Chairs: Arno Gutleb & Ian Crooks
Although traditional methods to assess inhalation toxicity rely on animal testing, decades of research have shown that alternatives, including new approach methodologies (NAMs), can replace animal studies in certain cases. Examples of NAMs are 2D lung cell culture systems, lung tissue systems such as lung slices, three-dimensional lung tissues that replicate the organotypic environment of the human lung, and ‘organ-on-a-chip’ technologies. However, achieving adequate exposure of these lung cells and tissues to study aerosols can be complex. Questions that need to be considered include 1) how to generate particular aerosols and determine the delivered dose, 2) which cells, tissues or systems most accurately represent actual human pulmonary response to the target exposure based on particle size, 3) how to assess the test aerosols’ particle size, 4) the exposure duration, 5) whether to implement single or repeat dosing, 6) where possible, should mimic the known or anticipated human exposure being modelled, and 7) whether the purpose of testing is hazard evaluation or for risk assessment. Further, the biological endpoints to be measured during or following exposure should be selected based on the scientific question under study. These can include simple measures of cytotoxicity or barrier function, and the release of cytokines or chemokines in response to lung inflammation or respiratory sensitization. Responses involved in lung diseases such as chronic obstructive pulmonary disease (COPD) can be investigated through adverse outcome pathways, additionally genotoxicity can be evaluated and in vitro to in vivo extrapolation could be applied. In this series of talks, these areas will be explored to demonstrate the challenges that arise in performing these assays and, more importantly, how to achieve standardised approaches for inhalation toxicity that include specific applications and identify research opportunities for other lung relevant endpoints.
Speakers
- Holger Behrsing – PRECISION-CUT LUNG SLICES PROVIDE AN IMMUNE-RESPONSIVE, LONG-TERM RESPIRATORY MODEL FOR COMPLEX ADVERSE EVENT DETECTION THAT IS AMENABLE FOR STANDARDIZED RESEARCH.
- Shigeaki Ito – ADVERSE OUTCOME PATHWAY (AOP)-BASED IN VITRO EVALUATION OF MUCUS HYPERSECRETION FOR COMPARATIVE TOXICOLOGICAL STUDY OF COMBUSTIBLE CIGARETTE SMOKE AND HEATED TOBACCO PRODUCT AEROSOLS
- Arno Gutleb – Implementing GIVIMP: A Practical Pathway Toward Quality and Compliance in In Vitro Toxicology
- Ian Crooks – Development of the in vitro micronucleus test in human-derived 3D EpiAirway tissues for exposure to aerosols from cigarettes, HTP and Vapour Products
- Michael Hollings – Assessment of cytotoxicity and mechanistic insights from a combination of three independent anatomical regions within the respiratory tract using in Vitro 3D human models following exposure to a 1R6F reference cigarette