Absorption, metabolism and elimination of N,N-dimethylformamide in humans.
Excretion of N,N-dimethylformamide (DMF) and DMF metabolites N-hydroxymethyl-N-methylformamide ("MF"), N-hydroxymethyl-formamide ("F") and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) has been monitored in the urine of volunteers during and after their 8-h exposure to DMF vapour at a concentration of 10, 30 and 60 mg.m-3. The pulmonary ventilation in these experiments was typically about 10 l.min-1 and the retention in the respiratory tract was 90%. After exposure to 30mg DMF.m-3, the yield of compound determined in the urine represented 0.3% (DMF), 22.3% ("MF"), 13.2% ("F") and 13.4% (AMCC) of the dose absorbed via the respiratory tract. The excretion curves of the particular compounds attained their maximum 6-8h (DMF), 6-8h ("MF"), 8-14h ("F") and 24-34h (AMCC) after the start of the exposure. The half-times of excretion were approximately 2, 4, 7 and 23 h respectively. In contrast to slow elimination of AMCC after exposure to DMF, AMCC was eliminated rapidly after AMCC intake. This discrepancy could be explained by rate-limiting reversible protein binding of a reactive metabolic intermediate of DMF, possibly methylisocyanate.
Mráz
J
J
Institute of Hygiene and Epidemiology, Prague, Czechoslovakia.
Nohová
H
H
D000042:Absorption; D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D004126:Dimethylformamide / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005559:Formamides / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012997:Solvents / Q000378:metabolism / Q000493:pharmacokinetics*
D005559:Formamides; D012997:Solvents; C052469:N-acetyl-S-(N-methylcarbamoyl)cysteine; C055906:N-hydroxymethylformamide; C042331:N-hydroxymethyl-N-methylformamide; D004126:Dimethylformamide; D000111:Acetylcysteine