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Estimating the impact of grouping misclassification on risk prediction when using the relative potency factors method to assess mixtures risk

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Environmental health risk assessments of chemical mixtures that rely on component approaches often begin by grouping the chemicals of concern according to toxicological similarity. Approaches that assume dose addition typically are used for groups of similarly-acting chemicals and those that assume response addition are used for groups of independently acting chemicals. Grouping criteria for similarity can include a common adverse outcome pathway (AOP) and similarly shaped dose-response curves, with the latter used in the relative potency factor (RPF) method for estimating mixture response. Independence of toxic action is generally assumed if there is evidence that the chemicals act by different mechanisms. Several questions arise about the potential for misclassification error in the mixture risk prediction. If a common AOP has been established, how much error could there be if the same dose-response curve shape is assumed for all chemicals, when the shapes truly differ and, conversely, what is the error potential if different shapes are assumed when they are not? In particular, how do those concerns impact the choice of index chemical and uncertainty of the RPF-estimated mixture response? What is the quantitative impact if dose additivity is assumed when complete or partial independence actually holds and vice versa? These concepts and implications will be presented with numerical examples in the context of uncertainty of the RPF-estimated mixture response, both regarding endpoint and numerical accuracy when representing the group.

Impact/Purpose

platform presentation abstract for Society of Toxicology annual meeting, March 2018

Citation

Swartout, Jeff. Estimating the impact of grouping misclassification on risk prediction when using the relative potency factors method to assess mixtures risk. Society of Toxicology, San Antonio, Texas, March 11 - 15, 2018.

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Last updated on August 01, 2017