Grantee Research Project Results
2024 Progress Report: 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 May 9, 2025
Project Period Covered by this Report: October 1, 2023 through September 30,2024
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: Children's Health , Health Effects , Biomarkers to Environmental Health and Risk Assessment , Endocrine Disruptors , Early Career Awards , Human Health , Safer Chemicals , Mixtures , Chemical Safety for Sustainability , CSS
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 (SA1). Next, we will prioritize exposure mixtures using epidemiologic analysis to identify mixtures most strongly associated with child health (SA2). Lastly, mixture toxicity assessments will be developed to assess prioritized exposures (SA3).
Progress Summary:
Specific Aims 1 & 2 of this project focus on the identifying prioritized mixtures for toxicological assessment. Under these aims, we have examined the types of real-world exposure mixtures that occurred in maternal participants in large, nationally relevant birth cohort and have examined how they relate to health outcomes measured among child participants. To date, major accomplishments include: 1) development of a strategy that identifies environmentally and health relevant candidate chemicals for subsequent mixtures analyses from large exposure database; 2) implementation of a mixtures health effect model that allows identification of a profiles of mixture exposure most associated with health outcomes in our population of interest; and (3) toxicological assessment of five real-world mixtures for changes in adipocyte formation, triglyceride storage, and binding of the transcription factor controlling adipocyte differentiation. Results show that several of the real-world mixtures appear to have synergistic or antagonist effects.
Future Activities:
The next year of the funding period will be used primarily for continued writing and submission of manuscripts resulting from execution of SA1-3. For SA1 and SA2, a manuscript is currently under development for Toxics that will be submitted by the end of 2024. Presentation of these findings are also planned for ISES 2025 in Atlanta, GA. For SA3, results of our assays will be presented at SOT 2025 with submission of a manuscript to Environmental Science and Technology in early 2025.
Journal Articles:
No journal articles submitted with this report: View all 1 publications for this projectSupplemental Keywords:
Environmental Chemicals, Mixtures, Child Health, PFAS
Progress and Final Reports:
Original AbstractThe 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.