Special communication Tob Control: first published as 10.1136/tc.2007.024158 on 28 March 2008. Downloaded from Mandated lowering of toxicants in cigarette smoke: a description of the World Health Organization TobReg proposal D M Burns,1 E Dybing,2 N Gray,3 S Hecht,4 C Anderson,1 T Sanner,5 R O’Connor,6 M Djordjevic,7 C Dresler,8 P Hainaut,9 M Jarvis,10 A Opperhuizen,11 K Straif9 See editorials, p 73–5 Preventing initiation of tobacco product use, differences between brands in the yields. promoting cessation of tobacco use, and protecting Nevertheless, these regimens continue to maintain 1 UCSD School of Medicine, San 2 the public from exposure to second hand smoke are Diego, California, USA; Division a ranking of brands by tar and nicotine yield per of Environmental Medicine, recognised by the World Health organization cigarette, and the rankings by yield per cigarette Norwegian Institute of Public (WHO) Framework Convention on Tobacco using these more intense regimens also do not 3 Health, Oslo, Norway; Cancer Control (FCTC) and by the WHO Study Group provide valid estimates of human exposure, or of Council of Victoria, Melbourne, on Tobacco Product Regulation (TobReg) as the the relative exposure, experienced by smokers Victoria, Australia; 4 University of Minnesota Cancer Center, most effective approaches to reducing tobacco when they smoke different brands of cigarettes. Minneapolis, Minnesota, USA; related morbidity and mortality. However, the A single machine testing regimen produces a single 5 Department of Environmental FCTC also recognises the need for tobacco product set of toxicant yields. In contrast to the machine, and Occupational Cancer, regulation in articles 9 and 10 of the treaty. In individual smokers vary the puffing pattern with Institute of Cancer Research, order to inform that process TobReg has developed The Norwegian Radium Hospital, which they smoke different cigarettes of the same Oslo, Norway; 6 Roswell Park a series of reports that begin to provide a scientific brand, and cigarette design changes can lead Research Institute, Buffalo, New foundation for tobacco product regulation.1–6 This smokers to systematically change how they puff 7 York, USA; Tobacco Control paper summarises a proposal, and the considera- cigarettes. Thus, even yields using these more Research Branch, National tions that led to it, developed by a joint intense smoking regimens have the potential to Cancer Institute, Bethesda, Maryland, USA; 8 Arkansas International Agency for Research on Cancer mislead smokers when expressed per cigarette and Department of Health, Little (IARC) and WHO working group, and approved the machine measured yields should not be used to Rock, Arkansas, USA; by TobReg, which presents performance standards support claims of reduced exposure or risk. 9 International Agency for for cigarettes and a strategy to use them to These limitations of machine measurements led Research on Cancer, Lyon, 10 mandate a reduction in the toxicant yields for to efforts to quantify actual human exposures in France; Royal Free and http://tobaccocontrol.bmj.com/ University College London cigarette smoke. smokers by measuring biomarkers in blood, urine, Medical School, London, UK; and saliva. However, since these biomarkers are 11 National Institute of Public WHY A NEW APPROACH WAS NECESSARY AND measured in human smokers they are influenced Health and the Environment (RIVM), The Netherlands OTHER APPROACHES CONSIDERED by characteristics of the individual, characteristics The most common measurements used historically of the individual’s smoking behaviour, as well as by Correspondence to: to categorise cigarette smoke have been machine characteristics of the product smoked.28 D Burns, 1120 Solana Drive, Del Distinguishing the differences in biomarker levels Mar, California 92014, USA; measured tar, nicotine and carbon monoxide [email protected] (TNCO) yields per cigarette based on the US due to variations between products from the Federal Trade Commission (FTC)/International differences due to smoker behaviour (eg who uses Received 6 November 2007 Standards Organization (ISO) testing regimen. the product and how they use it), is a formidable Accepted 19 December 2007 scientific challenge. Research is needed to resolve There is a current scientific consensus that these on September 30, 2021 by guest. Protected copyright. per cigarette yields do not provide valid estimates these issues in order to allow exposure biomarkers of human exposure or of relative human exposure to become an effective tool for product regulation. when smoking different brands of cigarettes.1 7–9 The multiplicity of brands on the market, self Communication of these measures to smokers as selection of smokers who use different products, estimates of their exposure or risk creates harm by and differences in how smokers of different misleading smokers to believe that differences in products use them, make the use of biomarkers exposures and risk are likely to occur with switch- of exposure in a regulatory strategy to monitor ing to cigarette brands with different machine- cigarette product differences problematic given the measured yields. This ongoing harm precludes current level of scientific knowledge. continued acceptance of current regulatory strate- Characterisation of the differences in harm gies based on per cigarette machine measured caused by different cigarettes would offer a power- TNCO levels and necessitates development of ful metric for product regulation. Markers of new regulatory approaches. biologically effective dose (levels of toxicants in Machine smoking regimens other than the FTC/ critical target organs or tissues) are likely to be ISO regimen have also been examined, particularly developed and validated in the future, and they are ones with more intense puffing parameters and expected to offer more precise measures of smoke which block some or all of the ventilation holes in uptake and better predictions of smoke toxicity.7 This paper is freely available cigarette filters. Examples include those developed Measures of injury or biomarkers of disease risk are online under the BMJ Journals unlocked scheme, see http:// by the US State of Massachusetts and the also likely to be validated in the future. They will tobaccocontrol.bmj.com/info/ Canadian Government. These regimens generally allow more rapid assessment of differences in unlocked.dtl produce higher yields per cigarette and reduce the disease risks than is currently available from 132 Tobacco Control 2008;17:132–141. doi:10.1136/tc.2007.024158 Special communication Tob Control: first published as 10.1136/tc.2007.024158 on 28 March 2008. Downloaded from epidemiological approaches measuring disease outcomes. These conditions.56 It recommends establishing levels for selected advances may allow assessment of differences in risk between toxicants per mg nicotine and prohibiting the sale or import of tobacco products in the future. Nevertheless, at this moment, cigarette brands that have yields above these levels. The purpose none of these measures have been validated as reliable of normalising toxicant levels per mg nicotine is to shift the independent predictors of differences in tobacco related disease interpretation of the measurement away from the quantity of risk among smokers using different products.10 the smoke generated per cigarette, and away from the The limitations of measures of human exposure and human misleading use of TNCO values as measures of human exposure injury suggest that, for the near future, product regulatory and risk. It moves towards product characterisation of smoke approaches may be limited to measures of the differences toxicity generated under standardised conditions. The toxicants between products in design characteristics, contents and currently recommended for mandated reductions by TobReg emissions rather than measures derived from their human use. and proposed levels are presented in table 1. It is generally assumed that product design characteristics, Available data on the variation in the toxicant levels for constituents and additives contribute to the toxicity of cigarette brands provided an initial set of observations used to cigarettes, the addictiveness of the product and the likelihood identify levels of reduction that have already been achieved by that new smokers will start or confirmed smokers will quit. some products on the existing market. The initial levels TobReg has examined the evidence supporting these assump- suggested for regulating tobacco specific nitrosamines (NNK tions and concluded that further research is likely to provide (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNN compelling evidence to establish these assumptions as true.45 (N9-nitrosonornicotine)) are the median values for the brands Nevertheless, the existing science base is currently not sufficient on the market, and for seven additional toxicants the levels to allow regulation of these characteristics based on their effects recommended are set at 125% of the median value of the on toxicity of the product either by establishing product toxicant per mg nicotine for the brands on the market being performance standards or by prohibiting the use of specific regulated. These initial levels are intended to be a first step in an design features or constituents.45In addition, TobReg felt that overall strategy to further reduce levels of toxicants in tobacco regulation of the end product of tobacco combustion (emis- smoke as our understanding of what is possible