WEAK CARCINOGENICITY OF 2-HYDROXYETHYL CARBAMATE IN STRAIN-A MICE - INDICATION THAT THIS IS NOT A PROXIMAL METABOLITE OF ETHYL CARBAMATE

Ethyl carbamate (EC, urethan) is carcinogenic probably because it is c onverted in vivo to vinyl carbamate and then to vinyl carbamate epoxid e, which reacts with DNA bases. We hypothesized that vinyl carbamate a rises from EC by oxidation to 2-hydroxy-EC (HEC) and dehydration of th e HEC, rather than by direct dehydrogenation of EC. In that case, HEC should be more carcinogenic than EC. In a previous test, HEC showed on ly borderline initiating activity for mouse skin, but its synthesis wa s poorly described. In the present study, HEC was synthesized by react ing ethylene carbonate with ammonia and was characterized. A single do se of HEC or EC in saline was injected i.p. into adult male strain A m ice, which were maintained for 16 weeks. HEC doses of 1.12, 4.6 and 11 .2 mmol/kg induced 0.16, 0.32 and 0.32 lung adenomas/mouse, respective ly. The 28% tumor incidence for the two highest doses was significantl y (P < 0.05) greater than that in controls injected with saline alone. The number of tumors/mouse with 4.6 mmol HEC/kg was one-fortieth of t hat for an equimolar dose of EC. The weak activity of HEC supports the view that HEC is not a proximal carcinogenic metabolite of EC, i.e. t hat vinyl carbamate is produced directly from EC.