Grantee Research Project Results
2023 Progress Report: 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 August 31, 2025
Project Period Covered by this Report: September 1, 2022 through August 31,2023
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: Safer Chemicals , Health Effects , Human Health , Air , Chemical Safety for Sustainability , New Approach Methods (NAMs) , Mixtures , CSS
Objective:
The purpose of this project is to develop a new approach methodology (NAM) based on high-throughput in vitro air-blood barrier arrays (ABBA) to predict respiratory tract inflammation risk. The specific objectives are to (1) produce defined polycyclic aromatic hydrocarbon (PAH) component and mixture solutions including secondary organic aerosols (SOA), (2) develop an air-blood barrier arrays (ABBA)-based new approach methodology (NAM) and determine full dose-response curves for PAH/ SOA components to derive inflammatory toxic equivalency factor (iTEF), and (3) analyze PAH/SOA mixtures for joint toxicities. Researchers will obtain full dose-response curves for air-blood barrier property degradation and will use neutrophil cell infiltration to test the ability to group PAHs according to a newly proposed iTEF. The research team will also analyze the joint toxicities of mixtures and the utility of iTEFs to predict mixtures toxicity. Deliverables include annual and final reports as well as a broadly useful new approach methodology (NAM) that is a practical, human cell-based alternative to the current rodent-based bronchoalveolar lavage-based respiratory tract inhalation toxicity assessments. Direct beneficiaries of this program include people exposed to air pollutants from ambient and occupational sources, children and older adults with asthma, chronic obstructive pulmonary disease (COPD), heart disease, or diabetes; households in the wildland-urban interface that are at risk for forest fires; human health, the environment, and the general public.
Progress Summary:
Naphthalene is one of the PAHs that are commonly found in the environment. Naphthalene from anthropogenic emissions can react with atmospheric oxidants to form SOA. Naphthalene has been identified as a potent carcinogen and an immunotoxicant by activating aryl hydrocarbon receptors (AhRs). However, the immunotoxicity of SOA derived from naphthalene in a physiologically relevant model has not been studied owing to the complex chemical properties of SOA. Here, we conduct a series of laboratory experiments that involve formation of SOA from naphthalene and investigation of SOA toxicity using the ABBA module. The ABBA module mimics the human lungs epithelium and endothelium interface, allowing for examination of the cell-cell interactions in the lung barriers to fully investigate the inflammatory responses of naphthalene SOA exposure. First, we generate naphthalene SOA under different NOx conditions in photooxidation experiments. The chemical composition of the naphthalene SOA is characterized by high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) and filter inlet for gas and aerosols time-of-flight chemical ionization mass spectrometer (FIGAERO-
ToF-CIMS). Then, we use the ABBA module to investigate the naphthalene SOA-induced reactive oxygen species (ROS) and interleukin-8 (IL-8) production at the epithelium and the endothelium interface, which represent the initiation and mediation of inflammatory cascades from naphthalene exposure to the epithelial cells and subsequent responses in the endothelial cells. The measured inflammatory responses can demonstrate the series of immunotoxic responses leading to the degradation of lung barrier function.
Future Activities:
The ABBA platform will be further refined for robustness and enhanced signal-to-noise. The range of PAH and PAH SOA to be evaluated will be expanded. PAH SOA characterization will be performed in more detail. Benchmark dose will be determined for the individual PAHs and their mixtures including SOA and iTEFs determined.
Journal Articles:
No journal articles submitted with this report: View all 1 publications for this projectSupplemental Keywords:
New Approach Methodologies (NAM), Lung, Inflammation, Polycyclic Aromatic Hydrocarbons (PAH), Secondary Organic Aerosols (SOA)Relevant Websites:
https://microfluidics.gatech.edu/
https://ng.chbe.gatech.edu/
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.