[en] 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.
Tallandier, Valentin ; Université de Liège - ULiège > GIGA > GIGA Neurosciences ; 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
Chalansonnet, M; Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519, Vandœuvre Cedex, France. Electronic address: monique.chalansonnet@inrs.fr
Merlen, L; Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519, Vandœuvre Cedex, France
Boucard, S; Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519, Vandœuvre Cedex, France
Thomas, A; Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519, Vandœuvre Cedex, France
Campo, P; 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
Pouyatos, B; Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519, Vandœuvre Cedex, France
Language :
English
Title :
An in vitro model to assess the peripheral vestibulotoxicity of aromatic solvents.
Bale, A.S., Meacham, C.A., Benignus, V.A., Bushnell, P.J., Shafer, T.J., Volatile organic compounds inhibit human and rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. Toxicol. Appl. Pharmacol. 205 (2005), 77–88, 10.1016/j.taap.2004.09.011.
Bartolami, S., Gaboyard, S., Quentin, J., Travo, C., Cavalier, M., Barhanin, J., Chabbert, C., Critical roles of transitional cells and Na/K-ATPase in the formation of vestibular endolymph. J. Neurosci. 31 (2011), 16541–16549, 10.1523/JNEUROSCI.2430-11.2011.
Calabrese, G., Martini, A., Sessa, G., Cellini, M., Bartolucci, G.B., Marcuzzo, G., De Rosa, E., Otoneurological study in workers exposed to styrene in the fiberglass industry. Int. Arch. Occup. Environ. Health 68 (1996), 219–223.
Calderón-Guzmán, D., Hernández-Islas, J.L., Espítia Vázquez, I.R., Barragán-Mejía, G., Hernández-García, E., Del Angel, D.S., Juárez-Olguín, H., Effect of toluene and cresols on Na+,K+-ATPase, and serotonin in rat brain. Regul. Toxicol. Pharmacol. 41 (2005), 1–5, 10.1016/j.yrtph.2004.09.005.
Campo, P., Maguin, K., Solvent-induced hearing loss: mechanisms and prevention strategy. Int. J. Occup. Med. Environ. Health 20 (2007), 265–270, 10.2478/v10001-007-0031-3.
Campo, P., Loquet, G., Blachère, V., Roure, M., Toluene and styrene intoxication route in the rat cochlea. Neurotoxicol. Teratol. 21 (1999), 427–434.
Campo, P., Lataye, R., Loquet, G., Bonnet, P., Styrene-induced hearing loss: a membrane insult. Hear. Res. 154 (2001), 170–180.
Cappaert, N.L., Klis, S.F., Baretta, A.B., Muijser, H., Smoorenburg, G.F., Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss. J. Assoc. Res. Otolaryngol. 1 (2000), 292–299, 10.1007/s101620010050.
Chen, G.-D., Chi, L.-H., Kostyniak, P.J., Henderson, D., Styrene induced alterations in biomarkers of exposure and effects in the cochlea: mechanisms of hearing loss. Toxicol. Sci. 98 (2007), 167–177, 10.1093/toxsci/kfm078.
Ciuman, R.R., Stria vascularis and vestibular dark cells: characterisation of main structures responsible for inner-ear homeostasis, and their pathophysiological relations. J. Laryngol. Otol., 123, 2009, 151, 10.1017/S0022215108002624.
Cruz, S.L., Balster, R.L., Woodward, J.J., Effects of volatile solvents on recombinant N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Br. J. Pharmacol. 131 (2000), 1303–1308, 10.1038/sj.bjp.0703666.
Diodovich, C., Bianchi, M.G., Bowe, G., Acquati, F., Taramelli, R., Parent-Massin, D., Gribaldo, L., Response of human cord blood cells to styrene exposure: evaluation of its effects on apoptosis and gene expression by genomic technology. Toxicology 200 (2004), 145–157, 10.1016/j.tox.2004.03.021.
Diodovich, C., Urani, C., Maurici, D., Malerba, I., Melchioretto, P., Orlandi, M., Zoia, L., Campi, V., Carfi’, M., Pellizzer, C., Gribaldo, L., Modulation of different stress pathways after styrene and styrene-7,8-oxide exposure in HepG2 cell line and normal human hepatocytes. J. Appl. Toxicol. 26 (2006), 317–325, 10.1002/jat.1142.
Fetoni, A.R., Rolesi, R., Paciello, F., Eramo, S.L.M., Grassi, C., Troiani, D., Paludetti, G., Styrene enhances the noise induced oxidative stress in the cochlea and affects differently mechanosensory and supporting cells. Free Radic. Biol. Med. 101 (2016), 211–225, 10.1016/j.freeradbiomed.2016.10.014.
Freeman, S., Priner, R., Elidan, J., Sohmer, H., Objective method for differentiating between drug-induced vestibulotoxicity and cochleotoxicity. Otol. Neurotol. 22 (2001), 70–75, 10.1097/00129492-200101000-00014.
Gaboyard, S., Chabbert, C., Travo, C., Bancel, F., Lehouelleur, J., Yamauchi, D., Marcus, D.C., Sans, A., Three-dimensional culture of newborn rat utricle using an extracellular matrix promotes formation of a cyst. Neuroscience 133 (2005), 253–265, 10.1016/j.neuroscience.2005.02.011.
Gagnaire, F., Marignac, B., Langlais, C., Bonnet, P., Ototoxicity in rats exposed to ortho-, meta- and para-xylene vapours for 13 weeks. Pharmacol. Toxicol. 89 (2001), 6–14, 10.1034/j.1600-0773.2001.d01-129.x.
Gagnaire, François, Langlais, C., Grossmann, S., Wild, P., Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks. Arch. Toxicol. 81 (2007), 127–143, 10.1007/s00204-006-0124-y.
Gagnaire, F., Marignac, B., Blachère, V., Grossmann, S., Langlais, C., The role of toxicokinetics in xylene-induced ototoxicity in the rat and guinea pig. Toxicology 231 (2007), 147–158, 10.1016/j.tox.2006.11.075.
Hibino, H., Kurachi, Y., Molecular and physiological bases of the K + circulation in the mammalian inner ear. Physiology 21 (2006), 336–345, 10.1152/physiol.00023.2006.
Hibino, H., Nin, F., Tsuzuki, C., Kurachi, Y., How is the highly positive endocochlear potential formed? The specific architecture of the stria vascularis and the roles of the ion-transport apparatus. Pflugers Arch. 459 (2010), 521–533, 10.1007/s00424-009-0754-z.
Hodgkinson, L., Prasher, D., Effects of industrial solvents on hearing and balance: a review. Noise Health 8 (2006), 114–133.
Kitasato, I., Yokota, M., Inouye, S., Igarashi, M., Comparative ototoxicity of ribostamycin, dactimicin, dibekacin, kanamycin, amikacin, tobramycin, gentamicin, sisomicin and netilmicin in the inner ear of guinea pigs. Chemotherapy 36 (1990), 155–168, 10.1159/000238762.
Lang, F., Vallon, V., Knipper, M., Wangemann, P., Functional significance of channels and transporters expressed in the inner ear and kidney. Am. J. Physiol. Cell Physiol. 293 (2007), C1187–C1208, 10.1152/ajpcell.00024.2007.
Loquet, G., Campo, P., Lataye, R., Comparison of toluene-induced and styrene-induced hearing losses. Neurotoxicol. Teratol. 21 (1999), 689–697.
Maguin, K., Lataye, R., Campo, P., Cossec, B., Burgart, M., Waniusiow, D., Ototoxicity of the three xylene isomers in the rat. Neurotoxicol. Teratol. 28 (2006), 648–656, 10.1016/j.ntt.2006.08.007.
Nakashima, T., Teranishi, M., Hibi, T., Kobayashi, M., Umemura, M., Vestibular and cochlear toxicity of aminoglycosides—a review. Acta Otolaryngol. 120 (2000), 904–911, 10.1080/00016480050218627.
Niklasson, M., Tham, R., Larsby, B., Eriksson, B., Effects of toluene, styrene, trichloroethylene, and trichloroethane on the vestibulo-and opto-oculo motor system in rats. Neurotoxicol. Teratol. 15 (1993), 327–334.
Shubin, A.V., Demidyuk, I.V., Komissarov, A.A., Rafieva, L.M., Kostrov, S.V., Cytoplasmic vacuolization in cell death and survival. Oncotarget 7 (2016), 55863–55889, 10.18632/oncotarget.10150.
Spicer, S.S., Schulte, B.A., Evidence for a medial K+ recycling pathway from inner hair cells. Hear. Res. 118 (1998), 1–12.
Sułkowski, W.J., Kowalska, S., Matyja, W., Guzek, W., Wesołowski, W., Szymczak, W., Kostrzewski, P., Effects of occupational exposure to a mixture of solvents on the inner ear: a field study. Int. J. Occup. Med. Environ. Health 15 (2002), 247–256.
Tallandier, V., Merlen, L., Boucard, S., Thomas, A., Venet, T., Chalansonnet, M., Gauchard, G., Campo, P., Pouyatos, B., Styrene alters potassium endolymphatic concentration in a model of cultured utricle explants. Toxicol. Vitr., 2020, 10.1016/j.tiv.2020.104915 104915.
Tham, R., Larsby, B., Eriksson, B., Niklasson, M., The effect of toluene on the vestibulo- and opto-oculomotor system in rats, pretreated with GABAergic drugs. Neurotoxicol. Teratol. 12 (1990), 307–311, 10.1016/0892-0362(90)90048-h.
Unlu, I., Kesici, G.G., Basturk, A., Kos, M., Yılmaz, O.H., A comparison of the effects of solvent and noise exposure on hearing, together and separately. Noise Health 16 (2014), 410–415, 10.4103/1463-1741.144422.
Vaalavirta, L., Tähti, H., Effects of selected organic solvents on the astrocyte membrane ATPase in vitro. Clin. Exp. Pharmacol. Physiol. 22 (1995), 293–294, 10.1111/j.1440-1681.1995.tb01999.x.
Vaalavirta, L., Tähti, H., Astrocyte membrane Na+, K(+)-ATPase and Mg(2+)-ATPase as targets of organic solvent impact. Life Sci. 57 (1995), 2223–2230, 10.1016/0024-3205(95)02214-4.
Vyskocil, A., Truchon, G., Leroux, T., Lemay, F., Gendron, M., Gagnon, F., Majidi, N.E., Boudjerida, A., Lim, S., Emond, C., Viau, C., A weight of evidence approach for the assessment of the ototoxic potential of industrial chemicals. Toxicol. Ind. Health 28 (2012), 796–819, 10.1177/0748233711425067.