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Comparison of urea-type reaction products of methylene diphenyl diisocyanate (MDI) and the bis-thiocarbamate methylene diphenyl diisocyanate cysteine methyl ester (MDI-CME).
Stetson SJ; Depree GJ; Siegel PD
Toxicologist 2003 Mar; 72(S-1):52
Diisocyanates (dNCOs) are a class of chemicals used worldwide in polyurethane products such as foams, spray paints and wood products. Diisocyanates have been associated with respiratory irritation, asthma, hypersensitivity pneumonitis, bronchitis, irritant and allergic dermatitis, and conjunctival irritation. They are the most commonly reported cause of chemically induced occupational asthma, but the antigenic component is unknown. Reaction of dNCO with free thiol gives rise to bis-thiocarbamate formation. It has been established that the bis-thiocarbamates can form rapidly, and although reversible, are more stable in biological systems than the parent dNCO. The urea-type reaction products obtained from the reactions of both methylamine and HSA with MDI and MDI-CME, were compared. Reactions were carried out under aqueous conditions and analyzed using HPLC, measurement of primary amine content, and 1 and 2-dimensional (D) gel electrophoresis. It was found that at least some of the reaction products of MDI and its bis-thiocarbamate were different. MDI was able to cross link HSA causing loss of primary amine and altered migration in 1D gels. Two methylamine reaction products were evident with the less polar product predominant. The MDI-CME caused no apparent loss of primary amine or 1D gel shift. HSA conjugation was noted by both 2D gel shifts and HPLC-UV analysis. The more polar methylamine MDI-CME product was predominant. This data, along with our previously reported MDI-CME (consecutive) hydrolysis kinetics, suggest potentially different antigenic products may be formed from reaction of MDI vs MDI-thiocarbamates to endogenous proteins.
Respiratory-irritants; Respiratory-system-disorders; Pulmonary-system-disorders; Dermatosis; Allergies; Hypersensitivity
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah