title: Benchmark Dose Analysis via Nonparametric Regression Modeling.
abstract: Estimation of benchmark doses (BMDs) in quantitative risk assessment traditionally is based upon parametric dose-response modeling. It is a well-known concern, however, that if the chosen parametric model is uncertain and/or misspecified, inaccurate and possibly unsafe low-dose inferences can result. We describe a nonparametric approach for estimating BMDs with quantal-response data based on an isotonic regression method, and also study use of corresponding, nonparametric, bootstrap-based confidence limits for the BMD. We explore the confidence limits' small-sample properties via a simulation study, and illustrate the calculations with an example from cancer risk assessment. It is seen that this nonparametric approach can provide a useful alternative for BMD estimation when faced with the problem of parametric model uncertainty.
authors.affiliation: Program in Statistics, University of Arizona, Tucson, AZ, USA.|BIO5 Institute, University of Arizona, Tucson, AZ, USA.|Department of Mathematics, University of Arizona, Tucson, AZ, USA.
authors.forename: Walter W
authors.initials: WW
authors.lastname: Piegorsch
authors.affiliation: Program in Applied Mathematics, University of Arizona, Tucson, AZ, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Program in Statistics, University of Arizona, Tucson, AZ, USA.|Department of Mathematics, University of Arizona, Tucson, AZ, USA.
authors.forename: Rabi N
authors.initials: RN
authors.lastname: Bhattacharya
authors.affiliation: Department of Statistical Science, Duke University, Durham, NC, USA.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Lin
mesh_terms: D000818:Animals; D019985:Benchmarking / Q000706:statistics & numerical data*; D002273:Carcinogens / Q000633:toxicity; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity; D006801:Humans; D015233:Models, Statistical; D009010:Monte Carlo Method; D012044:Regression Analysis; D018570:Risk Assessment / Q000379:methods* / Q000706:statistics & numerical data; D018709:Statistics, Nonparametric; D000069436:Toxicological Phenomena
chemical_list: D002273:Carcinogens; D005557:Formaldehyde
keywords: BMD; BMDL; Benchmark analysis; bootstrap confidence limits; dose-response analysis; isotonic regression; toxicological risk assessment