Biological monitoring of N,N-dimethylformamide. Reference value for N-methylcarbamoyl adduct at the N-terminal valine of globin as a biomarker of chronic occupational exposure

Abstract

Objectives. The recently identified metabolic product of the industrial solvent N,N-dimethylformamide (DMF), the N-methylcarbamoyl adduct at the N-terminal valine of globin, can be determined after chemical conversion to 3-methyl-5-isopropylhydantoin (MVH). Due to prolonged persistence of the adduct in human erythrocytes (lifetime: 4 months), MVH is a suitable biomarker of integrated exposure to DMF over a period of several months. Here we propose a reference value for MVH, used for biological monitoring of chronic occupational exposure to DMF.

Methods. The reference value for MVH was set equal to its steady-state level in a simulated repeated inhalation exposure to DMF (8 h/day, 5 days/week, ≥20 weeks) at a concentration corresponding to the occupational exposure limits MAK and TLV. The initial data on the toxicokinetic behavior of MVH were obtained after single percutaneous and inhalation exposures to DMF in volunteers. MVH was determined by gas chromatography-mass spectrometry according to Mráz et al.

Results. The steady-state level of MVH, attained after repeated inhalation exposure to DMF, 30 mg/m³, 8 h/day, 5 days/week, ≥20 weeks, was assessed to be approximately 135 nmol MVH/g globin.

Conclusions. We recommend the value of 135 nmol MVH/g globin to be used as a new reference value for biomonitoring of integrated exposure to DMF over a long period. The relationship between the MVH level in globin and the intensity of the exposure to DMF should be further tested in the field studies.