Posters

      In Vitro Test Systems for Aerosols Toxicology Assessment - Characterization of Exposure, Metabolism and Kinetics

      Knorr, A.; Dutertre, Q.; Majeed, S.; Mathis, C.; Frentzel, S.; Bentley, M. C.; Hoeng, J.; Vanscheeuwijck, P.

      Conference date
      Jan 12, 2016
      Conference name
      Systems Toxicology 2016 - Real World Applications and Opportunities
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      Topic
      Summary

      Direct exposure to inhaled mainstream cigarette smoke is known to cause smoking-related damage in the human lung. Aerosol exposure of human three dimensional (3D) organotypic airway epithelial tissue cultures, growing at the air-liquid interface is a well-established in vitro model enabling systems biology-based Reduced Risk Product (RRP*) assessment. The characterization of RRPs exposure is an essential part of the whole product assessment strategy. Smoke compounds such as nicotine or primary metabolites of smoke compounds (e.g. acrolein glutathione adducts) are assessed as exposure markers, which may be utilized for an insert-to-insert normalization of 3D tissue cultures. Moreover, the magnitude by which reduced glutathione (GSH) becomes depleted may also provide a valuable cellular stress marker when assessing the effect of RRP aerosol, compared to conventional cigarette smoke. Furthermore, investigations on the migration kinetics including adsorption and excretion occurring in 3D organotypic tissue cultures have been started to better understand the bioavailability of smoke compounds over time and to be able to link it to the observed impact on the exposed in vitro model. To better understand the role of xenobiotic metabolism after cigarette smoking, human subcellular liver and lung fraction models (microsomes, S9) have been established within a case study focused on phase I and phase II metabolism of furan type compounds to assess metabolite profiles and reactive metabolites relevant for toxicology. Finally, approaches using both subcellular fractions metabolism models and organotypic tissue cultures are in line with the 3R strategy to find an alternative for animal testing. The integration of the exposure characterization results together with the systems toxicology approach to measure the biological impact of the exposure has the potential to further highlight the mode of action associated to RRPs exposure. *Reduced-Risk Products ("RRPs") is the term we use to refer to products with the potential to reduce individual risk and population harm in comparison to smoking combustible cigarettes. 

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      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.