Presentations

      Explorative Toxicological Assessment of Consumer Products

      Lichtner, R. B.; H-Urban, H-J. Urban.; Stolle, K.; Schlage, W. K.; Peitsch, M. C.
      Conference date
      Oct 23, 2010
      Conference name
      BIT's Congress of International Drug Discovery Science and Technology
      Link to more information
      Link to more information
      Topic
      Summary

      Cigarette smoke from conventional tobacco products contains more than 5300 identified constituents, some of which are associated with smoking-related diseases in smokers. While there is considerable knowledge about the direct toxicity of cigarette smoke and some of its constituents at high test concentrations, far less is known about the subtle mechanistic effects of cigarette smoke and the individual constituents that may induce disease at biologically relevant concentrations in target tissues. A tiered approach to assess these mechanistic effects using in vitro-based assays was developed. Initially, the toxicological and pathophysiological profiles of single cigarette smoke constituents will be determined in viability, proliferation, and apoptosis assays. In subsequent tiers, a step-wise reduction of test compound numbers according to set criteria and assay outcomes will lead to more complex, mechanism-based assays for pathophysiological assessments. The immediate target of inhaled cigarette smoke is the lung; therefore, cultured primary human bronchial epithelial cells will be used for the initial assays. Compounds not active in viability, proliferation, or apoptosis assays may have specific modes of action that lead to adverse physiological effects (pathophysiology) in an intact organism. Examples are genotoxic compounds that either do not affect normal cell function in the short term (e.g., polycyclic aromatic hydrocarbons [PAH]) or have a non-genotoxic tumor-promoter-like activity or interference with receptor functions (e.g., estrogen receptors). Thus, assays are selected for assessing target-specific effects of single compounds. In the following tiers, systems biology approaches will be used to generate high density data (mRNA arrays, reverse proteomics arrays, gene copy number arrays) for correlation to functional data obtained at biologically relevant experimental conditions. This will enable the identification of new responsive genes, their implication in cellular pathways, and the understanding of compound-affected network perturbations in biological processes that lead to smoking-related diseases.

      PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
      ​
      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.