Abstract
1-Nitroguanine (NG), also known as picrate, guanidine nitro, and N’-nitroguanidine, is used by the military as a propellant. Oral rodent LD50 data are generally >5000 mg/kg. NG is neither an eye nor a skin irritant, and it is not a skin sensitizer. NG is not genotoxic. No inhalation data are available; however, there are data from both 14- and 90-day oral (feed) toxicity studies in male and female Sprague Dawley rats at dosages up to 1000 mg/kg/day. There were no deaths on these studies and the only effect considered possibly related to treatment was decreased weight in females at the high-dose level in the 90-day study. Mice at similar dosages were even less affected. The NOAEL for both rats and mice (oral) was 316 mg/kg/day. There was no evidence of developmental toxicity in Sprague-Dawley rats administered NG by oral gavage, and the free-standing NOAEL was 1000 mg/kg with material toxicity. In Wistar rats, there was high mortality (50%) at 500 mg/kg NG administered by oral gavage; there was decreased body weight, feed consumption, and notable clinical signs in the dams at this dose level. Fetal toxicity could not be determined in this group. NG demonstrated maternal toxicity at 1000 mg/kg in rabbits; however, there were no evident differences in the rate of fetal malformations across the test groups. A NOAEL of 316 mg/kg was identified for maternal and fetal toxicity in this study. In a two-generation study, it was concluded the NG did not cause reproductive or fertility effects at dosages up to 1000 mg/kg/day. Absorption was rapid, non-dose dependent, and resulted in an apparent volume of distribution (VD) of between 0.66 (IV) and 0.85-0.87 (oral) l/kg. Elimination was primarily through the urine as unchanged compound. Human experience with NG dates back 100 years; however, no actual studies on humans have been reported. Non-military uses include automotive airbags, anti-corrosive coatings, and pharmaceutical manufacturing. The point of departure for Workplace Environmental Exposure Level (WEEL) derivations was 316 mg/kg, and a WEEL of 7 mg/m3 as an 8-h time-weighted average (TWA) was recommended.
Subject
Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health,Toxicology