We have reported that inhalation exposure of rats to toluene causes permanent hearing loss, e.g. Pryor et al. Neurobehav. Toxicol. Teratol. 5, 53-62 (1983). Therefore, it was of considerable interest to examine the ototoxic potential of two structurally related solvents--mixed xylenes and styrene--compared with that of toluene. Male, weanling Fischer-344 rats were exposed to clean air or solvents in four identical 62.5 l Plexiglas chambers. Exposures to 800, 1000, and 1200 ppm were daily for 14 hours/day and lasted 6 weeks for mixed xylenes, 3 weeks for styrene. An additional experiment with xylenes examined the effect of exposure for only 4 (1700 ppm) or 8 (1450 ppm) hours or for 8 (1450 ppm) hours on three consecutive days to compare the results with those obtained with toluene under comparable exposure schedules. Both xylenes and styrene caused marked hearing loss as assessed by behavioral (conditioned avoidance) and electrophysiologic (brainstem auditory-evoked response) methods. Moreover, both solvents appeared to be more potent ototoxicants than toluene, as indicated by effective concentration, effective durations of exposure, and the range of frequencies affected.
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