title: A dose-response model incorporating nonlinear kinetics.
abstract: This paper introduces a dose-response model for toxic quantal response data based on hit theory applied to the dose unit as transformed by a nonlinear kinetic equation. When spontaneous background response is included in the model, the resulting dose-response model has four parameters. The maximum likelihood estimators and their large-sample properties are given. Likelihood ratio tests of interest are developed, including one for whether the model is one-hit in the transformed dose and one to check whether nonlinear kinetics is operative. The use of the model for low-dose extrapolation is presented. Finally, the procedures developed are illustrated on data from three animal carcinogenicity bioassays that show, respectively, concave, linear, and convex dose-response curves in the observed data.
mesh_terms: D000818:Animals; D003634:DDT / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D011042:Poisons / Q000633:toxicity*; D012306:Risk; D012439:Saccharin / Q000633:toxicity; D013223:Statistics as Topic; D014116:Toxicology / Q000379:methods*; D014752:Vinyl Chloride / Q000633:toxicity
chemical_list: D011042:Poisons; D003634:DDT; D012439:Saccharin; D014752:Vinyl Chloride