Grantee Research Project Results
2023 Progress Report: Wildfire Smoke Mixtures Toxicity Testing
EPA Grant Number: R840458Title: Wildfire Smoke Mixtures Toxicity Testing
Investigators: Rager, Julia , Reif, David , Jaspers, Ilona , Rebuli, Meghan E , Kim, Yong Ho
Institution: University of North Carolina at Chapel Hill , North Carolina State 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: $599,999
RFA: Development of Innovative Approaches to Assess the Toxicity of Chemical Mixtures Request for Applications (RFA) (2022) RFA Text | Recipients Lists
Research Category: Health Effects , Endocrine Disruptors , New Approach Methods (NAMs) , Early Career Awards , Human Health , Air , Safer Chemicals , Mixtures , Chemical Safety for Sustainability , Wildfires , CSS
Objective:
This proposal hypothesizes that individual chemicals in wildfire smoke induce in vitro responses that group according to biological pathways, informing mixtures-based joint toxicities that overlap with in vivo pulmonary responses and disease outcomes. This hypothesis will be tested through three objectives: (1) Establish qualitative membership of wildfire mixture components into pathway groupings through in vitro transcriptomic screening; (2) Quantify joint toxicities across pathway groupings and compare to whole biomass smoke mixture effects through in silico modeling; and (3) Relate in vitro wildfire chemical-induced signatures to similarly exposed mice and human pulmonary disease tissues to evaluate events along adverse outcome pathways (AOPs).
Progress Summary:
Accomplishments over the past year primarily concern Objectives 1 and 3. Regarding Objective 1, all in vitro exposure experiments were completed and genomic material was extracted for RNA sequencing. Regarding Objective 3, human transcriptomic signatures of canonical pulmonary disease processes were obtained from publicly available databases. In silico analyses were developed to relate these human transcriptomic data with our existing transcriptomic data from mice exposed to wildfire biomass smoke and identify human pulmonary diseases whose altered gene signatures overlap most closely with gene alterations induced by lab-simulated exposures to wildfire biomass smoke.
Future Activities:
Future activities concerning Objectives 1 and 2 include subminng genomic material for RNA sequencing and developing analysis pipelines for the resultng transcriptomic data including quantifying joint toxicites across pathway groupings and comparing to whole biomass smoke mixture effects through in silico modeling. Regarding Objective 3, a manuscript is being prepared that describes our in silico analysis relating transcriptomic signatures of human pulmonary disease with those of mice exposed to wildfire biomass smoke.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
| Other project views: | All 8 publications | 2 publications in selected types | All 2 journal articles |
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Koval LE, Carberry CK, Kim YH, McDermott E, Hartwell H, Jaspers I, Gilmour MI, Rager JE. Wildfire Variable Toxicity: Identifying Biomass Smoke Exposure Groupings through Transcriptomic Similarity Scoring . Environmental Science & Technology. November 2022; 56(23):17131-42. |
R840458 (2023) |
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Rager, JE and Rider CV. Wrangling Whole Mixtures Risk Assessment: Recent Advances in Determining Sufficient Similarity . Current Opinion in Toxicology. June 2023; 35:100417. |
R840458 (2023) |
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Supplemental Keywords:
In vitro, Joint Toxicity, Mixtures, Wildfire, Risk assessmentProgress 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.