Solvent-induced ototoxicity in rats: an atypical selective mid-frequency hearing deficit

Most previous reports of ototoxicity following exposure to several volatile organic solvents have restricted testing to the low- and mid-frequencies (2-20 kHz) of the hearing range in the rat (0.25-80 kHz). We report here that inhalation exposure to styrene, mixed xylene, toluene, and 1,1,2-trichloroethylene resulted in hearing dysfunction only in the mid-frequency range and spared function at lower and higher frequencies. Adult male Long Evans rats were exposed via inhalation (whole body) in flow-through chambers. The following exposures were used: styrene, 1600 ppm; 1,1,2-trichloroethylene, 3500 ppm; toluene, 2500 ppm; mixed xylenes, 1800 ppm (N = 7-8 per group, 8 h/day for 5 days), and n-butanol, 4000 ppm (N = 10/group, 6 h/day for 5 days). Testing of auditory function was conducted 5 to 8 weeks after exposure using reflex modification audiometry (RMA). RMA thresholds were determined for frequencies from 0.5 to 40 kHz. Results indicated increased RMA thresholds for the mid-frequency tones (e.g., 8 and 16 kHz), but not higher or lower tones, for all solvents except n-butanol. Toluene and xylene also increased thresholds at 24 kHz. These data indicate that for those solvents reported thus far to cause hearing loss, the deficit is restricted to mid-frequencies in rats.