N-METHYL-N'-NITROGUANIDINE - IRRITATION, SENSITIZATION, AND ACUTE ORAL TOXICITY, GENOTOXICITY, AND METHODS FOR ANALYSIS IN BIOLOGICAL SAMPLES

Currently, N-methyl-N-nitroguanidine (MNG) is being considered by the U.S. Air Force Armament Laboratory for use in explosive formulations. A mammalian toxicity profile has been performed which includes the ana lysis of chemical impurities and an assessment of the potential for th e metabolism of MNG to 1-methyl-3-nitro-1-nitrosoguanidine (MNNG). Pot ential in situ gastric conversion of MNG to MNNG is a toxicological co ncern because MNNG is both mutagenic and carcinogenic. The compound wa s also evaluated in several bioassays to assess its potential genotoxi c activity. The acute oral toxicity was determined in male and female Fischer 344 rats administered a single dose of MNG in corn oil. The ma ximum suspension of MNG that could be delivered, 1 mg MNG/kg body weig ht, produced no signs of toxic stress during the 14-day observation pe riod. The primary eye and skin irritation potential of MNG was determi ned in female New Zealand white rabbits using the Draize technique. MN G produced no irritation to intact skin but did produce mild conjuncti val irritation. The response of a single guinea pig to the dermal sens itization evaluation indicated that MNG is a weak sensitizer. The resu lts of three genetic tests indicated that MNG does not interact with g enetic material. Gastric contents and feces from treated animals showe d no evidence of conversion of MNG to MNNG.