The Fire Safe Cigareette Act of 1990 required the CPSC to develop information on the toxicity of low ignition potential cigarettes; the testing plan is detailed in this document. The testing is split into six different chapters: A) Overview and major considerations in the toxicity testing of low ignition-potential cigarettes, B) Smoking machine parameters for collection of total particulate matter and gases from low ignition-potential cigarettes, C) Assessing changes in topography and biological effects of tobacco smoke in humans, D) Analysis of toxic smoke constituents, E) Short-term tests for the evaluation of cigarette smoke toxicity, and F) In vivo bioassays for Carcinogencity. Budgets are included.
- Burns, D.M.
- Gairola, C.G.
- Harris, J.E.
- Hoffmann, D.
- Lee, B.C.
- Pillsbury, H.C. Jr
- Shopland, D.
- Health effects
Design changes which have measurably altered health effects of cigarette smoke, both for smokers and nonsmokers.
- Introduction of new/unconventional products
Research and development of novel nicotine delivery devices and experimental tobacco designs.
- Mainstream constituent yields
Modification of selected mainstream smoke constituents in response to health concerns.
- Measuring human smoking behavior
Measuring the effects of changes in human smoking behavior on intake of nicotine and smoke constituents.
- Measuring overall toxicity
Development of scientifically valid protocols and methods for testing the health and toxicity effects of changes in product design.
- Sidestream constituent yields
Modification of selected sidestream smoke constituents in response to health concerns.
- Smoke constituent testing
Development of methods for measurement of gas and particulate yields in mainstream and sidestream smoke.
- Toxicity and consumer intake
Development of scientifically valid procedures for measuring biological activity and neurological effects of nicotine and smoke constituents.
- Ignition potential (IP)
- Carcinogenic (Cancer-causing)
- Per puff delivery
Per puff tar, per puff nicotine, and per puff CO
- Carcinogenic (Cancer-causing)
- drug use
- Smoke Constituent
- Nitric oxides
- Hydrogen cyanide (HCN)
- Polynuclear aromatic hydrocarbons (PAHs)
- Named Organization
- Tobacco Institute
- Ames assay
- Gentoxicity tests
- Mutagenesis tests
- Smoke collection trap
- Filtrona smoking machine
- Salmonella assay
- Mammalian celltransformation assay
- Whole animal bioassay
- Inhalation bioassay
- Bioassays on mouse skin
- Fire Safe Cigarettes (Products)
- Paper (Design)
- Length (Design)
- Tobacco Weight (Design)
- Burn Rate (Design)
- Tar (Measures)
- Transfer to Smoke (Measures)
- Smoke Delivery/Transport (Measures)
- Smoke Constituents
- Puff Count (Measures)
- Test/Inhalation (Testing)
- Test/Smoke Machine (Testing)
- Test/Smoke Constituents (Testing)
- Test/Toxicity (Testing)
- Cancer (Health Effects)
- Secondhand Smoke/Toxicity
- Secondhand Smoke/Constituents
- Test/Animal Subject (Testing)
- Test/Smoking Behavior (Testing)
- nicotine technology
- Pressure Drop (Design)
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The CPSC staff recommends the following guidance plan after
reviewing the considerations of its expert panel and DHHS.
III. Assessment Plan
This plan provides guidance for the development of data
needed to evaluate the changes in toxicity associated with low
ignition-potential cigarettes. Performance-based, rather than
design-based, testing will be used to provide data specific to
cigarette prototypes. A screening paradigm that requires
acceptable performance levels by a candidate cigarette type at
one tier of tests before proceeding with the next tier is
recommended. This would allow early rejection of candidates
evaluated as unacceptable. However, definition of acceptable
levels of performance is beyond the scope of this plan and the
direction given by the Act. Therefore, the tests.are presented
in a sequence of tiers for screening without ascribing acceptable
levels of performance at each tier.
- Results of the recommended testing will be used to assess
the relative toxicity of low-ignition potential cigarettes. The
toxicity of a candidate low ignition cigarette should be compared
1) the specific marketed brand/type intended for
replacement, or comparable marketed brands/types for a non-
replacement candidate, and
2) standard reference cigarettes, such as the University of
Kentucky standard cigarettes mentioned in Chapter E, for
There are insufficient test methods and data on exposure to
cigarette smoke and resultant effects for the direct translation
of the results into absolute risks to humans. Since the overall
health goal is to avoid the production of greater or perhaps new
toxicities than that caused by existing cigarettes, a comparative
approach of assessing toxicity is appropriate.
Selection of the guidance plan tests assumes that no new
additives would be present in the candidate cigarettes and that
presently used additives would not exceed the levels in the
current cigarettes. Since toxic effects not considered by this
guidance plan could also occur, it is recommended that additives
exceeding the current maximum levels of use on a per unit weight
of tobacco basis must be disclosed to the U.S. Department of II
Health and Human Services. Confidential business information
status may be requested for the data disclosed.
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A. Smoking machine
The FTC method described in Chapter B is the basis for the
mechanical generation of smoke constituents. Puff volume,
frequency, and draw velocity may be modified as dictated by
behavioral data developed from human testing (Tier III), as
described in Chapter C. Unless consistent correlation of testing
results of mainstream and sidestream smokes can be shown, both
must be separately collected and tested.
B. Description of Tiers
An outline of four tiers is presented in Table 1. A
description of the tiers follows.
Tier I_- Analyses of chemicals
All constituents will be reported as per unit weight of
tobacco burned and per cigarette. Moisture, nicotine, tar (total
particulate matter- dry), and carbon monoxide will be measured
according to the FTC method, as described in Chapter B. Nitric
oxide will also be measured using the detector attachment to the
smoking machine. The gaseous phase will be analyzed for acidity,
reduction/oxidation potential, hydrogen cyanide, volatile
hydrocarbons, aldehydes, and volatile nitrosamines, as described
in Chapter D. The tar will be analyzed for phenols, catechols,
polyaromatic hydrocarbons, and tobacco-specific nitrosamines
Tier II - In vitro tests
The tar will be assayed for mutagenic activity with Ames'
Salmonella test with strains TA98, 100, and 1535. The tar will
also be assayed for malignant cell transforming activity, using
C3H/10T1/2 mouse embryo fibroblast cells. Both mutagenicity and
cell transformation assays are described in Chapter E.
Tier III - Human smoking behavior
Humans are typically the last experimental tier in testing
products with potential human health effects. An example is the
premarket testing of new drugs. Human testing to collect
topographical data is limited to a couple of weeks of exposure.
Smoking behavior, including puff volume, frequency, and draw
velocity of a selected group of human volunteers would be
monitored, as outlined in Chapter C. Carbon monoxide (breath or
blood) and cotinine (urinary, salivary, or blood) will serve as
biological markers of exposure to the smoke. If the smoking
behavior data is significantly different from the FTC smoking
machine settings such that an increase in exposure to the
analyzed chemicals might result, then the machine must be set to
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reflect these data before generating smoke constituents for page 5
further Tier I and II testing and then animal testing.
Tier IV - Animal tests
Inflammatory lung response to cigarette smoke in C57B1 mice
will be assayed as described in Chapter E. Tumor formation in
the upper respiratory tract of random-bred golden Syrian hamsters
from inhalation exposure and the skin, lungs, and other tissues
of Swiss albino Ha/ICR/Mil strain mice from skin painting
exposure will be examined. These two carcinogenicity tests are
described in Chapter F.
All testing must conform to good laboratory practices,
humane laboratory animal methods, and informed human consent
procedures accepted within the scientific community. Evaluations
of toxicity must be conducted by.scientists possessing
appropriate toxicological qualifications.
IV. First implementation step
Table 2 is a collection of direct cost estimates for Tiers
I, II, and IV. No estimates are available for Tier III.
Completion of all four testing tiers by successful low ignition
potential cigarette candidates might be considered expensive
relative to the present level of testing required by FTC
($330,000 for Tiers I, II, and IV vs. $3,500 for FTC; Table 2).
Therefore, a stepwise implementation of the plan is suggested.
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Estimated Direct Costs in 1993 U.S. Dollars
per brand or prototype
Tier I - Analyses of chemicals = $9,500
3500 FTC-required tar, nicotine, and carbon monoxide
250 Whole smoke:
= acidity (pH)
500 - reduction/oxidation potential
350 Gas phase
400 nitric oxide
600 volatile hydrocarbons
800 V.clatile nitrosamines
500 phenols, as phenol
800 tobacco specific nitrosamines
Tier II- In Vitro Tests = $9,350
1850 Salmonella mutagenicity (Ames' assay)
7500 mouse embryo fibroblast cell transformation
Tier IV - Animal Tests = $309,000
50,000 mouse inflammatory lung response
220,000 hamster upper respiratory tract carcinogenicity
39,000 mouse skin painting carcinogenicity
$327,850total for Tiers I, II, and IV
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A practical selection of recommended tests should comprise a
first step in the implentation of this health effects assessment
plan. Subsequent steps should consider the testing recommended
by this plan. The first step should include:
Smoke and condensate generated by machine according to the FTC
Tier I $5,050
whole smoke pH
tobacc-o specific nitrosamines
Tier II $1,850
Salmonella mutagenicity ("Ames") assay
$6,900 Estimated total per brand or prototype
The rationale for selecting these tests extends beyond cost
and time duration considerations. Levels of specific chemicals
(Tier I) as well as an indication of the genotoxicity of the
mixture (Tier II) are needed. Tar, nicotine, and carbon monoxide
are presently required by FTC. The pH of the whole smoke is
relevant to nicotine uptake. Benzo(a)pyrene is a known animal
and human carcinogen; however, cigarettes are not the only source
of exposure. The tobacco-specific nitrosamines are potent animal
carcinogens and tobacco is the only known source of human
exposure. No data are available on the human carcinogenicity of
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OVERVIEW AND MAJOR CONSIDERATIONS IN THE TOXICITY
TESTING OF LOW IGNITION-POTENTIAL CIGARETTES
Jeffrey Harris, M.D., Ph.D.
Internal Medicine Associates - 2
Wang Ambulatory Care Center 605
Massachusetts General Hospital
Boston, MA 02114
21 Aug 1992
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Both mainstream andsidestream cigarette smoke are complex
chemical mixtures. In view of this chemical complexity, it
should be no surprise that cigarette smoke has multiple, diverse
effects on human health. Nor should it be unexpected that
multiple chemicals in cigarette smoke contribute to any single
adverse health effect.
The diverse human health consequences of cigarettee smoking
are briefly reviewed. Many experimental laboratory models have
been developed to study the mechanisms of cigarette smoke-induced
disease. These laboratory models are not always convertible into
practical, standardized test systems that quantitatively compare
one cigarette prototype with another. In view of the
multiplicity of health effects and mechanisms of smoke-induced
health damage, no single test or battery of tests can capture all
possible health endpoints.
While analyses of smoke constituents and studies in
laboratory animals are feasible, human epidemiological studies
are not practical for short-term assessment of small differences
in the toxic effects of various cigarette prototypes. Cigarette
smoke samples for chemical analysis and biological testing need
to be collected in a manner that approximates human cigarette
puffing as closely as technically feasible.
In formulating a testing plan, the CPSC essentially has two
options: a design-based testing plan, in which individuaL,
pre-selected cigarette design parameters, such as paper porosity
or percent expanded tobacco, are systematically varied and
tested; and a performance-based testing plan, in which complete
cigarette prototypes, and not individual design parameters, are
Some testing protocols entail a "screening paradigm."
Multiple tests are performed in sequence. If a prototype fails
any particular test in the sequence, the prototype is rejected
and no further tests are performed. Other multi-test protocols
allow for tradeoffs among costs and benefits. An unfavorable
result at any point along the testing sequence does not
necessarily result in rejection.
The only governmentally-mandated, health-oriented testing of
commercial cigarette brands is the measurement and reporting of
"tar," nicotine and carbon monoxide in mainstream smoke by the
Federal Trade Commission. With this exception, none of the
toxicity tests described by the Expert Panel are routinely
performed on existing cigarette brands by any governmental
agency. The contents of currently marketed cigarettes are
proprietary information. Specific additives, tobacco
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composition, and other design features are not publicly