Grantee Research Project Results
A tiered hybrid experimental-computational strategy for rapid risk assessment of complex environmental mixtures using novel analytical and toxicological methods
EPA Grant Number: R840450Title: A tiered hybrid experimental-computational strategy for rapid risk assessment of complex environmental mixtures using novel analytical and toxicological methods
Investigators: Rusyn, Ivan , Chiu, Weihsueh A , Zhou, Yihui , Wright, Fred A.
Current Investigators: Rusyn, Ivan , Wright, Fred A. , Zhou, Yihui , Chiu, Weihsueh A
Institution: Texas A & M University , North Carolina State University
EPA Project Officer: Aja, Hayley
Project Period: September 1, 2022 through May 2, 2025
Project Amount: $750,000
RFA: Development of Innovative Approaches to Assess the Toxicity of Chemical Mixtures Request for Applications (RFA) (2022) RFA Text | Recipients Lists
Research Category: CSS , Chemical Safety for Sustainability , Endocrine Disruptors , Health Effects , Human Health , Mixtures , New Approach Methods (NAMs) , Predictive Toxicology , Safer Chemicals
Description:
Evaluation of composition and hazards of chemical mixtures, or complex products classified as UVCBs (unknown variable composition or biological substances), presents a multitude of challenges. These include the presence of unknown constituents, a limited basis for grouping additive and independent components, and the lack of toxicity data on most constituents, and whole mixtures or UVCBs. Recent disasters resulting in redistribution of complex chemical mixtures in the environment have provided this research group an opportunity to develop new approaches to rapid composition and hazard characterization to inform rapid decision-making.
Objective:
The long-term goal is to ensure timely risk-based assessment of mixtures and UVCBs that ensures human health protection from the toxicity of known/unknown components. The research team will accomplish this through integration of novel toxicological (i.e., human cell-based assays), analytical (i.e., ion mobility spectrometry-mass spectrometry), and modeling (i.e., interaction, mediation and dose reconstruction) methods. Researchers plan to demonstrate the application of these methods in the context of rapid risk assessment/management of sites contaminated with uncharacterized chemical mixtures.
Approach:
For all Aims, researchers will use (i) environmental samples collected during and after disasters where chemical re-distribution has been documented and quantified, as well as (ii) UVCB substances. Aim 1 will determine grouping of chemical mixture components for assessment of hazard(s) through integration of multi-phenotype/multi-tissue bioactivity data from a compendium of human induced pluripotent stem cell (iPSC)-derived cells. Aim 2 will develop approaches for prioritization of components in whole mixtures or UVCBs that are likely to contribute most to joint toxicity through mediation and interaction methods that integrate multi-dimensional analytical and in vitro bioactivity data. Aim 3 will evaluate prediction of joint toxicity of whole or defined mixtures and UVCBs through novel probabilistic additivity models of grouped (Aim 1) and prioritized (Aim 2) components. Aim 4 will be a demonstration of the integration of the proposed exposure, toxicological and modeling methods into a tiered hybrid experimental-computational strategy for rapid risk assessment of complex environmental mixtures and UVCBs.
Expected Results:
The main outcomes of this project will be a suite of analytical, in vitro, and computational methods and tools that can be applied in a tiered strategy for rapid quantitative characterization of the composition and hazards of complex environmental mixtures and UVCBs.
Publications and Presentations:
Publications have been submitted on this project: View all 3 publications for this projectJournal Articles:
Journal Articles have been submitted on this project: View all 3 journal articles for this projectSupplemental Keywords:
mixtures, risk assessment, analytical, toxicology, NAMs, UVCBsProgress 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.