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Exposure to aromatic organic solvents may induce hearing loss in rats, the cochlea being the primary target. The aim of this study which was carried out in rat, was to evaluate the impact of the hepatic metabolism of toluene on its ototoxic potency. To this end, the solvent hepatic metabolism was shifted by treating the rats with 50 mg/kg/d of phenobarbital (PhB), a potent inducer of the microsomal cytochromes P450 system, alcohol and aldehyde dehydrogenases, and glutathione-S-transferases. The two main urinary metabolites of the oxidative and conjugate pathways [hippuric (HA) and benzyl mercapturic acids (BMA) respectively] confirmed the efficacy of the PhB treatment. For the PhB-induced rats, the amount of excreted HA increased by 43% and the amount of BMA by 35%. Auditory function impairments were assessed using auditory-evoked potentials. On completion of the auditory tests, the organs of Corti were dissected to evaluate hair cell losses. The permanent auditory threshold shifts were approximately 15 dB greater in the toluene-exposed rats than in the PhB-induced rats. Both the functional and morphological data confirmed that PhB treatment can decrease the ototoxic potency of toluene.

The last ten years, the use of gentamicin has increased due to antibiotic resistance among bacterial pathogens. One of the side effects of gentamicin is its toxicity on hearing. Several authors had even pointed out synergistic effects of gentamicin and noise on hearing. It was therefore reasonable to think that the damaging effects of noise could be emphasized by a gentamicin treatment of the subjects. In order to test the applicability of the Leq8h for estimating the hazard of noise on animals treated with a non-ototoxic dose of gentamicin (40 mg/kg for 8 days), two experiments were carried out with guinea pigs. The animals were exposed to octave band noises centred at 8 kHz and treated with gentamicin either simultaneously or sequentially with regard to the noise exposure. Two noise exposures having different acoustic energy, respectively Leq8h = 85 dB and 98.8 dB SPL, were tested. The auditory function of the guinea pigs was tested by recording auditory-evoked potentials. The electrophysiological findings were completed by histological data. The gentamicin treatment tested in the current studies did not cause any auditory permanent threshold shift neither cochlear disruptions, although the treatment could be considered as approximately ten times the therapeutic dose used in human. The auditory deficit induced by the mixed exposures to noise and gentamicin did not worsen the noise effect alone in our experimental conditions. As a result, the European value recommended for noise exposure (Leq8h=85 dB) seems to be robust enough to protect gentamicin-treated workers.

The current experiments were undertaken to determine whether or not styrene-induced hearing loss in the rat depends more on the existence of a critical period between 14 and 21 weeks of age than on body weight. For these purposes, two experiments were carried out with mature Long-Evans rats. In the first experiment, two groups of 5-month old rats, but having different body weight (slim: 314 g vs. fat: 415 g) were exposed to 700 ppm styrene for 4 consecutive weeks, 5 days per week, 6 hours per day. In the second experiment, two groups of rats having the same weight: 345 g, but different ages (14- vs. 21- week old) were exposed to styrene in strictly identical experimental conditions. Auditory sensitivity was tested by recording evoked potentials from the inferior colliculus. Surface preparations of the organ of Corti were also performed to complete the investigation. At the end of the six week recovery period following the styrene exposure, a 7 dB permanent threshold shift (PTS) was obtained with the same age animals regardless of the body weight. Consequently, weight was not a major factor in styrene-induced hearing loss. Age was a more critical factor in determining higher sensitivity to styrene. Indeed, the three months old group had 23.5 dB PTS, whereas the five months old group had only a 7.7 dB PTS at 16 kHz. Thus, a 15 dB difference of PTS was obtained between the rats having the same weight but different age. While the weight does not play a major role in styrene ototoxicity, there is a critical period whose duration lasts more than three months and for which the susceptibility to styrene is enhanced.

Noise- and styrene-induced hearing and hair cell loss were studied in young (3 months) and aged (24-26 months) Long-Evans rats. The animals were exposed 6 h/d, 5 d/w for 4 weeks to (a) broadband noise centered at 8 kHz (92 or 97dB SPL), or b) styrene (700 ppm). Auditory sensitivity was tested by recording evoked potentials from the inferior colliculus. Histological analyses of the organ of Corti, stria vascularis, and the spiral ganglions were also performed. Aged controls showed outer hair cell (OHC) loss at the basal and apical regions of the organ of Corti, and an increase in pigmentation concomitant to a decrease in vascularization of the stria vascularis, along with elevated thresholds relative to young controls. The 92-dB noise caused similar threshold shifts in both age groups, whereas the 97-dB noise caused more threshold shifts in the aged group compared to the young group. Recovery of the hearing thresholds depended both on the intensity of the noise and on the age of the animals. Aged rats had minimal hair cell loss as a result of styrene exposure, whereas young animals showed significant OHC loss, particularly in third row. Despite significant loss of OHCs, the young subjects showed styrene-induced threshold shifts only at high frequencies. In summary, the data show that : (a) there is an influence of age on both noise-induced and styrene-induced threshold shift and hair cell loss in rats and (b) the cochlea appear to have a redundancy in the number of OHCs, thus threshold shift does not necessarily occur with significant OHC loss.

Toluene and styrene are industrial solvents that can severely damage the auditory function in adult rats. In the present study, toluene (1000 to 2000 ppm) and styrene doses (500 to 1500 ppm) were investigated according to the same schedule: 6 hours per day, 5 days per week, for 4 consecutive weeks. The auditory function of the animals was tested by recording evoked potentials from the inferior colliculus over a frequency range from 2 to 32 kHz, whereas pathological data were evaluated by conventional histologic techniques. The permanent threshold shifts (PTS) were obtained with a styrene dose 2.4 times lower than that of the toluene. The slope of the regression line (PTS/doses) was 2.1 steeper with styrene than that obtained with toluene in the same experimental conditions. The sequence of histopathological events along the organ of Corti, especially the orderliness and the location of the traumas, was similar for paired concentrations of styrene and toluene, which were respectively 650 ppm, 1500 ppm for the first match, and 850 ppm, 1750 ppm for the second one. Both electrophysiological and histological findings point out the higher ototoxic potency of the styrene compared to that of the toluene. Assumptions concerning the ototoxic mechanism are addressed in the present paper.

Inhaled toluene (from 1000 to 2000 ppm, 6 h/day, 5 days/week, 4 weeks) is anototoxic solvent that severely damaged the cochlea in adult Long-Evans rats. Auditory function was tested by recording near field potentials from the inferior colliculus. Surprisingly, the electrophysiologic results did not reflect all the cochlear damage observed by histology. Loss of outer hair cells of the organ of Corti occurred in all toluene-treated rats in middle and mid-apical turns, whereas the basal turn of the cochlea was fairly well preserved. The third row of outer hair cells was more injured than the second row, which itself was more injured than the first row. The locations of the cochlear lesions are reported in the present study with regard to the toluene dose.