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| Journal of the New Zealand Medical Association,
15-April-2005, Vol 118 No 1213
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Scope for regulation of cigarette smoke toxicity according to
brand differences in toxicant emissions
Murray Laugesen, Jefferson Fowles
Since 1990 in New Zealand, the Smoke-free Environments Act
has provided powers at Section 31 to regulate harmful constituents
‘contained in or generated in the smoke’ of tobacco products, once
the harmful constituents are named in regulations. The Ministry of
Health’s regulatory review of the regulations in 2004 included
consultation for regulations needed to give effect to Section 31, which also
gives powers to remove fire accelerants from paper, and to reduce the nicotine
content of cigarettes. Improved nicotine delivery devices are
needed,1 and more effective smoking cessation
methods. This paper, however, confines itself to the regulated reduction of
cigarette smoke toxicity.
Until now, the New Zealand comprehensive tobacco control
programme2 has focused on reducing prevalence
and consumption. A national quit campaign began in 1999. A law change in 2003
banned smoking in all workplaces and hospitality venues from December 2004.
Smoke toxicity per cigarette, has however, escaped policy attention.
This paper explores the feasibility and scope for reducing
the toxicity per cigarette with respect to cancer, cardiovascular, and
respiratory diseases. Scope for reducing toxicity seemed considerable—by
the ISO machine test, tar varied 100-fold among New Zealand
brands;3 and carcinogen NNK nine-fold among
Marlboro brands from 30 countries.4 What was
lacking was a method of assessing the combined risk from the various toxicants,
and of scoring the overall toxicity of each brand. Smoke constituents include
toxicants, such as carbon monoxide (CO), other vapour phase gases, particulates
(tar); and the main addictive constituent, nicotine.
Cancer
risk—Ethylene oxide, a known human carcinogen, has been found in
the vapour phase of cigarette smoke of fumigated and unfumigated
tobacco5 and in cigarette
smoke,6 but has not been tested alongside other
smoke carcinogens, even in British Columbia. Also un-quantified is the
contribution of tumour promoting agents (such as free radicals) in the smoke
stream, which almost certainly increases the cancer potency of the mixture in
relation to the sum of its individual carcinogens.
Respiratory disease
risk—Toxicants, such as aldehydes and acrolein, paralyse
respiratory cilia, and work with reactive oxygen species (ROS), estimated at
1014 molecules per puff, to kill alveolar and
bronchial epithelial cells.7 ROS in the vapour
phase exist so briefly that their measurement is not possible, and may account
for considerable unmeasured toxicity.
Cardiovascular disease
risk—Nicotine on its own increases heart rate but not
cardiovascular risk—in a randomised controlled trial of 3900 smokers
chewing nicotine gum over 5 years, neither its use nor its dose was associated
with cardiovascular hospitalisation or mortality
rates.8 Hydrogen cyanide (HCN) inhibits
cytochrome-c oxidase, blocking the cell from using its oxygen; the nervous
system and the heart are particularly sensitive. For this reason, the
Californian Environmental Protection Agency website assesses HCN as the most
potent cardiovascular toxicant in smoke.9
Sublethal doses can result in vascular lesions and myocardial toxicity in
animals.10 In fire victims, HCN may potentiate
the hypoxic effect of CO. HCN in plasma has a half-life of only 14
minutes10—so that smoking should seldom
lead to rising HCN levels during the day. Much less is known of the effects of
small repeated exposures.
Cigarette smoking carries a 10-fold excess sudden-death
risk, unmatched by any other coronary risk factor, and a 3.6 fold excess risk of
myocardial infarction.11 This risk is not due
to nicotine as
such8
or to oral tobacco, which has a disputed effect if any on cardiovascular
risk.12 Carbon monoxide, hydrogen cyanide, and
nicotine, by increasing demands on the heart via the sympathetic nervous system,
all tend to create a deficit of usable oxygen in the myocardium. Cigarette
smoking and oral snuff both increase plasma cotinine—but only smoking
facilitates the formation of thromboxane A2 which
enhances platelet stickiness and aggregation.13
Free radicals in smoke, through increasing platelet
aggregation, platelet activation, and inflammation, also play a critical role in
cardiovascular disease.14 Cigarette smoking
also inhibits the formation of endothelial nitric oxide, which normally protects
the endothelium from platelet aggregation; fresh cigarette smoke contains
100–600 mcg of nitric oxide per cigarette, which oxidises to nitrogen
dioxide over a few minutes. Nitric oxide smoke emission is proportional to the
nitrate level in unburnt tobacco,15 but was not
ranked as a smoke toxicant.9
Identification of leading
toxicants—The leading smoke toxicants
identified9 are largely products of combustion,
and in the gas phase, rather than in the particulates. Most of the estimated
toxicity9 was found to have come from a limited
number of constituents in the smoke.16 The
usual cellulose acetate filter traps particulates, but not gases.
Method of
testing—Regulation of cigarette smoke emissions for harm reduction
purposes requires a method of inter-brand comparison which reflects the inhaled
volume of mainstream smoke and the resultant toxicant exposure of the smoker.
Since 1990, New Zealand regulations have prescribed the ISO smoking machine
method (see Glossary) for measuring emissions as the basis of tar ratings on the
side of the cigarette pack. This method tends to underestimate the average
amount of mainstream smoke inhaled per cigarette from all cigarettes, and
particularly from low yield cigarettes. The smoker’s toxicant exposure is
correspondingly underestimated:
MethodSelection
of emission measurement methods that approximate human smoke
exposure—To obtain a machine reading to better approximate human
smoking, and in the absence of puffing measurements for New Zealand smokers, the
machine smoking formula used in this paper to compare brands, is: toxicant
exposure equals toxicant yield (as tested) divided by nicotine yield (as
tested). The machine smoke test used was the Health Canada intensive method (see
Glossary).
Estimation
of toxicity of the emissions—The
state of California has recognised over 800 compounds as causing cancer, of
which the 158 found in cigarette smoke were
reviewed.9 Of these, cancer potency units (the
greater the CPU the greater the cancer risk at a given dose) were available for
40 known or suspected human carcinogens.
CPUs were multiplied by per cigarette smoke emissions
and divided by 20m3, the daily breathing rate,
to estimate the cancer risk index (CRI) for each carcinogen. For other diseases,
17 toxicants with published reference exposure levels (RELs) were found: the
lower the REL the greater the risk at a given dose. Yield levels divided by
RELs, and by 20m3, measured the non-cancer risk
index (NCRI) for each non-cancer toxicant.
Selection of
brands—We included all commercially available filter-tipped
manufactured cigarette brands with published emissions data from intensive
machine smoking, tested at the same independent laboratory—Labstat Inc,
Kitchener, Ontario —19 medium nicotine brands (15 British Columbian, four
Australian brands), and 17 low nicotine brands (five British Columbian, 11
Australian, and New Zealand’s top-selling low nicotine brand, Holiday
Extra mild20).
The overseas data were from overseas
websites.21 22 The Canadian brand
‘Players Premiere king size’ was not included, as that brand is no
longer sold; its nicotine yield was 1.87 mg—apparently unacceptable to
Canadian smokers.23 Eclipse, a brand that
‘heats rather than burns’ tobacco, Omni, a cigarette including
palladium in its tobacco, and many other brands were excluded due to the lack of
full published toxicant emission data based on intensive smoking machine
methods.24
Selection of
toxicants—To compare brand toxicity, we selected the top 10
carcinogens with the highest cancer risk index per cigarette per
day11 (Table 1)
after eliminating acetamide, thought to act through a non-genotoxic
mechanism of carcinogenesis. For cardiovascular and respiratory risk, we
included the known toxicants9 as listed in
Table 2.
For cardiovascular toxicity, hydrogen cyanide, carbon
monoxide, and arsenic9 were included, but
cresols (a separate and therefore expensive test accounting for 7% of
cardiovascular toxicity) were omitted, as was phenol (0.5% of cardiovascular
toxicity). Some toxicants had multiple toxic effects, so that 13 toxicants, as
listed in Table 1 and 2, were sufficient to compare brands: carbon monoxide,
hydrogen cyanide, arsenic, lead, cadmium, and chromium; acetaldehyde, acrolein,
and formaldehyde; and butadiene, acrylonitrile, benzene, ethylene oxide, and
NNN. Cancer potency estimates were not available for NNK. Ammonia and pH were
measured, but not used to estimate the free base form of the nicotine. Nicotine
was noted (not as a toxicant) to permit estimation of toxicant to nicotine
emission ratios, as a measure of toxicant exposures.
Estimation of toxicity
by cause-of-death grouping—The Californian Environmental Protection
Agency database lists each toxicant’s target disease
groupings.10 Based on the toxicant emissions in
each brand’s smoke, the cancer, cardiovascular, and respiratory risks were
calculated for different brands, separately for ISO and for intensive machine
testing.. For example, the cardiovascular risk index was estimated as in Table 2
as the sum of NCRIs for hydrogen cyanide, arsenic, benzene, and carbon monoxide
in the mainstream smoke of that brand, with cresols and phenol not measured on
this occasion.
Estimation of overall
brand toxicity—We then weighted the relative toxicity estimate for
each disease group according to each group’s relative contributions to New
Zealand cigarette mortality in 2000, whereby 39% of cigarette deaths were
attributed to cancer, 26% to cardiovascular, and 25% to respiratory mortality.
Another 10% were due to other medical causes of death, which have not been
attributed to specified toxicants.25
For each brand and disease group, we standardised the
toxicity against the average toxicity of the 15 British Columbian medium
nicotine brands under intensive machine smoking, scored as 1.00—based on
the fact that British Columbia was the only jurisdiction which had published
tests on all brands sold. To estimate the scope for toxicity reduction for
smokers of the popular New Zealand HEM brand, we compared its toxicity with that
of the least toxic of the other 36 brands reviewed.
Table 1. Carcinogenic toxicants in the smoke of New
Zealand Holiday Extra-mild cigarettes, 2002
* Fraction based on ISO
readings, Fowles and Dybing 2003.9 Table 1
www.tobaccocontrol.com;
#Arsenic was present but not quantifiable. The
value given is half of the lowest detected amount in the smoke of Canadian
brands ** Estimated risk includes
approximately 19% from carcinogens of known potency not measured for this
cigarette (Based on reported ISO yields for all carcinogens
9 Table 1) Of the top 10
carcinogens,9 acetamide and
N-nitrosopyrrolidine were not measured. Chromium was present but not
quantifiable.
Table 2. Cardiovascular and respiratory toxicants in
the smoke of New Zealand Holiday Extra mild cigarettes, 2002
NQ= Not quantifiable; NM=Not measured; *Arsenic was
detected, but was not quantifiable. The value given is half of that of the
lowest level detected in the smoke of Canadian brands; # Machine smoke measured
under ISO conditions. Fowles and Dybing 2003.9
**Fraction based on ISO readings, from Fowles and Dybing
2003.9 Table 1 www.tobaccocontrol.com
Results
Table 1Four carcinogens accounted for 76%
of the identifiable cancer risk of HEM: 1,3-butadiene (45%); and acrylonitrile,
acetaldehyde, and benzene, a further 31%. Ethylene oxide, a known carcinogen, is
included here—using the reported value of 9
ug/cigarette.5 To allow for identifiable
carcinogens not measured, we left 19% of the carcinogenic risk unattributed to
any toxicant, on the basis of published CPUs and ISO
emissions.9 Using published tables based on ISO
smoking conditions,9, Table 1 87% of the
identifiable carcinogenic risk was in the vapour phase, and 13% in the
particulate phase.
Cancer risk based on CRIs
versus cigarette cancer mortality—We updated the previous
estimate9 of the percentage of cigarette cancer
deaths accounted for by CRIs, using lifetime lung cancer risks from the American
Cancer Society’s Cancer Prevention Study II in the 1980s, against CRIs
estimated using intensive smoking machine testing results from Table 1,
otherwise using yield data from 9 Table 1
scaled upwards to mimic intensive smoking, using the intense to ISO ratio (2.15)
for summary CRIs for emissions as reported for Canadian regular cigarettes. On
this basis, approximately 35% of lifetime cigarette cancers (lung and other
sites) were explained by CRIs (27% of lung cancer in men, and 76% of lung cancer
in women).26
Table 2Hydrogen cyanide was found in both
vapour and particulate phases. Its very low REL indicated that even one
cigarette smoked was sufficient to exceed this threshold and produce a toxic
effect. Hydrogen cyanide made up 89% of the identifiable and measurable
cardiovascular toxicity of HEM mainstream cigarette smoke, and carbon monoxide
only 2.5%. For respiratory toxicity, acrolein, and cadmium were the most toxic
per unit weight but when the quantity in smoke was considered, acrolein made up
97% of the estimated respiratory toxicity of HEM smoke. Vapour-phase toxicants
contributed over half of cardiovascular toxicity and virtually all of
respiratory toxicity.
Table 3For the three most powerful
toxicants, HEM had the highest toxicant/nicotine ratios among the 37 low and
medium nicotine brands. On toxicant emissions alone, it was not the highest. The
overall toxicity per brand in the far right column attributes 10% of relative
toxicity to those toxicants (unknown, so not reducible by any known means)
responsible for ‘other medical’ causes of
death.25 This accounts for the somewhat lower
reductions obtained in the last column, compared with the second to last column
for cancer.
The lead level in HEM smoke was second highest of 37 brands
at 40 nanograms per cigarette, and the highest for lead/nicotine. In contrast,
HEM gave the lowest NNN/nicotine ratio. The NNN/nicotine ratio varied by a
factor of 6.4 between brands. Nicotine varied among medium nicotine brands from
0.9 mg to 1.3 mg per cigarette when tested under ISO smoking conditions (not
shown in Table 3), and varied more, from 1.5 to 3.2 mg per cigarette, under
intense machine smoking.
Among low nicotine brands, nicotine varied from 0.4 mg to
0.89 mg under ISO smoking conditions, and from 1.5 to 2.9 mg under intense
smoking conditions. Thus under intensive smoking conditions, ‘low’
and ‘medium’ nicotine cigarettes gave similar values and ranges for
nicotine yields. Across brands, the toxicant to nicotine ratios varied from 1.8
for tar/nicotine by either method, to 3.3 to 3.4 for acrolein/nicotine, for ISO
and intensive methods respectively. Under ISO test conditions, HCN/nicotine and
butadiene/nicotine varied four fold between brands, but under intensive test
conditions both varied less—HCN/nicotine varied 2-fold and
butadiene/nicotine 2.4-fold.
Comparing relative toxicity, low yield brands (relative
average toxicity 1.17, SD 0.16) were 19% more potent overall than medium yield
brands (relative average toxicity 0.98, SD 0.11), based on the toxicant to
nicotine ratio (p<0.01), standardised against Canadian medium-nicotine brands
(relative toxicity 1.00).
Spreadsheet estimates show that if HEM nitrosamine (NNN)
emissions were increased five-fold to the levels seen in the US Marlboro
brands,24 HEM’s overall toxicity would
have increased by (only) 0.1%.
DiscussionThe main findings
Strengths and weaknesses of this studyStrengths—For
the first time, this study shows how cigarette brands can be scored by a summary
measure of overall brand toxicity, based on leading toxicants and their target
organs, assessed by toxicological risk assessment methods.
Test results includes all brands with published test results
from the same independent laboratory, Labstat Inc, using Health Canada intensive
smoking conditions; others were not considered.
Weaknesses and
limitations—Reproductive and developmental toxicity effects were
not considered. The two leading toxicants in this category, arsenic and
1,3-butadiene,16 were already given weight in
Table 1, and so brand rankings would not greatly change if this extra toxicity
effects category was included. Only British Columbia displayed chemical
emissions under intense conditions for all or most brands sold. New Zealand,
thus far, has tested only one New Zealand brand (HEM) under intense smoking
conditions.20 Holiday regular, the highest
volume-selling New Zealand cigarette, was tested in 2002 by ISO method
only.20
The toxicant to nicotine ratio adjusts for compensatory
over-smoking in low yield brands, and its usefulness for medium-nicotine brands
may need reassessment once puff volume data is known for New Zealand smokers and
brands. A lack of cigarette engineering information on filter ventilation,
filter efficiency, or paper porosity precluded further elucidation of the
reasons for brand to brand differences found in smoke emissions. The toxicity
estimates are not absolute, but relative, and compare only the identifiable,
measurable toxicants in mainstream smoke.
This study compares cigarettes and their machine-generated
smoke, but does not allow for how smokers smoke their cigarette, and how much
they inhale.
Table 1 gives the estimated cancer risk of smoking one
cigarette daily over a lifetime. As estimated, the identified carcinogenic
emissions account for 35% of cigarette cancer mortality. For non-cancer risk
there is no method to link toxicity level to absolute levels of disease risk; we
cannot estimate how much of the total cardiovascular and respiratory risk has
been identified, or how much the estimated reduction in emissions will translate
into reduced toxicant absorption and decreases in mortality.
The percentage differences between the toxicity of HEM and
Export A full flavor in Table 3 may not reflect reductions in toxicity
obtainable for the total market. HEM is the only brand fully tested to date, and
its relative toxicity may be higher or lower than the New Zealand all-brand
average.
Comparison of results with current knowledgeIn a toxicity-regulated cigarette,
unidentified or unmeasured toxicants in smoke, such as free radicals, may or may
not reduce in parallel to the reductions anticipated for known toxicant
emissions, may not do so immediately, and the time required for effective
switching to reduced-toxicant brands is
uncertain.27
The risk assessment approach, using toxicological data
largely from animal studies for toxicity, emphasises the vapour phase rather
than tar or particulates (Table 1), and emphasises the vapour phase carcinogens
1,3-butadiene and benzene (Table 1) rather than the tar constituents
nitrosamines, and benzo(alpha)pyrene. For cardiovascular toxicity, risk
assessment emphasises HCN rather than CO (Table 2).
The test results for HEM only apply to the cigarettes
sampled for testing. For tar and nicotine at least, the results were confirmed
by almost identical results from cigarettes purchased 6 months later. The
manufacturer (BAT) reported the HEM brand yielded 0.8 mg nicotine on ISO testing
in 2002,3 but manufacturers’ reports had
not previously been checked by an independent laboratory.
What this study meansOverall smoke cancer risk indices
can be estimated, and non-cancer indices also, but with less certainty. The
overall toxicity of brands can be compared, based on each toxicant’s
potency per microgram and the amount of each in that brand’s smoke. The
relative toxicity scores for each brand allow comparison of brands across
countries and time periods, if identical methods and, as in this study, the same
laboratory is used. Potency factors may be revised by expert groups from time to
time, and emissions will change also. Thus relative toxicity scores may need
revision at least annually.
The toxicant to nicotine
ratio—This ratio could only be used because all the cigarettes were
of commercial design, so that tar and nicotine varied within narrow limits.
Research cigarettes if low in nicotine yield at 0.05 mg, and with tar at
10 mg,—have a tar/nicotine ratio of
200:1.28
Cancer risk (Table
3)—As addicted smokers may tend to seize on any excuse to keep
smoking, undue claims of lessened toxicity or disease prevention are unhelpful.
Conversely, unduly conservative estimates may discourage regulators from
removing excess toxicants. This paper suggests that regulation based on
exploiting existing brand differences (without using charcoal filters) could
lower the identifiable cancer risk of
HEM by 37%. As identifiable risk represents about 35% of total cigarette cancer
risk, the overall total cigarette cancer risk reduction achievable (if, and only
if, this brand’s toxicity was representative of all brands) would be (0.35
x 37%) =13% or 224 of the 1732 cigarette cancer deaths in
2000.25
Non-cancer toxicity.(Table
2)—With respiratory disease, and particularly with cardiovascular
disease, we lacked sufficient clinical or toxicological data to determine the
total non-cancer fraction of total toxicity represented by the toxicants in
Table 2.
Overall toxicity (Table
3)—If the cigarette with the highest overall toxicological risk
estimate (HEM in this case) was re-engineered to achieve the toxicant/nicotine
emission of the average of 15 Canadian medium nicotine brands, its identifiable
toxicity would reduce 28%. If re-engineered to achieve those of the least toxic
brand, Export A full flavor, HEM’s identifiable toxicity could be reduced
by 39%.
Nitrosamines—We
confirm great variation in nitrosamine levels. Marlboro cigarettes sold in New
Zealand were imported from the United States. HEM’s NNN emission in Table
1 on intensive testing is eight times lower than for US Marlboro cigarettes
machine smoked less intensively.24 Regulation
can force highly toxic brands off the market, but if regulation is confined to
nitrosamines, it will do little for New Zealand smokers. Less than 0.1% of
cigarette cancer deaths would be prevented (Table 1), and none of the 60% of
cigarette deaths due to non-cancer causes.25
Comprehensive regulation of all leading cigarette toxicants is required.
Lag
times—After implementation of the regulations, the interval before
death rates decreased would vary with the disease. Half of the achievable
reduction in cardiovascular risk can be expected within a year of
implementation, achieving full effect on cigarette mortality within 10 to 15
years, based on the known effects of stopping
smoking.29
Regulations to require regular monitoring, brand by brand
disclosures of tobacco constituents and emissions, and reductions in leading
emissions across all cigarettes, are now overdue. Though many toxicants remain
unidentified or unmeasured this paper provides a framework for comparing and
substantially reducing the identifiable toxicity of both manufactured and
hand-rolled cigarettes.
Author information:
Murray Laugesen, Public Health Physician, Health New Zealand Ltd,
Devonport, Auckland; Jefferson Fowles, Senior Scientist, ESR (Institute of
Environmental Science and Research), Porirua.
Potential conflict of
interest: The authors are co-inventors for a patent
Apparatus and methods for testing toxicity of
cigarette smoke, NZP 537968, 28 January 2005.
Acknowledgements:
ASH New Zealand Inc. (Action on Smoking and Health) Auckland (www.ash.org.nz) funded this study.
Correspondence: Dr
Murray Laugesen, Health New Zealand Ltd, PO Box 32 099, Devonport, Auckland.
(0274) 884 375; email: laugesen@healthnz.co.nz
References:
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