A case-control study of cancer among du pont employees with potential for exposure to dimethylformamide.

This case-control study was undertaken to determine whether the risk of developing cancers of the buccal cavity and pharynx (N = 39), liver (N = 6), prostate (N = 43), testis (N = 11), or malignant melanoma of the skin (N = 39) is related to exposure to dimethylformamide (DMF). Case and control subjects were obtained from four Du Pont plants. DMF is produced at one plant and used at the other three. Cancer cases identified from the company Cancer Registry comprise those reported among active male employees at the study plants during 1956 to 1985. For each case, two control subjects were selected, matched on sex, payroll class (wage or salary), birth year, and plant. To determine whether an employee could have been exposed to DMF during his career at the plant, all jobs with potential for exposure to DMF were identified. Each job was assigned an exposure ranking based on DMF industrial hygiene air monitoring, DMF metabolite (measured as N-methylformamide in urine) monitoring, and knowledge of the evolution of manufacturing processes and workplace exposure controls. Each employee's DMF exposure pattern was then characterized as (a) ever v never having been exposed to DMF and (b) highest DMF exposure experienced. Summary analyses for all plants combined showed no statistically significant association between ever having been exposed to DMF and subsequent development of cancers of the buccal cavity and pharynx, liver, malignant melanoma, prostate, and testis. Examined by plant site, prostate cancer at one plant was significantly elevated, based on three case subjects exposed out of four.(ABSTRACT TRUNCATED AT 250 WORDS)

Gas chromatographic method for the determination of N-acetyl-S-(N-methylcarbamoyl)cysteine, a metabolite of N,N-dimethylformamide and N-methylformamide, in human urine.

A simple method has been developed for the determination of N-acetyl-S-(N-methylcarbamoyl)cysteine in human urine. Treatment of a urine sample (1 ml) with ethanol (2 ml) and potassium carbonate (1.5 g) produces ethyl N-methylcarbamate, which is extracted into ethanol and measured by packed column gas chromatography with nitrogen-sensitive detection. The limit of quantitation in human urine is 1 microgram/ml and the between-sample coefficient of variation is 5-11%. Simultaneously, N,N-dimethylformamide, N-methylformamide and formamide can also be determined.

Identification by proton NMR of N-(hydroxymethyl)-N-methylformamide as the major urinary metabolite of N,N-dimethylformamide in mice.

Urine samples from mice which had received N,N-dimethylformamide were investigated by high field 1H-NMR spectroscopy. The most prominent signals in the N-CH3 region had chemical shifts identical with those of N,N-dimethylformamide (delta 2.85, 3.01) and N-(hydroxymethyl)-N-methylformamide (delta 2.91, 3.05). Resonances downfield of delta 7.5 (from formyl protons) also coincided with those of the reference formamides. When [14C]methyl-labelled N,N-dimethylformamide was injected and urine samples investigated by radio thin layer chromatography, the major area of radioactivity corresponded to the Rf of N-(hydroxymethyl)-N-methylformamide. Dimethylamine and methylamine were found to be minor metabolites of N,N-dimethylformamide.

In vivo metabolism of dimethylformamide and relationship to toxicity in the male rat.

After in vivo administration of dimethylformamide (DMF) to male rats, about 50% of the dose is excreted in urine as N-hydroxymethyl-N-methylformamide (DMF-OH) and about 4% as N-methylformamide (NMF). NMF is not a product of DMF-OH biotransformation but is directly formed from DMF. Comparison of the acute toxicity of DMF, DMF-OH and NMF shows that NMF is more toxic than DMF-OH, which is itself more toxic than DMF. This study explains the different toxicity profile of DMF and NMF which until recently was believed to represent the main metabolite of DMF.