Low-level toluene disrupts auditory function in guinea pigs.
Low-level toluene disrupts auditory function in guinea pigs.
复制标题
低浓度的甲苯会破坏豚鼠的听觉功能。
DOI：
10.1006/taap.2000.8978
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Fechter,LD
中科院分区：
文献类型：
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作者：
McWilliams,ML;Chen,GD;Fechter,LD
甲苯似乎对人类听觉系统有不良影响，但很难估计其效力，因为它通常与噪声暴露一起存在于工作场所;工作场所噪声暴露通常变化很大。专门用于评估甲苯耳毒性的研究仅限于在单一实验室动物模型（大鼠）中进行的高剂量研究。在吸入暴露5天（6小时/天）后，在浓度为1000 ppm甲苯和更高浓度甲苯时观察到永久性听力损失。OSHA对甲苯的阈值限值仅为100 ppm。目前的研究重点是在豚鼠中急性甲苯耳毒性的发作，并提出一种作用机制。在本研究中，提供了甲苯对豚鼠听觉功能损害的证据，其浓度远低于研究大鼠永久性损害所用的浓度。功能受损与外毛细胞能量代谢减少有关。使用畸变产物耳声发射（DPOAE）进行听觉功能评估，随后使用表面制备物测量毛细胞中琥珀酸脱氢酶（SDH）染色密度。在暴露于250、500和1000 ppm甲苯的受试者中观察到豚鼠听觉功能暂时中断，每天8小时，每周5天，持续1周和4周。浓度低至250 ppm的甲苯能够急性破坏豚鼠的听觉功能，500和1000 ppm的甲苯产生更大的急性功能障碍。SDH染色表明，降低酶活性的中频区的耳蜗发生急性甲苯暴露后。虽然听觉功能障碍在暴露1至4周之间进展，但这些受试者并未出现永久性丧失，也未观察到毛细胞死亡。本研究确定了低甲苯浓度下豚鼠听觉系统受损的早期证据和毛细胞能量产生受损的证据。虽然即使是短暂的听觉障碍也会影响工作场所的安全，但必须对从这种急性影响到永久性损害的过渡进行额外的研究。
Toluene appears to have adverse effects on the human auditory system, but it is difficult to estimate its potency since it is commonly present in the workplace in combination with noise exposure; workplace noise exposures are often highly variable. Studies designed to assess toluene ototoxicity specifically have been limited to high-dose studies in a single laboratory animal model, the rat. Here permanent hearing loss has been observed at concentrations of 1000 ppm toluene and greater after inhalation exposure for 5 days, 6 h/day. The OSHA threshold limit value for toluene is only 100 ppm. The current study focuses on the onset of toluene ototoxicity acutely in the guinea pig and in adducing a mechanism of effect. In this study, evidence is presented for the impairment of auditory function by toluene in the guinea pig, at a concentration substantially lower than that used for studying permanent impairment in the rat. The impaired function was correlated with reduced energy metabolism in outer hair cells. Assessment of auditory function was made using distortion product otoacoustic emissions (DPOAE) with subsequent measurement of succinate dehydrogenase (SDH) staining density in hair cells using surface preparations. Temporary disruption of auditory function in guinea pigs is seen in subjects exposed to 250, 500, and 1000 ppm toluene for 8 h/day, 5 day/week for 1 and 4 weeks. Concentrations as low as 250 ppm toluene were able to disrupt auditory function acutely in the guinea pig, and 500 and 1000 ppm toluene produced greater acute dysfunction. SDH staining suggests that reduced enzyme activity in the midfrequency region of the cochlea occurs acutely following toluene exposure. Although the auditory dysfunction progressed between 1 and 4 weeks of exposure, a permanent loss did not develop for these subjects and hair cell death was not seen. The current study identifies early evidence of auditory system impairment in the guinea pig at low toluene concentration and evidence for impairment of energy production in hair cells. While even a transient auditory impairment has implications for workplace safety, additional study on the transition from such acute effects to permanent impairment is essential.