Fechter Laurence D, Gearhart Caroline, Fulton Sherry, Campbell Jerry, Fisher Jeffrey, Na Kwangsam, Cocker David, Nelson-Miller Alisa, Moon Patrick, Pouyatos Benoit
Loma Linda VA Medical Center, Loma Linda, California 92357, USA.
Toxicol Sci. 2007 Aug;98(2):542-51. doi: 10.1093/toxsci/kfm109. Epub 2007 May 21.
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.
已知在高暴露水平且暴露时间通常长达4 - 16周的情况下，乙苯和甲苯各自都具有耳毒性潜力。乙苯和甲苯都是JP - 8喷气燃料的次要成分；最近已确定这种燃料会增加对噪声性听力损失的易感性。因此，本研究评估了以三个实验室中发现的平均比例混合暴露于乙苯和甲苯的耳毒性潜力。大鼠通过吸入接触乙苯和甲苯，其中一半同时接受93 - 95分贝的倍频程带噪声（OBN）。另一组仅接受噪声暴露，旨在造成轻微但永久性的听觉损伤，同时还包括一个未暴露的对照组。在两项独立实验中，根据初步试验研究，以4000毫克/立方米的总碳氢化合物，连续5天每天暴露6小时，或连续2周每周暴露5天，甲苯浓度为400 ppm，乙苯浓度为660 ppm。使用畸变产物耳声发射和复合动作电位测试评估听觉功能损伤。完成这些测试后，解剖柯蒂氏器以评估毛细胞损失情况。通过在乙苯和甲苯暴露后的两个时间点采集未用于听觉测试的额外大鼠的关键器官，评估溶剂的摄取和消除情况。同样，鉴于有观点认为溶剂 - 噪声暴露可能导致氧化应激，所以还测量了谷胱甘肽（GSH）水平。单独以4000毫克/立方米暴露6小时的乙苯和甲苯本身并未损害耳蜗功能或导致毛细胞损失。然而，当与93分贝的OBN暴露相结合时，混合溶剂加噪声确实导致了听觉功能损失，并且外毛细胞死亡明显增强，超过了单独噪声造成的损失。未发现因乙苯和甲苯暴露导致肺、肝或脑中总GSH损失的证据。
