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Development of an in vitro approach to point-of-contact inhalation toxicity testing of volatile compounds, using organotypic culture and air-liquid interface exposure.

Authors
  • Mistry, Artik1
  • Bowen, Larry E1
  • Dzierlenga, Michael W1
  • Hartman, Jessica K1
  • Slattery, Scott D2
  • 1 ScitoVation, LLC, Durham, NC 27713, United States. , (United States)
  • 2 ScitoVation, LLC, Durham, NC 27713, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Toxicology in vitro : an international journal published in association with BIBRA
Publication Date
Dec 01, 2020
Volume
69
Pages
104968–104968
Identifiers
DOI: 10.1016/j.tiv.2020.104968
PMID: 32805374
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In vitro chemical risk assessment using human cells is emerging as an alternative to in vivo animal testing with reduced costs, fewer animal welfare concerns, and the possibility of greater human health relevance. In vitro inhalation toxicity testing of volatile compounds poses particular challenges. Here we report our efforts to establish a testing protocol in our own lab using the EpiAirway bronchial epithelium cell culture model and the Vitrocell 12/12 system for air-liquid interface (ALI) exposures. For purposes of method development, we used methyl iodide (MeI) as a test compound. We examined viability, cytotoxicity, and epithelial integrity responses. Dose-dependent, reproducible responses were observed with all assays. EpiAirway and BEAS-2B cytotoxicity responses to acute exposure were roughly similar, but EpiAirway was more resistant than BEAS-2B by the viability measurement, suggesting a proliferative response at low MeI concentrations. If wells were sealed to prevent evaporation, in-solution MeI concentration-response could be used to predict the response to MeI vapor within 2-fold by converting from the media- to the air-concentration at equilibrium using the blood:air partition coefficient for MeI. The long-term stability of EpiAirway cultures enabled repeated exposures over a 5-d period, which produced responses at lower concentrations than did acute exposure. Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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