Human cell-based in vitro systems to assess respiratory toxicity: a case study using silanes

Area of Science:

• Toxicology
• Inhalation Exposure
• Respiratory System

Background:

• Inhalation is a primary route for human chemical exposure.
• Developing accurate in vitro methods is crucial for predicting respiratory toxicity and managing risks.
• The IN vitro Systems to PredIct REspiratory toxicity Initiative-2 (INSPIRE-2) focuses on advanced cell-based models.

Purpose of the Study:

• To evaluate two in vitro cell systems for predicting respiratory tract toxicity from inhaled chemicals.
• To assess the toxic effects of triethoxysilane (TES) and trimethoxysilane (TMS) using these models.

Main Methods:

• Exposed BEAS-2B cells and MucilAir reconstructed human tissue models to TES and TMS vapors at the air-liquid interface.
• Assessed cell viability, cytotoxicity, inflammatory marker secretion, tissue morphology, barrier integrity, and ciliary function.
• Examined recovery of MucilAir tissues over 7 days.

Main Results:

• Both BEAS-2B cells and MucilAir tissues provided valuable toxicity data.
• BEAS-2B cells showed higher sensitivity for cell viability and inflammatory markers.
• MucilAir tissues offered insights into morphology, barrier function, and ciliary activity, with TMS generally more toxic than TES.

Conclusions:

• The evaluated in vitro systems effectively predict the potential toxicity of inhaled chemicals.
• These models are valuable tools for risk assessment and understanding human respiratory responses to chemical exposure.
• The study demonstrated the utility of these systems for calculating human equivalent concentrations.