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

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 71 (1999) (p. 1049)

CAS No.: (a) 101-68-8 (monomer) and (b) 26447-40-5
Chem. Abstr. Name: 1,1¢-Methylenebis(4-isocyanatobenzene)

5. Summary of Data Reported and Evaluation

5.1 Exposure data

4,4¢-Methylenediphenyl diisocyanate is used for the production of polyurethane coatings and elastomers.

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 Animal carcinogenicity data

Polymeric 4,4¢-methylenediphenyl diisocyanate containing 44.8–50.2% monomeric 4,4¢-methylenediphenyl diisocyanate was tested for carcinogenicity by inhalation in rats. An increased incidence of lung tumours was observed.

5.4 Other relevant data

The major urinary metabolites of 4,4¢-methylenediphenyl diisocyanate are 4,4¢-methylenedianiline and N-acetyl-4,4¢-methylenedianiline, both of which also form haemoglobin adducts in exposed workers and rats. 4,4¢-Methylenediphenyl diisocyanate is an irritant and a sensitizer; exposure by inhalation produces asthma among workers.

4,4¢-Methylenediphenyl diisocyanate forms low-level DNA adducts in vivo and induces mutations in bacteria and chromosomal aberrations and sister chromatid exchanges in human lymphocyte cultures.

5.5 Evaluation

There is inadequate evidence for the carcinogenicity of 4,4¢-methylenediphenyl diisocyanate or polymeric 4,4¢-methylenediphenyl diisocyanate in humans.

There is limited evidence in experimental animals for the carcinogenicity of a mixture containing monomeric and polymeric 4,4¢-methylenediphenyl diisocyanate.

Overall evaluation

4,4¢-Methylenediphenyl diisocyanate (industrial preparation) is not classifiable as to its carcinogenicity to humans (Group 3).

Previous evaluations: Vol. 19 (1979); Suppl. 7 (1987)

For definition of the italicized terms, see Preamble Evaluation.


For 101-68-8 (monomer)

For 26447-40-5

Last updated: 13 April 1999

    See Also:
       Toxicological Abbreviations