Factors affecting toluene-induced ototoxicity in rats.

Seven experiments with young male Fischer rats were done to examine concentration and exposure parameters necessary and sufficient to cause toluene-induced ototoxicity. Hearing loss, measured by behavioral and electrophysiologic methods, was repeatedly observed after as few as 2 weeks of exposure to 1000 ppm toluene for 14 hours per day, but lower concentrations (400 and 700 ppm) were without effect even after 16 weeks of exposure. Three-day exposures to 1500 ppm for 14 hours per day or 2000 ppm for 8 hours per day were ototoxic, whereas single exposures to 4000 ppm for 4 hours or 2000 ppm for 8 hours were without effect. Intermittent exposure to 3000 ppm for 30 minutes every hour for 8 hours per day caused hearing loss within 2 weeks, but a similar exposure schedule for 4 hours per day was ineffective even after 9 weeks. The results of these experiments repeatedly confirmed our earlier finding that toluene causes hearing loss in rats and defined many of the exposure parameters important to this effect. The results are discussed in terms of their relevance to industrial exposure, industrial accidents, and, especially, voluntary, high-level exposure by solvent abusers.