Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519, Vandœuvre Cedex, France; DevAH EA 3450 - Développement, Adaptation et Handicap, Régulations cardio-respiratoires et de la motricité, Université de Lorraine, F-54500, Vandœuvre. France.
Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519, Vandœuvre Cedex, France.
Neurotoxicology. 2021 May;84:105-113. doi: 10.1016/j.neuro.2021.03.002. Epub 2021 Mar 17.
Epidemiological and experimental studies indicate that a number of aromatic solvents widely used in the industry can affect hearing and balance following chronic exposure. Animal studies demonstrated that long-term exposure to aromatic solvents directly damages the auditory receptor within the inner ear: the cochlea. However, no information is available on their effect on the vestibular receptor, which shares many structural features with the cochlea and is also localized in inner ear. The aim of this study was to use an in vitro approach to assess and compare the vestibular toxicity of different aromatic solvents (toluene, ethylbenzene, styrene and ortho-, meta-, para-xylene), all of which have well known cochleotoxic properties. We used a three-dimensional culture model of rat utricles ("cysts") with preserved functional sensory and secretory epithelia, and containing a potassium-rich (K) endolymph-like fluid for this study. Variations in K concentrations in this model were considered as biomarkers of toxicity of the substances tested. After 72 h exposure, o-xylene, ethylbenzene and styrene decreased the K concentration by 78 %, 37 % and 28 %, respectively. O- xylene and styrene both caused histopathological alterations in secretory and sensory epithelial areas after 72 h exposure, whereas no anomalies were observed in ethylbenzene-exposed samples. These in vitro results suggest that some widely used aromatic solvents might have vestibulotoxic properties (o-xylene, styrene and ethylbenzene), whereas others may not (p-xylene, m-xylene, toluene). Our results also indicate that variations in endolymphatic K concentration may be a more sensitive marker of vestibular toxicity than histopathological events. Finally, this study suggests that cochleotoxic solvents might not be necessarily vestibulotoxic, and vice versa.
流行病学和实验研究表明，许多工业中广泛使用的芳香族溶剂在长期接触后会影响听力和平衡。动物研究表明，长期暴露于芳香族溶剂会直接损害内耳中的听觉受体：耳蜗。然而，目前尚无关于它们对前庭受体影响的信息，前庭受体与耳蜗具有许多结构特征，并且也位于内耳中。本研究旨在使用体外方法评估和比较不同芳香族溶剂（甲苯、乙苯、苯乙烯和邻、间、对二甲苯）的前庭毒性，这些溶剂均具有众所周知的耳蜗毒性。我们使用了一种具有保留功能感觉和分泌上皮的大鼠前庭“囊肿”的三维培养模型，并使用富含钾的（K）内淋巴样液体进行了此项研究。该模型中 K 浓度的变化被认为是测试物质毒性的生物标志物。暴露 72 小时后，邻二甲苯、乙苯和苯乙烯分别使 K 浓度降低了 78%、37%和 28%。暴露 72 小时后，邻二甲苯和苯乙烯均导致分泌和感觉上皮区域出现组织病理学改变，而乙苯暴露的样本未观察到异常。这些体外结果表明，一些广泛使用的芳香族溶剂可能具有前庭毒性（邻二甲苯、苯乙烯和乙苯），而其他溶剂可能没有（对二甲苯、间二甲苯、甲苯）。我们的结果还表明，内淋巴 K 浓度的变化可能比组织病理学事件更能敏感地反映前庭毒性。最后，本研究表明，耳蜗毒性溶剂不一定具有前庭毒性，反之亦然。
