5.3Measurestoassesstheeffectivenessof … · tunity to study changes in the ... and behaviour, as in the case of “light” and low-tar cigarettes ... tiveness or consumer appeal

5.3 Measures to assess the effectiveness oftobacco product regulation

231

IInnttrroodduuccttiioonn

Tobacco product regulation is arapidly emerging area in tobaccocontrol. Scientists, policy makers,and international public healthorganisations have called forcomprehensive regulation of toba-cco products with the aim ofprotecting public health. A handfulof countries and jurisdictions havealready adopted legislation requiringreporting and testing of tobaccoproduct contents and emissions.Articles 9 and 10 of the WHOFramework Convention on TobaccoControl (FCTC) contain the require-ments for regulation of tobaccoproduct contents and emissions, aswell as manufacturers’ disclosuresabout the product (Figure 5.6).As the regulatory landscape

evolves around the world, it isessential to evaluate the effec-tiveness of new regulations andtheir impact on the product itself andon the population, in order todetermine whether regulations aremeeting public health goals. Theemergence of new legislation andregulatory standards for tobaccoproducts provides a unique oppor-tunity to study changes in theproduct and in health outcomesover time and across countries andregions. Because product regu-lations cannot be assessed throughrandomised clinical trials, re-

searchers and public health officialsmust employ quasi-experimentaldesigns and utilise opportunities for“natural experiments” throughmaking comparative observations(Fong et al., 2006a). Additionally, itis important to begin collectingbaseline data and developingmeasures and protocols forevaluation, so that the impact offuture regulations can be assessed.In 1999, a WHO Conference on theRegulation of Tobacco Productsconcluded that “The regulatoryprocess must be guided by the bestavailable science and the effectstracked so as to maximize healthbenefits, minimize unintended con-sequences, and thereby fosterself-correction.” (WHO, 2000).The ultimate test of the impact of

a regulation intended to protectpublic health is to demonstrate areduction in morbidity or mortalityassociated with the regulation.However, it can take decades forsome effects, such as changes incancer incidence, to be seen. Thus,measures to assess productregulation have historically focusedon the product itself, although suchmeasures have significant limita-tions for predicting human risk. Theneed for in-depth product evaluationunder actual conditions of use issupported by the history of thedevelopment and promotion of“light” cigarettes. Based on stan-

dardised machine smoking mea-surements, the average sales-weighted tar and nicotine yield forUS cigarettes decreased by about70% between the 1950s and 1990s(Hoffman & Hoffman, 2001). Scien-tists and public health officialsinitially supported this trend in the1960s and 1970s (Parascandola,2005), and it took decades beforeepidemiologic studies provideddefinitive evidence that changes incigarettes designed to lower smokeyields did not in fact lead to anysignificant decrease in the tobacco-related disease burden (Burns et al.,2001). We now know that much ofthe apparent decline was due to theuse of filter ventilation, whichproduces markedly reduced ma-chine measured yields, but notnecessarily on the amounts smo-kers actually take in (Kozlowski etal., 1998a).Laboratory-based product testing

remains vitally important, despite itslimitations for predicting human risk.First, it supports monitoring ofadherence to laws intended toregulate features of product designand performance, such as emissionlimits based on machine mea-surements and low ignition pro-pensity laws. Second, it allows forthe measurement of differencesbetween products or changes inproducts that may impact exposure,such as comparing cigarettes that

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heat versus burn tobacco orcigarettes containing tobacco withhigh versus low tobacco-specificnitrosamine (TSNA) levels. Third,systematic product testing isimportant because it contributes tothe development of general ex-pertise and capacity for tobaccoproduct regulation. Historically,most product-related expertisehas been limited to the tobaccoindustry, and public health scien-tists have been at a disadvantagein understanding the relevance ofproduct characteristics for healthand behaviour, as in the case of“light” and low-tar cigarettes(Parascandola, 2005). Whiledoubtless new, more sophis-ticated technologies and mea-sures will be developed, suchprogress will be limited without anetwork of experienced, publichealth oriented scientists andtechnicians. The task of tobacco product

evaluation is complicated by thefact that regulatory requirements

are still evolving; for manypotential outcomes validatedstandard measures have not yetbeen identified. While the FCTCmandates regulation and reportingof tobacco product contents andemissions, guidance for imple-mentation of these articles is stillunder development by the Con-ference of the Parties (COP)(http://www.who.int/tobacco/fctc/cop/en/). Thus, it is not clear yetwhich specific measures will berequired in the implementation ofthe FCTC. This section will review existing

measures relevant to tobaccoproduct regulation as well asdiscuss challenges and researchneeds. First, the characteristics ofsome existing tobacco productregulations will be described toillustrate the range and types ofprovisions used in currentregulations. Second, the sectionwill cover proximal measures forassessing tobacco product regu-lations, which focus on the product

itself. Measures of productcontent, design and emissions willbe discussed, including thelimitations of smoking machineprotocols for assessing actualhuman exposure. Third, thesection will address distal mea-sures as well, which focus on theimpact of regulations for humanexposure and risk, including bio-markers and surveillance acti-vities.

EExxiissttiinngg ttoobbaaccccoo pprroodduuccttrreegguullaattiioonnss

Tobacco product regulation re-mains in its early stages but isevolving rapidly. A number ofcountries and jurisdictions haveadopted product regulations,including ingredient disclosurelaws, limits on tar and nicotineyields, low ignition propensity (firesafety) standards, or bans onadditives, such as candy fla-vourings. However, there is littleuniformity across jurisdictions in

• RReegguullaattiioonn ooff tthhee ccoonntteennttss ooff ttoobbaaccccoo pprroodduuccttss.. The Conference of the Parties, in consultation with competentinternational bodies, shall propose guidelines for testing and measuring the contents and emissions of tobaccoproducts, and for the regulation of these contents and emissions. Each Party shall, where approved by competentnational authorities, adopt and implement effective legislative, executive and administrative or other measures forsuch testing and measuring, and for such regulation.

• RReegguullaattiioonn ooff ttoobbaaccccoo pprroodduucctt ddiisscclloossuurreess. Each Party shall, in accordance with its national law, adopt and implementeffective legislative, executive, administrative or other measures requiring manufacturers and importers of tobaccoproducts to disclose to governmental authorities information about the contents and emissions of tobacco products.Each Party shall further adopt and implement effective measures for public disclosure of information about the toxicconstituents of the tobacco products and the emissions that they may produce.

WHO (2003)

FFiigguurree 55..66 WWHHOO FFCCTTCC AArrttiicclleess 99 aanndd 1100:: RReegguullaattiioonn ooff tthhee ccoonntteennttss ooff ttoobbaaccccoo pprroodduuccttss aanndd RReegguullaattiioonnooff ttoobbaaccccoo pprroodduucctt ddiisscclloossuurreess,, rreessppeeccttiivveellyy


Measures to assess the effectiveness of tobacco product regulation

233

the content of these laws. Somejurisdictions require constituentdisclosure only, while others setstandards or limits on content oremissions. Moreover, while someproduct standards target toxicproperties directly (such as byestablishing maximum tar orcarbon monoxide limits), otherstarget properties that, while notdirectly harmful, affect addic-tiveness or consumer appeal(such as by controlling flavouradditives that affect the appeal ofthe product to children). Currently, there is no cen-

tralized, systematic monitoring oftobacco product regulations. Thedata collected in Tobacco ControlCountry Profiles 2003 includessome information on regulation formany countries (Shafey et al.,2003). However, the availabledata does not specify the details ofthe regulations (i.e. which con-stituents are regulated, whatproduct standards or limits areimposed) and it is not updatedregularly. As countries continue todebate and enact new tobaccoproduct regulations, there is aneed for comprehensive trackingof the evolving regulatory en-vironment. A few countries and juris-

dictions have adopted tobaccoproduct regulations and provideearly models of the types ofregulatory mechanisms that maybe implemented more widely.There are also a number ofcountries that have adoptedInternational Organization forStandards (ISO) emission limitsfor tar and nicotine aimed atreducing tobacco related harm,including Brazil, Thailand, China,

South Africa, and Malaysia, aswell as the European Union (EU). There are at least five main

types of tobacco product regu-lations that can currently beobserved: 1) regulations thatrequire disclosure of productinformation (such as tar andnicotine content) (Figure 5.7); 2)regulations intended to reduceproduct toxicity and harm (such asmaximum emission limits for tarand nicotine) (Figure 5.8); 3)regulations intended to reduce theaddictiveness and/or attrac-tiveness of tobacco products(such as bans on ingredients thatimpact nicotine delivery or banson flavour additives that maymake a product more attractive tochildren) (Figure 5.9); 4) regu-lations intended to prevent firescaused by cigarettes (ignitionpropensity laws) (Figure 5.10);and 5) bans (or removal of bans)on product categories (Figure5.11). A few examples are pro-vided in Table 5.15 to illustrate therange of different types of productregulations that are currentlybeing implemented or discussed.A more detailed presentation

of country specific regulationsfollows:

Canada:

The Tobacco Reporting Regu-lations, developed under theauthority of the 1997 Tobacco Act,require manufacturers and im-porters of tobacco products toCanada to submit to the Ministerof Health information on tobaccoproduct composition and emis-sions. This includes, for smokedproducts, information on more

than 40 toxic emissions in bothmainstream and sidestreamsmoke under two differentsmoking regimens, and informa-tion on more than 20 specificconstituents of whole/unburnedtobacco (http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/legislation/reg/index_e.html).

Brazil:

The National Health SurveillanceAgency (ANVISA) is charged withregulating a wide variety of con-sumer products in the interest ofpublic health, including cigarettesand other tobacco products.ANVISA resolution No. 46 (March21, 2001) establishes maximumtar, nicotine, and carbonmonoxide yields for cigarettes,and the tobacco industry isrequired to submit annual reportsthat identify and list by brand allingredients and additives in everytobacco product produced inBrazil (http://www. anvisa.gov.br/eng/tobacco/index.htm).

European Union:

In effect since 2004, a directive ofthe European Parliament to Mem-ber States limits the maximumyield of tar, nicotine, and carbonmonoxide in cigarettes manu-factured or marketed in the EU (10mg tar, 1 mg nicotine, and 10 mgcarbon monoxide). The directivealso requires the tobacco industryto submit to Member States a listof ingredients, and quantitiesthereof, used in the manufactureof those tobacco products bybrand name and type (http://ec.europa.eu/health/ph_determinants



234

/life_style/Tobacco/tobacco_en.htm).

United States:

The Comprehensive SmokingEducation Act of 1984 andComprehensive Smokeless Toba-cco Health Education Act of 1986require cigarette and smokelesstobacco manufacturers to submita list of ingredients added totobacco to the Secretary of Healthand Human Services. However,the law requires that the list notidentify the specific brand orcompany using the ingredients.Smokeless tobacco manufac-

turers must also report thequantity of nicotine in eachproduct according to standardmeasures. (Centers for DiseaseControl and Prevention, 1997a;http://www.cdc.gov/tobacco/FCLA/terms.htm).

Massachusetts:

Manufacturers of cigarettes andsmokeless tobacco products soldin Massachusetts must report theproduct’s nicotine yield accordingto a standardised protocol. TheState also proposed a regulationrequiring reporting of all ingre-dients added to cigarettes by

brand, but this regulation wasbarred by a federal court(http://www.mass.gov/dph/mtcp/legal/prodreg.htm).

New York State:

In 2004, New York State becamethe first jurisdiction in the world toimplement reduced ignition pro-pensity (RIP) standards forcigarettes; Canada became thefirst country to do so in 2005. Boththe New York State and Canadianlaws stipulate that at least 75% ofcigarettes must self-extinguishbefore burning the full length oftheir tobacco columns using a

PolicyProduct ddiisscclloossuurree regulation

Uses made of the data

PPoolliiccyy--ssppeecciiffiicc mmeeddiiaattoorrssCompliance with regulation• Completeness of data• Accuracy of data

MMooddeerraattoorrss• Availability of data• Other information sources

OOuuttccoommeess• Policy effectiveness• Public awareness

FFiigguurree 55..77 CCoonncceeppttuuaall ffrraammeewwoorrkk ffoorr tthhee eevvaalluuaattiioonn ooff pprroodduucctt ddiisscclloossuurree rreeqquuiirreemmeennttss



235

PPoolliiccyyPPoolliicciieess ttoo rreedduuccee ttooxxiicciittyy• Emission standards• Design requirements

IInncciiddeennttaall eeffffeeccttss• Tobacco use

behaviour• Product marketing• Product related

beliefs and attitudes

TToottaall ttoobbaaccccoo uusseeGGeenneerraall mmeeddiiaattoorrssShort-term measures• Exposures• Toxicity

OOuuttccoommeessLong-term measures• Disease outcomes

MMooddeerraattoorrss 22• Demographics• Biological factors

PPoolliiccyy--ssppeecciiffiicc mmeeddiiaattoorrssCompliance with regulation• Product design and

performanceIndustry innovation

MMooddeerraattoorrss 11• Product related


TToobbaaccccoo iinndduussttrryymmaarrkkeettiinngg

FFiigguurree 55..88 CCoonncceeppttuuaall ffrraammeewwoorrkk ffoorr tthhee eevvaalluuaattiioonn ooff ppoolliicciieess ttoo rreedduuccee ttoobbaaccccoo ttooxxiicciittyy



236

PPoolliiccyyPPrroodduucctt rreegguullaattiioonnss ttoo rreedduucceeaaddddiiccttiivveenneessss//aattttrraaccttiivveenneessss ooffttoobbaaccccoo pprroodduuccttss

IInncciiddeennttaall eeffffeeccttss• Product marketing• Product related

beliefs and attitudes• Product toxicity

GGeenneerraall mmeeddiiaattoorrss• Sensory perception• Consumer reaction

Brand shiftingChange in consumptionChange in how smokedReduced attractiveness

OOuuttccoommeess• Quitting• Reduced consumption• Patterns of tobacco use

behaviour• Reduced initiation

MMooddeerraattoorrss 22• Demographics• Biological factors


performanceIndustry innovationConsumer awareness

MMooddeerraattoorrss 11• Product related


• Tobacco use behaviours

TToobbaaccccoo iinndduussttrryymmaarrkkeettiinngg

FFiigguurree 55..99 CCoonncceeppttuuaall ffrraammeewwoorrkk ffoorr tthhee eevvaalluuaattiioonn ooff ppoolliicciieess ttoo rreedduuccee tthhee aattttrraaccttiivveenneessss aanndd//oorraaddddiiccttiivveenneessss ooff ttoobbaaccccoo pprroodduuccttss



237

standardised method for asses-sing ignition propensity. Both lawsuse the American Society forTesting and Materials (ASTM)method, which involves posi-tioning a cigarette on one of threestandard substrates to generatesufficient heat to continue burning,and thus potentially cause ignitionof bedding or upholstered furniture(ASTM E2187-04 Standard TestMethod for Measuring the IgnitionStrength of Cigarettes; http://www.astm.org/cgi-bin/SoftCart.exe/

database.cart/redline_pages/e2187.htm?E+mystore).So far, no jurisdiction has suc-

cessfully enacted comprehensiveregulations governing the design,contents, and emissions oftobacco products. Product per-formance standards, for example,could be used to reduce knownharmful emissions. Currentlyavailable data and methods areinsufficient to allow for a quan-titative estimate of the publichealth impact of reductions in

specific constituents in tobaccosmoke. However, evidence showsthat there is a wide variationglobally between countries andcigarette brands in emissions oftar, nicotine, and carbon mon-oxide, as well as majorcarcinogens, suggesting thatreductions are feasible and arejustifiable on a precautionarybasis. A survey of transnationaland locally-produced cigarettes in35 countries found, when mea-sured by a standardised machine

IInncciiddeennttaall eeffffeeccttss• Industry innovation• Patterns of tobacco use

behaviour• Product marketing

PPoolliiccyyReduced ignition propensitycigarettes

PPoolliiccyy ssppeecciiffiicc--mmeeddiiaattoorrssCompliance with regulation• Product design and

performance

OOuuttccoommeess• Cigarette-caused fires

(expected reduction)

FFiigguurree 55..1100 CCoonncceeppttuuaall ffrraammeewwoorrkk ffoorr tthhee eevvaalluuaattiioonn ooff ttoobbaaccccoo pprroodduucctt rreegguullaattiioonn ttoo rreedduuccee ffiirreess



238

IInncciiddeennttaall eeffffeeccttss• Changes in beliefs about harmfulness of remaining products

• Changes in product types

• Product design and performance

• Product marketing• Smuggling


performanceIndustry innovation

MMooddeerraattoorrss• Demographics• Biological factors• Dependence

GGeenneerraall mmeeddiiaattoorrssChoices made by user of bannedproducts• Attitude to remaining

products

OOuuttccoommeess• Mix of products used• Tobacco use behaviour

Way products usedQuitting

• Health outcomes

PPoolliiccyyProduct regulation

BBaann pprroodduucctt ccaatteeggoorriieess

FFiigguurree 55..1111 CCoonncceeppttuuaall ffrraammeewwoorrkk ffoorr tthhee eevvaalluuaattiioonn ooff ttoobbaaccccoo pprroodduucctt rreegguullaattiioonn ttoo bbaann ssppeecciiffiicc pprroodduuccttccaatteeggoorriieess



239

smoking protocol, wide variation inemissions of tar (6.8 to 21.6 mg),nicotine (0.5 to 1.6 mg), andcarbon monoxide (5.9 to 17.4 mg),with cigarettes from the EasternMediterranean, Southeast Asia,and Western Pacific WHO regionsreporting higher deliveries thanthose from other regions (Calafatet al., 2004). Further analysesfrom this survey have revealedthat mainstream smoke levels oftobacco-specific nitrosamines(TSNAs) and poly-cyclic aromatichydrocarbons (PAHs) also varywidely across countries, includingwithin the same multinationalbrand (Wu et al., 2005; Ding et al.,2006). Given the observed varia-tion, one regulatory proposalinvolves a system for controllingtoxins and carcinogens in

cigarettes by the establishment ofupper limits based on the medianof the existing market (Gray &Boyle, 2002). There have alsobeen proposals to reduce nicotineto non-addictive levels to preventthe development of nicotineaddiction in young people(Benowitz & Henningfield, 1994).However, so far such proposalshave not been implemented in anyregulations, and currently there isinsufficient evidence to predictwhat the potential impact of suchregulations would be on healthoutcomes or smoking behaviour. Regulations requiring tobacco

product disclosure, as required inFCTC Article 10, also have anessential role. In order to effec-tively establish product standardsand regulate manufacture of the

product, regulators must havevalid information about productdesign, contents, and emissions.Standardised reporting and dis-closure by manufacturers assistsregulators in monitoring changingtrends in product design acrossthe market that may impact publichealth. Additionally, such dis-closures allow for more effectiveevaluation of the impact andpotential unintended effects ofnew regulatory requirements onproduct design and emissions. In order to guide evaluation of

tobacco product regulations, it isimportant to have a conceptualmodel of the proximal and distaleffects of the regulation, taking intoaccount other factors that mediateor moderate those effects (policy-specific mediators, general

RReegguullaattiioonn TTyyppee RReeqquuiirreemmeennttss

PPrroodduucctt DDiisscclloossuurree Reporting of 40 constituents in mainstream and sidestream smoke and 20 specificExample: Canada constituents of whole/burned tobacco according to specified protocols.Tobacco Reporting Regulation

RReedduuccee HHaarrmm Maximum cigarette emission yields: 10 mg tar, 1 mg nicotine, and 10 mg Example: European Union caron monoxide determined by specified machine testing method.Directive 2001/37/EC

RReedduuccee AAddddiiccttiivveenneessss aanndd//oorr Proposed ban on additives that increase the addictiveness of tobacco products.AAttttrraaccttiivveenneessss

RReedduuccee CCiiggaarreettttee--CCaauusseedd FFiirreess Mandatory performance standards require that at least 75% of cigarettes must self-Example: New York State extinguish before burning the full length of their tobacco columns, utilizing theFire Safety Standard for Cigarettes American Society for Testing and Materials (ASTM) method for measuring ignition

propensity.

PPrroodduucctt BBaannss Prohibits sale and marketing of “all products for oral use, except those intended toExample: European Union be smoked or chewed, make wholly or partly of tobacco.”Directives 2001/37/EC, 92/41/EEC

Table 5.15 Product Regulations



240

mediators, and outcomes). Themodel should also include otherincidental effects of a regulationthat are important to evaluating theimpact of a regulation on publichealth. As a general framework, itis likely that the impact of tobaccoproduct regulations on intendedhealth outcomes will be moderatedby changes in product design andperformance, product marketing,product-related beliefs and atti-tudes, and tobacco use behaviour,which in turn are expected toinfluence exposures to tobaccoconstituents and emissions. However, because tobacco

product regulations can have arange of different goals, multipleconceptual models are needed tounderstand different types ofregulations, just as a variety ofmethods and measures areneeded for evaluating differentregulations. Five generalized logicmodels are provided to guide thedevelopment of evaluations oftobacco product regulations(Figures 5.7 to 5.11). These fivelogic models reflect the five majortypes of tobacco product regu-lations identified above (dis-closure, reducing product harm,reducing product addictiveness/attractiveness, preventing fires,product bans). The logic modelsall start with the introduction of anew policy and then proceed toshow a pathway to proximal anddistal variables or constructs to beused in assessing the effects ofthe regulation. Key mediators andmoderators, along with incidentaleffects, are also identified forinclusion in evaluations. Forexample, a regulation requiring

manufacturers to disclose productinformation to consumers shouldbe evaluated ultimately in terms ofits impact on public awareness ofthe information communicatedand the effectiveness of thosecommunications in successfullyinforming the public about productcharacteristics. Those effects maybe moderated by the availability ofrelevant data and the presence ofother information sources. Incontrast, a regulation that aims toreduce product toxicity and harmshould be evaluated ultimately interms of its impact on diseaseoutcomes. Short-term measuresof changes in exposures ortoxicity, such as use of bio-markers, may substitute for actualmeasures of disease outcome.These outcomes are likely to bemoderated by demographic andbiological factors, as well asconsumers’ product related atti-tudes and behaviours. Thus, thesetwo types of regulations requirevery different logic models for theirevaluation. Before developing anevaluation plan or protocol, it isimportant to have a logic modelthat maps out the goals of theregulation and relevant factors thatare expected to influence itseffectiveness.

PPrrooxxiimmaall mmeeaassuurreess

The most proximal measures ofthe effectiveness of a tobaccoproduct regulation include mea-sures of the product itself. The firststep in evaluating a performancestandard regulation, for example,is to measure compliance throughproduct testing. For reduced

ignition propensity cigarette laws:does the product meet the full-length burn testing requirementsspecific in the regulation? For tarand nicotine limits: does the pro-duct meet the specified maximumtar and nicotine thresholdaccording to the standardised testmethod required in the legislation?The specific testing that isrequired will depend on therequirements and goals of the law.There are a wide variety ofproduct characteristics that couldpotentially be subject to or beaffected by regulation. In additionto assessing compliance, assess-ment of tobacco productcharacteristics is important forinforming the development of newor modified regulations and foridentifying potential unanticipatedproduct changes. Both tobacco and tobacco

smoke are very complex matrices,consisting of thousands of com-pounds. Over 3044 constituentshave been isolated from tobacco(Roberts, 1988); it is estimatedthat there are over 4800 com-pounds in mainstream cigarettesmoke (Green & Rodgman, 1996).At least 69 carcinogens have beenidentified in cigarette smoke,including 11 classified as Group 1known human carcinogens byIARC (Hoffmann & Hoffmann,1997). Moreover, the compositionof cigarettes and cigarette smokehas changed substantially sincethe 1950s, as the product itselfhas changed, with changes intobacco blend, processing tech-niques, cigarette design, theintroduction of filters, and use ofadditives (Hoffmann & Hoffmann,



241

1997). At the same time, it isessential to study the productunder actual conditions of use,because differences in smokingbehaviour can have a substantialinfluence on product emissions. However, because of the

complexity of tobacco smoke, it isextremely difficult to estimate thehealth effects of specificconstituents in tobacco andtobacco smoke. There have beenefforts to quantify the relativecontribution to risk of individualtobacco smoke constituents,particularly for cancer, but suchestimates are fraught with un-certainty and numerous assump-tions. Possibly the most com-prehensive such risk assessment,including cancer and non-cancerrisk indices for 158 knownhazardous chemicals in cigarettesmoke, found that these knownrisk agents underestimated ob-served cancer rates in cigarettesmokers by 5-fold, suggesting thatactual exposures were drama-tically underestimated and/or thatother important carcinogens ormechanisms of action exist thatwere not included in the risk

assessment (Fowles & Dybing,2003). Further research is neededto understand the individual andcombined effects of the manyconstituents in tobacco andtobacco smoke.

SSaammpplliinngg aanndd pprreeppaarraattiioonn

To effectively monitor products asused by consumers, it is essentialto follow an effective protocol forobtaining product samples andstoring and preparing the productfor analysis. Products should bepurchased from a range of retailvendors to ensure that the producttested is representative of theproduct available to consumersand that different manufacturinglot numbers are represented in thesample. In addition, a rigorousprotocol should be employed forstoring samples. For example,cigarettes and smokeless tobaccoshould be stored at –70° Celsiusin vacuum sealed bags to preventthe effects of aging. Sources ofguidelines and protocols forsampling and preparation areavailable in Table 5.16.

PPrroodduucctt ccoonntteenntt

Official testing of cigarettes hasgenerally focused on measure-ments of cigarette smoke con-stituents (i.e. tar, nicotine, andcarbon monoxide) using standardmachine smoking protocols ratherthan of the unburned tobaccoitself. However, the composition ofsmoke is directly dependent onthe profile of constituents in thetobacco (Fischer et al., 1990).While cigarette design featuresand human smoking behaviourcan dramatically vary the content(both qualitatively and quan-titatively) of the smoke and thesmoker’s exposure, the charac-teristics of the tobacco are equallyimportant. Moreover, there is widevariation in the concentration ofnicotine and other importantconstituents in the tobacco filter incigarettes from different brandsand countries around the world(IARC, 2004). Additionally, trendsin tobacco processing andblending over time may impactpublic health. For example, whileincreasing tobacco nitrate levelswas seen as a way of reducing

SSaammpplliinngg IISSOO 88224433:: 22000066 CCiiggaarreetttteess:: SSaammpplliinngg

SSaammppllee PPrreeppaarraattiioonn ISO 3402: 1999 Tobacco and Tobacco Products: Atmosphere for Conditioning and Testing

Health Canada: Preparation of Cigarettes from Packaged Leaf Tobacco for Testing (HealthCanada, 1999a)

US Centers for Disease Control and Prevention: Protocol to Measure the Quantity ofNicotine Contained in Smokeless Tobacco Products Manufactured, Imported, or Packagedin the United States (Centers for Disease Control and Prevention, 1997a).

ISO: International Organization for Standardization (www.ISO.org)

Table 5.16 Sampling and Preparations Standards



242

PAHs in tobacco smoke in the1960s, in the 1980s scientistsrecognized that increased nitratelevels were also increasing theyield of nitrosamines in tobaccoand smoke (Brunnemann &Hoffmann, 1982; Fischer et al.,1989a). Measurement of con-stituents in tobacco can providethe earliest point of monitoring forregulation and possible interven-tion.

There are a range of wellestablished methods for mea-suring the chemical charac-teristics of tobacco that have longbeen in use by tobacco manu-facturers and agricultural scien-tists. Since the 1950s, there havebeen significant developments inanalytical methods for studyingtobacco products with theintroduction of technologies suchas gas chromatography and massspectrometry (Green & Rodgman,1996). There are three standardsetting organisations that havedeveloped and adopted methodsfor analysis of tobacco andcigarette smoke: the InternationalOrganization for Standardization(ISO), the Association ofAnalytical Communities Inter-national (AOAC), and the Co-operation Center for ScientificResearch Relative to Tobacco(CORESTA). The CORESTAboard is made up of 14 membercompanies from the tobaccoindustry (http://www.coresta.org/Home_Page/Presentation%20of %20CORESTA_April07.pdf).Additionally, the tobacco-

related efforts of ISO havehistorically been driven primarilyby the needs of industry and, thus,

they have not adopted methodsfor many areas of particularinterest to public health (i.e.emissions as driven by usersbehaviour, free-base nicotine,presence of carcinogens) (Bialous& Yach, 2001). Additionally,Health Canada and the USCenters for Disease Control andPrevention (CDC) have publishedofficial methods for manufacturerreporting of tobacco constituents.Table 5.17 summarizes theexisting methods for whole tobac-co analysis and their sources.While an exhaustive discussion oftobacco constituents and asso-ciated methods is beyond thescope of this section, a few keyagents are discussed here whichhave particular relevance andimportance for product regulation.

Nicotine:

Standardised protocols forextracting and measuring nicotinein whole tobacco using gaschromatographic analysis havebeen adopted and widely used byindustrial and professionalorganisations (ISO (15152: 2003),CORESTA (No. 62, Feb 2005),AOAC (920.35)), as well as publichealth agencies (Health Canada,Massachusetts Department ofPublic Health, CDC). It is im-portant to measure nicotine levelsin tobacco as nicotine is theprimary driver of smoking be-haviour and addiction, and thelevel of nicotine in tobacco is anessential predictor of nicotinelevels in smoke emissions de-livered to the tobacco user. Arecent report found that nicotine

levels in US cigarettes haveincreased from 1998 to 2005 byabout 11%, and concluded thatthis trend was due primarily to anincrease in nicotine in the rawtobacco used in cigarettes(Connolly et al., 2007).The Massachusetts Depart-

ment of Health and the CDC alsorequire reporting of the amount ofnicotine that is present in theunprotonated, free-base form insmokeless tobacco. This form ofnicotine is absorbed more easilythrough the mucosal membranesin the mouth (Brunnemann &Hoffmann, 1974). Measurementsof unprotonated nicotine content intobacco provide a more accurateassessment of the quantity ofnicotine in the product that isdelivered to the user (Hoffmann etal., 1995). Free nicotine content intobacco can be calculated usingthe Henderson-Hasselbalch equa-tion, which is based on measuredpH and nicotine content. Thisinformation is important forunderstanding trends in productuse and for providing a basis formonitoring and regulating nicotinecontent in the product. A CDCstudy that measured free nicotinein popular brands of smokelesstobacco, found that the brandswith the largest amount ofunprotonated nicotine also are themost frequently sold (Richter &Spierto, 2003). In smokelesstobacco products, manipulation oftobacco pH and free-base nicotinelevels has also been used by thetobacco industry as part of a“graduation strategy,” wherebynovice users are introduced toproducts with lower nicotine



243

delivery and eventually progressto higher delivery products(Connolly, 1995; Tomar et al.,1995). Thus, continued monitoringof pH levels and free-basenicotine in tobacco is important formonitoring the addiction potentialof products (see following sub-section on constituents in

mainstream and sidestream to-bacco smoke).

Nitrosamines:

Tobacco-specific N-nitrosamines(TSNAs), N-nitrosonornicotine(NNN), 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK),

N-nitrosoanatabine (NAT), and N-nitrosoanabasine (NAB) are pre-sent in both unburned tobaccoand tobacco smoke. NNN andNNK play a significant role incancer induction by tobaccoproducts (Hecht, 1998). TheTSNAs are formed from tobaccoalkaloids during the curing and

AAnnaallyyttee AAnnaallyyssiiss MMeetthhoodd PPrroottooccoollss

NNiiccoottiinnee Gas chromatographic analysis Health Canada; CORESTA No. 62, Feb 2005;CDC; AOAC 920.35

TToottaall MMooiissttuurree Weight before and after heating in CDC; AOAC 966.02oven at 99° C

ppHH pH meter Health Canada; CDC

FFrreeee NNiiccoottiinnee Calculated from pH and nicotine Centers for Disease Control and Preventionusing the Henderson-Hasselbalch (1997a): Massachusetts Department of Publicequation Health

NNiittrroossaammiinneess Gas chromatographic analysis Health Canada; CORESTA (under develop-ment); CDC (Song & Ashley, 1999)

NNiittrraatteess Continuous Flow Analysis Health Canada; CORESTA No. 36, Nov 1994

MMeettaallss Atomic absorption spectroscopy Health Canada; IARC (1986)(AAS) analysis

AAmmmmoonniiaa High Performance Liquid Health CanadaChromatography (HPLC)

HHuummeeccttaannttss Gas chromatographic analysis

PPeessttiicciiddee rreessiidduueess Gas chromatographic analysis CORESTA No. 2, May 1997; ISO 4389:2000

ISO: http://www.iso.orgCORESTA: http://www.coresta.org/AOAC: http://eoma.aoac.org/methodsHealth Canada: http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/legislation/reg/index_e.htmlMassachusetts: http://www.mass.gov/dph/mtcp/legal/prodreg.htmCDC: US Centers for Disease Control and Prevention: Protocol to Measure the Quantity of Nicotine Contained in Smokeless TobaccoProducts Manufactured, Imported, or Packaged in the United States. Federal Register. Vol. 62, No. 85, Friday, May 2, 1997. p. 24115 - 24117 (recommended method for determination of organochlorinepesticide residues on tobacco)

Table 5.17 Whole Tobacco Analysis Methods



244

processing of tobacco. Studieshave suggested that the tobaccoblend may be the most importantdeterminant of TSNAs (UK Labo-ratory of the Government Che-mist, 2000; Harris, 2001). Orientaland flue-cured Virginia tobaccoscontain lower levels of nitrate andTSNAs, while higher levels arefound in air-cured burley tobaccos(Fischer et al., 1989a; Bush et al.,2001; Peele et al., 2001).NNN and NNK make a likely

target for surveillance andregulation as they play a signi-ficant role in tobacco-relatedcancer, are measurable even intrace quantities, and are specificto tobacco. Moreover, in recentyears it has been demonstratedthat use of new curing tech-nologies can considerably reducethe levels of TSNA, especiallyNNK, or even completely elimi-nate them (Bush et al., 2001;Peele et al., 2001). A study con-ducted by the CDC comparingTSNA levels in cigarettespurchased in 13 countries and theUSA, found that in 11 of the 13countries locally-purchased Marl-boro cigarettes had significantlyhigher TSNA levels than locallypopular non-US brands pur-chased in the same country(Ashley et al., 2003). Methods formeasuring NNN and NNK havebeen adopted by Health Canadafor regulation.

Additives/flavourings:

Additives may include both naturaland synthetic agents that impart orenhance flavour. There are hun-dreds of additives that are used in

tobacco products. While in somecountries agents may be screenedfor their direct toxicity, little isknown about the fate of theseagents after the combustion pro-cess. Additionally, additives areused to make tobacco smoke lessharsh and to increase nicotinedelivery, thus impacting thephysiological effects of smokingand resulting behaviours. Ammo-nium compounds raise the alka-linity of smoke, which increasesthe level of “free” nicotinedelivered to the smoker, and havebeen employed as an additive incigarettes (Henningfield et al.,2004). Menthol, a chemical com-pound which acts as a mild localanesthetic, has been added tocigarettes beginning in the 1920sand 1930s to mask the harshnessof tobacco smoke (Reid, 1993).

Detecting flavouringcompounds and other additives iscomplicated by the fact that theymay be present in very smallquantities and, more importantly,researchers and regulators maylack specific information abouttheir presence. Regulators rely oninformation from annual reports ofadditives used and their quantitiesby cigarette brand, such as in theEU, but many countries do not yethave such requirements. Becauseof the hundreds of additives thatmay be in use, testing for many ofthem is impractical. At least onestudy has quantified the presenceof 12 potentially toxic flavour-related compounds in cigarettetobacco, including coumarine andsafrole, and found that 62% of 68brands tested contained one ormore of these 12 compounds

(Stanfill & Ashley, 2000). The UKDepartment of Health maintains alist of permitted additives totobacco products (now numberingover 600) along with maximuminclusion limits, although theireffects after combustion havegenerally not been tested (http://www.advisorybodies.doh.gov.uk/scoth/technicaladvisorygroup/additiveslist.pdf).Evaluation of the impact of

product regulations that controladditives is limited by inadequateinformation and scientific dataabout the presence of additives inproducts by brand, and theirpotential effects on behaviour andhealth outcomes.

PPrroodduucctt ddeessiiggnn

Cigarette design has evolved overthe past half century, with theintroduction of filters, changes intobacco processing techniques,and the introduction of new ma-terials and technologies. Theresulting changes in productdesign and characteristics canhave a substantial impact on theexposure a smoker receives. Thetypes of materials used in filtersand filter design can alter thechemical composition of thesmoke that is inhaled, includingthe levels of carbon monoxide andother harmful constituents. Addi-tionally, use of expanded orreconstituted tobacco in cigarettescan affect tar and nicotine yieldsand the profile of constituents.Cigarette length, circumference,and packing density can also alterthe chemical composition of thesmoke (Hoffmann & Hoffmann,



245

1997). Specific design featureshave also been employed toreduce cigarette ignition pro-pensity, such as reduced tobaccodensity, reduced paper porosity,decreased circumference, and theremoval or reduction of burnadditives.Physical characteristics of

tobacco products should bemeasured in order to inform thedevelopment and implementationof tobacco product regulationsand to support evaluation ofregulations. The WHO StudyGroup on Tobacco Product Regu-lation (TobReg) has provided arecommended list for productcharacteristics to be reported bymanufacturers for all brands on anannual basis (WHO Study Groupon Tobacco Product Regulation,2004; http://www.who.int/tobacco/

global_interaction/tobreg/goa_2003_principles/en/index.html).Table 5.18 includes the

TobReg recommendations andadditional product characteristicsthat should be measured toassess the impact of regulation onproduct design; referencenumbers are provided for officiallaboratory protocols where theyexist. This list is not exhaustiveand should be revised regularly toaccount for new types of productsand design innovations, such asnew potential reduced exposureproducts (PREPs) that employunconventional technology. Theseproduct characteristics are notnecessarily direct targets ofregulation or indicators of effec-tiveness of regulations in allcases. They should be con-sidered, however, as useful

measures for supporting thedevelopment and implementationof regulations, such as byrevealing unexpected productchanges in response to regu-lations (see following section onventilation). Because most of themeasures are routinely used bymanufacturers in product charac-terization and quality control, suchinformation should be requestedfrom manufacturers by regulatorswhere possible.

Cigarette ventilation:

Since the 1960s, cigarette filterventilation has been the dominantdesign feature employed bymanufacturers to reduce machinemeasured tar and nicotine yields(Kozlowski et al., 2006). Smallpinholes on cigarette filters allow

PPrroodduucctt CChhaarraacctteerriissttiiccss MMeeaassuurreemmeennttss

Raw Materials Tobacco blend, weight of tobacco, percentage of reconstituted tobacco, percentageof expanded tobacco, moisture content, firmness, contaminants (i.e. glass,pesticides, heavy metals).

Filter Type, length, weight, density, ventilationa, draw resistanceb, fiber residues,charcoal content.

Cigarette Body Rod length, tipping paper length, diameterc, air permeabilityd.

Emission Aerosol particle size with and without filter.

Ignition Propensity Percent self-extinguishing.

aISO 9512: 2002 Cigarettes - Determination of ventilation - Definitions and measurement principlesbISO 6565: 2002 Tobacco and tobacco products - Draw resistance of cigarettes and pressure drop of filter rods - Standard conditionsand measurementcISO 2971: 1998 Cigarettes and filter rods - Determination of nominal diameter - Method using a laser beam measuring apparatusdISO 2965: 1997 Materials used as cigarette papers, filter plug wrap and filter joining paper, including materials having an orientedpermeable zone - Determination of air permeability

Table 5.18 Product Characteristics to be Measured to Assess Impact of Product Regulation



246

the smoke to be diluted by airdrawn in by the smoker. However,studies have shown that smokerstend to place their fingers overthese vent holes in order to derivea desired level of nicotine(Kozlowski et al., 1980). Addi-tionally, smokers puff harder tocompensate and the greater flowthrough the cylinder also reducesthe proportion of air that comes inthrough the vent holes. Because ofthis flexibility in the cigarettedesign, machine measured ISO/FTC tar yields do not reflect theactual range of exposures smokersreceive. A study comparingventilation (measured as thepercentage of air drawn throughthe filter vents) across 32 brands ofUS cigarettes, with FTC tar yieldsranging from 1 mg to 18 mg, foundthat the degree of ventilation (from0 to 83%) varied inversely withstandard tar, nicotine, and COyields, suggesting that ventilation isa key determinant of machinemeasured yields (Centers forDisease Control and Prevention,1997b). Similarly, another studyaccounted for 95% of the variancein ISO measured levels as afunction of extent of filter venting(King & Borland, 2004). A recent study assessed how

UK cigarette manufacturers modi-fied their products in order tocomply with the EC 10-1-10maximum yield regulation. Com-paring 10 cigarette brands beforeand after the regulation wasimposed, they found that machinemeasured tar was reduced from11-13 mg to 10 mg for each brand,carbon monoxide yields droppedsignificantly from a median of 13

to 10 mg, as well as nicotine froma median of 1.0 mg to 0.9 mg.However, the only product designfeature that showed consistentchange was the amount of filterventilation, as the median in-creased by 479% from 1999 to2005. In contrast, other productdesign characteristics that weremeasured in the study, includingfilter weight, filter length, andtobacco length, showed nochanges (O’Connor et al., 2006a).This study illustrates the im-portance of monitoring productdesign over time against abaseline level to understand howproducts are modified in responseto new regulations, and whetherthe public health objectives of theregulation are being met. Analternative proposal involves im-posing maximum tar, nicotine, andcarbon monoxide yields along witha ban on filter vents (Kozlowski &O’Connor, 2002; Kozlowski et al.,2006). Amount of ventilation should be

measured in cigarettes, particularlyfor evaluating the introduction ofnew regulatory limits on emissions.Additionally, given the elasticity inexposures from ventilated ciga-rettes, measurements of emissionsshould take this variability intoaccount, such as by measuringemissions in relation to a fixedamount of nicotine or per milligramof nicotine.

Reduced ignition propensity:

Reduced ignition propensity (RIP)regulations are relatively new, solimited data is available on theirimpact and effectiveness. One

study conducted to evaluate theimpact of the New York law, foundthat the average percentage offull-length burns was 10% for fiveleading brands sold in New Yorkafter the law went into effect,compared with 99.8% for cigarettebrands from California andMassachusetts (Connolly et al.,2005). These findings confirm thatthe law did result in changes to theproduct design that achieved theaims of the legislation. Producttesting can be used to assesscompliance and product per-formance following the intro-duction of RIP laws. It is alsoimportant to evaluate smokers’reactions to changes in cigarettedesign to identify potential un-intended effects on smokingbehaviour. A survey of adult smo-kers’ reactions to RIP cigarettesfound that while smokers in NewYork State were more likely toreport that their cigarettes wentout between puffs, they were nomore likely than smokers in stateswithout RIP laws to reportdifferences in cigarette taste,suggesting that RIP cigarette lawsdo not substantially impactconsumer acceptability (O’Connoret al., 2006b). Moreover, proximalmeasures of the product itself can-not assess more distal outcomes,such as changes in the number offires caused by cigarettes. Distalmeasures and surveillance arediscussed in the following section.

PPrroodduucctt EEmmiissssiioonnss

Measuring the contents andcharacteristics of tobacco smokehas been the primary focus of



247

tobacco product testing andregulation efforts since the 1960s.Measuring the contents of tobaccosmoke provides direct informationabout the agents the smoker isexposed to. However, thesemeasures also have substantiallimitations; while they allow for theidentification of important con-stituents in tobacco smoke, theydo not necessarily reflect expo-sure under actual smoking con-ditions. Measurements of productemissions have typically relied onmachine collection of tobaccosmoke, which does not reflectactual human smoking behaviour.This section will review variousmachine smoking protocols, andtheir limitations, and will thendiscuss specific constituents intobacco smoke that have beenproposed for surveillance andregulation.

Machine smoking methods:

Machine smoking methods formeasuring tar, nicotine, carbonmonoxide, and other constituentsin cigarette smoke have beenwidely used in many countriesover the past 30 years. Theprocedure involves having a ma-chine “smoke” cigarettes ac-cording to fixed parameters thatdetermine the frequency, duration,and volume of puffs, as well as thebutt length. The particulate matteris collected onto a Cambridge filterpad made of extremely finediameter glass fibers. Mainstreamsmoke particulates are collectedon filter pads located behind thecigarette port, while sidestreamsmoke is collected with the use ofBAT “fishtail” devices, which allow

smoke from the end of thecigarette to travel up a glassenclosure to a filter pad located atthe top. Filter pads are weighedbefore and after a “smoking” run todetermine the Total ParticulateMatter (TPM) (the amount ofparticulates accumulated on thefilter pad). A solvent is used toremove the chemicals from thefilter pads, and once this ex-traction is complete, variouschemical and physical separationtechniques are used to isolate thedesired component(s). Once thedesired chemical has beenisolated, various analytical me-thods (such as gas chro-matography with mass spec-trometry) are used to determinethe amount of chemical collected.Gas phase chemicals, such ascarbon monoxide, may passthrough the filter pads and intocollection bags for measurement.To ensure consistency across

measurements, standard para-meters are used to control themachine’s puffing activity. Theparameters most widely in usewere based on a protocol outlinedby the US Department ofAgriculture (Ogg, 1964); a similarprotocol had been proposed byAmerican Tobacco Companyresearchers in 1936 (Bradford etal., 1936). The protocol called for2-second, 35-mL puffs to be takenuntil a 23-mm butt lengthremained on the cigarette. Theseparameters were somewhatarbitrarily selected based oninformal observations; Ogg repor-tedly stated that he arrived at theparameters he chose by informallyobserving people smoking, timingthem with the aid of a stopwatch,

and measuring the length of the“unsmoked” cigarette left in theashtray (Harold & Pillsbury, 1996).When the US Federal TradeCommission adopted this methodfor use in its testing laboratory, theagency acknowledged that theseparameters were not intended tomimic the smoking behaviour ofany particular individual or evenan “average” smoker, but theapplication of a uniform standardwould, they stated, allow formeaningful comparisons acrossproducts (Press release, August 1,1967). ISO adopted a similar setof parameters in their cigarettetesting method (ISO Standard3308: 2000 (4th edition), RoutineAnalytical Cigarette-SmokingMachine: Definitions and StandardConditions).However, beginning in the

1980s, a more profound under-standing of smoking behaviourrevealed that smokers whoswitched to cigarettes with lowermachine measured tar and nico-tine yields modified their smokingbehaviour to compensate bytaking more frequent puffs, in-haling the smoke more deeply,covering up filter ventilation holes,and smoking more of eachcigarette (Benowitz et al., 1983;National Cancer Institute, 2001).More accurate measures of theactual smoke exposure of a givenindividual can be obtained throughthe study of smoking topography,where the smoker uses amouthpiece connected to a devicethat measures parameters of smo-king behaviour (such as number ofpuffs, puff volume, duration,velocity, and the intervals betweenpuffs) (Djordjevic et al., 2000; Lee



248

et al., 2003). However, whilesmoking topography measure-ments are valid for assessingindividual exposure, the para-meters vary widely across thepopulation and no single set ofsmoking parameters can effec-tively represent this variation. Because of growing concerns

about the validity of the FTC/ISOparameters, alternative machinesmoking regimens have beenproposed. In particular, the FTCand ISO smoking regimens do notaccount for the fact that smokersmay cover ventilation holes withtheir fingers, and alternativesmoking regimens have attem-pted to address this. TheCommonwealth of Massachusettsin the USA currently testscigarettes with a 45 mL puff drawntwice per minute with 50% of thefilter vent holes blocked(Commonwealth of Massachu-setts, 2007). Canadian govern-ment testing standards require amore intensive smoking regimen,where 55 mL puffs are drawntwice per minute with 100% of thevent holes blocked (HealthCanada, 1999b). While theseregimens also cannot representthe wide variation in humansmoking patterns, they may beless likely to underestimate actualhuman exposure by using moreintense puffing parameters. Thismay be especially important forlower yield products for whichsmokers may compensate withmore intense puffing behaviour. A “compensatory” machine

smoking regimen was proposed;rather than smoking all brandsusing the same puffing regimen,

the compensatory regimenattempts to mimic the systematicdifferences in human smokingacross different products, wherebylower nicotine yield brands aresmoked more intensely. It wassuggested that the puff volumeand puff frequency be variedaccording to the ISO nicotineyield. For brands with <10 mg tar,a 40 mL puff is taken every 60seconds. With every decrease of0.1 mg nicotine, the puff volumerises by 4 mL and the pufffrequency falls by 4 seconds. Forexample, a cigarette with 0.5 mgnicotine under the ISO methodwould be smoked at 60 mL puffsevery 40 seconds, whereas a 0.1mg cigarette would be smoked at76 mL puffs every 24 seconds(Kozlowski & O’Connor, 2000).Another alternative is to tieanalysis of constituents to a fixednicotine level whereby cigarettesare smoked to predeterminednicotine yields and the levels ofother constituents assessed fromthat (Hammond et al., 2007b).Alternatively, TobReg of WHO hasrecommended use of yields permg of nicotine, using standardpuffing regimens. (WHO StudyGroup on Tobacco Product Regu-lation, 2004).A recent study compared the

performance of these four smo-king regimens against actualhuman smoking patterns andbiological measures of exposureto assess how well they reflectactual exposures smokers arelikely to receive (Table 5.19)(Hammond et al., 2006b). The aimof the study was to comparemeasures of smoke volume and

nicotine uptake among humansmokers against the puffingvariables and nicotine yieldsgenerated by the four smokingregimens, as well as a HumanMimic regimen where brands weremachine smoked using puffingbehaviour recorded from humansmokers in the study. Participantsin the study smoked cigarettesthrough a portable smokingtopography device to record theirsmoking behaviour, and they alsoprovided saliva samples to beanalyzed for cotinine. The studyfound that, using the HumanMimic condition as a benchmark,subjects were exposed to tar,nicotine, and carbon monoxidelevels that were 2 to 4 timesgreater than the ISO yields,suggesting that the ISO standardseriously underestimates actualhuman exposure. Moreover, whilethe Canadian intense smokingconditions are considered torepresent the maximum emissionsto which a smoker is likely to beexposed, the study found that totalsmoke volume was not sig-nificantly different from the actualsmoke volume as measured in theparticipants when smoking theirusual brand. Among thosesubjects who were experimentallyswitched to a lower yield brand, allfour smoking regimens produceda lower volume of smoke than theHuman Mimic. Comparing thesefindings to the measured salivarycotinine levels further reveals thelimitations of machine smokingmethods. The yields from theMassachusetts, Canadian, andCompensatory regimens were nobetter at predicting measures of



249

nicotine uptake than the ISOyields. Even the Human Mimiccondition was only moderatelycorrelated with salivary cotininelevels, reflecting the wide varia-bility in uptake based on nicotinemetabolism among smokers evenwhen smoking the same brand. Asubsequent study comparingemissions data from 238Canadian cigarette brands testedunder ISO and “Canadian intense”machine smoking conditions,found that the more intenseprotocol was not necessarily morerepresentative of actual humansmoking behaviour and exposure(Hammond et al., 2007b).Standardised machine testing

regimens lack validity as measuresof actual human exposure. Despiteits limitations, however, machinetesting using ISO and alternativeparameters remains valuable forinforming the development andimplementation of product regu-

lations and, where relevant, formeasuring basic compliance withconstituent limits based onstandardised machine testingregimens. The WHO Study Groupon Tobacco Product Regulation(TobReg) has recommended thatstandardised machine smokingtests be used by scientists andregulators “to the extent that itprovides a basis for a comparisonof the results with new testingprotocols until protocols that reflectvariations in human smokingbehaviour according to differentcigarette designs are developed.”(WHO Study Group on TobaccoProduct Regulation, 2004). Despiteits limitations for predicting actualhuman exposures, machine testingcan provide important informationon cigarette engineering and howdifferences in cigarette design mayaffect smoke emissions. There remains a need for

further development of methods

for collecting smoke emissionsthat are more representative ofactual human smoking exposures.Additionally, some promisingapproaches to account for varia-tions in smoking behaviour basedon nicotine titration warrant furtherdevelopment, including measure-ment of constituent yields permilligram of nicotine and analysisof cigarette filter stains (Strasseret al., 2006)

CCoonnssttiittuueennttss iinn mmaaiinnssttrreeaammaanndd ssiiddeessttrreeaamm ttoobbaaccccoossmmookkee

Mainstream cigarette smoke is acomplex and dynamic mixture ofthousands of constituents that aredistributed between a vapourphase and a particulate phase(Jenkins et al., 2000). Since the1950s, following the first epi-demiologic studies linking smo-king and lung cancer, dozens of

FFTTCC IISSOO MMaassssaacchhuusseettttss CCaannaaddiiaann CCoommppeennssaattoorryy

Puff Volume (mL) 35 35 45 55 40

Puff Duration (seconds) 2 2 2 2 2

Interpuff Interval 60 60 30 30 30(seconds)

Ventilation Hole Blockage (%) 0 0 50 100 50

Butt Length 23 mm or Filter Filter length + 8 Filter length + 8 Filter length + 8filter + 3 length + 8 mm or filter mm or filter mm or filtermm mm or overwrap overwrap + 3 mm overwap + 3 mm

filter over- + 3 mmwrap+ 3mm

Adapted from Hammond et al., (2006b)

Table 5.19 Recommended Machine-Smoking Regimes for Cigarette Testing



250

carcinogens and other harmfulconstituents have been identifiedin tobacco smoke. The primaryfocus has been on PAHs, such asbenzo [a]pyrene and TSNAs, suchas NNK, which are considered tobe major lung carcinogens (Hecht,1999). Carbon monoxide incigarette smoke has also beenextensively studied and is likely tocontribute to atherosclerosis, andother cardiovascular diseases, byreducing delivery of oxygenthrough the body (US Departmentof Health and Human Services,2004). It is not possible to discussthe significance of each constituentin this section, but a thorough list ofmajor toxic and carcinogenicconstituents in the vapour phaseand particulate matter of cigarettesmoke is provided in IARCMonograph 83 (IARC, 2004). TheWHO TobReg study group hasdeveloped a recommended list ofconstituents to be reported ormeasured in mainstream andsidestream smoke (2004). Addi-tionally, Health Canada requiresmanufacturers to report more than40 specific constituents annuallyfor each brand in both mainstreamand sidestream smoke. Thoughessentially the same list ofconstituents is measured for bothmainstream and sidestreamsmoke, it is important to domeasurements for both types ofemissions because their quantitiesmay differ. These constituents arelisted in Table 5.20.A few compounds believed to

be particularly important are brieflydiscussed here:

Nicotine:

Measuring nicotine emissions iscentral to evaluating the addictivepotential of tobacco products.Standardised methods for mea-suring nicotine in machine collectedsmoke have been widely used, buttheir ability to predict actual nicotineintake is restricted by the limitationsof standardised machine smokingparameters. It is also important tomeasure the proportion of nicotinethat is available in the unpro-tonated, free-base form, which ismore easily absorbed by the body.Research has shown that levels offree-base nicotine vary sub-stantially across different types oftobacco and tobacco productbrands, and that the tobaccoindustry has manipulated the free-nicotine content of tobaccoproducts through additives, such asammonia (Ferris et al., 2006). Alaboratory smoking device and agas chromatograph-mass spec-trometer were used to measure theamount of free-base nicotine in theparticulate matter of mainstreamcigarette smoke, and found thatsignificant amounts of nicotine inthe particulate matter can be infree-base form (Pankow et al.,2003). Similarly, a research groupfrom the CDC found that themeasured ranges of free-basenicotine in smoke particulate matterwere remarkably similar over thedifferent tar and nicotine deliverycategories of full-flavoured, light,and ultra-light cigarette brands,sug-gesting that standard tar andnicotine yields do not provide avalid estimate of actual nicotineemissions (Watson et al., 2004b).

Polycyclic aromatic hydrocar-bons:

Polycyclic aromatic hydrocarbons(PAHs) are a diverse group ofcarcinogens formed during theincomplete combustion of organicmaterial, such as tobacco. They arefound in tobacco smoke, broiledfoods, and in occupational settings,such as iron and steel foundries.Benzo[a]pyrene is the best knownmember of this class of compoundsand has been classified by an IARCexpert panel as “carcinogenic tohumans” (Straif et al., 2005).

N-Nitrosamines:

Tobacco smoke nitrosamines(TSNAs) include a large group ofcarcinogens that are known toinduce tumours in a variety ofanimal species. TSNAs, such asNNN and NNK, are chemicallyrelated to nicotine and nornicotine,a secondary amine tobacco alk-aloid, and are thus only found intobacco products. An IARCworking group on smokelesstobacco and tobacco-relatednitrosamines concluded that ex-posure to NNN and NNK is“carcinogenic to humans” (Cog-liano et al., 2004).

Aromatic amines:

Aromatic amines were first iden-tified as carcinogens in workers inthe dye industry. Of these, 4-aminobiphemyl and 2-naphthy-lamine are well-established humanbladder carcinogens (IARC, 1987).The 1999 Massachusetts

Benchmark Study provided the



251

most comprehensive data to dateon the profile of smoke emissionsof contemporary cigarettes. Eigh-teen leading cigarette brands fromthe USA delivering a range of tarvalues (from 1 mg to 26 mg percigarette according to FTC para-meters) were screened for 44constituents using both the FTC

and Massachusetts machinesmoking methods. The primaryconstituents varied dramaticallyacross the brands, including totaltar (6.1 mg to 48.7 mg percigarette), carbon monoxide (11.0mg to 40.7 mg per cigarette), andnicotine (0.50 mg to 3.32 mg percigarette) (Borgerding et al., 2000;

IARC, 2004). The study alsoillustrated the limitations of ISO tarand nicotine yields for predictingdoses of specific toxins andcarcinogens in tobacco smoke.One analysis of the Benchmarkdata showed that FTC tar, nico-tine, and carbon monoxide yieldswere poor predictors of TSNA

HHeeaalltthh CCaannaaddaa TToobbRReegg MMiimmiimmuumm

NNiittrroossaammiinneess NNN, NNK, NAT, NABAAccrryylloonniittrriillee33,, 44 AAmmiinnoobbiipphheennyyll11,,22 AAmmiinnoonnaapphhtthhaalleenneeAAmmmmoonniiaaAArrsseenniicc ArsenicBBeennzzeenneeBBeennzzoo[[aa]]ppyyrreennee11,,33--BBuuttaaddiieenneeCCaaddmmiiuumm CadmiumCCaarrbboonnyyllssCChhrroommiiuumm ChromiumEEuuggeennooll

FormeldahydeHHyyddrrooggeenn CCyyaanniiddee Hydrogen CyanideIIssoopprreenneeLLeeaadd LeadMMeerrccuurryy MercuryNNiicckkeell NickelNNiittrrooggeenn OOxxiiddeess Nitrogen OxidesPPhheennoolliiccssPPyyrriiddiinneeQQuuiinnoolliinneeSSeelleenniiuumm SeleniumSSttyyrreenneeTToolluueenneeFFiilltteerr eeffffiicciieennccyyppHHTTaarr,, nniiccoottiinnee,, ccaarrbboonn Tar, nicotine/free nicotine, carbon monoxidemmoonnooxxiiddee

Ratio of nicotine-free dry particulate matter to nicotine yield

Table 5.20 Emissions Candidates for Surveillance



252

yield per cigarette, suggesting thatinformation about the tobaccoblend could be more informativefor predicting TSNA emissions(Harris, 2001). Indeed, measured yields of

constituents can vary substantiallydepending on the smokingparameters used for machinemeasurements. One analysisfound that the yields of six IARCGroup I carcinogens (benzene,cadmium, 2-aminonaphthalene,nickel, chromium, and 4-amino-biphenyl) in mainstream smoke,were an average of 2-4 timeshigher when measured by themore intense Health Canadaparameters than by ISO para-meters (IARC, 2004). Anotherstudy of mainstream smoke fromthree popular brands of UScigarettes purchased on the openmarket in 29 countries worldwide,showed little variation in tar andnicotine, but substantial dif-ferences in the yields of NNN andNNK within each brand (Gray et al.,2000). Additionally, analyses haveshown that blocking filter ventilationholes can alter the characteristicsof mainstream smoke, includingincreasing the delivered doses ofspecific carcinogens and hazar-dous agents (Brunnemann et al.,1990). These analyses suggestthat standard ISO machinemeasured tar and nicotine ratingscannot be relied upon to estimateemissions of toxic constituents.Further research is needed tounderstand how varying smokingparameters may affect thecontents of cigarette smoke. Cigarette smoke is also highly

dynamic, and the profile of smoke

constituents varies over time andacross puffs in response tochanges in temperature anddilution of smoke and otherfactors. The distribution of indi-vidual constituents across theparticulate and gas phases ofsmoke also changes over time;volatile and semi-volatile com-pounds, such as benzene and1,3-butadiene, can be present insignificant quantities in bothphases. Recently, a high through-put method for analyzing volatileorganic compounds in smoke waspublished (Polzin et al., 2007).However, measuring this dynamicmix in real-time to determine howexposure varies over a series ofpuffs, for example, is extremelycomplex. Efforts have been madeto characterize volatile com-pounds in smoke in real-timeusing time-of-flight mass spec-trometry, but this application isexperimental and requires state ofthe art equipment (Adam et al.,2006).

DDiissttaall mmeeaassuurreess

Biological Impact:

The ultimate test of the success oftobacco product regulations inprotecting public health would beto observe actual reductions intobacco-related disease inci-dence. Population level trends inlung cancer incidence, forexample, have reflected changesin cigarette smoking over time.However, such long-term healthoutcomes do not represent aneffective target for regulation,because of the delay between

exposure and the appearance ofdisease symptoms, which can, aswith cancer, take decades. Biomarkers of exposure and

biological impact show substantialpromise for assessing earlyeffects of tobacco use that arerelevant for later disease out-comes. Disease risk is presumedto be a function of the amount,site, and duration of theexposures. Thus, biomarkers ofexposure may provide moreaccurate prediction of diseaseoutcomes than standard mea-sures of tobacco consumption. Inparticular, there are substantialdifferences in how individuals usetobacco products, and how theirbodies respond to chemicalagents in tobacco smoke that arenot reflected by simply measuringnumber of cigarettes per day oruse of standardised machinesmoking to predict exposures.Additionally, biomarkers may playa particularly important role in theassessment of how differencesbetween products or changes inproduct design or constituentsmay impact health. For example,biomarkers of toxic effects orbiological damage can provideearly indications of the impact ofpotential reduced exposure pro-ducts or constituent limits ondisease outcomes. Biomarkers can be divided into

at least two major categories(Hatsukami et al., 2006):

• Biomarkers of internal expo-sure: biomarkers that provide adirect or indirect measure ofthe quantity of a tobacco-derived constituent or



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metabolite in the body. Thesewill not always be closelyrelated to intake because ofdifferences in rates ofmetabolism.

• Biomarkers of potential harm:biomarkers that measure abiological effect or binding of atobacco constituent ormetabolite in a target organ ortissue. For example, carci-nogen-DNA adducts can beused to measure the presenceand activity of a specificcarcinogen in target tissue.Further along, this alsoincludes biomarkers thatmeasure actual damage to or-gans or tissues, such asgenetic mutations or chro-mosomal aberrations, whichmay or may not lead todisease. It is important to distinguish

between biomarkers of exposureversus biomarkers of biologiceffects or disease; it may bepossible to show a reduction inexposure while the impact ondisease outcomes remains un-certain. Additionally, it is helpful todistinguish between biomarkersspecific to a particular chemical,such as NNAL, and biomarkersthat assess the impact of complexexposures, such as urinemutagenicity. With the rise of genomics and

advances in molecular biology thefield of cancer-related biomarkerresearch has advanced con-siderably over the past 25 years(Schmidt, 2006), but to date thereis “no comprehensive set ofbiomarkers of carcinogen expo-sure or biological effects as a

predictive measure of the totalcarcinogenicity related to expo-sure to tobacco or tobacco smoke”(Hatsukami et al., 2006). TheInstitute of Medicine reportClearing the Smoke: Assessingthe Science Base for TobaccoHarm Reduction, cited the needfor biomarker development in theirprincipal research recom-mendations: “Although candidatedisease-specific surrogate mar-kers are currently available, furthervalidation of these markers isneeded. In addition, otherbiomarkers that accurately reflectmechanisms of disease must bedeveloped to serve as inter-mediate indicators of disease anddisease risk.” (Institute of Medicine,2001). Another expert committee,that assembled to identify keyresearch needs related to tobaccoharm reduction, also includedamong its recommendations theneed to identify and validatebiomarkers that are predictive oflater disease development(Hatsukami et al., 2002). Manybiomarkers are currently used inresearch to study biologic effects oftobacco products or potentialreductions in exposure frommodified products. Table 5.21 listsa panel of biomarkers that havebeen recommended as the mostpromising for use in research onpotential reduced exposure pro-ducts. However, these biomarkersare not necessarily ready for use ina regulatory setting as they requirebetter characterization of theirrelation to health risks and disease. A candidate biomarker must go

through a process of validationthat establishes the qualitative and

quantitative relationship of thebiomarker to a specific exposure(i.e. a chemical in tobacco smoke)and to a selected end-point (i.e.cancer) (International Programmeon Chemical Safety, 1993). Thereare several issues to consider inevaluating a candidate biomarkerincluding: understanding of therole of the biomarker along adisease pathway, amount ofsupportive dose-response data(e.g. quantitative data correlatinglevels of the biomarker withsmoking status and with diseaseendpoints), specificity (is it specificfor exposure to tobacco toxi-cants?), sensitivity (are availabletests sufficiently sensitive to detectquantities within a rangeencountered in the population andto detect meaningful changes),and reproducibility (e.g. intra-subject reliability) (Institute ofMedicine, 2001). Supportive datafor a biomarker’s association withtobacco use should ideally includedifferences between tobaccousers and non-users, a decreasewith cessation of tobacco use, adose-response relationship withquantity or frequency of use, and adecrease with reduced smoking(Hatsukami et al., 2006). Addi-tionally, identification of multiplebiomarkers along a continuumfrom exposure to early diseaseeffects can provide a more robustprofile of the relationship betweenexposure and disease risk.

Biomarkers of internal expo-sure:

Biomarkers of internal exposurecan potentially provide a more



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accurate estimate of actualexposure received by the smokerthan can be inferred frommachine-based cigarette ratingsor number of cigarettes smoked.For example, it was found thatover an approximately 10-foldrange in FTC cigarette ratingsthere was little or no significantdifference in blood nicotine levelsin several studies, demonstratingthat FTC ratings do not reflect

actual uptake of nicotine by thesmoker (Benowitz, 1996b). Nicotine metabolites have

been widely used as biomarkersof general exposure to tobaccoproducts, including exposure tosmokeless tobacco and toenvironmental tobacco smoke(ETS [referred to in this volume assecondhand smoke (SHS)])among nonsmokers (Benowitz etal., 1994; Benowitz, 1999).

Cotinine is the most widely usedmetabolite, as it has a relativelylong elimination half-life of 16hours (compared to only twohours for nicotine) and can beeasily measured in urine, serum,or saliva. Nicotine has also beenmeasured in hair and toenails asa means of assessing exposure toSHS in large scale epidemiologicstudies, although the reliability ofthese measures may be in-fluenced by hair treatment, andother factors, and requires furtherevaluation (Al-Delaimy, 2002; AlDelaimy et al., 2002). Nicotine andits metabolites also make effectivebiomarkers because they are highlyspecific to tobacco exposure(unless the subject is using nicotinereplacement therapy).Carbon monoxide (CO) expo-

sure has also been used as abiomarker for exposure to tobaccosmoke. CO can be measured inexhaled air, as CO boost beforeand after cigarette smoking, and inblood as carboxyhemoglobin(Benowitz, 2003). While CO is notspecific to tobacco, it can serve asa reliable short-term measure ofsmoking. The minor tobaccoalkaloids anabasine and anata-bine, which are specific to tobaccoproducts and can be measured inurine, have also been used instudies for verifying smokingstatus (Jacob et al., 2002).Chemically-specific biomarkers

can be used to assess exposureto particular toxins and carci-nogens in tobacco and smoke,which may be valuable forevaluating the impact of productperformance standards targetingspecific constituents. Among the

GGeenneerraall TToobbaaccccoo EExxppoossuurreeNicotine/Cotinine Carbon Monoxide

CCaanncceerrNNALNNAL Glucs3-Aminobiphenyl 4-Aminobiphenyl Sister chromatid exchange

NNoonnmmaalliiggnnaanntt LLuunngg DDiisseeaasseeMacrophages

CCaarrddiioovvaassccuullaarr DDiisseeaasseeFlow-mediated dilationCirculating endothelial precursor cellsFibrinogenHomocysteineWhite blood cell countC-reactive proteinslCAM1Glucose-clamping studies

Adapted from Hatsukami et. al. (2006)

*Held in February, 2004, and sponsored by the National Cancer Institute, the NationalInstitute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and theCenters for Disease Control and Prevention.

Table 5.21 Panel of Biomarkers: Recommended by 2004 Conference*

on Methods and Biomarkers to Assess Potential Reduced ExposureTobacco Products (PREPS)



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chemical biomarkers, NNAL andits glucuronides (NNAL-Glucs),which are metabolites of NNK, areparticularly useful because theyare specific for exposure totobacco products (as NNK is atobacco-specific carcinogen)(Hecht, 2002). NNAL and NNAL-Glucs are measured in urine andhave been used to quantify levelsof NNK uptake in smokers andsmokeless tobacco users, and toassess changes followingcessation or product switching(Hecht et al., 2002; Hatsukami etal., 2004; Joseph et al., 2005;Lemmonds et al., 2005).

Biomarkers of potential harm:

DNA adducts potentially provide adirect measure of tobacco-inducedDNA damage. Adducts are formedwhen chemical carcinogens bind toDNA, which can alter the structureof the DNA and is believed to be animportant step in the pathway tocancer. Protein adducts have alsobeen used to determine levels ofcarcinogen exposure and activity,since most carcinogen meta-bolites that react with DNA will alsoreact with proteins, such ashemoglobin, and they are morereadily measured than DNAadducts (Ogawa et al., 2006).Hemoglobin (Hb) adducts ofaromatic amines, particularly 3-and 4-aminobiphenyl, have shownpromise for use in studies oftobacco-related carcinogen expo-sure. They have been shown to behigher in smokers than non-smokers (Bryant et al., 1987;Phillips, 2002), and have also beenused to measure exposure to

carcinogens in secondhand smoke(Hammond et al., 1993). Aromaticamines are not specific to cigarettesmoke exposure, however, andcan also be associated withoccupational and other chemicalexposures. Among the complex bio-

markers of DNA damage andpotential harm, urine mutagenicityand sister chromatid exchangesare the most promising asindicators of potential cancereffects. Both of these measureshave been found to be higher insmokers than nonsmokers and to decrease on cessation(Vijayalaxmi & Evans, 1982; DeMarini, 2004). However, themeasured effects may be causedby diet or other factors, as well ascigarette smoke, and thesedifferences may reflect other riskbehaviour patterns associated withsmoking. Development of complexmeasures that assess thecombined effects of tobacco toxinsand carcinogens is importantbecause chemically-specific bio-markers, while they may havegreater specificity in relation toexposure, may be misleading as ameasure of disease risk. Areduction in uptake of a singletobacco smoke constituent insmokers, such as NNAL, may notnecessarily provide any meaningfulreduction in risk. Consumers mayinterpret a claim of reduction in asingle chemical exposure asindicating a health benefit. Thus,such measures should be put inthe context of overall hazard froma complex product.Biomarkers of potential harm

have been used in the research

context, such as in clinical studiesof potential reduced exposuretobacco products (Breland et al.,2006). However, at this point,none of these biomarkers havebeen recommended for wide-spread use in regulation becausetheir relationship to risk and healthoutcomes has not beensufficiently characterized.

SSuurrvveeiillllaannccee

Comprehensive surveillance isessential to assess the impact ofregulation on tobacco product useand effects across the population.However, this remains a challengebecause capacity and infra-structure for surveillance is limitedin many countries (Jha &Chaloupka, 2000). Thus, theextent of surveillance efforts andavailable infrastructure is likely tovary widely between countries. Acomprehensive surveillanceprogramme could potentially coveran enormous range of information.Broadly, surveillance effortsshould address changes in thedesign and performance of theproduct itself, marketing activity,beliefs and attitudes aroundtobacco product use, tobacco usebehaviours, including initiation andcessation, and health outcomes.Suggested construct areas forpost-marketing surveillance aredrawn from published recom-mendations and are listed in Table5.22 (Institute of Medicine, 2001;Hatsukami et al., 2005). In addition to measuring

potential changes in specifictobacco constituent exposures, itis important to track tobacco



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product use and risk beliefs inrelation to product regulations.Product modifications in responseto regulation may impact tobaccouse behaviour. Additionally,experience with “light” cigaretteshas provided substantial evidencethat smokers believe theseproducts to be less harmful(Cohen, 1996a; Giovino et al.,2000; Ashley et al., 2001;Shiffman et al., 2001). Estab-lishment of regulatory performancestandards or constituent upperlimits, for example, may bemisinterpreted as “safe” levels ofexposure. While laboratoryevaluation of product design andemissions can provide earlywarning of potential adverseeffects, comprehensive post-mar-keting surveillance is essential toensure that regulations areachieving their aims. Additionally,independent technical and re-search capacity and infrastructureare needed to track changes intobacco products and users’behaviour.Establishing laboratory research

and testing capacity is a crucialstep in supporting surveillanceactivities to inform evaluation oftobacco product regulation. Inaddition to tobacco productregulations, governments mayhave research capacity forstudying other aspects of tobaccoproducts. The objective of stan-dardised product testing is toassess product performance andcharacterize the delivery of par-ticular constituents known to beimportant for public health, suchas carbon monoxide, nicotine, andnitrosamines. In contrast, the

goals of research efforts are tounderstand better the nature oftobacco products, how they work,their effects, and how they mightbe modified to alter their effects.While testing operations adhere tostandardised protocols, researchendeavors aim for flexibility anddevelopment of new methods andmeasures for ongoing scientificdiscovery and analysis. The WHOStudy Group on Tobacco ProductRegulation has highlighted howboth research and testing capacityare essential and must becoordinated (WHO Study Groupon Tobacco Product Regulation,2004). For example, as tobaccoproducts change, new productsare introduced, and new scientificmethods become available; there-fore, it may be necessary todevelop new performancestandards. Additionally, previousefforts to promote productmodification to protect publichealth, through lowering mea-sured tar and nicotine yields incigarettes, were undermined by alack of expertise on tobaccoproducts and smoking behaviourin the public health community(Parascandola, 2005). Thus far,tobacco testing and measurementstandards have been primarilydriven by the interests of thetobacco industry; thus it isimportant that the public healthcommunity develop capacity andexpertise in this area to ensurethat product regulations serve theaims of public health (Bialous &Yach, 2001).In 2005, WHO convened the

first meeting of the TobaccoLaboratory Network (TobLabNet),

which included more than 25laboratories from 20 countries.The primary goal of the meetingwas to establish a global networkof government, university, andindependent laboratories tostrengthen national and regionalcapacity for the testing andresearch of the contents andemissions of tobacco productspursuant to Article 9 of the WHOFCTC. Future activities of thenetwork may include trainingprogrammes and development ofcommon measures and protocols(http://www.who.int/tobacco/global_interaction/tobreg/ laboratory/en/index.html). More details aboutrecommended equipment, per-sonnel, and resources for opera-ting a tobacco product testinglaboratory are provided byTobReg (2004). There is asubstantial need for support anddevelopment of laboratory capa-city independent of the tobaccoindustry in countries around theworld with the purpose ofachieving public health goals.

SSuummmmaarryy

Articles 9 and 10 of the WHOFCTC call for ratifying nations toadopt policies for the regulationand disclosure of tobacco productcontents and emissions. Thischapter focuses on a review of themethods and measures forevaluating policies that areintended to regulate tobaccoproducts. There are currently fivemain types: 1) regulations thatrequire disclosure of productinformation; 2) regulations inten-ded to reduce product toxicity and



257

harm; 3) regulations intended toreduce the addictiveness and/orattractiveness of tobacco pro-ducts; 4) regulations intended toprevent fires caused by cigarettes;and 5) bans (or removal of bans)on product categories. Theselection of specific constructsand methods for evaluation willvary depending on the goals of thespecific policy. However, as ageneral framework, it is likely thatthe impact of tobacco productregulations on intended healthoutcomes will be moderated bychanges in product design,performance, marketing, product-related beliefs and attitudes, andtobacco use behaviour, which inturn are expected to influenceexposures to tobacco constituentsand emissions. Thus, evaluationsshould not be limited to assessingcompliance within the intendedeffects of a regulation, but shouldalso consider unintended effects

of responses, such as tobaccoindustry innovation, that mayinterfere with the impact of theregulation.There is a need for a

centralized database that would,at a minimum, characterizedifferent product regulations sothat the effects of different policiescan be compared. Additionally, asa condition permitting tobaccoproduct sales, governmentsshould require (if they do notalready) tobacco product manu-facturers to regularly discloseinformation about their products atthe finest level of brandsubcategory, including sales andmarketing data, product content,and design features. This isneeded to inform the develop-ment, implementation, andevaluation of effective regulations.Additionally, ongoing surveillanceis required to assess the impact oftobacco product regulation on the

tobacco product market and onthe population, as well as to detectindustry responses and otherunanticipated consequences ofregulation. The challenges ofmeasurement associated withevaluating the effects of tobaccoproduct regulations should not beunderestimated. For example,many governments have enactedmaximum smoke emissions stan-dards (i.e. tar, nicotine, andcarbon monoxide) based onstandardised machine testingprotocols for the purpose ofreducing exposure to theconstituents in tobacco productsand resultant harm. However,based on the evidence reviewedin this Handbook, it is notrecommended that yields fromstandard machine testing pro-tocols, such as the ISO cigarettetesting method (ISO Standard3308:2000 (4th edition)), be usedto assess or predict human

TToobbaaccccoo PPrroodduucctt DDeessiiggnn aanndd PPeerrffoorrmmaannccee Product contents, design features (filter, cigarette body),emissions of constituents that modify toxicity and addiction, additives, ignition propensity.

MMaarrkkeettiinngg AAccttiivviittyy Product packaging and labelling, advertising content,promotional materials.

BBeelliieeffss aanndd AAttttiittuuddeess Product awareness, understanding of product design and regulation, risk perception, sensory responses.

TToobbaaccccoo UUssee BBeehhaavviioouurrss History, current use, brand use, quit attempts/history,addiction/dependence, readiness and intentions to quit, demographics, smoking topography.

HHeeaalltthh OOuuttccoommeess Biomarkers of toxin exposures, biomarkers of early biologicaleffects, tobacco-related disease incidence.

OOtthheerr OOuuttccoommeess Fires caused by cigarettes.

Table 5.22 Surveillance Construct Categories



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exposure. Emission yields derivedfrom these protocols are not validmeasures of actual humanexposure. In order to evaluate theeffectiveness of product regula-

tions aimed at reducing harm,measures of human use andexposure are essential. There isan urgent need to identify validmethods and measures for

assessing human exposure andharm that have practical utility forevaluating tobacco productregulations.


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