New findings in the metabolism of N,N-dimethylformamide--consequences for evaluation of occupational risk.

Using a novel gas chromatographic method, specific mercapturic acids produced in the biotransformation of several formamide analogues have been quantified. Thus, N-acetyl-S-(N-methylcarbamoyl)cysteine, derived from an important industrial solvent N,N-dimethylformamide, was found to be a minor metabolite in rodents but an important one in humans. Because manifestations of hepatotoxicity of formamide analogues were always linked with the production of mercapturic acids, the risk from exposure to DMF in humans appears to be higher than that estimated from toxicological experiments on laboratory animals.

Effect of ethanol on the urinary excretion of mandelic and phenylglyoxylic acids after human exposure to styrene.

Administration of ethanol in several doses during human exposure to styrene can inhibit the urinary mandelic and phenylglyoxylic acid excretion in a way similar to that reported when ethanol was administered as a single dose. Sensitivity to this inhibitory effect has been found to differ with individual subjects. Differences in long-term consumption of ethanol resulting in different induction of the oxidizing enzymes are suggested to account for this finding.

Differences between rodents and humans in the metabolic toxification of N,N-dimethylformamide.

The widely used industrial solvent N,N-dimethylformamide (DMF) causes liver damage in occupationally exposed persons and is suspected of involvement in the generation of certain occupational malignancies. Here the extent of the biotransformation of DMF to three urinary metabolites has been compared in humans and rodents. The metabolites, which were quantified by gas chromatography (GC) are N-(hydroxymethyl)-N-methylformamide (HMMF), which yielded N-methylformamide on GC analysis, a species which decomposed to formamide on GC analysis, and N-acetyl-S-(N-methylcarbamoyl) cysteine (AMCC), measured after derivatization with ethanol to give ethyl N-methylcarbamate.

Urinary excretion of mandelic and phenylglyoxylic acids after human exposure to styrene vapour.

The kinetics of the urinary excretion of mandelic and phenylglyoxylic acids were studied in volunteers exposed to the known concentrations of styrene vapour. The level and the time of exposure were suitably changed to simulate situations in the industrial environment. The aim was to find out the reasons for the contradictory reports in the literature and to verify parameters characterizing the course of excretion of both metabolites.

Biological monitoring of persons exposed to methanol vapours.

Five volunteers were exposed to constant and suitably graded concentrations of methanol vapours for a period of 8 h. The retention of methanol in the lungs and the course of its excretion in urine were monitored at single and at daily repeated exposures. From the concentration in inspired air, lung retention, minute lung ventilation and duration of exposure, the methanol dose retained in the organism of the experimental subjects was calculated.