N-Methyl-N'-Nitroguanidine: Irritation, Sensitization, and Acute Oral Toxicity, Genotoxicity, and Methods for Analysis in Biological Samples

Abstract

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 analysis of chemical impurities and an assessment of the potential for the metabolism of MNG to 1-methyl-3-nitro-1-nitrosoguanidine (MNNG). Potential in situ gastric conversion of MNG to MNNG is a toxicological concern because MNNG is both mutagenic and carcinogenic. The compound was also evaluated in several bioassays to assess its potential genotoxic activity. The acute oral toxicity was determined in male and female Fischer 344 rats administered a single dose of MNG in corn oil. The maximum suspension of MNG that could be delivered, 1 mg MNG/kg body weight, produced no signs of toxic stress during the 14-day observation period. The primary eye and skin irritation potential of MNG was determined in female New Zealand white rabbits using the Draize technique. MNG produced no irritation to intact skin but did produce mild conjunctival irritation. The response of a single guinea pig to the dermal sensitization evaluation indicated that MNG is a weak sensitizer. The results of three genetic tests indicated that MNG does not interact with genetic material. Gastric contents and feces from treated animals showed no evidence of conversion of MNG to MNNG.

Comparative Toxicological Evaluation of UV‐Degraded versus Parent‐Insensitive Munition Compound 1‐Methyl‐3‐Nitroguanidine in Fathead Minnow

“…The chemical 1‐methyl‐3‐nitroguanidine (MeNQ) is currently under evaluation by the US Army Combat Capabilities Development Command as a potential component in propellant/warhead formulations to replace the traditional high explosives and melt base ingredients 2,4,6‐trinitrotoluene and hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine in formulations (Aubert and Roos ; Reinke ). Daily oral exposures of MeNQ to male and female rats at dosages up to 1250 mg/kg per day in corn oil for 14 d did not induce any signs of toxicity (Reinke ), corroborating an early study that showed that MeNQ was not acutely toxic at 1000 mg/kg in male and female rats (Kinkead et al ). Information on the toxicity of MeNQ to aquatic organisms was not found in the available literature.…”

Mode of action evaluation for reduced reproduction in Daphnia pulex exposed to the insensitive munition, 1-methyl-3-nitro-1-nitroguanidine (MeNQ)

“…Among the chemicals suitable for use as constituents in IM formulations, 1-methyl-3nitroguanidine (MeNQ) (Aubert and Roos 2014;Reinke 2016) has had relatively little characterization of potential health and ecotoxicological hazard. While the ecotoxicity of dinitroanisole (DNAN), nitroguanidine (NQ), and nitrotriazolone (NTO), the components of IMX-101, a principal TNT replacement, has been widely investigated (Lent et al 2015(Lent et al , 2016(Lent et al , 2018Lotufo et al 2018;Gust et al 2018Gust et al , 2021Johnson et al 2017;Kennedy et al 2015Kennedy et al , 2017Quinn et al 2014;Stanley et al 2015), only two studies describing MeNQ toxicity in mammalian exposures (Kinkead et al 1993;Reinke 2016) and our laboratory's three recent MeNQ ecotoxicological evaluations (Lotufo et al 2020(Lotufo et al , 2021Gust et al 2021) are the only studies presently available. In these ecotoxicology studies, the lethal effects of MeNQ in both acute and chronic aquatic exposures were only observed at high exposure concentrations (≥ 2186 mg/ L) for a broad range of target species including both aquatic invertebrates (Daphnia pulex, Chironomus dilutus, Lumbriculus variegatus, Hydra littoralis, Hyalella azteca) and vertebrates (Pimephales promelas, Rana pipiens).…”