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Benchmark Dose Modeling Approaches for Volatile Organic Chemicals Using a Novel Air-Liquid Interface In Vitro

Adam M Speen1,2, Jessica R Murray2, Quentin Todd Krantz2

  • 1Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, Tennessee 37830, USA.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|April 15, 2022
PubMed
Summary
This summary is machine-generated.

This study introduces a novel air-liquid interface (ALI) cell culture system for evaluating volatile organic chemical (VOC) toxicity. The system accurately predicts potential health effects by analyzing gene expression in airway cells exposed to VOCs.

Keywords:
in vitroVOCbenchmark dosecell culture exposure systeminhalationtranscriptomics

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Area of Science:

  • Toxicology
  • In vitro toxicology
  • Airway epithelial cell biology

Background:

  • Inhalation is the primary route for volatile organic chemical (VOC) exposure.
  • Traditional in vitro methods face challenges with VOCs due to poor solubility and chemical properties.
  • Direct application or submerged exposures are common but may not accurately reflect inhalation exposure.

Purpose of the Study:

  • To develop and validate a novel air-liquid interface (ALI) cell culture system for assessing VOC toxicity.
  • To evaluate gene expression, cytotoxicity, and cell viability in response to various VOCs.
  • To establish molecular-based points-of-departure for human airway epithelial cells exposed to VOCs.

Main Methods:

  • Utilized an ALI exposure system in a 24-well format for cell culture.
  • Exposed BEAS-2B and primary normal human bronchial epithelial cells (pHBEC) to multiple VOC concentrations.
  • Analyzed gene expression using benchmark dose (BMD) modeling and assessed cytotoxicity and cell viability.

Main Results:

  • VOC exposure at tested concentrations caused only minor changes in cell viability.
  • BMD modeling of gene expression revealed sensitive gene sets.
  • The most sensitive gene sets correlated with known adverse health effects from epidemiological and in vivo studies.

Conclusions:

  • The developed ALI exposure system provides a physiologically relevant in vitro approach for VOC safety testing.
  • This method allows for the evaluation of molecular responses to VOCs in human airway epithelial cells.
  • The findings support the use of ALI exposure for establishing reliable toxicological endpoints for VOCs.