Biomarkers of toluene diisocyanate and thermal degradation products of polyurethane, with special reference to the sample preparation

Abstract

The amines corresponding to 2,4- and 2,6-toluene diisocyanate (TDI) and 4,4′-methylenediphenyl diisocyanate viz. 2,4- and 2,6-toluenediamine (TDA) and 4,4′-methylenedianiline (MDA), respectively, in urine and plasma were determined under different hydrolysis conditions. The release and stability of 2,4-TDA, 2,6-TDA and 4,4′-MDA with time were studied in (A): plasma and urine from workers exposed to TDI and thermal degradation products of MDI-based polyurethane (PUR); (B) for MDI and TDI urea and urethane derivatives and (C) for 2,4-TDA, 2,6-TDA, 4,4′-MDA and trideuterated 2,4- and 2,6-TDA and dideuterated 4,4′-MDA at 100 °C, using HCl, H 2SO 4 and NaOH. In the biological samples an increased release of 2,4-TDA, 2,6-TDA and 4,4′-MDA with hydrolysis time was found using acidic conditions. Alkaline hydrolysis released twice more. The hydrolysis recoveries of amines, from urethane derivatives, were 20–50% with HCl and 10–20% with H 2SO 4 (48 h); using alkaline conditions it was 30–50% (4h). For urea derivatives, the hydrolysis recoveries of amines were 25–35% for both HC1 and H 2SO 4 and about 20–40% (48 h) for alkaline conditions. Losses of the free amines spiked in water and urine were observed using HCl or NaOH but much less using H 2SO 4. Increasing the hydrolysis time from 16 to 32 h did not result in an increase of more than 10% of the amount of amines relased. Decreasing the hydrolysis time to 8 h, decreased the amount of amines released by about 50%. Molecular sieve fractionation of plasma from workers showed that the dominating part of the biomarkers was bonded to macromolecules <10 kDa and in urine the biomarkers were bonded to molecules <5 kDa.