Effect of alcohol and aldehyde dehydrogenase inhibitors on the toxicity of 3-nitropropanol in rats.
The nitrocompounds 3-nitropropanol (NPOH) and 3-nitropropionic acid (NPA) were shown to be equally toxic when injected intraperitoneally into male Wistar rats. The LD50 for NPOH was 0.58 mmol/kg and for NPA it was 0.56 mmol/kg. NPOH was rapidly metabolized to NPA but this conversion was suppressed by prior administration of ethanol or 4-methylpyrazole to inhibit alcohol dehydrogenase. Administration of ethanol or 4-methylpyrazole before NPOH protected rats from intoxication. However, if the alcohol dehydrogenase inhibitors were given after the nitroalcohol, toxicity still occurred. Administration of the aldehyde dehydrogenase inhibitor diethyldithiocarbamic acid had little effect on the conversion of NPOH to NPA and did not alter the toxicity of NPOH. It was concluded that NPOH and NPA are equally toxic to rats but that NPOH is toxic due to its being rapidly converted to NPA.
D000433:1-Propanol / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000818:Animals; D004050:Ditiocarb / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D000077604:Fomepizole; D007928:Lethal Dose 50; D008297:Male; D009574:Nitro Compounds; D020005:Propanols; D011422:Propionates / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009574:Nitro Compounds; D020005:Propanols; D011422:Propionates; D011720:Pyrazoles; C024522:3-nitro-1-propanol; D000431:Ethanol; D000077604:Fomepizole; D000433:1-Propanol; D004050:Ditiocarb; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; C015392:3-nitropropionic acid