatial frequency, temporal frequency and stimulus co ntrast revealed parallel functions, displaced for differences in absol ute sensitivity. Additionally, diazepam produced similar effects in ra ts and human volunteers. A quantitative cross-species map was develope d to illustrate the prediction of human effects from rat data. Exposur e to carbon disulfide produced changes in rat VEP-derived contrast sen sitivity functions, which resembled psychophysically-measured loss of visual contrast sensitivity in human workers exposed to organic solven ts. The results of these continuing efforts should help indicate how w ell animal electrophysiological measures predict human neurotoxicity. (C) 1994 Intox Press, Inc.