Biological monitoring of workers exposed to N, N-dimethylfomamide. I. Methods of analysis.

Some methods for analysing N,N-dimethylformamide and its metabolites [hydroxymethyl-N-methylformamide, hydroxymethylformamide and N-acetyl-S-(N-methylcarbamoyl)cysteine] in the urine of exposed workers are described. Unchanged dimethylformamide was measured after pretreatment of urine (2 ml) with silica gel cartridges and elution with methanol. The gas chromatographic analysis using a nitrogen phosphor detector made it possible to detect N,N-dimethylformamide in urine even when workers were exposed to low concentrations of the solvent (about 1 mg/m3). N-Hydroxymethyl-N-methylformamide and N-hydroxymethylformamide were analysed as N-methylformamide and formamide respectively after direct injection of urine into the gas chromatograph. The injection port temperature played an important role in the gas chromatographic determination of these products. Reliable results were obtained when direct or split injections were performed at 250 degrees C. The splitless injection gave the same reliable results at 150 degrees C. In urine samples from occupationally non-exposed persons, N-methylformamide could not be detected. In contrast, formamide (or its precursor, hydroxymethylformamide) was present in every urine sample. Our results in respect of 19 urine samples analysed with the injection port of the gas chromatograph at 250 degrees C gave a mean of 8.6 mg/l of formamide. N-Acetyl-S-(N-methylcarbamoyl)cysteine was determined using a modified method for analysing organic acid in urine samples. The metabolite was extracted with ethyl ether in an acid environment, treated with a silylating reagent and measured by gas chromatography/mass spectrometry.