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Ototoxicity of industrial chemicals alone or in combination with noise

A. Vyskocil¹* T. Leroux³*, G. Truchon², F. Lemay¹ , F. Gagnon¹, M. Gendron³, S. Botez², N. El Majidi¹, S.Lim¹ , A. Boudjerida¹, C. Emond¹, C. Viau¹
 

Introduction

There is increasing epidemiological evidence that exposure to some solvents, metals, asphyxiants and other substances is associated in humans with a risk of hearing loss. On the contrary, the interaction of chemicals and noise has received little attention. This project was undertaken to develop a database of toxicological data from the primary literature, allowing the identification of ototoxic substances and substances that interact with the noise present in the work environment. Critical toxicological data were compiled for chemical substances included in the Quebec regulation (Regulation Respecting Occupational Health and Safety).

Methods

The data were evaluated only for realistic exposure concentrations up to:

  • the short-term exposure limit value, or
  • the ceiling value, or
  • 5 times the 8-h time weighted average exposure limit value (TWAEV) for human data, or
  • 100 times the 8-h TWAEV or the ceiling value for animal studies.

    We took into consideration the number of studies and for each study the following parameters: studied species, number of subjects or animals, exposure route, characteristics of control groups, exposure levels, audiometric and statistical tests, dose/effect relationship and when available, mechanisms of action.

    Using a systematic weight of evidence approach, the information from both human and animal studies was examined. At first, a weight of evidence qualifier was given for both the ototoxicity and the interaction with noise : "strong", "medium", "weak", "absent" or "no study found". Note that weight of evidence qualifier "absent" should not be regarded as evidence that a substance is not ototoxic or that it does not interact with noise.

    We built a weight of evidence table (see
    Table 1) that allowed us to combine the information from both human and animal studies on ototoxicity of chemicals and their interaction with noise. Human data were given more weight in the overall assessment. For example, a "strong" evidence from animal studies combined with an "absence" of evidence from the available human studies yielded a "medium" evidence overall.

    Regarding the final conclusion about the ototoxic potential of substances or their interaction with noise, a substance bearing an overall qualifier of "strong evidence" of ototoxicity or interaction with noise was considered as an "ototoxic substance" or as a substance for which there is an "evidence of interaction" with noise. Those with "medium evidence" overall were rated "possibly ototoxic" or "possible interaction". We considered the ototoxic potential of those with only "weak evidence" as "non conclusive". Finally, those for which there was absence of evidence bore the mention "no evidence" of ototoxicity or interaction with noise.

Table 1. Weight of evidence approach for the assessment of ototoxicity of industrial chemicals

 

Weight of evidence of studies
 
Human studiesAnimal studiesOverall
SSS
SMS
SWS
SAS
SXS
MSS
MMM
MWM
MAM
MXM
WSM
WMW
WWW
WAW
WXW
ASM
AMW
AWW
AAA
AXA
XSM
XMW
XWW
XAA
XXX
Conclusion
 
OtotoxicityInteraction with noise
OI
OI
OI
OI
OI
OI
POPI
POPI
POPI
POPI
POPI
NCNC
NCNC
NCNC
NCNC
POPI
NCNC
NCNC
NENE
NENE
POPI
NCNC
NCNC
NENE
XX


 

Strength of evidence about ototoxicity: S = strong; M = medium; W = weak; A = absent; X = no study found
Conclusion about ototoxicity: O = ototoxic substance; PO = possibly ototoxic substance; NC = non conclusive; NE = no evidence; X = no documentation
Conclusion about interaction with noise: I = Evidence of interaction; PI = Possible interaction; NC = Non conclusive; NE = No evidence; X = No documentation
 

Product datasheets
 

ProductConclusion about          
ototoxicity
Conclusion about           
Interaction with noise
AcrylonitrileNon conclusiveNon conclusive
alpha-Methyl styreneNon conclusiveNo documentation
Carbon disulfideNon conclusiveNon conclusive
Carbon monoxideNo evidencePossible interaction
Cyanides (as CN)Non conclusiveNo documentation
EnfluraneNo evidenceNo documentation
Ethyl alcoholNo evidenceNo documentation
Ethyl benzenePossibly ototoxic substanceNon conclusive
HexachlorobenzeneNo evidenceNon documentation
Hydrogen cyanide (as CN)No evidenceNon conclusive
Lead and inorganic compounds (as Pb)Ototoxic substanceNo evidence
Mercury, Alkyl compounds (as Hg)Non conclusiveNo documentation
Mercury, inorganic compoundsNon conclusiveNo documentation
Mercury, mercury vapor (as Hg)Non conclusiveNo documentation
Methyl chloroformNo evidenceNo documentation
Methylene chlorideNo evidenceNo documentation
n-Butyl alcoholNon conclusiveNo documentation
n-HeptaneNon conclusiveNo documentation
n-HexanePossibly ototoxic substanceNo documentation
NicotineNo evidenceNo evidence
Parathion Non conclusiveNo documentation
PerchloroethyleneNo evidenceNo documentation
p-tert-ButyltolueneNo evidenceNo documentation
Styrene (monomer)Ototoxic substanceNon conclusive
Tin, Organic compounds (as Sn)Non conclusiveNo documentation
TolueneOtotoxic substanceEvidence of interaction
TrichloroethyleneOtotoxic substanceNon conclusive
Welding fumes (not otherwise classified) Non conclusiveNon conclusive
Xylene (o-,m-,p- isomers)Possibly ototoxic substanceNo documentation

* Corresponding author : adolf.vyskocil@UMontreal.ca
** Production of this document was supported by the IRSST (Grants 99-542 and 99-745)


¹ Groupe de recherche interdisciplinaire en santé- Département de santé environnementale et santé au travail, Université de Montréal
² Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST)
³ École d'orthophonie et d'audiologie, Université de Montréal

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