Numerous experiments have shown that the aromatic
solvents can affect the auditory system in the rat, the cochlea being targeted first.
Solvents differ in cochleotoxic potency: for example,
styrene is more ototoxic than
toluene or
xylenes. The goal of this study was to determine the relative
ototoxicity of the three isomers of
xylene (o-, m- or
p-xylene). Moreover, by dosing with the two urinary metabolites of
xylene, methylhippuric (MHAs) and mercapturic
acids (MBAs), this study points toward a causal relationship between the cochleotoxic effects and potential reactive intermediates arising from the biotransformation of the parent molecules. Separate groups of rats were exposed by inhalation to one isomer following this schedule: 1800 ppm, 6 h/d, 5 d/wk for 3 wk. Auditory thresholds were determined with brainstem-auditory evoked potentials. Morphological analysis of the organ of Corti was performed by counting both sensory and spiral ganglion cells. Among the three isomers, only
p-xylene was cochleotoxic. A 39-dB permanent threshold shift was obtained over the tested frequencies range from 8 to 20 kHz. Whereas outer hair cells were largely injured, no significant morphological change was observed within spiral ganglia. The concentrations of urinary p-, o- or m-MHA were greater (p-MHA: 33.2 g/g; o-MHA: 7.8 g/g; m-MHA: 20.4 g/g) than those obtained for MBAs (p-MBA: 0.04 g/g; o-MBA: 6.2 g/g; m-MBA: 0.03 g/g). Besides, there is a large difference between o-MBA (6.2 g/g) and p-MBA (0.04 g/g). As a result, since the
cysteine conjugates are not determinant in the ototoxic process of
xylenes, the location of the methyl groups around the
benzene nucleus could play a key role.