Grantee Research Project Results
Developing an Integrated Framework for Evaluating Toxicity of Real-Life Chemical Mixtures
EPA Grant Number: R840460Title: Developing an Integrated Framework for Evaluating Toxicity of Real-Life Chemical Mixtures
Investigators: Pearce, John L , Hunt, Kelly , Bain, Lisa , Baldwin, William
Institution: Medical University of South Carolina , Clemson University
EPA Project Officer: Aja, Hayley
Project Period: October 1, 2022 through September 30, 2025
Project Amount: $599,998
RFA: Development of Innovative Approaches to Assess the Toxicity of Chemical Mixtures Request for Applications (RFA) (2022) RFA Text | Recipients Lists
Research Category: Safer Chemicals , Children's Health , Health Effects , Biomarkers to Environmental Health and Risk Assessment , Human Health , Chemical Safety for Sustainability , Mixtures , CSS , Early Career Awards
Objective:
The overarching objective of this project is to improve how real-life exposure to multiple chemicals is considered in toxicity assessments of chemical mixtures. This will be achieved in stages. First, we will identify real-life chemical mixtures from biological samples taken during a large epidemiologic birth cohort study. Next, we will prioritize exposure mixtures using epidemiologic analysis to identify mixtures most strongly associated with child health. Lastly, mixture toxicity assessments will be developed to assess prioritized exposures.
Approach:
Our framework will integrate exposure science, epidemiologic analysis, and predictive toxicology to improve identification, prioritization, and toxicological assessment of environmentally relevant chemical mixtures. The driving innovation centers on development of real-life exposure profiles that identify environmentally relevant chemical mixtures, support epidemiologic analysis, and provide inputs for predictive toxicological models seeking to quantify the effect of a chemical mixture. Modern statistical learning tools will be applied to identify and characterize a range of observed exposure profiles and epidemiological mixtures analysis will be used to estimate joint health effects that support prioritization of health-relevant mixtures for toxicity assessment. Predictive toxicological models will then assess prioritized environmentally relevant mixtures for assessment of a mixture effect using molecular and cellular endpoints.
Expected Results:
Accomplishing this research will provide an innovative framework for toxicological assessment of real-world exposure mixtures across a broad range of biological endpoints. The resulting tools will provide a valuable resource to risk assessors and the broader scientific community interested in risk assessment of chemical mixtures.
Supplemental Keywords:
biomarkers; children’s health; epidemiology; EDCs; OCPs, PBDEs, PCBs, PFAS, metals; obesity, self-organizing maps , adipocytes, PPAR, cellular differentiation, 3T3 cells, progesterone receptor, androgen receptorProgress and Final Reports:
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.