title: Test chamber exposure of humans to 1,6-hexamethylene diisocyanate and isophorone diisocyanate.
abstract: An isocyanate generation apparatus was developed and stable isocyanate atmospheres were obtained. At a concentration of 5 micrograms 1,6-hexamethylene diisocyanate (HDI) per m3 the precision was found to be 7% (n = 5). Three volunteers were each exposed to three different concentrations of HDI (11.9, 20.5, and 22.1 micrograms/m3) and three concentrations of isophorone diisocyanate (IPDI) (12.1, 17.7, and 50.7 micrograms/m3), in an exposure chamber. The duration of the exposure was 2 h. Urine and blood samples were collected, and hydrolysed under alkaline conditions to the HDI and IPDI corresponding amines, 1,6-hexamethylene diamine (HDA) and isophorone diamine (IPDA), determined as their pentafluoropropionic anhydride amides (HDA-PFPA and IPDA-PFPA). The HDA- and IPDA-PFPA derivatives were analysed using liquid chromatography mass spectrometry with thermospray monitoring negative ions. When working up samples from the exposed persons without hydrolysis, no HDA or IPDA was seen. The average urinary excretion of the corresponding amine was 39% for HDI and 27% for IPDI. An association between the estimated inhaled dose and the total excreted amount was seen. The average urinary elimination half-time for HDA was 2.5 h and for IPDA, 2.8 h. The hydrolysis condition giving the highest yield of HDA and IPDA in urine was found to be hydrolysis with 3 M sodium hydroxide during 4 h. No HDA or IPDA could be found in hydrolysed plasma (< ca 0.1 micrograms/l).
authors.affiliation: Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Tinnerberg
authors.forename: G
authors.initials: G
authors.lastname: Skarping
authors.forename: M
authors.initials: M
authors.lastname: Dalene
authors.forename: L
authors.initials: L
authors.lastname: Hagmar
mesh_terms: D000328:Adult; D015415:Biomarkers; D002853:Chromatography, Liquid; D003485:Cyanates / Q000032:analysis / Q000633:toxicity*; D003514:Cyclohexylamines / Q000097:blood / Q000652:urine; D003959:Diamines / Q000097:blood / Q000652:urine; D004784:Environmental Monitoring; D006801:Humans; D006868:Hydrolysis; D017953:Isocyanates / Q000032:analysis / Q000633:toxicity*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D016273:Occupational Exposure; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003485:Cyanates; D003514:Cyclohexylamines; D003959:Diamines; D017953:Isocyanates; C015262:1,6-hexamethylene diisocyanate; C015301:isophorone diisocyanate; C052964:isophorone diamine; C007297:1,6-diaminohexane