Grantee Research Project Results
2024 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: Packard, Benjamin H
Project Period: September 1, 2022 through May 9, 2025
Project Period Covered by this Report: September 1, 2023 through August 31,2024
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: Health Effects , Endocrine Disruptors , New Approach Methods (NAMs) , Human Health , Air , Safer Chemicals , Mixtures , Chemical Safety for Sustainability , 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:
PAH derived secondary organic aerosols (SOA) have been generated from photooxidation of naphthalene along with SOA derived from natural hydrocarbon emitted from trees (α-pinene). These two systems have been studied extensively in our prior work, in which naphthalene SOA shows higher toxicity than α-pinene SOA. The same differences in inflammatory toxicity response between these SOAs was observed by the air-blood barrier array (ABBA) platform, demonstrating the capability of this new platform although with lower than desired sensitivity. Much of the project effort in this past year has been work to lower background signal and improve sensitivity.
Accomplishments for NAM improvement include better standardization and quality control (QC) of the ABBA platform including accounting for biological variability of human cells used to construct the ABBA. Improved protocols for obtaining tissue barrier properties using the non-invasive trans-epithelial/endothelial electrical resistance (TEER) measures with higher throughput and robustness was developed. The TEER readouts are being used to develop methods of cell culture and sample exposure that reduce background signal and enhance sensitivity.
Future Activities:
The L-ABBA platform will be further refined for lower background signal, improved sensitivity, and ability to extrapolate L-ABBA dose response to human exposures. Specific activities include incorporation of macrophage and more chronic exposure of PAH and SOA before obtaining the inflammation readouts to determine iTEFs.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 3 publications | 1 publications in selected types | All 1 journal articles |
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Viola H, Chen LH, Jo S, Washington K, Selva C, Li A, Feng D, Giacalone V, Stephenson S, Cottrill K, Mohammed A. High Throughput Quantitation of Human Neutrophil Recruitment and Functional Responses in an Air-Blood Barrier Array. bioRxiv. 2024:2024-05. |
R840452 (2024) |
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Supplemental Keywords:
New Approach Methodologies (NAM), Lung, Inflammation, Polycyclic Aromatic Hydrocarbons (PAH), Secondary Organic Aerosols (SOA)Relevant Websites:
Takayama lab Exit
Ng Research Group Exit
Progress 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.