Benchmark profile and inferences for joint-exposure quantal data in quantitative risk assessment

Abstract

In risk assessment, it is often desired to make inferences on the minimum dose levels (benchmark doses or BMDs) at which a specific benchmark risk (BMR) is attained. The estimation and inferences of BMDs are well understood in the case of an adverse response to a single-exposure agent. However, the theory of finding BMDs and making inferences on the BMDs is much less developed for cases where the adverse effect of two hazardous agents is studied simultaneously. Deutsch and Piegorsch [2012. Benchmark dose profiles for joint-action quantal data in quantitative risk assessment. Biometrics 68(4):1313–22] proposed a benchmark modeling paradigm in dual exposure setting—adapted from the single-exposure setting—and developed a strategy for conducting full benchmark analysis with joint-action quantal data, and they further extended the proposed benchmark paradigm to continuous response outcomes [Deutsch, R. C., and W. W. Piegorsch. 2013. Benchmark dose profiles for joint-action continuous data in quantitative risk assessment. Biometrical Journal 55(5):741–54]. In their 2012 article, Deutsch and Piegorsch worked exclusively with the complementary log link for modeling the risk with quantal data. The focus of the current paper is on the logit link; particularly, we consider an Abbott-adjusted [A method of computing the effectiveness of an insecticide. Journal of Economic Entomology 18(2):265–7] log-logistic model for the analysis of quantal data with nonzero background response. We discuss the estimation of the benchmark profile (BMP)—a collection of benchmark points which induce the prespecified BMR—and propose different methods for building benchmark inferences in studies involving two hazardous agents. We perform Monte Carlo simulation studies to evaluate the characteristics of the confidence limits. An example is given to illustrate the use of the proposed methods.