title: Toxicokinetics of 2,4- and 2,6-toluenediamine in hydrolysed urine and plasma after occupational exposure to 2,4- and 2,6- toluene diisocyanate.
abstract: OBJECTIVE
  To assess the toxicokinetics of 2,4- and 2,6- toluenediisocyanate (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 anhydride (PFPA) derivatives after acidic hydrolysis of plasma (P-TDA, ng/ml) and urine (U-TDA, microgram/h).
  
  
  RESULTS
  In one of the plants the P-2,4-TDA concentrations were 0.4-1 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 before 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 corresponding values for P-2,6-TDA were 12-29 and 8-17 ng/ml, respectively. The urinary elimination rates (U-TDA, microgram/h) for 2,4-TDA before the holiday were 0.04-0.54 and 0.02-0.18 microgram/h afterwards. The corresponding values for 2,6-TDA were 0.18-0.76 microgram/h before and 0.09-0.27 microgram/h after the holiday. The half life in urine ranged between 5.8 and 11 days for 2,4- and 2,6-TDA. The differences in exposure were 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 micrograms/m3 in one plant and in the other between 10 and 120 micrograms/m3.
  
  
  CONCLUSIONS
  The half life in plasma of chronically exposed workers for 2,4-and 2,6-TDA was twice as long as for volunteers with short term exposure. An indication of a two phase elimination pattern in urine was found. The first 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 adducts in the body.
authors.affiliation: Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Lind
authors.forename: M
authors.initials: M
authors.lastname: Dalene
authors.forename: G
authors.initials: G
authors.lastname: Skarping
authors.forename: L
authors.initials: L
authors.lastname: Hagmar
mesh_terms: D000397:Air Pollution / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D007536:Isomerism; D016273:Occupational Exposure; D010655:Phenylenediamines / Q000097:blood / Q000378:metabolism* / Q000652:urine; D014051:Toluene 2,4-Diisocyanate / Q000032:analysis / Q000493:pharmacokinetics*
chemical_list: D010655:Phenylenediamines; D014051:Toluene 2,4-Diisocyanate; C026942:2,6-diisocyanatotoluene; C025235:2,6-diaminotoluene; C010914:2,4-diaminotoluene