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An Approach Using NAMs for the Evaluation of Inhalation Toxicity in OSCPP Chemical Registrations(BOSC)

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  • Overview
Background/Overview: Traditional in vitro dosing methods require submerged exposure of cells in chemicals solubilized in dimethyl sulfoxide (DMSO) or water diluted into cell culture medium. However, approximately 30% of chemicals nominated for study in the U.S Environmental Protection Agency’s (EPA) chemical substance inventory are insoluble in DMSO, water, or are volatile/semi-volatile, thus their toxicity cannot be adequately assessed using traditional in vitro dosing methods. To circumvent the difficulties in screening toxic effects in volatile/insoluble chemicals, we developed a cell culture exposure system (CCES) that permits cells to be exposed to multiple concentrations at air-liquid interface (ALI) in a 24-well format. ALI exposure methods permit direct pollutant-to-cell interaction with the test article at physiological conditions, providing a more realistic exposure paradigm. Relevancy to EPA Program/Regional Research Needs/Priorities: This research addresses the needs reflected in the need for New Approach Methods (NAMs) and recent research objectives by OPP and OPPT into the impact portal vs systemic exposure to volatile and aerosolized chemicals have on in-vitro human airway models. The novel approach undertaken by this study also supports the agency’s focus on in vitro methodologies to support existing in vivo testing methods.

Impact/Purpose

Impact/Potential Implications of the Findings: The data from this project characterizes the impact volatile organic chemicals have on human airway epithelial cells. The data generated will be useful to state, federal, and other regulatory agencies in the development of hazard assessments for chemicals routinely used in volatile and aerosolized forms. The chemicals studied are comprised of biocide formulations, preservatives, fertilizers, pesticides, refrigerants, and combustion products. Importantly, the data presented here will be highly valuable for regulators to make scientifically based decisions on the variable and adverse effects of volatile chemicals on human inhalation health and inform future in vitro and in vivo toxicity studies.

Citation

Higuchi, M., A. Speen, AND J. Murray. An Approach Using NAMs for the Evaluation of Inhalation Toxicity in OSCPP Chemical Registrations(BOSC). U.S. EPA Board of Scientific Counselors (BOSC) Meeting-Virtual, RTP, NC - Virtual, February 08, 2021.
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Last updated on June 01, 2021
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