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ToxSci Advance Access originally published online on July 27, 2009
Toxicological Sciences 2009 111(2):362-371; doi:10.1093/toxsci/kfp169
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Toluene-Induced Hearing Loss in the Guinea Pig

Delphine Waniusiow*, Pierre Campo*,1, Thomas Venet*, Benoît Cossec*, Frédéric Cosnier*, Dominique Beydon*, Benoît Rieger*, Manuella Burgart*, Luc Ferrari{dagger} and Cécile Parietti-Winkler{ddagger},§

* Département Polluants et Santé Rue du Morvan, Institut National de Recherche et de Sécurité, 54519 Vandœuvre Cédex, France {dagger} National Institute for Health and Medical Research (INSERM) ERI 11, Faculty of Pharmacy of Nancy, Nancy University, 54500 Nancy, France {ddagger} Department of ENT, University Hospital of Nancy, 54000 Nancy, France § National Institute for Health and Medical Research (INSERM), U954, Faculty of Medicine, Nancy University, 54000 Nancy, France

1 To whom correspondence should be addressed. Fax: +33-38-350-2155. E-mail: Pierre.campo{at}inrs.fr.

Received April 16, 2009; accepted July 16, 2009


  Abstract

Toluene is a high-production industrial solvent, which can disrupt the auditory system in rats. However, toluene-induced hearing loss is species dependent. For instance, despite long-lasting exposures to high concentrations of aromatic solvent, no study has yet succeeded in causing convincing hearing loss in the guinea pig. This latter species can be characterized by two metabolic particularities: a high amount of hepatic cytochrome P-450s (P-450s) and a high concentration of glutathione in the cochlea. It is therefore likely that the efficiency of both the hepatic and cochlear metabolisms plays a key role in the innocuousness of the hearing of guinea pigs to exposure to solvent. The present study was carried out to test the auditory resistance to toluene in glutathione-depleted guinea pigs whose the P-450 activity was partly inhibited. To this end, animals on a low-protein diet received a general P-450 inhibitor, namely SKF525-A. Meanwhile, they were exposed to 1750 ppm toluene for 4 weeks, 5 days/week, 6 h/day. Auditory function was tested by electrocochleography and completed by histological analyses. For the first time, a significant toluene-induced hearing loss was provoked in the P-450–inhibited guinea pigs. However, the ototoxic process caused by the solvent exposure was different from that observed in the rat. Only the stria vascularis and the spiral fibers were disrupted in the apical coil of the cochlea. The protective mechanisms developed by guinea pigs are discussed in the present publication.

Key Words: ototoxicity; toluene; glutathione; cytochrome; diet; SKF525-A; hearing loss.


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