The Toxicity of Single Doses of N-Nitrodimethylamine in Rodents

ABSTRACT

The acute oral, intraperitoneal and intravenous toxicity of single doses of N-nitrodimethylamine (N-nitro-DMA), the oxidized analog of the potent carcinogen, N-nitrosodimethylamine (N-nitroso-DMA), were studied in rats. The ip LD50 of N-nitro-DMA was 897 (861-934) mg/kg. After ip or po doses larger than 1500 mg/kg rats remained conscious, but initially had no righting reflex; at ip or po doses between 700 and 1500 mg/kg rats were ataxic and lethargic. Rats appeared normal from 4-24 hr after dosing but became increasingly lethargic thereafter and were prostrate after 48 hr. Bloody fluid issued from the mouth and anus, a few rats had hematuria and death occurred 2-4 days after dosing. Focal areas of hemorrhage were found in the stomach and intestine and variable amounts of clear fluid in the peritoneum. The liver appeared normal in all rats. The ip LD50 in the mouse was 399 mg/kg and all deaths occurred within 24 hr. Pretreatment of rats with pyrazole or SKF //52 5A increased survival time after N-nitro-DMA intoxication, while pretreatment with phenobarbital decreased it. None of these pretreatments altered overall mortality. Neither hepatic necrosis nor increased plasma transaminase activities were found in rats dosed ip with 700 mg/kg, a dose which killed 30% of treated rats. While these observations suggest that reduction of N-nitro to N-nitroso-DMA may be involved in the expression of the acute toxicity of N-nitro-DMA, toxicologically significant amounts of N-nitroso-DMA do not appear to be formed in the liver in vivo after single doses of N-nitro-DMA.