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.

Potentiation of Chemical Ototoxicity by Noise

“…However, when vapor inhalation was followed by broadband noise exposure at 93 dB SPL (for 5 days), greater temporary threshold shifts (25 to 30 dB) were observed 3 days after treatment, with only partial recovery of DPOAE thresholds, resulting in permanent threshold shifts of 10 to 15 dB 4 weeks after cessation of treatment. 17 The permanency of these threshold shifts was confirmed by the greater number and extent of missing outer hair cells in the solvent/noise group compared with that in the noise alone, solvent alone, or control groups.…”

Recent findings and emerging questions in cochlear noise injury

“…Environmental factors that amplify cochlear oxidative stress and impair blood flow might therefore be anticipated to exacerbate noise injury. New evidence supports such an effect by volatile industrial compounds such as toluene and ethylbenzene (Fechter et al, 2007), smoking (Uchida et al, 2005; Wild et al, 2005), and hyperlipidemia (Chang et al, 2007). These factors may interact synergistically.…”

SOD2 V16A SNP in the Mitochondrial Targeting Sequence is Associated with Noise Induced Hearing Loss in Chinese Workers

“…Noise is the best-known and one of the most studied environmental factors causing hearing loss. Several other environmental factors, such as organic solvents, heavy metals, and heat can augment the effect of noise [2][3][4][5][6][7]. In addition, individual factors such as smoking, drinking, high blood pressure, and cholesterol levels also can influence the susceptibility to noise [8][9][10][11][12].…”