A weight of evidence approach for the assessment of the ototoxic potential of industrial chemicals

Abstract

There is accumulating epidemiological evidence that exposure to some solvents, metals, asphyxiants and other substances in humans is associated with an increased risk of acquiring hearing loss. Furthermore, simultaneous and successive exposure to certain chemicals along with noise can increase the susceptibility to noise-induced hearing loss. There are no regulations that require hearing monitoring of workers who are employed at locations in which occupational exposure to potentially ototoxic chemicals occurs in the absence of noise exposure. This project was undertaken to develop a toxicological database allowing the identification of possible ototoxic substances present in the work environment alone or in combination with noise exposure. Critical toxicological data were compiled for chemical substances included in the Quebec occupational health regulation. The data were evaluated only for noise exposure levels that can be encountered in the workplace and for realistic exposure concentrations up to the short-term exposure limit or ceiling value (CV) or 5 times the 8-h time-weighted average occupational exposure limit (TWA OEL) for human data and up to 100 times the 8-h TWA OEL or CV for animal studies. In total, 224 studies (in 150 articles of which 44 evaluated the combined exposure to noise and a chemical) covering 29 substances were evaluated using a weight of evidence approach. For the majority of cases where potential ototoxicity was previously proposed, there is a paucity of toxicological data in the primary literature. Human and animal studies indicate that lead, styrene, toluene and trichloroethylene are ototoxic and ethyl benzene, n-hexane and p-xylene are possibly ototoxic at concentrations that are relevant to the occupational setting. Carbon monoxide appears to exacerbate noise-induced hearing dysfunction. Toluene interacts with noise to induce more severe hearing losses than the noise alone.

Ototoxic Substances at the Workplace: a Brief Update

“…The full report is available in French only; an English article in a scientifi c journal was published more than two years later (6).…”

“…This observation is also documented in IRSST's fi che toxicologique on xylene, although the Canadian authors consider "xylene (o-, m-, p-isomers)" as "possibly ototoxic" in the original version of their review. In the subsequent English journal article this ranking was limited to pxylene alone (6).…”

Evaluation of the effects of exposure to organic solvents and hazardous noise among US Air Force Reserve personnel

“…Similar challenges have also been noted in other occupational health studies. [10,[63][64][65] Secondly, most of the solvent exposure levels were determined from historical occupational industrial hygiene records and purchasing records. Exposure levels (none, low and medium) were estimated based on the amount of study solvent annotated in workplace exposure summaries, ordered and/or used in each workplace and were not necessarily based on individual monitoring.…”

Noise-Induced Hearing Loss in Korean Workers: Co-Exposure to Organic Solvents and Heavy Metals in Nationwide Industries

“…A possible reason for the null findings of the ototoxic effects of solvents include diluted observation due to the dominant effect of noise; this is because workplaces using these chemicals are likely to be accompanied by excessive noise as well [32], [33]. A few recent studies suggest that the effect of noise can be enhanced by ototoxic chemical exposure [34]–[38].…”