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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

Biomimetic In Vitro Models for Assessment of Occupational Respirable Aerosol Hazards

Inhalation of respirable particles in the workplace can cause lung disease. Risk assessment of respirable particles exposure has been challenging because of the large number of new particulate chemicals used in the workplace and the limited availability of appropriate in vitro models for toxicity assessment of respirable particles. To address this challenge, scientists at NIOSH developed in vitro cell culture models that allow simple, rapid, and specific testing of respirable particle toxicity as well as detailed mechanistic investigations of exposure effects. The models employ human lung cells for potential use in the screening of occupational respiratory hazards and for potential use in risk assessment. Considerations include determining the relevant in vitro doses to reflect potential occupational exposures, specific lung cell types, and disease endpoints. In vitro models are being used to assess both acute toxicity hazard and cancer hazard from long term exposure to low doses of particles (Kornberg et al. 2019). Further improvements to these in vitro models are being made by integrating the 3D liquid-air interface platform to simulate the complexity of real respirable particle airway exposure conditions. Successful development of this integrated system will facilitate rapid and realistic assessment of respirable particle toxicities.