Does the polymorphism of cytochrome P-450 2E1 affect the metabolism of N,N-dimethylformamide? Comparison of the half-lives of urinary N-methylformamide

The aim of this study was to clarify whether phenotypic variation exists wh en subjects with different genotypes of cytochrome P450 2E1 (CYP2E1) are ex posed to N,N-dimethylformamide (DMF). The genotypes of CYP2E1 were confirme d in 123 healthy male volunteer subjects. Of the 123 subjects, the numbers of c1 homozygotes, c2 heterozygotes, and c2 homozygotes were 77, 45, and 1, respectively. Seven of the c1 homozygotes, five of the c2 heterozygotes, a nd the one c2 homozygote (mean age: 22.7 years, range: 20-27 years) were ex posed to DMF vapor twice, once via the skin and once via the lung, for a to tal of 8 h per subject at a concentration below 10 ppm, the occupational ex posure limit recommended by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, at 27 degreesC and 44% relative humidity. Exposure levels were 6.2 +/- 1.0 ppm in dermal exposure and 7.1 +/- 1.0 ppm in inha lation exposure. Urine samples were collected until 72 h after exposure. Th e half-lives of urinary N-methylformamide (NMF) were obtained as the phenot ype. The average urinary NMF half-lives of the c1 homozygotes, the c2 heter ozygotes, and the c2 homozygote were 3.86 +/- 1.90, 4.38 +/- 1.53, and 4.2 h after dermal exposure, and 1.58 +/- 0.42, 1.84 +/- 0.61, and 3.2 h after respiratory exposure. The NMF half-lives of the c1 homozygotes were not sig nificantly different from those of the c2 heterozygotes, and there were no differences between the NMF half-lives on the subjects with and without the c2 allele. Even though the data were obtained from only one c2 homozygote, it is noteworthy that the NMF half-life of this subject was slightly less than that of the c1 homozygotes after respiratory exposure.