title: Susceptibility to the ototoxic properties of toluene is species specific.
abstract: Toluene is the most widely used industrial solvent. It has been shown to be ototoxic in mice and rats, and to increase permanent threshold shift in conjunction with exposure to noise. Chinchillas are widely used for studying noise effects on the cochlea. The present study was initiated to study toluene and noise interaction in chinchillas. Thirty-three chinchillas were exposed to a 95 dBA 500 Hz octave band noise plus 2000 ppm toluene, 8 or 12 h per day for 10 days. Auditory function was estimated using the auditory brainstem response (ABR) to tones between 500 Hz and 16 kHz. There was no effect on the ABR of toluene alone. Noise alone produced a threshold shift. There was no interaction of noise and toluene on the ear. The present study suggests that chinchillas are markedly less susceptible to the ototoxic effect of toluene than mice and rats. A working hypothesis as to the species differences was that chinchilla liver was able to detoxify the toluene. Hepatic microsomes from chinchillas, rats and humans were tested for their ability to convert toluene to the more water-soluble compound - benzyl alcohol. Chinchilla livers were found to contain more of the P450 enzymes CYP2E1 and CYP2B than rats or humans. In addition, the data show that the P450 enzymes are more active in chinchillas than in rats and humans. In conclusion, the results suggest that rats and mice are a more appropriate model for human toluene ototoxicity. However, chinchillas may provide a valuable model for investigating how ototoxic agents can be detoxified to less damaging compounds.
authors.affiliation: Hearing Loss Prevention Section, Engineering and Physical Hazards Branch, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, OH 45226, USA. rrd1@cdc.gov
authors.forename: Rickie R
authors.initials: RR
authors.lastname: Davis
authors.forename: William J
authors.initials: WJ
authors.lastname: Murphy
authors.forename: John E
authors.initials: JE
authors.lastname: Snawder
authors.forename: Cynthia A F
authors.initials: CA
authors.lastname: Striley
authors.forename: Donald
authors.initials: D
authors.lastname: Henderson
authors.forename: Amir
authors.initials: A
authors.lastname: Khan
authors.forename: Edward F
authors.initials: EF
authors.lastname: Krieg
mesh_terms: D000818:Animals; D019905:Benzyl Alcohol / Q000378:metabolism; D002682:Chinchilla / Q000502:physiology*; D003051:Cochlea / Q000187:drug effects* / Q000293:injuries; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006317:Hearing Loss, Noise-Induced / Q000209:etiology; D006801:Humans; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009622:Noise / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014050:Toluene / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D014050:Toluene; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1; D019905:Benzyl Alcohol