TOXICOKINETICS OF 2,4-TOLUENEDIAMINE AND 2,6-TOLUENEDIAMINE IN HYDROLYZED URINE AND PLASMA AFTER OCCUPATIONAL EXPOSURE TO 2,4-TOLUENEDIISOCYANATE AND 2,6-TOLUENEDIISOCYANATE

Objectives-To assess the toxicokinetics of 2,4- and 2,6- toluenediisoc yanate (TDI) in chronically exposed subjects. Methods-Blood and urine, from 11 workers at two flexible foam polyurethane production plants, were sampled. By gas chromatography-mass spectrometry (GC-MS) 2,4- and 2,6-toluene diamine (TDA) were measured as pentafluoropropionic anhyd ride (PFPA) derivatives after acidic hydrolysis of plasma (P-TDA, ng/m l) and urine (U-TDA, mu g/h). Results-In one of the plants the P-2,4-T DA concentrations were 0 . 41 ng/ml before a four to five week holiday and 0 . 2-0 . 5 ng/ml afterwards. The corresponding values for P-2,6- TDA were 2-6 and 0 . 5-2 ng/ml respectively. In the other plant the P- 2,4-TDA concentrations were 2-23 ng/ml before the holiday and 0 . 5-6 ng/ml afterwards and the P-2,6-TDA concentrations were 7-24 ng/ml befo re and 3-6 ng/ml afterwards. The P-2,4-TDA concentrations were 2-24 ng /ml before a 12 day holiday, and 1-14 ng/ml afterwards. The correspond ing values for P-2,6-TDA were 12-29 and 8-17 ng/ml, respectively. The urinary elimination rates (U-TDA, mu g/h) for 2,4-TDA before the holid ay were 0 . 04-0 . 54 and 0 . 02-0 . 18 mu g/h afterwards. The corresp onding values for 2,6-TDA were 0 . 18-0 . 76 mu g/h before and 0 . 09- 0 . 27 mu g/h after the holiday. The halflife in urine ranged between 5 . 8 and 11 days for 2,4- and 2,6-TDA. The differences in exposure we re reflected by the P-TDA concentrations. The mean half life in plasma was 21 (range 14-34) days for 2,4-TDA and 21 (16-26) days for 2,6-TDA . The TDI air concentrations varied between 0 . 4 and 4 mu g/m(3) in o ne plant and in the other between 10 and 120 mu g/m(3). Conclusions-Th e half life in plasma of chronically exposed workers for 2,4-and 2,6-T DA was twice as long as for volunteers with short term exposure. An in dication of a two phase elimination pattern in urine was found. The fi rst phase was related to the more recent exposure and the second, much slower one was probably related to release of TDA in urine from TDI a dducts in the body.