Grantee Research Project Results
2023 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, 2022 through September 30,2023
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 objective of the project is to improve how real-life exposures to multiple chemicals are considered in toxicity assessments of chemical mixtures. The project will advance this area by seeking to develop innovative methods that improve how realistic exposure levels are used to perform efficient toxicity assessments of potential mixture effects. To begin, we will identify the range of realistic exposure mixtures observed among mothers (n=604) participating in a large, national birth cohort study using chemical concentration data obtained from biological samples collected during the 1st trimester. Next, we will prioritize which exposure mixtures present the strongest health risk by estimating joint effects of differing combinations on clinical measures of early childhood weight gain. Lastly, the characteristics of the prioritized mixtures will be used to guide predictive toxicological models that efficiently assess potentially harmful chemical combinations. This research provides an innovative framework for toxicological assessment of real-world exposure mixtures across a broad range of biological endpoints, resulting in tools that will be valuable to risk assessors and the broader scientific community interested in health effects and risk assessment of chemical mixtures.
Specific aims for the project include:
• Specific Aim 1 (SA1): Identify real-life mixtures through construction of novel ontology maps that precisely define environmentally relevant exposure profiles to multiple chemicals.
• Specific Aim 2 (SA2): Use epidemiologic mixtures analysis to support prioritization of health-relevant mixtures for use in toxicity studies.
• Specific Aim 3 (SA3): Develop a mixtures toxicity assessment that efficiently evaluates prioritized chemical mixtures using real-life exposure scenarios.
Progress Summary:
The Medical University of South Carolina’s project seeks to advance research on how multiple chemicals are considered in toxicity assessments. To achieve, we proposed to leverage epidemiologic evidence from a birth cohort study of chemical mixtures to identify realistic exposure combinations that warrant toxicity testing. Major accomplishments include: (SA1) identification of the range real-world exposure mixtures experienced by the birth cohort; (SA2) examination of real-world exposure mixtures associated with child measures of body composition; and (SA3) toxicological assessment of several real-world mixtures for changes in adipocyte formation, triglyceride storage, and binding of the transcription factor controlling adipocyte differentiation.
Future Activities:
For SA1, we will continue to enhance our approach for identification of the real-world exposure mixtures by continuing to pursue data standardization approaches and dissimilarity metrics that optimize pattern recognition in complex environmental data. For SA2, we plan to continue work focused on identification of health effects of real-world exposure mixtures. We will continue our work using child measures of body composition as the primary outcome. For SA3, we will continue to develop our toxicity assessment tools for mixtures using changes in adipocyte formation, triglyceride storage, and binding of the transcription factor controlling adipocyte differentiation as outcomes. We plan to expand the number of chemicals assessed and refine testing for interactions.
Journal Articles:
No journal articles submitted with this report: View all 1 publications for this projectSupplemental Keywords:
Environmental Chemicals, Mixtures, Child Health, PFASProgress 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.