International Agency for Research on Cancer (IARC) - Summaries & Evaluations

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 71 (1999) (p. 829)

CAS No.: 108-88-3
Chem. Abstr. Name: Methylbenzene

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Toluene is an industrial chemical produced in high volume, that is used in blending gasoline and as a solvent. Occupational exposure to toluene is extensive and occurs in its production and during the manufacture and use of toluene-containing paints, thinners, cleaning agents, coatings and adhesives. It is commonly detected in ambient air and at low levels in water.

5.2 Human carcinogenicity data

Toluene was mentioned as an exposure in eight studies. Two were community-based case–control studies, one of which involved brain cancer and one involved several types of cancer. Of the six industry-based studies, three were analysed as cohort studies and three were configured as nested case–control studies of one or a few types of cancer. In two of the studies, that of shoe-manufacturing workers in the United States and particularly that of Swedish rotogravure printers, it was believed that toluene was the predominant exposure; in the other studies, there were probably concomitant exposures. Cancers of most sites were not significantly associated with toluene exposure in any study. Stomach cancer mortality was significantly elevated in the Swedish rotogravure printers study, it was slightly, though not significantly, elevated in two other studies, and it was not associated at all in a fourth. Rates of lung cancer were significantly elevated in the cohort of shoe manufacturers and in the Swedish cohort of rotogravure printers, but was not associated at all in two other studies. Colorectal cancer was significantly elevated in the Swedish rotogravure printers study and in the Canadian case–control study, and colon cancer was nonsignificantly elevated in the shoe manufacturers cohort. While results on leukaemias and lymphomas generally showed no association, these were based on small numbers. Considering the multiple exposure circumstances in most studies and the weak consistency of findings, these results are not strong enough to conclude that there is an association.

5.3 Animal carcinogenicity data

Toluene was tested for carcinogenicity by inhalation exposure in one study in mice and in one study in rats. No significant increase in the incidence of tumours was observed. Repeated application of toluene to the skin of mice did not result in an increased incidence of skin tumours.

5.4 Other relevant data

Toluene is mainly converted to benzyl alcohol and excreted as hippurate. Its toxicokinetics in humans have been extensively studied.

Toluene toxicity is most prominent in the central nervous system after acute and chronic exposure. Reproductive toxicity has been observed in exposed humans and rats.

In the more recent cytogenetic studies in occupationally exposed populations, increases in chromosomal aberrations (two studies), micronuclei (one study) and of DNA strand breaks (one study) have been described. These effects have also been observed in rats and mice in some studies and in cultured mammalian cells. DNA adducts have not been detected.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of toluene.

There is evidence suggesting lack of carcinogenicity of toluene in experimental animals.

Overall evaluation

Toluene is not classifiable as to its carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 47 (1989)


Last updated: 13 April 1999

    See Also:
       Toxicological Abbreviations
       Toluene (EHC 52, 1986)
       Toluene (ICSC)
       Toluene (WHO Food Additives Series 16)
       TOLUENE (JECFA Evaluation)