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.
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
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Crofton
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Lassiter
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D020001:1-Butanol; D000161:Acoustic Stimulation; D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001299:Audiometry; D001309:Auditory Threshold / Q000187:drug effects; D000440:Butanols / Q000008:administration & dosage / Q000633:toxicity; D006315:Hearing Loss, Functional / Q000139:chemically induced*; D008297:Male; D051381:Rats; D020058:Styrene; D013343:Styrenes / Q000008:administration & dosage / Q000633:toxicity*; D014050:Toluene / Q000008:administration & dosage / Q000633:toxicity*; D014241:Trichloroethylene / Q000008:administration & dosage / Q000633:toxicity*; D014992:Xylenes / Q000008:administration & dosage / Q000633:toxicity*
D000440:Butanols; D013343:Styrenes; D014992:Xylenes; D014241:Trichloroethylene; D014050:Toluene; D020058:Styrene; D020001:1-Butanol