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Smoke toxicants

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Tobacco smoke is a complex mixture of over 5000 identified compounds [1]. Approximately 150 are known to have specific toxicological properties and these can be termed ‘tobacco smoke toxicants’.

There have been numerous attempts to draw up lists of relevant cigarette smoke toxicants, all of which vary in the number and identity of cigarette smoke  constituents. 

Examples of these lists include:-

  • Cysteine Index [2]
  • Herzfeld Index  [3]
  • Hoffmann Lists [4,5]
  • Relative Exposure Index [6]
  • Relative Toxicity [7]
  • Emissions from tobacco products [8]
  • Application of risk assessment principles [9]
  • Cancer risks [10]
  • Mandated lowering of toxicants in cigarette smoke [11]

There is a significant body of scientific literature identifying tobacco smoke constituents potentially responsible for the adverse health effects of cigarette smoking focusing on the three major diseases (cancer, chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD)) [12,13].

We are interested in any potential regulatory frameworks and product modifications aimed at risk reduction and identifying which toxicants are associated with the development of cancer, COPD and CVD. Providing a quantitative estimate of the contribution of specific toxicants to disease processes could assist in focusing research priorities to reduce exposure to particular smoke compounds.

It must be noted that tobacco smoke is a complex mixture and constituents may interact to enhance or inhibit the hazardous properties of tobacco smoke. A complete risk assessment model would need to incorporate these factors.

The importance of relevant risk assessment models

There has been an increasing trend towards prioritising tobacco smoke constituents in relation to their contribution to disease. There have been two papers published in recent years, Fowles and Dybing [9] and Burns [11], which are of particular interest.

Fowles and Dybing’s paper [9] described the calculation of a ranking, made up of a cancer potency factor – or non-cancer reference exposure level – and the amount of the chemical constituent present in cigarette smoke. The aim was to give individual chemical risk indices for cancer, cardiovascular effects, or non-cancer effects.

We have been reviewing the data used by Fowles and Dybing [9] to determine if the various risk indices used are biologically plausible in relation to the main smoking-relating diseases. In some instances, potency figures and reference exposure levels have been derived from organs and tissues – such as neural tissue – not related to cigarette smoke toxicology in the respiratory and cardiovascular systems.

We believe that there is a need to build models as relevant as possible to smoking related diseases.

Our Approach

Researchers are looking for ways to increase the relevant data used in risk assessment models and minimise the use of arbitrary uncertainty factors – for example using the European Food Safety Authority Margin of Exposure (MOE) model [14], which is designed to segregate risk management actions into high or low priority and is endorsed by the EU scientific committee on consumer products, although not for tobacco product assessment [15].

In addition, physiologically-based pharmacokinetic (PBPK) modelling – incorporating known differences in reactions of toxicological test systems, including in vitro and in vivo models, is potentially able to enhance the risk assessment procedures.


  1. Rodgman, A., Perfetti, T.A. (2009). The chemical components of tobacco and tobacco smoke. CRC press, Florida, USA. pp. 1259. ISBN 978-1-4200-7883-1.
  2. Leuchtenberger, C., Leuchtenberger, L., Zbinden I. (1974). Gas vapour phase constituents and SH reactivity of cigarette smoke influence lung cultures. Nature. 247: 565-567.
  3. Herzfeld, L., (1982). A Prophylactic Plan for Reducing Risks to Smokers. Notabene Medici. 12: 808-816.
  4. Hoffmann, D., Hecht, S.S. (1990). Advances in tobacco carcinogenesis. In: Cooper, C.S and Grover, P.L (Eds), Chemical Carcinogenesis and Mutagenesis I (Handbook of Experimental Pharmacology). Springer-Verlag, Heidelberg. Volume 94, pp. 63-102. ISBN: 03-8751-182-2.
  5. Hoffmann, D.. Hoffmann, I., (1997). The changing cigarette, 1950-1995. Journal of toxicology and environmental health. 50: 307-364.
  6. Rickert, W. S., Kaiserman, M. J., (1998). Development of an index for mainstream tobacco smoke based on chemical composition. Relative exposure index. Presented at the 52nd Tobacco Scientists’ Research Conference.
  7. Smith, C. J., Hansch, C., (2000). The relative toxicity of compounds in mainstream cigarette smoke condensate. Food and Chemical Toxicology. 38: 637-646.
  8. Department of Justice, Canada, 2000. Tobacco reporting regulations. SOR/2000-273.
  9. Fowles, J., Dybing, E., (2003). Application of toxicological risk assessment principles to the chemical constituents of cigarette smoke. Tobacco Control. 12: 424-430.
  10. Hecht, S.S., (2006). Cigarette smoking: cancer risks, carcinogens and mechanisms. Langenbeck’s Archives of Surgery. 391: 603-613.
  11. Burns, D. M., Dybing, E., Gray, N., Hecht, S., Anderson, C., Sanner, T., O’Connor, R., Djordevic, M., Dresler, C., Hainaut, P., Jarvis, M., Opperhuizen, A., Straif, K., (2008). Mandated Lowering of Toxicants in Cigarette Smoke: A Description of the World Health Organization TobReg Proposal. Tobacco Control. 17: 132-141.
  12. Stratton, K., Shetty, P., Wallace, R., Bondurant, S., (2001). Executive summary. In: Clearing the smoke. Assessing the science base for tobacco harm reduction. Nat. Acad. Press, Washington, pp. 1. ISBN: 0-309-07282-4.
  13. Rodgman, A., Green, C., (2003a). Toxic chemicals in cigarette mainstream smoke – hazard and hoopla. Beitrage Zur Tabakforschung International. 20: 481-538.
  14. European Food Safety Authority. EFSA/WHO International conference with support of ILSI Europe on risk assessment of compounds that are both genotoxic and carcinogenic Opens new window.
  15. European Commission (EC), Scientific Committee on Health and Environmental Risks/Scientific Committee on Consumer Products/Scientific Committee on Emerging and Newly Identified Health Risks (SCHER/SCCP/SCENIHR) 2009, Scientific opinion on ‘Risk assessment methodologies and approaches for mutagenic and carcinogenic substances’ Opens new window.
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