Grantee Research Project Results
Development of a quantitative adverse outcome pathway (qAOP) network to assess neurodevelopmental toxicity of per- and polyfluoroalkyl substances (PFAs) mixture in C. elegans
EPA Grant Number: R840453Title: Development of a quantitative adverse outcome pathway (qAOP) network to assess neurodevelopmental toxicity of per- and polyfluoroalkyl substances (PFAs) mixture in C. elegans
Investigators: Tang, Lili , Wang, Jia-Sheng , Huang, Qingguo , Shen, Ye
Current Investigators: Tang, Lili , Huang, Qingguo , Wang, Jia-Sheng , Shen, Ye
Institution: University of Georgia
EPA Project Officer: Aja, Hayley
Project Period: September 1, 2022 through August 31, 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: Safer Chemicals , Health Effects , Human Health , PFAS Treatment , Chemical Safety for Sustainability , New Approach Methods (NAMs) , Mixtures , Non-Vertebrate Animal Testing , CSS , Children's Health
Objective:
This project aims to development a quantitative AOP network with advanced mixtures risk assessment for assessing developmental neurotoxicity of per- and polyfluoroalkyl substances (PFAs) mixture at multiple levels of biological organization using the nematode C. elegans, which can be integrated in a manner useful to hazard and /or risk assessment.
Approach:
The objective will be achieved through the following research tasks to: 1) construct an environmentally relevant and representative PFAs reference mixture, which is the top 10 most abundant PFAs derived from the currently available data and analyses generated by Dr. Huang’s laboratory (Co-PI of the project). 2) conduct systematic experiments to evaluate the developmental neurotoxicity (DNT) of individual PFAs and reference mixture in C. elegans, and to develop qAOP network for providing much more precision for mixture assessment; 3) perform assessment of whole mixture in water samples by evaluating sufficient similarity to reference mixture.
Expected Results:
Results of this project will include new scientific data and improve fundamental knowledge on DNT testing that have not been conducted in-depth for PFAs. Commonalities among responses to PFAs mixtures at different levels of biological organization will be identified. The qAOP network, integrated with non-mammalian C. elegans with support of statistical models will be developed and to contribute databases that are useful for mixture-based hazard and dose-response assessments. The sufficiently similarity method for whole mixture assessment will be quantitatively estimated to reflect the real-world chemical mixtures. Results will be organized into reports and peer-reviewed publications that will be widely disseminated via websites, project reports, journal publications, workshop/conference presentations, extension work and outreach. Results of this project will be advancements in hazard assessment of chemical mixtures, and will be very useful resources in addressing contaminants of concern and improving local/state decision-making through greater integration and more meaningful use of mechanistic data.
Publications and Presentations:
Publications have been submitted on this project: View all 1 publications for this projectJournal Articles:
Journal Articles have been submitted on this project: View all 1 journal articles for this projectSupplemental Keywords:
PFAs, qAOP, Mixtures Assessment, Developmental Neurotoxicity, C. elegansProgress 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.