Empirical evaluation of sufficient similarity in dose—Response for environmental risk assessment of chemical mixtures

When toxicity data are not available for a chemical mixture of concern, U.S. Environmental Protection Agency (EPA) guidelines allow risk assessment to be based on data for a surrogate mixture considered “sufficiently similar” in terms of chemical composition and component proportions. As a supplementary approach, using statistical equivalence testing logic and mixed model theory we have developed methodology to define sufficient similarity in dose—response for mixtures of many chemicals containing the same components with different ratios. Dose—response data from a mixture of 11 xenoestrogens and the endogenous hormone, 17ß-estradiol are used to illustrate the method.