N-methylcarbamoyl adducts at the N-terminal valine of globin in workers exposed to N,N-dimethylformamide.
N,N-dimethylformamide (DMF) is a commonly used industrial solvent. The formation of some metabolites of DMF in humans occurs via N-methyl-carbamoylated species (e.g. N-methylcarbamoylated glutathione). The aim of our study was to investigate whether DMF leads to N-methylcarbamoylated adducts at the N-terminal valine of haemoglobin (Hb). Therefore, Hb adduct levels of ten DMF exposed workers and ten controls were analysed by a specific and sensitive detection method using capillary gas chromatography and a mass selective detector (GC/MS). Using this method we were able to show for the first time that Hb adducts are formed during the metabolism of DMF in humans. The general population, however, shows still unidentified background levels of this adduct which are on average lower by a factor of 50. The pathway for the formation of the investigated DMF-Hb adduct in workers exposed to DMF is still unknown. As identical adducts were also found after exposure to methylisocyanate (MIC), our work indicates the formation of MIC during the metabolism of DMF. The formation of Hb adducts with DMF and its relevance for occupational health is a subject of further research.
Angerer
J
J
Institute and Outpatient Clinic of Occupational- Social and Environmental Medicine, University Erlangen-Nürnberg, Erlangen, Germany.
Göen
T
T
Krämer
A
A
Käfferlein
H U
HU
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D016022:Case-Control Studies; D002617:Chemical Industry; D002849:Chromatography, Gas; D004126:Dimethylformamide / Q000737:chemistry*; D005914:Globins / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D016273:Occupational Exposure; D012680:Sensitivity and Specificity; D012997:Solvents; D014633:Valine / Q000737:chemistry*
D006571:Heterocyclic Compounds; D012997:Solvents; C052469:N-acetyl-S-(N-methylcarbamoyl)cysteine; C011374:s-trioxane; D004126:Dimethylformamide; D005914:Globins; D014633:Valine; D000111:Acetylcysteine