ABSTRACT
Modeling ........................................................................................... 129 4.5 Component-Based Approaches, Test Designs, and Methods ....................... 132
4.5.1 Fixed-Ratio Design ........................................................................... 132 4.5.2 Assessment of the Complete Concentration-Response Surface ...... 134
4.5.2.1 Research Aim and Experimental Design........................... 134 4.5.2.2 Data Analysis: Judging Deviations from CA and IA ......... 136
4.5.3 Fractionated Factorial Design ........................................................... 142 4.5.4 Isoboles ............................................................................................. 143 4.5.5 A in the Presence of B ....................................................................... 143 4.5.6 Point Design ...................................................................................... 143
4.6 Whole Mixture Approaches, Test Designs, and Methods ............................ 144 4.6.1 Bioassays ........................................................................................... 145 4.6.2 Biosensors ......................................................................................... 146 4.6.3 Fractionation Methods, TIE, and EDA ............................................. 147 4.6.4 Similarity of Mixtures ...................................................................... 148
4.7 Case Studies .................................................................................................. 150 4.7.1 Case Study 1: A Whole Mixture Approach from
“Eco”toxicology ................................................................................ 150 4.7.2 Case Study 2: A Component-Based Approach from “Human”
Toxicology ........................................................................................ 151
This chapter discusses test design, analysis, and assessment of results for mixture concentration-response analysis. This chapter does not cover test designs for other types of experiments in (mixture) toxicity research, such as designs for physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling, or uptake elimination kinetics measurements, or capture-recapture studies for assessing mixed chemical exposure to wildlife. Mixture concentration-response analyses have been performed and discussed since the early days of mixture toxicity research (Bliss 1939) and encompass a large body of literature. In this chapter we do not aim to present new statistical designs and analysis methods. The goals of this chapter are rather to give an overview of the approaches that do exist in the literature, to specify which test design and statistical method can be used for which research aim, and to indicate potential pitfalls when results are assessed. In this way we hope to provide general guidelines for setting up mixture toxicity concentration-response experiments. The researcher can then, after deciding on the design and statistical model, make more detailed decisions, such as on number of replicates and concentrations or doses to test after performing a power analysis. Yet, specific subjects, such as power analysis, are beyond the scope of this chapter.
