BAT Science - Smoke exposure models

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Smoke exposure models


Our smoke exposure research includes both literature based research into toxicants found in tobacco smoke as well as an extensive laboratory based research programme investigating the effects of tobacco smoke exposure using in vitro models.

We perform reviews of external literature for tobacco smoke constituent lists and enhanced risk assessment procedures and are working to develop an integrated risk assessment model for tobacco smoke constituents. There have been numerous attempts to draw up lists of and prioritise relevant cigarette smoke toxicants, all of which vary in the number, identity and order placed on cigarette smoke constituents. This review process and its results are described on the following page:-

The majority of our in-house pre-clinical research programmes focus on the development of relatively short-term in vitro tests to assess the biological effects of our products on these test systems. These in vitro models should help us understand and investigate the mechanisms of smoke toxicity and potentially disease mechanisms. Our work focuses on cancer, chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). A similar approach is used by other industries who are interested in using in vitro models in order to reduce animal experimentation – the standard approach for testing pharmaceuticals and cosmetics. In Europe the interest of various companies in the use of in vitro models is represented by an organization called The In Vitro Testing Platform (IVTIP). For more information about IVTIP please see the following page:-

How cigarette smoke is collected and presented to the in vitro model system needs careful consideration and studies over the years have attempted to develop relevant and appropriate cigarette smoke test substances and systems. The merits and intricacies of these systems are discussed in the following pages:-

Cigarette smoke generation

Whole cigarette smoke is a complex aerosol made up of over 5,000 components [1] that are distributed between the particulate and gas phases. The particulate phase makes up only a small percentage of the total weight of mainstream smoke (approximately 5%) and is comprised of multiple constituents including heterocyclic amines, polyaromatic hydrocarbons and nicotine. The remaining 95% is the gaseous phase which also contains multiple compounds including acetaldehyde, ammonia, carbon monoxide and various nitrogen oxides.

Smoke aerosol broken down by its different exposure techniques

For experimental purposes, smoke is generated from cigarettes machine-smoked under specific smoking regimes. The composition of cigarette smoke varies when different regimes are used [2].
There are three main forms of cigarette smoke that can be evaluated using in vitro model test systems:-

  1. Whole smoke - Whole cigarette smoke activity can be assessed using specifically designed aerosol delivery systems, enabling a more physically relevant assessment of the effects of cigarette smoke [4-5]. With such a system both phases of cigarette smoke, particulate and gaseous may be assessed in combination or separately.

  2. Total particulate matter (TPM) - Routine in vitro testing of cigarette smoke traditionally assesses the particulate phase activity of cigarette smoke. Particulate phases can be easily trapped onto Cambridge filter pads and extracted and re-suspended in solvent.

  3. Aqueous extracts - Components of the gas phase may also induce toxicological and biological effects. As the compounds and some components of the particulate phase are water soluble, aqueous cigarette smoke extracts can be generated as cigarette smoke is bubbled through cell culture media [3].

All three forms of cigarette smoke are investigated in our research programme using appropriately designed in vitro models.

  1. Rodgman, A., Perfetti, T.A., (2009). The chemical components of tobacco and tobacco smoke. CRC press, ISBN 978-1-4200-7883-1.
  2. Rickert, W.S., Trivedi, A.H., Momin, R.A., Wright, W.G., and Lauterbach, J.H. (2007). Effect of smoking conditions and methods of collection on the mutagenicity and cytotoxicity of cigarette mainstream smoke. Toxicological Sciences. 96: 285-93.
  3. Bernhard, D., Huck, C.W., Jakschitz, T., Pfister, G., Henderson, B., Bonn, G.K., Wick, G. (2004). Development and evaluation of an in vitro model for the analysis of cigarette smoke effects on cultured cells and tissues. Journal of Pharmacological and Toxicological Methods. 50: 45-51.
  4. Phillips, J., Kluss, B., Richter, A., Massey, E. (2005). Exposure of bronchial epithelial cells to whole cigarette smoke: assessment of cellular responses. Alternatives to Laboratory Animals. 33 (3): 239-248. Abstract and citation link 
  5. Aufderheide, M., Gressmann, H. (2007). A modified Ames assay reveals the mutagenicity of native cigarette mainstream smoke and its gas vapour phase. Experimental and Toxicologic Pathology. 58: 383-92.
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