Biological monitoring of occupational exposure to N,N-dimethylacetamide with identification of a new metabolite

Aims: To study the concentration of N,N-dimethylacetamide (DMA) and its metabolite, N-methylacetamide (NMA), in urine of workers occupationally exposed to DMA in a factory producing synthetic acrylic fibres. Methods: During the first phase, 223 workers exposed to low environmental concentrations of DMA provided urine samples at the end of a work shift. High concentrations of the unmodified solvent and its metabolite were found in a group of workers whose job was to start up machinery. The second and third phases focused on conditions favouring high uptake of DMA. Results: The highest concentrations of unmodified solvent and NMA were found in the urine of workers recently engaged in starting up machinery. NMA in urine was 1.5-173.6 mg/g creatinine (median 20.5). In spite of the low environmental concentration, about 20% of the urine concentration of NMA was higher than 30 mg/g creatinine. Dermal absorption of DMA was high. A shower and a change of clothing at the end of the work shift, and washing away any solvent left on the skin, ensured that dermal absorption of DMA did not continue. This significantly reduced the NMA urinary concentration at values lower than 30 mg/g creatinine. In some urine samples, S-acetamidomethyl-mercapturic acid was identified by NMR analysis; this is probably a metabolite of N,N-dimethylacetamide-it has never before been identified in humans or animals. Conclusions: Even at low environmental concentrations of DMA, dermal absorption can be considerable. Unmodified DMA and NMA concentrations in urine are good biomarkers for monitoring occupational exposure to the solvent.