The toxicity of a series of esters of acrylic and methacrylic acids was determined in groups of mice, and the resultant LD50 values were analyzed with the use of the mathematical models of Free and Wilson and of Hansch to relate structure of the compounds to toxicity. Both models proved valuable in relating structures to toxicity parameters, but the more useful method for predicting toxicity was the Hansch model.
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References
1.
Free, S.M., JR., and Wilson, J.W.: A Mathematical Contribution to Structure-Activity Studies, J Med Chem7:395-399, 1964.
2.
Hansch, C., and Fujita, T.: Q-σ-π Analysis. A Method for the Correlation of Biological Activity and Chemical Structure, J Amer Chem Soc86:1616-1626, 1964.
3.
Snedecor, G.N., and Cochran, W.G.: Statistical Methods, Ames, Iowa: Iowa University Press, 1967, chapter 13.
4.
Hammett, L.P. : The Effect of Structure upon Reactions of Organic Compounds. Benzene Derivatives, J Amer Chem Soc59:96-103, 1937.
5.
Taft, W.R., JR. : Linear Free Energy Relationships from Rates of Esterification and Hydrolysis of Aliphatic and Ortho-substituted Benzoate Esters, J Amer Chem Soc74:2729-2732, 1952 .
6.
Deichmann, W. : Toxicity of Methyl, Ethyl and N-Butyl Methacrylate , J Ind Hyg Toxicol23:343-351, 1941.
7.
Spealman, C.R. ; Main, R.J.; Haag , H.B.; and Larson, P.S.: Monomeric Methyl Methacrylate, Studies on Toxicity, Ind Med14:292-298, 1945.
8.
Pozzani, U.C. ; Weil, C.S.; and Carpenter , C.P.: Subacute Vapor Toxicity and Range-Finding Data for Ethyl Acrylate, J Ind Hyg Toxicol31:311-316, 1949.
9.
Treon, J.F.; Sigmon, H.; Wright, H.; and Kitzmiller, K.V. : The Toxicity of Methyl and Ethyl Acrylate , J Ind Hyg Toxicol31: 317-326, 1949.
10.
Cornfield, J., and Mantel, N.: Some New Aspects of the Application of Maximum Likelihood to the Calculation of the Dosage Response Curve, Amer Stat Assn J45:181-210, 1950.
11.
Iwasa, J.; Fujita, T.; and Hansch, C.: Substituent Constants for Aliphatic Functions Obtained from Partition Coefficients , J Med Chem8:150-153, 1965.
12.
Del Re, G.: A Simple MO-LCAO Method for the Calculation of Charge Distributions in Saturated Organic Molecules, J Chem Soc4031-4040, 1958.
13.
Berthod, H. , and Pullman, A.: Sur le Calcul des Caracteristiques du Squelette σ des Molecules Conjuguees, J Chem Phys62:942-946, 1965.
14.
Hine, J.: Physical Organic Chemistry, 3rd ed, New York: McGraw-Hill Co., Inc., 1962, p 285.
15.
Penniston, J.T.; Beckett, L.; Bentley , D.L.; and Hansch, C.: Passive Permeation of Organic Compounds through Biological Tissues: a Non-Steady-State Theory , Mol Pharm5:333-341, 1969.