Metabolic changes in human plasma samples among workers exposed to diisocyanate products

Introduction: In the European Union (EU), the total used amount of diisocyanates is 2.5 million tons per year. Diisocyanates are highly reactive chemicals, containing two isocyanate functional groups. Additionally, diisocyanates are the main cause of occupational asthma in the EU and they are skin sensitizers and irritants. The aim of this study was to assess metabolic changes in human plasma samples after occupational exposure to diisocyanates. Another goal was to identify markers of biological alterations, which are relevant for the diisocyanate adverse outcome pathways. Methods: This study has used samples and data provided by the previous carried out project of HBM4EU. The study population was recruited from Finland and Belgium, including 81 diisocyanate (4,4'-methylenediphenyl diisocyanate or hexamethylene diisocyanate) exposed workers and 40 non-exposed controls. Non-targeted metabolomics was used to assess metabolic changes in plasma samples. Samples were analyzed with two distinct chromatographic retention mechanisms in both positive and negative ionization mode, measured with a high-resolution mass spectrometer. Results: Differences in metabolite profiles between exposed workers and controls were observed. Additionally, variations were observed in metabolite profiles between individuals from Finland and Belgium. Especially higher 5-aminovaleric acid betaine, tetradecenoylcarnitine, lysophosphocholine 18:1 and lower N1-Methyl-4-pyridone-3-carboxamide levels were observed in exposed workers compared to controls. Conclusions: This study is the first to assess metabolite changes in human plasma samples after occupational exposure to diisocyanates. Exposure to diisocyanates was observed to effect on fatty acid metabolism but these results need to be validated in future studies. The results of this study may be utilized in search for effect biomarkers.