Structure-toxicity relationship of aliphatic nitriles.
Acute toxicity, in vitro metabolism and structure-toxicity relationship of aliphatic mononitriles were examined in mice pretreated with carbon tetrachloride (CCl4). The LD50 in mice pretreated with CCl4 (LD50-CCl4) was increased in most nitriles compared to that in untreated animals (LD50-cont.) with different degrees among compounds. Microsomal metabolism of nitriles to CN- was completely inhibited when microsomes were prepared from livers of mice pretreated with CCl4. Log (1/LD50-CCl4) was a linear function of partition coefficient, log P, i.e., log (1/LD50-CCl4) = -0.371 log P-0.152, and the equation was statistically significant (P less than 0.01), provided aceto- and 3-hydroxypropionitrile were omitted from the analysis. These two compounds seem to be different from the others in exerting the biological effect.
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D003486:Cyanides / Q000378:metabolism; D004347:Drug Interactions; D007928:Lethal Dose 50; D008297:Male; D008433:Mathematics; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D009570:Nitriles / Q000633:toxicity*; D013329:Structure-Activity Relationship
D003486:Cyanides; D009570:Nitriles; D002251:Carbon Tetrachloride