Project 2 will explicitly test whether the assumptions are valid for the Toxic Equivalency Factors (TEF) model used for saxitoxin congeners by the World Health Organization and Food and Agriculture Organization of the United Nations, and United States Food and Drug Administration. The TEF model assumes toxicological concentration additivity (i.e., parallel dose-response curves) with only potency differing across different congeners. The Bayesian Multiple Index Model (BMIM) will test this assumption, comparing a single index model (equivalent to this assumption) against a more flexible multiple-index model. If TEF’s assumptions seem to hold when actually tested, then Project 2 will provide updated estimates for TEF based on larger (and tribally generated) datasets, which may have a major impact on public health guidance.
 

Project 2 is one of the first research programs in climate change mixture molecular toxicology. There is a growing interest in climate change impacts on the exposome (human exposure to complex mixtures of chemical and non-chemical stressors), 51-53 but the toxicological community has had limited engagement with climate change research. While air pollution epidemiology has increasingly considered the impacts of mixture combinations, 54,55 there is much less information available on climate-impacted dietary exposure mixture toxicity. This project uses some of the most cutting-edge approaches for assessing the complex health effects of exposure mixtures, including Bayesian Multiple Index Modeling, to examine how paralytic shellfish poisoning toxins whose bioavailability56 and congener distributions are anticipated to shift under climate change may collectively contribute to changes in molecular toxicity (sodium receptor channel binding).