Ototoxic potential of industrial chemicals

Introduction

There is accumulating epidemiological evidence that exposure to some solvents, metals, asphyxiants and other substances in humans is associated with an increased risk of hearing loss. This project was undertaken to develop a toxicological database allowing the identification of possible ototoxic substances present in the work environment. Critical toxicological data were compiled for chemical substances included in the Quebec Occupational Health Regulation.

Methods

The data were evaluated only for realistic exposure concentrations up to the short-term exposure limit or ceiling value or five times the 8-h time weighted average exposure limit value(TWAEV) for human data and up to 100 times the 8-h TWAEV or ceiling value for animal studies.

Using a systematic weight of evidence approach, the information from both human and animal studies was examined.

At first, information from each source was given a weight of evidence qualifier for ototoxicity: strong, medium, weak, absent or “no study found”. We took into consideration the following parameters: studied specie, number of subjects, exposure way, characteristics of control groups, exposure levels, audiometric and statistical tests, dose/effect relation. Table 1 shows how this information was combined to yield an overall assessment of the ototoxic potential of a given substance. Human data were generally given more weight in the overall assessment. When no human studies were available, which is different from the absence of evidence from the available human studies, the overall assessment was deemed the same as that from animal studies.

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. Table 1 shows how the information from both types of studies were combined to yield an overall assessment and corollary conclusion about the ototoxicity of the investigated chemicals.

Human data were generally given more weight in the overall assessment. When no human studies were available, or when good quality human studies showed absence of evidence of an ototoxic effect, the overall assessment was one degree lower than that resulting from the animal studies. 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 chemical substances, all substances bearing a “strong evidence” of ototoxicity overall are considered “ototoxic”. Those with “medium evidence” overall are rated “possibly ototoxic”. We consider the ototoxic potential of those with only “weak evidence” as “non conclusive”. Finally, those for which there is absence of evidence overall bear the mention “no evidence”.

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

Human	Animal	Overall	Conclusion
S	S	S	O
S	M	S	O
S	W	S	O
S	A	S	O
S	X	S	O
M	S	S	O
M	M	M	PO
M	W	M	PO
M	A	M	PO
M	X	M	PO
W	S	M	PO
W	M	W	NC
W	W	W	NC
W	A	W	NC
W	X	W	NC
A	S	M	PO
A	M	W	NC
A	W	A	NE
A	A	A	NE
A	X	A	NE
X	S	S	O
X	M	M	PO
X	W	W	NC
X	A	A	NE

 

Product datasheets

* Corresponding author : adolf.vyskocil@UMontreal.CA
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