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

(Group 2B)

For definition of Groups, see Preamble Evaluation.

VOL.: 71 (1999) (p. 865)

Commercial toluene diisocyanate mixtures
CAS No.: 26471-62-5
Chem. Abstr. Name: 1,3-Diisocyanatomethylbenzene

2,4-Toluene diisocyanate
CAS No.: 584-84-9
Chem. Abstr. Name: 2,4-Diisocyanato-1-methylbenzene

2,6-Toluene diisocyanate
CAS No.: 91-08-7
Chem. Abstr. Name: 1,3-Diisocyanato-2-methylbenzene

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Toluene diisocyanates are industrial chemicals produced in large volumes. Exposure to toluene diisocyanates may occur during their production and in the processing and handling of polyurethane foams.

5.2 Human carcinogenicity data

The risk of cancer associated with occupational exposure to isocyanates has been examined in three industrial cohort studies and in a population-based case–control study of several types of cancer. No strong association or consistent pattern has emerged.

5.3 Experimental data

Commercial mixtures of 2,4- and 2,6-toluene diisocyanates were tested for carcinogenicity in mice and rats by gavage and by inhalation exposure. Administration by gavage induced a dose-related increase in the incidence of subcutaneous fibromas and fibrosarcomas (combined) in male rats, together with an increase in the incidence of pancreatic acinar-cell adenomas in male rats and in pancreatic islet-cell adenomas, neoplastic nodules of the liver and mammary gland fibroadenomas in female rats. In female mice, dose-related increases in the combined incidence of haemangiomas and haemangiosarcomas and of hepatocellular adenomas were observed; no treatment-related tumour was seen in male mice, possibly due to poor survival. No treatment-related tumour was observed after exposure of mice or rats to commercial toluene diisocyanate by inhalation, although the results of the study with rats have not been reported fully.

5.4 Other relevant data

Toluene diisocyanates are metabolized to toluene diamines in humans and rats. Toluene diisocyanates are irritants and respiratory sensitizers in humans and rats.

Toluene diisocyanate did not induce micronuclei in mammalian erythrocytes in vivo. It induced DNA damage and chromosomal aberrations but not sister chromatid exchanges in human lymphocytes in vitro. It induced gene mutation and sister chromatid exchanges but not DNA damage or chromosomal aberrations in rodent cells in vitro. It induced sex-linked mutations in Drosophila and in some experiments was mutagenic in bacteria. The presence of an exogenous metabolic activation system led to inconsistent results, sometimes enhancing and at other times eliminating the genotoxic effects of toluene diisocyanate.

5.5 Evaluation

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

There is sufficient evidence for the carcinogenicity of toluene diisocyanates in experimental animals.

Overall evaluation

Toluene diisocyanates are possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.


Toluene diisocyanate

2,4-Toluene diisocyanate

2,6-Toluene diisocyanate

Previous evaluations: Vol. 39 (1986); Suppl. 7 (1987)

Last updated: 13 April 1999

    See Also:
       Toxicological Abbreviations
       Toluene diisocyanates (EHC 75, 1987)