The hearing loss associated with exposure to toluene is not caused by a metabolite

Pryor, Gordon T.; Rebert, Charles S.; Kassay, K M; Kuiper, Heather C.; Gordon, R. D.

doi:10.1016/0361-9230(91)90290-z

Cited by 30 publications

(20 citation statements)

References 17 publications

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“…As shown in Figures 3 and 4, no signs of synergistic or additive interactions were found in the 90-day subchronic exposures to 100 ppm, 200 ppm, and 500 ppm toluene. This supports the fi ndings from other studies on toluene ototoxicity in rats, where hearing impairment occurred when a certain threshold of toluene exposure was exceeded [4,7,15,23,29,31]. However, contrary to what may have been expected, the exposure to 500 ppm toluene and noise was followed by the same changes in hearing thresholds and CDP loss as the exposure to noise only, while exposure to 100 ppm and 200 ppm toluene and noise was followed by a slightly lower decrease in auditory sensitivity than the exposure to noise alone.…”

Section: Statisticssupporting

confidence: 91%

“…Toluene differs from styrene in that it exerts the ototoxicity by itself, while its main metabolites (hippuric and benzyl mercapturic acids) have little ototoxic potency [7,14,26]. The ototoxicity following toluene exposure without concomitant noise exposure has only been shown in rats after exposure to the concentrations considerably higher than the mandatory occupational exposure levels (OEL).…”

Section: Discussionmentioning

confidence: 99%

“…The possible ototoxic effect of toluene was fi rst reported in rats by Pryor et al [1], and subsequent studies demonstrated hearing loss in rats after exposure to toluene [2][3][4][5][6][7][8][9][10][11], styrene [8,[12][13][14][15][16][17][18], xylene [8,9,12], ethyl benzene [19,20], trichloroethylene [8,9,[21][22][23][24], chlorobenzene [9], and n-heptane [25]. The ototoxic potency of the different solvents varies signifi cantly [9,14,26], but when rats were exposed to different combinations of organic solvents, the auditory impairment was additive with respect to the potency of the solvents under study [9].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…However, a certain threshold level of toluene exposure has to be exceeded, before even a prolonged exposure can induce the signs of ototoxicity [4,7,23,29], and corresponding to the threshold concentration in exposure, there seems to be a threshold concentration of toluene in blood of 40-60 μg/ml, before any auditory impairment is evident. It further seems to be toluene itself rather than its metabolites that is responsible for OHC loss [7]. At present, the risk of human auditory impairment due to organic solvent exposure seems to be primarily a problem concerning the effect of combined exposure to solvents and chinchillas and guinea pigs are not [35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

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Hazards to Hearing from Combined Exposure to Toluene and Noise in Rats

Lund

Kristiansen²

2008

International Journal of Occupational Medicine and Environmental Health

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Introduction:The main risk of hearing impairment from workplace exposure to organic solvents may stem from the potentiation of effects caused by concomitant noise exposure. The aim of the present study was to identify the main hazards from combined long-term, low-level exposure to noise and aromatic organic solvents, like toluene, in rats. Material and Methods: The rats were exposed to steady-state, wide-band noise (WBN) and 0 ppm, 100 ppm, 200 ppm and 500 ppm toluene for 90 days. Hearing was assessed using Auditory Brain Stem Responses (ABR) and Distortion Product Oto-Acoustic Emissions (DPOAE) eight weeks after exposure. The impact of noise composition on the interaction between solvent and noise exposure was investigated in rats exposed for 10 days either to 0 ppm, 500 ppm, 1000 ppm or 1500 ppm toluene and either WBN or impulse noise. ABR and DPOAE tests were performed before and two weeks after exposure. Results: Long-term exposure of rats to WBN and toluene at 500 ppm or less did not show any increase in hearing impairment, compared to the rats exposed to noise only. Synergistic interaction was demonstrated in short-term exposure to 1500 ppm toluene and both to WBN and impulse noise, but hearing impairment was much larger when following exposure to impulse noise. Conclusion: In combined exposure to low-levels of noise and toluene, even a long-term exposure did not reveal a potential hazard of hearing impairment. Synergistic interaction in combined short-term exposure to toluene and noise was noted both with respect to WBN and impulse noise, but the impulse noise was much more disruptive than WBN at the same level of noise exposure. The ototoxicity of organic solvents may primarily be a hazard also to human hearing due to the exacerbation of hearing loss by a possible co-exposure to especially harmful noise, such as impulse noise.

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Section: Statisticssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hazards to Hearing from Combined Exposure to Toluene and Noise in Rats

Lund

Kristiansen²

2008

International Journal of Occupational Medicine and Environmental Health

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Physiological Factors Predisposing to Neurotoxicity

Ray

1997

Archives of Toxicology

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Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks

et al. 2006

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Male Sprague-Dawley rats were exposed to ethylbenzene (200, 400, 600 and 800 ppm) and to two mixed xylenes (250, 500, 1,000 and 2,000 ppm total compounds) by inhalation, 6 h/day, 6 days/week for 13 weeks and sacrificed for morphological investigation 8 weeks after the end of exposure. Brainstem auditory-evoked responses were used to determine auditory thresholds at different frequencies. Ethylbenzene produced moderate to severe ototoxicity in rats exposed to the four concentrations studied. Increased thresholds were observed at 2, 4, 8 and 16 kHz in rats exposed to 400, 600 and 800 ppm ethylbenzene. Moderate to severe losses of outer hair cells of the organ of Corti occurred in animals exposed to the four concentrations studied. Exposure to both mixed xylenes produced ototoxicity characterized by increased auditory thresholds and losses of outer hair cells. Ototoxicity potentiation caused by ethylbenzene was observed. Depending on the mixed xylene studied and the area of the concentration-response curves taken into account, the concentrations of ethylbenzene in mixed xylenes necessary to cause a given ototoxicity were 1.7-2.8 times less than those of pure ethylbenzene. Given the high ototoxicity of ethylbenzene, the safety margin of less or equal to two (LOAEL/TWA) might be too small to protect workers from the potential risk of ototoxicity. Moreover, the enhanced ototoxicity of ethylbenzene and para-xylene observed in mixed xylenes should encourage the production of mixed xylenes with the lowest possible concentrations of ethylbenzene and para-xylene.

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The hearing loss associated with exposure to toluene is not caused by a metabolite

Cited by 30 publications

References 17 publications

Hazards to Hearing from Combined Exposure to Toluene and Noise in Rats

Hazards to Hearing from Combined Exposure to Toluene and Noise in Rats

Physiological Factors Predisposing to Neurotoxicity

Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks

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