Effect on hearing and balance of a co-exposure to a low-frequency noise associated with carbon disulfide (CS2)

Carbon disulfide (CS2) is a solvent used in the manufacture of cellulose, viscose fibers and sponges. Co-exposures to CS2 and noise are common. Occupational exposures to CS2 have been shown to cause low-frequency hearing loss and balance disorders when noise was also present. However, the effects of CS2 on the cochlea and the vestibule are still unknown today.<br/>
The general objective of this work was to study, in a rat model, the effects of CS2 and low frequency noises on the auditory and vestibular systems in order to determine:<br/>
(1) whether the toxicity of CS2 is central and / or peripheral, and whether it is aggravated by co-exposure to noise; <br/>
(2) if the toxicity of CS2 is equivalent and / or comparable at the level of the auditory system and the vestibular system; <br/>
(3) if the deleterious effects of CS2 on auditory and vestibular functions (if any) are temporary or permanent;<br/>
(4) whether the functional adverse effects of exposures are representative of the histopathological damage (if any).;<br/>
(5) the adequacy of occupational exposure threshold limit values for noise (LEX, 8h) and CS2 (TWA,8h = 5 ppm and TWACT = 25 ppm in Europe) in the context of co-exposures.<br/>
To answer these questions, Long Evans rats were exposed to different concentrations of CS2 and low-frequency noises. The temporary and permanent effects of these exposures were evaluated by measurements of vestibular functions (post-rotatory nystagmus and behavioral tests) and cochlear functions (ototacoustic emissions). Moreover, histological analyses of the inner ear and a quantification of the expression of neurotoxicity genes in the cerebellum were performed.<br/>
The main results are the following: <br/>
(1) Exposure to CS2 at 250 ppm broadened the frequency range affected by low frequency noise, but decreased hearing loss in the range affected by the noise (below 6 kHz). This latter effect was more accentuated when the CS2 exposures were intermittent. <br/>
(2) Exposure to CS2 shortened the duration and decreased the number of saccades of the nystagmus, these effects being exacerbated when low frequency noise was also present. At low CS2 concentrations, we observed a complete recovery during the 4 weeks following the end of exposure, but these effects persisted at the highest concentration (500ppm). <br/>
(3) The behavioral and histological analyses (vestibule and cochlea), as well as the quantification of the neurotoxic markers in the cerebellum, did not reveal any major change.<br/>
In the experimental context of this study, CS2 did not appear ototoxic in rats since no histological impairment of the inner ear was observed. However, due to a probable action on the central nervous system, it could exacerbate the temporary effects of noise on both systems (extension of PDA losses to high frequencies and greater the decrease in nystagmus parameters).<br/>
In a prevention point of view, these results suggest that the TWA,8h of CS2 offers a satisfactory safety margin in noisy environment since significant effects on PDA and nystagmus were only observed at and above 250 ppm for 6h (40 x TWA,8h). On the other hand, only 15 min/h exposure to CS2 at 250 ppm (10 x TWACT) resulted in different PDA losses than for noise alone. This leads us to question the level of protection offered by the TWACT for CS2 in case of co-exposure with noise.<br/>
The data of this study do not allow us to know the precise mechanism of interaction of CS2 with the noise. However the absence of histological modifications in the peripheral receptors, of behavioral changes, as well as the lack of major changes in markers of neurotoxicity in the brain, suggest a temporary neurochemical modification of the efferent reflex arcs (hair cells, middle ear reflex, vestibulo-ocular reflex).