Carcinogenic Risk of Toluene Diisocyanate and 4,4′-Methylenediphenyl Diisocyanate: Epidemiological and Experimental Evidence
- 1 January 2001
- journal article
- review article
- Published by Taylor & Francis Ltd in Critical Reviews in Toxicology
- Vol. 31 (6), 737-772
- https://doi.org/10.1080/20014091111974
Abstract
Diisocyanates are highly reactive compounds widely used, for example, in the production of polyure-thane foams, elastomers, paints, and adhesives. The high chemical reactivity of these compounds is also reflected in their toxicity: diisocyanates are one of the most important causes of occupational asthma but also other adverse effects, such as irritation and toxic reactions, have been described in exposed subjects. One of the open questions is whether occupational isocyanate exposure is a carcinogenic hazard. The few epidemiological studies available have been based on young cohorts and short follow-up and are not conclusive. Toluene diisocyanate (TDI) has been classified as carcinogenic in animals on the basis of gavage administration studies, but no conclusions are available on inhalation exposure. For 4,4′-methylene diphenyldiisocyanate (MDI) there is suggestive evidence for carcinoge-nicity in rats. The possible carcinogenic mechanism of TDI and MDI is not clear. Both chemicals have been positive in a number of short-term tests inducing gene mutations and chromosomal damage. The reactive form could be either the diisocyanate itself or may derive from the metabolic activation of the aromatic diamine derivatives formed by hydrolysis. TDI and MDI react with DNA in vivo and in vitro. However, the structure of the adducts has not been identified. Especially from the in vivo experiment it is not known if the adducts are a product from the reaction with the isocyanate or the corresponding amine. In conclusion, both TDI and MDI are highly reactive chemicals that bind to DNA and are probably genotoxic. The alleged animal carcinogenicity of TDI and MDI would suggest that occupational exposure to these compounds is a carcinogenic risk. The few epidemiological studies available have not, however, been able to clarify if TDI and MDI are occupational carcinogens.Keywords
This publication has 83 references indexed in Scilit:
- Hemoglobin adducts and urine metabolites of 4,4′-methylenedianiline after 4,4′-methylenediphenyl diisocyanate exposure of ratsChemico-Biological Interactions, 1995
- 32P-postlabeling analysis of DNA adducts formed in vitro and in rat skin by methylenediphenyl-4,4'-diisocyanate (MDI)Toxicology Letters, 1995
- Toluene Diisocyanate: an Assessment of Carcinogenic Risk Following Oral and Inhalation ExposureToxicology and Industrial Health, 1995
- Chemical mutagenesis testing in Drosophila. X. Results of 70 coded chemicals tested for the national toxicology‐programEnvironmental and Molecular Mutagenesis, 1994
- The fifth plot of the Carcinogenic Potency Database: results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989.Environmental Health Perspectives, 1993
- Indication of Dna Strand Breaks in Human White Blood Cells after In Vitro Exposure to Toluene Diisocyanate (TDI)Toxicology and Industrial Health, 1992
- Isolation of methylcarbamoyl-adducts of adenine and cytosine following in vitro reaction of methyl isocyanate with calf thymus DNAChemico-Biological Interactions, 1989
- Chromosome aberrations and sister-chromatid exchanges induced by technical grade toluene diisocyanate and methylenediphenyl diisocyanate in cultured human lymphocytesToxicology Letters, 1987
- Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F1miceJournal of Toxicology and Environmental Health, 1986
- Long-term toxicity and carcinogenicity studies with 2,4/2,6-toluene-diisocyanate (80/20) in rats and miceToxicology Letters, 1983