Chairs: Tanja Hansen & Anderas Stucki
Inhalation is considered an important route of occupational and environmental exposure to chemicals, particles and fibres including advanced materials and microplastics. Despite its significance, in vitro tools for testing inhalable compounds are not yet fully established for regulatory decision-making purposes. Even though numerous in vitro methods are being used to identify and characterize the hazard of inhalable substances, significant challenges persist, including extrapolation to and retrospectivity for humans This currently restricts their full implementation in human risk assessment, in particular in a regulatory context. This session will provide guidance towards standardization and harmonization as well as highlights research gaps regarding the complete experimental design to generate data for regulatory use. This includes cell culture models, exposure protocols, dosimetry, and concepts for dose extrapolation to implement the results in risk assessment.
In the current literature, many studies with ALI cell culture models focus on rather short exposures with common readouts such as cytotoxicity, viability, permeability and release of pro-inflammatory mediators and are thus restricted to acute portal-of-entry effects rather than adverse effects that are developed due to repeated (long term) exposure. To gain information on mechanisms of local respiratory toxicity after acute to repeated exposure, employment of sensitive and predictive markers for adverse outcomes (e.g. toxicogenomic or proteomics) might be a step forward. The predictive power of in-vitro inhalation models will be enhanced by applying the Adverse Outcome Pathways (AOP) framework, which casually links key events (KE) relevant to in vitro-in vivo extrapolation (IVIVE).
Speakers
- Tanja Hansen – In-vitro toolbox for predicting inhalation toxicity in humans
- Yann LANDKOCZ – Standardization of cell Air-Liquid Interface studies to assess the toxicity of air pollutants
- Jo Wallace – ADVANCING RESPIRATORY TRACT CELL CULTURE NAM MODELS FOR RISK-BASED DECISION MAKING
- Barbara Rothen-Rutishauser – Harmonizing Lung Cell Models: Insights from Inter-Laboratory Comparison Studies
- Flemming R. Cassee – Impact of in vitro dosimetry on IVIVE and risk assessment.
- Ulla Vogel – ADVERSE OUTCOME PATHWAYS (AOPS) AND SELECTION OF BIOMARKERS