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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. Botez¹, N. El Majidi¹, A. Boudjerida¹, S. Lim¹, 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 and interaction with noise of industrial chemicals

Weight of evidence of studies

 

Conclusion

Human studies

Animal studies

Overall

Ototoxicity

Interaction
with noise

S

S

S

O

I

S

M

S

O

I

S

W

S

O

I

S

A

S

O

I

S

X

S

O

I

M

S

S

O

I

M

M

M

PO

PI

M

W

M

PO

PI

M

A

M

PO

PI

M

X

M

PO

PI

W

S

M

PO

PI

W

M

W

NC

NC

W

W

W

NC

NC

W

A

W

NC

NC

W

X

W

NC

NC

A

S

M

PO

PI

A

M

W

NC

NC

A

W

W

NC

NC

A

A

A

NE

NE

A

X

A

NE

NE

X

S

M

PO

PI

X

M

W

NC

NC

X

W

W

NC

NC

X

A

A

NE

NE

X

X

X

X

X

Strength of evidence about ototoxicity or interaction with noise: S = Strong; M = Medium; W= Weak; = 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

https://espum.umontreal.ca/

Product

Conclusion about
Ototoxicity

Conclusion about
Interaction with noise

Acrylonitrile

Non conclusive

Non conclusive

alpha-Methyl styrene

Non conclusive

No documentation

Carbon disulfide

Non conclusive

Non conclusive

Carbon monoxide

No evidence

Possible interaction

Cyanides (as CN)

Non conclusive

No documentation

Enflurane

No evidence

No documentation

Ethyl alcohol

No evidence

No documentation

Ethyl benzene

Possibly ototoxic substance

Non conclusive

Hexachlorobenzene

No evidence

No documentation

Hydrogen cyanide (as CN)

No evidence

Non conclusive

Lead and inorganic compounds (as Pb)

Ototoxic substance

No evidence

Mercury, Alkyl compounds (as Hg)

Non conclusive

No documentation

Mercury, inorganic compounds

Non conclusive

No documentation

Mercury, mercury vapor (as Hg)

Non conclusive

No documentation

Methyl chloroform

No evidence

No documentation

Methylene chloride

No evidence

No documentation

n-Butyl alcohol

Non conclusive

No documentation

n-Heptane

Non conclusive

No documentation

n-Hexane

Possibly ototoxic substance

No documentation

Nicotine

No evidence

No evidence

Parathion

Non conclusive

No documentation

Perchloroethylene

No evidence

No documentation

p-tert-Butyltoluene

No evidence

No documentation

Styrene (monomer)

Ototoxic substance

Non conclusive

Tin, Organic compounds (as Sn)

Non conclusive

No documentation

Toluene

Ototoxic substance

Evidence of interaction

Trichloroethylene

Ototoxic substance

Non conclusive

Welding fumes (not otherwise classified)

Non conclusive

Non conclusive

Xylene (o-,m-,p- isomers)

Possibly ototoxic substance

No documentation

* Corresponding author : Adolf Vyskocil

** Production of this document was supported by the IRSST (Grants 99-542 and 99-745)

¹ Institut de recherche en santé publique de l'Université de Montréal. Département de santé environmentale et de santé au travail, Université de Montréal. 
² Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST), Montréal.
³ École d’orthophonie et d’audiologie, Université de Montréal.