A measure of tumorigenic potency incorporating dose-response shape.

Many researchers have considered the problem of ranking chemical agents based on their carcinogenic potency. Sawyer et al. (1984, Biometrics 40, 27-40) proposed a carcinogenic potency estimate that incorporates both intercurrent mortality and background tumor rates. Since then, many authors have either generalized the method outlined by Sawyer et al. or developed their own method based on a slightly different adjustment for treatment-related changes in survival. None of these methods, however, has estimated the shape of the dose-response curve and incorporated such an estimate in potency estimation. In this manuscript, a measure of tumorigenic potency is proposed that utilizes the estimated shape of the dose-response relationship, in addition to estimated dose effects, in order to rank chemicals on the basis of carcinogenic risk. Comparison of this new measure to that of Sawyer et al. is done using a large database of animal carcinogenicity experiments from the National Cancer Institute and the National Toxicology Program.

[1]  G. R. Walsh,et al.  Methods Of Optimization , 1976 .

[2]  J C Bailar,et al.  One-hit models of carcinogenesis: conservative or not? , 1988, Risk analysis : an official publication of the Society for Risk Analysis.

[3]  M. Gallo,et al.  The fallacy of ranking possible carcinogen hazards using the TD50. , 1990, Risk analysis : an official publication of the Society for Risk Analysis.

[4]  S. L. Brown.  Quantitative risk assessment of environmental hazards. , 1985, Annual review of public health.

[5]  D G Hoel,et al.  Issues concerning the estimation of the TD50. , 1987, Risk analysis : an official publication of the Society for Risk Analysis.

[6]  Modeling the effect of dose on the lifetime tumor rate from an animal carcinogenicity experiment. , 1991, Biometrics.

[7]  K S Crump,et al.  Correlation between carcinogenic potency of chemicals in animals and humans. , 1988, Risk Analysis.

[8]  D. Gaylor,et al.  Carcinogenic potency correlations: real or artifactual? , 1991, Journal of toxicology and environmental health.

[9]  Bailer Aj,et al.  Effects of treatment-induced mortality and tumor-induced mortality on tests for carcinogenicity in small samples. , 1988 .

[10]  David G. Hoel,et al.  Some Tautologous Aspects of the Comparison of Carcinogenic Potency in Rats and Mice , 1985 .

[11]  L. Gold,et al.  Ranking possible carcinogenic hazards. , 1987, Science.

[12]  D G Hoel,et al.  Statistical analysis of survival experiments. , 1972, Journal of the National Cancer Institute.

[13]  Louise Ryan,et al.  Estimating Carcinogenic Potency from a Rodent Tumorigenicity Experiment , 1987 .

[14]  C. Portier,et al.  Concordance of carcinogenic response between rodent species: potency dependence and potential underestimation. , 1992, Risk analysis : an official publication of the Society for Risk Analysis.

[15]  Barbara McKnight,et al.  Tests for differences in tumor incidence based on animal carcinogenesis experiments , 1984 .

[16]  Malcolm C. Pike,et al.  The TD50: a proposed general convention for the numerical description of the carcinogenic potency of chemicals in chronic-exposure animal experiments. , 1984 .

[17]  C. Portier,et al.  An index of tumorigenic potency. , 1993, Biometrics.

[18]  D G Hoel,et al.  Age-specific models of mortality and tumor onset for historical control animals in the National Toxicology Program's carcinogenicity experiments. , 1986, Cancer research.

[19]  M. Pike,et al.  A carcinogenic potency database of the standardized results of animal bioassays , 1984, Environmental health perspectives.

[20]  D G Hoel,et al.  Nonlinearity of dose-response functions for carcinogenicity. , 1994, Environmental health perspectives.

[21]  M. Pike,et al.  Calculation of carcinogenic potency from long-term animal carcinogenesis experiments. , 1984, Biometrics.