Metabolism studies of N,N-dimethylformamide

Summary In acute and subacute inhalation studies rats and dogs were exposed to N,N-dimethylformamide. In addition dogs were subjected to subchronic inhalation tests.The rats were subjected to N,N-dimethylformamide concentrations of 21, 146 or 2005 ppm during the 3-hr trial. During the 6-hr exposure they were subjected to 29 or 170 ppm.In the case of repeated exposures on rats the average concentration was 350 ppm.In the 6-hr test dogs were exposed to 20, 32, 143 or 172 ppm. In the 5-day test (6 hrs/day) they were exposed to 23 or 59 ppm, and in the 4-week test (6 hrs/day) the concentration was 20 ppm (MAC).The metabolisation of N,N-dimethylformamide was studied in rats and dogs. Methods for the analytical determination of the unchanged active substance and its metabolites (N-methylformamide and formamide) in blood and urine were developed.In addition to the already known metabolite N-methylformamide, a further metabolite, formamide, was found in the urine of rats and dogs. The elimination rate of N-methylformamide and formamide differed in dogs and rats. The elimination rate in dogs was much slower. In the group of dogs subjected to repeated inhalation of 59 ppm an accumulation of N-methylformamide was determined in the blood and urine. In the case of rats exposed to substantially higher subacute N,N-dimethylformamide concentration (350 ppm) this phenomenon was not observed.In the MAC-range (20 ppm) the dogs of the subacute and subchronic group showed no signs of accumulation.The results of the liver and kidney function studies in dogs exposed to 20 ppm N,N-dimethylformamide for 4 weeks were normal.