Catherine%20St.%20Hilaire,%20Amy%20M.%20Brownawell,%20Michael%20C.%20Falk,%20Keith%20Lenghaus,%20Kara%20D.%20Lewis,%20Paula%20M.%20Nixon

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Can Tobacco Reduce the Risk of Smoking?
Catherine St. Hilaire, Amy M. Brownawell, Michael
C. Falk, Keith Lenghaus, Kara D. Lewis, Paula M.
Nixon The Life Sciences Research Office, 9650
Rockville Pike, Bethesda, Maryland 20814.
www.LSRO.org
BACKGROUND
DEVELOPMENT AND TESTING OF POTENTIALLY
REDUCED-RISK CIGARETTES

• Smoking is estimated to kill more than 400,000
  people annually in the United States and 5
  million worldwide. Without effective
  intervention, this number could increase to 10
  million deaths per year by the early part of this
  century.
• Despite consistent messages emphasizing the
  importance of remaining tobacco free, there are
  1.5 million new daily cigarette smokers in the
  U.S. every year, recruited mostly among
  individuals under 20 years of age.

PAST 1950s Addition of Filters and Modification
in Tobacco Processing The introduction of filters
and changes in tobacco pressing significantly
reduced the delivery of tar in cigarettes in the
1950s Russell, 1993. Epidemiologic evidence
has shown that these changes reduced the risk of
lung cancer by one-half Peto, 1986.
1960s-1970s Development of Low-Yield
Cigarettes A concerted U.S. research effort to
develop a less hazardous cigarette began in 1968
with the formation of the Less Hazardous
Cigarette Working Group (later renamed as the
Tobacco Working Group), which was housed within
the National Cancer Institute and included
scientists from NCI, academia and the tobacco
industry. The development of a less hazardous
cigarette had broad support in the public health
community because of the clear dose-response
relationship between exposure and mortality risk
and the lack of proven cessation strategies.
Parascandola, 2005.

• PRESENT
• New Generation Potentially Reduced-Risk
  Cigarettes
• Cigarette-like Products
• This approach is based on empirical evidence that
  lowering the temperature to which tobacco is
  exposed results in lower levels of many of the
  toxins found in smoke. Two innovative products
  have been marketed that use technologies that
  primarily heat tobacco rather than burn itR.J.
  Reynolds Tobacco Companys Eclipse and Philip
  Morris Accord/Oasis.
• Cigarettes with Modified Tobacco
• Contain tobacco with reduced levels of
  tobacco-specific nitrosamines (TSNAs).
• Cigarettes with Modified Filters
• In some countries such as Japan, many cigarette
  brands have filters that contain activated
  charcoal. Such cigarettes have reduced levels of
  vapor-phase toxins. Philip Morris recently
  developed a modified Marlboro-branded cigarette
  by adding a charcoal filter and altering the
  tobacco blend.
• Testing Modified Cigarettes
• Pre-Market
• Product Content and Design, Smoke Composition
• Smoke from conventional cigarettes contains
  many toxic substances. In this phase of
• testing, smoke from the modified cigarette is
  chemically analyzed and compared to
• smoke from a conventional cigarette.
• Toxicology/Comparative Potency Assessment
• Preclinical studies may include in vitro assays
  and testing in appropriate animal models to
• and comparison of results from the modified and
  conventional cigarettes.
• Human Exposure/Dose Assessment
• Comparative assessment of actual exposure and
  internal dose would be included in this

Testing Low-Yield Cigarettes Pre-Market
Identification of toxic components Amount of tar
(defined as the total particulate matter minus
water and nicotine) and nicotine had been
demonstrated to correlate with increased
tumorigenicity in mouse skin painting studies.
Assessment of product characteristics and
emissions Animal Studies Cigarettes modified to
reduce or dilute tar and nicotine yields showed
statistically significant differences in
tumorigenicity in mouse skin studies compared
with a standard reference cigarette typical of
the market in 1970. Emissions Tar and nicotine
yields were measured by machine under
standardized smoking conditions (FTC method).
Human Exposure Assessment Preliminary findings
showed that smokers who switched to low-yield
cigarettes did not increase the number of
cigarettes smoked (the standard method to
determine exposure levels in epidemiologic
studies). Post-Market Assessment of population
effects Despite the recognition of the importance
of ongoing monitoring/surveillance, funding
priorities changed in the late 1970s and no funds
were allocated for this task.
From http//www.oas.samhsa.gov/nhsda/2k2nsduh/Resu
lts/2k2results.htmfig6.4 downloaded 23-11-2005

• The number of daily smokers in the U.S. has
  consistently been in the range of 30-45 million
  for the past twenty years and tobacco use is
  increasingly concentrated in low-income and
  marginalized populations.

IMPACT ON PUBLIC HEALTH THEN AND NOW
Current evidence indicates that little or no
health benefit resulted from smokers switching to
low-tar products. In 2001, NCI published the 13th
edition of its monograph series on Smoking and
Tobacco Control. The authors concluded that,
because smokers tended to change the way they
smoked low-yield cigarettes (in order to
compensate for reduced nicotine levels), exposure
to cancer-causing toxicants was not reduced and
the incidence of lung cancer did not decrease as
anticipated. Reduced-yield cigarettes had the
characteristic of elasticity which allowed
smokers to increase the amount of smoke they
inhaled National Institutes of Health, 2001.
When evidence of this phenomenon emerged in the
early 1980s, the Surgeon Generals 1981 report
on The Changing Cigarette warned that, for
those who switch to lower-tar cigarettes, the
benefits are minimal.
The LSRO project goal is to improve the
assessment process so that the adverse health
effects in continuing smokers are decreased. The
less hazardous cigarette effort of 30 years ago
had at least two major factors that contributed
to its failure1)scientific uncertainty in
critical areas such as the role of nicotine in
the smoking habit and 2) a loss of funding at a
critical time in the processafter the product(s)
were out on the market but before assessment of
actual effects were conducted. The failure of
the reduced-yield program to reduce lung cancer
incidence, coupled with the belief that many
individuals who may have quit chose to smoke
light cigarettes instead, highlights the
importance and the challenge of ensuring that
this experience is not repeated. While scientific
understanding has advanced over the past 30-40
years, many critical gaps in our understanding
remain. The purpose of the LSRO project is to
characterize the current state of scientific
understanding and make recommendations for the
evaluation of current and future modified
cigarettes.
Compiled from US census data http//www.census.gov
and NHIS data from http//www.cdc.gov/nchs/fastat
s/smoking.htm
Thus, despite substantial progress in reducing
the prevalence of smoking in the US (by
discouraging initiation and encouraging
cessation), a relatively consistent number of
approximately 30-45 million adults continue to
smoke and remain at risk of smoking-related death
and disease. Tobacco Harm Reduction (THR) is a
complementary approach to ongoing efforts aimed
at eliminating tobacco use and associated harm.
THR is aimed at reducing death and disease caused
by continued smoking.
LSRO has been asked to conduct a project related
to one approach to tobacco harm reductionthe
development of potentially reduced-risk
cigarettes. This project is being funded by
Philip Morris USA.
Poster presented at the Society for Risk
Analysis (SRA) Annual Meeting, December 6 2005.