Ototoxicity of toluene in rats

Toluene is a major industrial solvent and substance of abuse which is ototoxic in rats as shown by both behavioral testing and measurement of brainstem auditory evoked response (BAER) thresholds. The objective of this investigation was to examine the morphological (hair cell loss) and functional (BAER threshold elevations) changes resulting from toluene administration. In the preliminary experiment, 5 male Sprague-Dawley rats were dosed by gavage to 0.5 ml toluene/kg body weight/day in corn oil for 21 days then consecutively to 1.0 ml toluene/kg/day for 21 days. In the main experiment, eight male Sprague-Dawley rats were dosed by gavage for eight weeks with 1.0 ml toluene/kg body weight/day in corn oil. Five and six control rats, respectively, received corn oil only. BAER thresholds were recorded from four toluene-treated and four control rats prior to dosing (main experiment) and from all rats after dosing (both experiments). Loss of outer hair cells occurred in all toluene-treated rats in the middle and basal turns of the organ of Corti, with the greatest loss in the third row and progressively less in the second and first rows. This loss was more severe in toluene-treated rats that demonstrated elevated BAER thresholds in midfrequency regions, typically 2-8 kHz. These experiments demonstrate that auditory changes are associated with cochlear hair cell loss in toluene-treated rats. These ototoxic effects of toluene contrast with those of other known ototoxicants, e.g., aminoglycoside antibiotics, in terms of the position of hair cell lesion in the organ of Corti and in the pattern of hair cell loss.