ToxSci Advance Access originally published online on May 21, 2007
Toxicological Sciences 2007 98(2):542-551; doi:10.1093/toxsci/kfm109
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Published by Oxford University Press 2007.
Promotion of Noise-Induced Cochlear Injury by Toluene and Ethylbenzene in the Rat
* Loma Linda VA Medical Center, Loma Linda, California 92357
The University of Georgia, Georgia
CE-CERT, University of California, Riverside, California
Loma Linda University School of Medicine, Loma Linda, California
1 To whom correspondence should be addressed at Research Service (151), Loma Linda VA Medical Center, 11201 Benton Street, Loma Linda, CA 92357. E-mail: Larry.fechter{at}med.va.gov.
Received March 15, 2007; accepted April 28, 2007
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Abstract |
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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/m3 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/m3 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.
Key Words: ethylbenzene + toluene; jet fuel; auditory function; ototoxicity.