Toluene Diisocyanate: an Assessment of Carcinogenic Risk Following Oral and Inhalation Exposure
- 1 January 1995
- journal article
- research article
- Published by SAGE Publications in Toxicology and Industrial Health
- Vol. 11 (1), 13-32
- https://doi.org/10.1177/074823379501100102
Abstract
Although respiratory sensitization and pulmonary irritation have been the subject of particular studies with toluene diisocyanate (TDI), in recent years the potential carcinogenicity of TDI has been a reason for concern and speculation. This has arisen from the expectation that following exposure to TDI the chemical would hydrolyze at aqueous tissue surfaces to give rise to toluene diamine (TDA), a mutagen and rodent carcinogen. The chemistry of TDI suggests that the reaction with biological NH2 groups such as those on proteins, and polymerization to oligoureas, will compete with the hydrolysis reaction. This has been shown with results of in vitro studies where conjugation to protein occurs without detectable formation of TDA when protein solutions in saline are exposed to TDI vapor. Lower pH levels leading to high protonation of biological NH2 groups facilitate hydrolysis of TDI to TDA and subsequent formation of polyureas. These observations are consistent with comparative toxicokinetic studies in rats, which demonstrate significant levels of TDA following oral dosing with TDI - due to the acidic environment in the stomach - but not after inhalation. These results provide an explanation for the tumors observed in rodents after oral dosing of TDI in com oil, but not after inhalation. Inhalation is the relevant route of human exposure for TDI and the toxicokinetics of TDI exposure at occupational exposure limits have been studied. These data provide a means by which quantitative estimates of the risk of carcinogenicity possibly resulting from the intermediate formation of TDA during TDI exposure can be obtained. Several calculations have been made, allKeywords
This publication has 12 references indexed in Scilit:
- Route-Dependent Comparative Metabolism of [14C]Toluene 2,4-Diisocyanate and [14C]Toluene 2,4-Diamine in Fischer 344 RatsToxicology and Applied Pharmacology, 1994
- Assessment of safety/risk of chemicals: inception and evolution of the ADI and dose-response modeling proceduresToxicology Letters, 1991
- Biological monitoring of isocyanates and related aminesInternationales Archiv für Arbeitsmedizin, 1991
- Chromatographic determination of amines in biological fluids with special reference to the biological monitoring of isocyanates and amines : II. Determination of 2,4- and 2,6-toluenediamine using glass capillary gas chromatography and selected ion monitoringJournal of Chromatography A, 1989
- Chromosome aberrations and sister-chromatid exchanges induced by technical grade toluene diisocyanate and methylenediphenyl diisocyanate in cultured human lymphocytesToxicology Letters, 1987
- Determination of occupational exposure to toluene diisocyanate by biological monitoringJournal of Chromatography A, 1986
- Long-term toxicity and carcinogenicity studies with 2,4/2,6-toluene-diisocyanate (80/20) in rats and miceToxicology Letters, 1983
- Mutagenic action of isocyanates used in the production of polyurethanes.Scandinavian Journal of Work, Environment & Health, 1980
- Some Phenolic Metabolites of 2, 4-Diaminotoluene in the Rabbit, Rat and Guinea-pigXenobiotica, 1976
- Respiratory effects in toluene diisocyanate manufacture: a multidisciplinary approach.Environmental Health Perspectives, 1975