Protein adducts as biomarkers of exposure to aromatic diisocyanates in workers manufacturing polyurethane (PUR) foam† Kirsi S€ akkinen, Jarkko Tornaeus, Antti Hesso, Ari Hirvonen, Harri Vainio, Hannu Norppa and Christina Rosenberg * Received 25th October 2010, Accepted 31st January 2011 DOI: 10.1039/c0em00595a This work was undertaken to investigate the usefulness of diisocyanate-related protein adducts in blood samples as biomarkers of occupational exposure to toluene diisocyanate (TDI; 2,4- and 2,6-isomers) and 4,4 0 -methylenediphenyl diisocyanate (MDI). Quantification of adducts as toluene diamines (TDAs) and methylenedianiline (MDA) was performed on perfluoroacylated derivatives by gas chromatography-mass spectrometry (GC-MS/MS) in negative chemical ionisation mode. TDI-derived adducts were found in 77% of plasma and in 59% of globin samples from exposed workers manufacturing flexible polyurethane foam. The plasma levels ranged from 0.003 to 0.58 nmol mL 1 and those in globin from 0.012 to 0.33 nmol g 1 . The 2,6-isomer amounted to about two-thirds of the sum concentration of TDA isomers. MDI-derived adducts were detected in 3.5% of plasma and in 7% of globin samples from exposed workers manufacturing rigid polyurethane foam. A good correlation was found between the sum of TDA isomers in urine and that in plasma. The relationship between globin adducts and urinary metabolites was ambiguous. Monitoring TDI-derived TDA in plasma thus appears to be an appropriate method for assessing occupational exposure. Contrary to TDI exposure, adducts in plasma or globin were not useful in assessing workers’ exposure to MDI. An important outcome of the study was that no amine-related adducts were detected in globin samples from TDI- or MDI-exposed workers, alleviating concerns that TDI or MDI might pose a carcinogenic hazard. Further studies are nevertheless required to judge whether diisocyanates per se could be such a hazard. Introduction Isocyanates are characterised by the NCO group which contains two double bonds and is very reactive. The main application of diisocyanates is in the manufacture of polyurethanes (PURs) for flexible and rigid foams, elastomers, paints, lacquers and glues. The production of diisocyanates amounts to more than six million tonnes worldwide and is expected to grow 10–15% annually. 1 The most abundant diisocyanates used in industry are the aromatic diisocyanates toluene diisocyanate (TDI; 2,4- and Work Environment Development, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland. E-mail: Christina. Rosenberg@ttl.fi † Electronic supplementary information (ESI) available: Tables S1 and S2: TDI-derived plasma and globin adducts and urinary TDA in workers manufacturing flexible PUR foam. See DOI: 10.1039/c0em00595a Environmental impact This work was undertaken to investigate the usefulness of diisocyanate-related protein adducts in blood samples as biomarkers of occupational exposure to toluene diisocyanate (TDI) and 4,4 0 -methylenediphenyl diisocyanate (MDI). The paper reports concen- trations of diisocyanate-derived adducts in plasma and globin in workers whose diisocyanate exposure profile had been previously characterised by air and urine analysis. Determining plasma adducts proved to be a reliable method for biomonitoring exposure to TDI, whereas inconsistent results were found for globin adduct levels. Analysis of MDI-derived plasma and globin adducts was not an appropriate method for assessing MDI exposure. As previously, urinalysis of methylenedianiline (MDA) is still recommended. Adducts derived from toluene diamine (TDA) or MDA could not be detected in globin samples from the diisocyanate exposed workers in this study, thus alleviating concerns that occupational exposure TDI or MDI might pose a carcinogenic hazard. Further studies are nevertheless required to judge whether diisocyanates per se could be such a hazard. This journal is ª The Royal Society of Chemistry 2011 J. Environ. Monit., 2011, 13, 957–965 | 957 Dynamic Article Links C < Journal of Environmental Monitoring Cite this: J. Environ. Monit., 2011, 13, 957 www.rsc.org/jem PAPER