Biological monitoring of isocyanates and related amines

Summary Two men were exposed to toluene diisocyanate (TDI) atmospheres at three different air concentrations (ca. 25, 50 and 70g/m³) . The TDI atmospheres were generated by a gas-phase permeation method, and the exposures were performed in an 8-m³ stainless-steel test chamber. The effective exposure period was 4h. The isomeric composition of the air in the test chamber was 30% 2,4-TDI and 70% 2,6-TDI. The concentration of TDI in air of the test chamber was determined by an HPLC method using the 9-(N-methyl-amino-methyl)-anthracene reagent and by a continuous-monitoring filter-tape instrument. Following the hydrolysis of plasma and urine, the related amines, 2,4-toluenediamine (2,4-TDA) and 2,6-toluenediamine (2,6-TDA), were determined as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas chromatography using selected ion monitoring (SIM) in the electron-impact mode. In plasma, 2,4- and 2,6-TDA showed a rapid-phase elimination half-time of ca. 2–5 h, and that for the slow phase was > 6 days. A connection was observed between concentrations of 2,4- and 2,6-TDI in air and the levels of 2,4- and 2,6-TDA in plasma. The cumulated amount of 2,4-TDA excreted in the urine over 24 h was ca. 15%–19% of the estimated inhaled dose of 2,4-TDI, and that of 2,6-TDA was ca. 17%–23% of the inhaled dose of 2,6-TDI. A connection was found between the cumulated (24-h) urinary excretion of 2,4- and 2,6-TDA and the air concentration of 2,4- and 2,6-TDI in the test chamber. A connection was also observed between the rate of urinary excretion of 2,4- and 2,6-TDA over the last 2h of exposure and the air concentration of 2,4- and 2,6-TDI in the test chamber. Biological monitoring of exposure to monomeric 2,4- and 2,6-TDI by the analysis of 2,4- and 2,6-TDA in biological media is feasible. A method based on 24-h urine sampling and determination levels of 2,4- and 2,6-TDA in hydrolysed urine is recommended. However, exposure to TDI is often associated with aerosols containing polymeric TDI, and we do not know whether analysis of TDA in urine can also be used as a marker of exposure to TDI prepolymers.