Use of Mathematical Models in the Study of Structure-Toxicity Relationships of Dental Compounds: I. Esters of Acrylic and Methacrylic Acids

Abstract

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

Free, S.M., JR. , and Wilson, J.W. : A Mathematical Contribution to Structure-Activity Studies, J Med Chem 7:395-399, 1964.

Hansch, C. , and Fujita, T. : Q-σ-π Analysis. A Method for the Correlation of Biological Activity and Chemical Structure, J Amer Chem Soc 86:1616-1626, 1964.

Snedecor, G.N. , and Cochran, W.G. : Statistical Methods, Ames, Iowa: Iowa University Press, 1967, chapter 13.

Hammett, L.P. : The Effect of Structure upon Reactions of Organic Compounds. Benzene Derivatives, J Amer Chem Soc 59:96-103, 1937.

Taft, W.R. , JR. : Linear Free Energy Relationships from Rates of Esterification and Hydrolysis of Aliphatic and Ortho-substituted Benzoate Esters, J Amer Chem Soc 74:2729-2732, 1952 .

Deichmann, W. : Toxicity of Methyl, Ethyl and N-Butyl Methacrylate , J Ind Hyg Toxicol 23:343-351, 1941.

Spealman, C.R. ; Main, R.J. ; Haag , H.B. ; and Larson, P.S. : Monomeric Methyl Methacrylate, Studies on Toxicity, Ind Med 14:292-298, 1945.

Pozzani, U.C. ; Weil, C.S. ; and Carpenter , C.P. : Subacute Vapor Toxicity and Range-Finding Data for Ethyl Acrylate, J Ind Hyg Toxicol 31:311-316, 1949.

Treon, J.F. ; Sigmon, H. ; Wright, H. ; and Kitzmiller, K.V. : The Toxicity of Methyl and Ethyl Acrylate , J Ind Hyg Toxicol 31: 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 J 45:181-210, 1950.

11.

Iwasa, J. ; Fujita, T. ; and Hansch, C. : Substituent Constants for Aliphatic Functions Obtained from Partition Coefficients , J Med Chem 8:150-153, 1965.

12.

Del Re, G. : A Simple MO-LCAO Method for the Calculation of Charge Distributions in Saturated Organic Molecules, J Chem Soc 4031-4040, 1958.

13.

Berthod, H. , and Pullman, A. : Sur le Calcul des Caracteristiques du Squelette σ des Molecules Conjuguees, J Chem Phys 62:942-946, 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 Pharm 5:333-341, 1969.