Printed in Great Britain 1 Some Aspects of the Metabolism of Urethane and N - Hydroxyurethane in Rodents BY R . NERY

1. Urethane and N-hydroxyurethane are interconvertible in Cand C57 mice. 2. In newborn C57/DBA hybrid mice, prior treatment with 3-methylcholanthrene or urethane stimulated the N-hydroxylation of urethane; SKF 525A inhibited the N-hydroxylation at 24hr. but stimulated it at 48hr. after administration. 3. Liver homogenates of CBA and C3H mice, and of Chester Beatty and hooded rats, but not whole-body homogenates of 1-day-old C57/DBA mice or lung homogenate of 3-week-old Chester Beatty rats, metabolized urethane into N-hydr-oxyurethane in small but definite amounts. 4. Nitrite was detected in the bodies of newborn C57/DBA hybrid mice treated with lethal doses ofurethane or N-hydroxyurethane; nitrite formation from N-hydroxyurethane was stimulated by pretreatment of the animals with 3-methylcholanthrene. 5. The rate of catabolism of N-hydroxyurethane by C57/DBA mice was faster in 8-day-old than in 1-day-old animals of the same sex, and faster in females than in males of the same age. 6. Liver slices of several species of rats and mice catabolized N-hydroxyurethane at rates that varied with the age and sex of animals of the same species; liver homogenates or microsomes were less effective than slices from the same liver. 7. The enzyme activity was destroyed by boiling or freezing the liver; it was inhibited by increasing substrate concentration and by urethane, n-butyl carbamate, cyanide, p-benzoquinone or 2,4-dinitrophenol, but not by p-chloromercuribenzoate or menadione. 8. The catabolism of N-hydroxyurethane by liver slices from adult H-strain rats was not oxygen-dependent. 9. Lung homogenates of 4-week-old female Chester Beatty rats catabolized N-hydroxyurethane at 40% of the rate of liver slices from the same source. 10. O-Acetyland O-ethoxycarbonyl-N-hydroxyurethane were rapidly deacylated by liver homogenates from adult hooded rats and adult C57 mice, and by human erythrocytes. 11. N-Hydroxyurethane reacted rapidly with pyridoxal phosphate at pH7-4 and 37°. 12. The rate of decomposition of Nhydroxyurethane in 01 N-sodium hydroxide was increased by Ni2+, Cu2+, Mn2+ and [Fe(CN)6]3and decreased by Cr2 , Zn2+, Co2+, Mg2+ and Fe2 . 13. Attempts to synthesize sulphonates of N-hydroxyurethane gave ethyl hydrogen sulphate, probably via rearrangement of the unstable O-sulphonate.