title: Promotion of noise-induced cochlear injury by toluene and ethylbenzene in the rat.
abstract: Ethylbenzene + toluene are known individually to have ototoxic potential at high exposure levels and with prolonged exposure times generally of 4-16 weeks. Both ethylbenzene + toluene are minor constituents of JP-8 jet fuel; this fuel has recently been determined to promote susceptibility to noise-induced hearing loss. Therefore, the current study evaluates the ototoxic potential of combined exposure to ethylbenzene + toluene exposure in a ratio calculated from the average found in three laboratories. Rats received ethylbenzene + toluene by inhalation and half of them were subjected simultaneously to an octave band of noise (OBN) of 93-95 dB. Another group received only the noise exposure which was designed to produce a small, but permanent auditory impairment while an unexposed control group was also included. In two separate experiments, exposures occurred either repeatedly on 5 successive days for 1 week or for 5 days on 2 successive weeks to 4000 mg/m(3) total hydrocarbons for 6 h based upon initial pilot studies. The concentration of toluene was 400 ppm and the concentration of ethylbenzene was 660 ppm. Impairments in auditory function were assessed using distortion product otoacoustic emissions and compound action potential testing. Following completion of these tests, the organs of Corti were dissected to permit evaluation of hair cell loss. The uptake and elimination of the solvents was assessed by harvesting key organs at two time points following ethylbenzene + toluene exposure from additional rats not used for auditory testing. Similarly, glutathione (GSH) levels were measured in light of suggestions that oxidative stress might result from solvent-noise exposures. Ethylbenzene + toluene exposure by itself at 4000 mg/m(3) for 6 h did not impair cochlear function or yield a loss of hair cells. However, when combined with a 93-dB OBN exposure combined solvent + noise did yield a loss in auditory function and a clear potentiation of outer hair cell death that exceeded the loss produced by noise alone. No evidence was found for a loss in total GSH in lung, liver, or brain as a consequence of ethylbenzene + toluene exposure.
authors.affiliation: Loma Linda VA Medical Center, Loma Linda, California 92357, USA. Larry.fechter@med.va.gov
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Fechter
authors.forename: Caroline
authors.initials: C
authors.lastname: Gearhart
authors.forename: Sherry
authors.initials: S
authors.lastname: Fulton
authors.forename: Jerry
authors.initials: J
authors.lastname: Campbell
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fisher
authors.forename: Kwangsam
authors.initials: K
authors.lastname: Na
authors.forename: David
authors.initials: D
authors.lastname: Cocker
authors.forename: Alisa
authors.initials: A
authors.lastname: Nelson-Miller
authors.forename: Patrick
authors.initials: P
authors.lastname: Moon
authors.forename: Benoit
authors.initials: B
authors.lastname: Pouyatos
mesh_terms: D000395:Air Pollutants, Occupational / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D001555:Benzene Derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006317:Hearing Loss, Noise-Induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009622:Noise / Q000009:adverse effects*; D051381:Rats; D020318:Rats, Long-Evans; D012997:Solvents / Q000493:pharmacokinetics / Q000633:toxicity*; D014050:Toluene / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000395:Air Pollutants, Occupational; D001555:Benzene Derivatives; D012997:Solvents; D014050:Toluene; D005978:Glutathione; C004912:ethylbenzene