Julia Hoeng, Anita Iskandar, Filippo Zanetti
Philip Morris International
The studies used human cells grown in three-dimensional culture systems. The cultures were grown on top of an artificial membrane at the air-liquid interface, allowing them to develop ‘organotypic’ tissue complexity. Testcigarette is the Tobacco Heating System 2.2 (THS), a new technology that heats tobacco without burning it. The endpoints are shown in measurements of cytotoxicity, alterations in tissue morphology (histology), impact on processes involved in the metabolism of toxicants (xenobiotic metabolism response), secretion of pro-inflammatory mediators, and perturbation of genome-wide gene profiles. The nasal study also looked at ciliary function.
Several professionals in the scientific world have increasingly acknowledged that in assessing the toxicity of chemicals, drugs and consumer products, animal use should be minimized and, where possible, data should be acquired using alternative in vitro based methodologies. This is part of the widely-recognized set of principles known as the ‘3Rs’ of scientific animal research:
Replace: whenever possible, use methods which avoid or replace the use of animals
Reduce: use methods which minimize the number of animals used per experiment
Refine: use methods which minimize suffering and improve animal welfare
One of the goals of ‘21st Century Toxicology’, as set-out in the U.S. National Research Council’s landmark Vision and Strategy report, is to replace in vivo testing methodologies with in vitro procedures on human cells, followed by computational systems biology modelling to determine toxicological risk. The U.S. Food and Drug Administration has identified ‘modernizing toxicology’ as one of its priority areas and has furthermore explicitly expressed an interest in learning about new toxicity testing procedures that could help it meet these goals.
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