Interaction of aromatic isocyanates with n-acetyl-lcysteine under physiological conditions

Abstract

Isocyanates are of toxicological relevance since they are considered to cause occupational asthma. The majority of polyurethanes is based on aromatic diisocyanates (e.g., TDI and MDI), they are used for foams, elastomers, adhesives and coatings. Therefore we studied reactions of p-tolylisocyanate (pTI), 2,4-toluene diisocyanate (TDI) and 4,4- methylenediphenyl diisocyanate (MDI) with N-acetyl-L-cysteine (AcCys) with different molar ratios in aqueous buffer solutions of pH 5.0 - 7.4. Type and amounts of products formed in these reactions were identified and quantified. Conjugates of AcCys and the aromatic isocyanates have been synthesized and characterized as reference materials. Conjugates and ureas were found to be the main products. The ratio of these two compounds varied with the ratio of AcCys to isocyanate. Approximately 90 % of pTI conjugate were found for the 10 : 1 ratio, approximately 40 % conjugate for the 10 : 5 and around 15 % for the 10 : 15 ratio. For TDI yields of conjugate were comparable. Ureas, apart from minor amounts of TDA-urea could not be determined quantitatively due to formation of oligomeric ureas with different end groups. Minor amounts of MDI-conjugates were found apart from high amounts of insoluble material, which proved to be unreacted MDI encapsulated by oligomeric ureas. The reaction of the -SH group with the isocyanate moiety is independent of the pH of the solution in the range studied. No diamine, i.e. 2,4-TDA or 4,4-MDA, could be detected in reactions of the diisocyanates 2,4-TDI or 4,4-MDI. Small amounts of p-toluidine (pTA) were found in the reaction of the mono isocyanate pTI when it was in excess with respect to AcCys. Reactions of the isocyanates with an aqueous buffer solution of pH 6.5 in the absence of AcCys gave ureas as main products, while significant amounts of unreacted diisocyanates remained encapsulated in the mixture. No 2,4-TDA or 4,4-MDA was detected under these conditions. Again small amounts of pTA were formed from the reaction of pTI with water.