Acrylate and methacrylate esters: relationship of hemolytic activity and in vivo toxicity.
Quantitative hemolysis assays of acrylate and methacrylate esters provided estimates of the intrinsic hemolytic activity (Hi, the slope of the concentration-response curve) and the concentrations effecting 5% (H5) and 50% (H50) hemolysis. The dependence of hemolytic activity and LD50 (mice) on physical properties (lipophilicity, molar refraction, and molecular volume) of the esters was determined by multiple regression analysis. The observed correlations were: Hi, R2 = 0.94; H5, R2 = 0.95; H50, R2 = 0.94; and LD50, R2 (all compounds) = 0.80, R2 (all compounds less the methyl esters) = 0.94. The difference of the methyl esters was associated with the smaller steric volume of the methyl ester substituent and the presence (methacrylates) or absence (acrylates) of the branched methyl group. Associative steric contributions of the branched methyl group and the ester substituents were probably responsible for greater variability in the methyacrylate series. The results were consistent with the conclusion that the mechanism of the action of the esters is membrane mediated and relatively nonspecific and that in vivo biotransformation was not a significant factor. Also, long-term toxic liability of the esters may be more closely related to intrinsic toxicity than acute toxicity.
D000179:Acrylates / Q000633:toxicity*; D000818:Animals; D006461:Hemolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008689:Methacrylates / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D012044:Regression Analysis
D000179:Acrylates; D008689:Methacrylates