Grantee Research Project Results
High-Throughput Lung Damage and Inflammation Assessment of Polyaromatic Hydrocarbon Mixtures
EPA Grant Number: R840452Title: High-Throughput Lung Damage and Inflammation Assessment of Polyaromatic Hydrocarbon Mixtures
Investigators: Takayama, Shuichi , Ng, Nga Lee
Institution: Georgia Institute of Technology
EPA Project Officer: Aja, Hayley
Project Period: September 1, 2022 through May 9, 2025
Project Amount: $749,999
RFA: Development of Innovative Approaches to Assess the Toxicity of Chemical Mixtures Request for Applications (RFA) (2022) RFA Text | Recipients Lists
Research Category: Air , CSS , Chemical Safety for Sustainability , Endocrine Disruptors , Health Effects , Human Health , Mixtures , New Approach Methods (NAMs) , Safer Chemicals
Description:
This project hypothesizes that lung inflammatory risks from exposure to polyaromatic hydrocarbons (PAHs) can be predicted using a New Approach Methodology (NAM) based on an in vitro air-blood barrier array (ABBA). Respiratory tract inflammation risk will be assessed by using the ABBA to perform high-throughput neutrophil infiltration analysis and also by measuring changes in barrier breakdown. The NAM will be used to group PAHs according to a newly proposed inflammatory toxic equivalency factors (iTEFs). Joint toxicities of mixtures will also be analyzed and utility of iTEFs to predict toxicities of mixtures tested.
Objective:
Aim 1. Produce defined PAH component and mixture solutions/suspensions including secondary organic aerosol (SOA)
Aim 2. Develop an ABBA-based NAM and determine full dose-response curves for PAH/SOA
components to derive iTEFs
Aim 3. Analyze PAH/SOA mixtures for joint toxicities
Approach:
A high-throughput (96 well plate format), human cell-based ABBA will be developed and exposed to different doses of PAH components and PAH-derived secondary organic aerosol (SOA). Barrier breakdown will be evaluated through trans-epithelial electrical resistance (TEER) and inflammation by neutrophil transmigration count. These full dose-response curves will be used to determine the EC50 and benchmark dose (BMD). These measures will be utilized to determine PAH components iTEFs. An algorithm to predict iTEF of mixtures from PAH component iTEFs will be developed and refined through experimental analysis using the NAM.
Expected Results:
This project is expected to develop a broadly useful NAM that is a practical, human cell-based alternative to the current, rodent bronchoalveolar lavage (BAL)-based respiratory tract inhalation toxicity assessments. The NAM will group individual PAHs according to their relative inhalation toxicities. Joint toxicity of PAH mixtures will be predicted using the individual component iTEFs. Exploratory studies will reveal how much more toxic PAH-derived SOA are relative to their parent PAH.
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 1 journal articles for this projectSupplemental Keywords:
Risk Assessment, Innovative technology, Biology, Engineering, Climate changeProgress 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.