Similarities of toluene and o-cresol neuroexcitation in rats.

Exposure to high concentrations of toluene vapors, or to intravenous o-cresol (a toluene metabolite) at about 0.9 mg/min, caused excitation of the somatosensory evoked potential (SEP) and EEG of Fischer 344 rats. SEP excitation was characterized by a large increase in a positive waveform at about 20-50 msec. Prolonged exposure to either compound caused numerous oscillations to appear from 20 msec to the end of the recording (150 msec). Both substances induced an increase in EEG beta activity and caused a large increase in activity at 5 Hz. Toluene exposed rats were lightly anesthetized, while o-cresol rats were conscious but hyperreactive. If exposure was continued, both sets of rats had involuntary muscle movements and tremors. Benzoic acid and hippuric acid, also metabolites of toluene, were similarly tested. Neither caused neuroexcitation (about 2.4 mg/min IV, 144 mg total dose). It was concluded, therefore, that metabolically derived cresols are plausible candidates for the neuroexcitatory properties of toluene.