Product Design
Cigarette Additive Fate Studies: A Research Proposal
Abstract
Proposes research studies to examine the fate of radiolabeled additives applied to tobacco, paper and filters. States menthol and nicotine migration data are well documented, but the route of pyrolyzed additives have not been studied. Describes four phases of research including: selecting chemicals to be tested, synthesizing radiolabeled additives, optimizing cigarette additions, and fabricating a total smoke recovery system. Indicates: cigarettes will be smoked under Federal Trade Commission [FTC] conditions on a puff-by-puff basis, migration rates will be examined, and mainstream/sidestream smoke, butts, and residual ash components will be quantified. Outlines resources and budget needed, and requests additional funding to complete the project.
User-Contributed Notes
Fields
- Author
- Gains, Lawrence H. (Lor, Organic Research Chemist, 1979)
- Recipient
- Heck, Jonathan Daniel (LOR Life Sciences Manager, 1994)Also Diplomate, American Board of Toxicology 1995
- Minnemeyer, Harry Joseph, Ph.D. (Lorillard R&D Dept.; worked on nicotine augmentation project)
- Norman, Vello, Ph.D. (LOR R&D VP)Physical chemist employed by Lorillard since 1970's, V.P. in charge of R & D since 1991.
- Reid, Jack R. (Lor, Sr. Research Organic Chemist, 1979)
- Schultz, Frederick J., Ph.D. (VP of Lorillard, Inc. '89-95)
- Hypothesis
- Design changes over timeChanges in cigarette design over the past half century.
- FTC machine testing and ratingsDesign changes to achieve altered FTC smoke machine tar and nicotine ratings, with or without measured changes in human intake.
- Inhalation ProfileAre cigarettes designed to cater to individual inhalation profiles?
- Mainstream constituent yieldsModification of selected mainstream smoke constituents in response to health concerns.
- Nicotine transport, transfer, and uptakeDesign changes which alter nicotine delivery or effect how the product causes and maintains dependence, including transfer of nicotine from tobacco to smoke, and uptake into the body.
- Sidestream constituent yieldsModification of selected sidestream smoke constituents in response to health concerns.
- Smoke constituent testingDevelopment of methods for measurement of gas and particulate yields in mainstream and sidestream smoke.
- Use of additivesModification of tobacco products through use of additives and measuring effects on dependence, behavior, and toxicity.
- Use of filters, paper, and ventilationModification of tobacco products through use of filters, paper, and ventilation, and measuring effects on dependence, behavior, and toxicity.
- Use of tobacco processing/ blendsModification of tobacco products through changes in tobacco processing and use of blends, and measuring effects on dependence, behavior, and toxicity.
- Keyword
- Aerosol
- Brand differences
- Controlled profile
- Delivery modification
- Menthol delivery (Smoke menthol, menthol yield)
- Nicotine delivery (Smoke nicotine or nicotine yield)
- Per puff deliveryPer puff tar, per puff nicotine, and per puff CO
- Puff count
- Pyrolysis
- Reaction products
- Total particulate matter (TPM or Tar)
- Volatile nicotine
- Additive
- Licorice (Licorice Fluid Extract, Powder, and Root)
- Menthol (dl- Menthol or l-Menthol)
- Tartaric acid
- Smoke Constituent
- Menthol
- Nicotine
- Total particulate matter
- Design Component
- Ash formation
- Burn additive
- Cellulose acetate filter (CA filter, Conventional filter)
- Flavorant
- Humectant
- Nicotine transfer efficiency (NTE)
- Named Organization
- *British American Tobacco Company Limited BAT (See British-American Tobacco Co.)Defense
- *EPA ( use United States Environmental Protection Agency)
- Federal Trade Commission (Enforcement agency for laws against deceptive advertising)Enforces laws against false and deceptive advertising, including ads for tobacco products. Ensures proper display of health warnings in ads and on tobacco products;collects and reports to Congress information concerning cigarette and smokeless tobacco advertising, sales expenditures, and the tar, nicotine, and carbon monoxide content of cigarettes.
- Lorillard Tobacco Co. (American cigarette manufacturer)American cigarette manufacturer; makes Kent, MaxSatin, Newport, Old Gold, Style, and True cigarettes.
- Philip Morris Companies Inc. (Parent company of Philip Morris USA, Kraft, Miller)America's seventh-largest industrial enterprise in 1993, owns Kraft, Miller Brewing, General Foods, and more.
- R.J. Reynolds Tobacco Co. (Cigarette manufacturer (Camel, Winston, Doral))Cigarette manufacturer (Camel, Winston, Doral)
- Research Triangle Institute
- Tobacco Chemists Research Conference (Formerly known as the Tobacco Science Research Conference)
- Tobacco Research Committee (British Industry Research Organization)
- University of Kentucky
- Subject
- additives
- aerosol (technology)
- Experimental Technology (Technology)
- Filters (Design)
- Formulas (Design)
- Paper (Design)
- Particle Size (Technology)
- Puff Count (Measures)
- Reaction Processes (Technology)
- Secondhand Smoke/Constituents
- @smoke_constituents_measures
- Test/Butt Analysis (Testing)
- Test/Smoke Condensate (Testing)
- Test/Smoke Constituents (Testing)
- Test/Smoke Machine (Testing)
- Transfer to Smoke (Measures)
Document Images
Accession number 2578
Lorillard Research Center
Greensboro
Cigarette Additive Fate Studies:
A Research Proposal
Submitted by: L. H. Gains
Report number: Y Date: Oc+-oror 16, lr9o
Summary or Abstract:
Cigarette additive fate studies are proposed. Compounds to be
studied would be selected from current production tobacco
additives, investigational paper and filter additives, and
potential synthetic additives of current interest. Radiolabelled
compounds would be synthesized and applied to cigarette tobacco,
paper, or filters. Migration and equilibration of the additives
over time within the unburned cigarette would be measured. Equil-
ibrated cigarettes would be smoked under standard conditions in a
total smoke recovery apparatus. Distribution of the radioactivity
in main stream and side stream smoke particulate and gas phases
would be determined. Radioactive compounds formed upon smoking of
the test cigarettes would be identified and quantitated.
/1p:PERM1
Xc: J. D. Heck
H. J. Minnemeyer
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J. R. Reid
F. J. Schultz W
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INTRODUCTION
A presently under-investigated area of tobacco chemistry is the
determination of the fate of chemical additives between the time
they are first applied to tobacco, paper, or filter rods and
extending up to and including their ultimate consumption by
smoking of the cigarettes fabricated with these materials. The
importance of knowledge about the distribution of additives and
their combustion products in smoke streams is recognized (1, 2, 3,
4, 5). However, we have no complete, systematic fate studies for
any of our current production materials. With the exception of
nicotine and menthol, we have generated no information on the
migration and equilibration behavior of these materials within the
cigarette itself. Nor do we have data on the transfer of
additives from tobacco, paper, and filters into the various smoke
streams of a burning cigarette. Most especially, we lack data on
the pyrolysis and decomposition products for almost all of our
production materials. The available technical literature contains
only limited data for relatively few of our current production
materials. In addition to present production compounds, a number
of filter and paper additives are under current investigation by
us, but no data on the fate of these compounds is available.
Finally, numerous non-production flavorants have been evaluated
and found to be of interest to us, but again there are no data on
the fate of these compounds after their application to cigarette
components.
I propose that a research project be initiated to investigate the
fate of radioactively labelled tobacco, filter, and paper addi-
tives. As has been pointed out by numerous others, the most
unequivocal technique for studying the fate of cigarette additives
is the addition of labeled compounds to cigarette components (2,
5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20).
Labeled compounds can be added to cigarettes in such extremely
small amounts that no difficulty is experienced in obtaining
cigarettes with normal burning characteristics. Moreover, the
literature is replete with the details for preparing spiked
cigarettes and the particulars for constructing an apparatus by
which to collect the total combustion products for analysis.
The project as envisioned will encompass four phases. The first
phase is primarily organizational and includes such activities as
selection and prioritization of test articles, design of radio-
labelling syntheses for the first group of test articles, and
fabrication and optimization of cigarette spiking and total smoke
recovery equipment needed to perform the experimental phases.
Several phase one activities are already in progress.
Execution of the radiolabelling syntheses for the first few test
articles will commence as part of the second phase of the project.
Syntheses for three materials have previously been authorized with
one compound completed and two syntheses currently in progress.
Delivery of smoke components into the various smoke streams has
been shown to be quite sensitive to the distribution of the
precursors within the cigarette prior to smoking (2, 3, 4, 21).
Therefore, a major activity in the second phase will be studies to
determine the equilibration and distribution of additives among
the various components of a cigarette. These studies will include
determination of the time course and quantitation of migration of
additives from tobacco into the filter and/or paper as well as the
other permutations appropriate for additives applied initially to
filters and papers instead of the tobacco. These data will be
essential for design of material balance studies under the third
phase which will focus on the transfer and partitioning,of addi-
tives to the various smoke streams and retention in ash and on the
butt. The fourth and most advanced phase of the experiments will
have as its primary objective the characterization and identifi-
cation of the specific radioactive chemical entities obtained upon
smoking of the test cigarettes. Phase four may also include
puff-by-puff studies for selected additives.
SPECIFIC PROPOSAL OBJECTIVES
Compounds selected for fate study would come from three additive
categories. For each category, the specific objectives of the
fate study proposal are listed below.
Category I. Current Production Tobacco Additives.
OBJECTIVES
1. To determine the equilibration behavior of'the additives
within the tobacco column.
2. To determine the rate and extent of migration of the
additives into cigarette papers.
3. To determine the rate and extent of migration of the
additives into cigarette filters.
4. To measure the material balance and partitioning of
the additives among the main stream smoke and side
stream smoke particulate and gas phases, and residual
content in ash and cigarette butt.
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5. To identify and quantitate the chemical entities which
result when the precursor additives are smoked under
standard FTC conditions.
6. To examine the puff-by-puff behavior of the
additives.
Category II. Materials Under Investigation Which Are
Applied to Papers or Filters Rather Than to Tobacco.
OBJECTIVES
1. To determine the rate and extent of migration of the
additives into the tobacco column.
2. To determine the rate and extent of migration of the
additives into cigarette papers or filters.
3. To determine the equilibration behavior of the
additives within the cigarette as a whole.
4. To measure the material balance and partitioning of
the additives among the main stream smoke and side
stream smoke gas and particulate phases and residual
content in ash and cigarette butt.
5. To identify and quantitate the chemical entities
which result when the precursor additives are smoked
under standard FTC conditions.
6. To examine the puff-by-puff behavior of the
additives. -
Category III. Synthetic Materials of Interest Which Could
Be Applied to Tobacco, Papers, or Filters as Future
Production Ingredients.
OBJECTIVES
1. To determine the rate and extent of migration of the
additives from the site of application into the other
cigarette components.
2. To determine the equilibration behavior of the
additives in the cigarette as a whole.
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3. To measure the material balance and partitioning of
the additives among the main stream smoke and side
stream smoke gas and particulate phases and residual
content in ash and cigarette butt.
4. To identify and quantitate the chemical entities
which are delivered in main stream smoke particulate
and gas phases when the precursor additives are
smoked under standard FTC conditions.
LITERATURE REVIEW SUMMARY
There is an extensive literature reporting on additive studies
both with and without the use of isotopically labelled materials.
The objectives of these studies have been diverse and sometimes
complex. Objectives as stated by various authors have included:
the study of the transfer of additives from tobacco to smoke (2,
20, 22, 23, 24, 25, 26, 27, 28, 29); additive material balance
studies (9, 13, 16, 30, 31); the identification and total
distribution of combustion and pyrolysis products in smoke (32);
the mechanisms of smoke formation (3, 5, 6, 21, 33); contribution
of additives to the particle size distribution in smoke aerosols
(17); reaction mechanisms in the burning cigarette (14); thermal
decomposition of tobacco components (34); transfer of compounds
and their degradation products to smoke (35, 36, 37); the
pyrosynthesis of smoke compounds (38, 39, 40); study of
precursor-product relationships (7, 15, 18, 41, 42); and fate
studies (1, 43, 44, 45, 46, 47).
Most of these objectives may be sorted into one of three groups:
studies which obtain information on the disposition, over time, of
an additive within the intact, unburned cigarette, i.e. migration
and equilibration studies; studies which obtain information on the
the distribution of an additive and its products in the various
fractions obtained from a burning cigarette, i.e. material balance
studies; and studies which quantitate and identify the specific
compounds formed by an additive during the smoking of a cigarette,
i.e. product-precursor studies. For clarity, I shall define a
"complete fate study" to mean a study which includes determina-
tions in all three of the above-listed areas. Until a very recent
report which describes studies on five additional compounds, only
vanillin and menthol had been subjected to "complete fate" studies
according to this definition (48). More typically, studies are
limited to one or two of the three areas. For example, the degree
of pyrolysis and the degree to which the intact additive survives
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the smoking of the cigarette have been reported for a number of
compounds (3, 5, 9, 13, 16, 24, 25, 27, 29, 30, 38, 45, 46, 47)
but in only a few instances have the pyrolysis products been
identified and quantitated (18, 28, 32,. 33, 37, 49).
A few workers have reported results from additive studies which
did not make use of isotopically labelled materials. In 1963 some
Japanese workers employed gas chromatography (GC) and spectro-
photometric techniques to investigate the thermal degradation of
native and added nitrogenous tobacco components (34). Others have
used similar techniques to study the transfer and distribution of
menthol (35), sterols (24), and glycyrrhizic acid (50) from
tobacco to smoke streams. Another non-labelled study sought to
compare transfer rates of the exogenous and endogenous portions of
tobacco compounds (27). In 1979, a non-label study determined
that additive transfer to smoke streams depended on compound
volatility (22).
The majority of additive studies have employed isotopic tracers,
and most of these have involved radioactive compounds. Table I
summarizes data for the specific cigarette additives which have
been studied, the type of label used if any, and the specific
objectives of the respective studies as stated by the authors.
For the various types of additive studies, both an apparatus for
application of the subject additives and a means for recovering
the various smoke streams for subsequent analyses are required.
Devices which may be used to recover both main stream and side
stream smoke fractions have been reviewed at the 1990 TCRC (51). A
number of earlier reports describe the methods used by workers
investigating various aspects of additive fate studies. At the
1960 TCRC, Holmes' group at Philip Morris described design and
construction of an apparatus for material balance studies and its
application to the study of glycerol distribution in smoke streams
(52, 53). A 1966 article by others at Philip Morris presented a
detailed schematic of their "total combustion product cigarette
smoking machine" which they used to analyze radioactive cigarette
paper (31). At the 1968 TCRC, Newell and her group at R J
Reynolds reported on the distribution of C-14 labelled menthol in
the main stream and side stream smoke fractions and presented a
description of their smoking apparatus (46). Also in 1968, a
group at BAT reported their evaluation of an apparatus for
determining the mass balance of C-14 activity from a burning
cigarette (13). Another group, under Jenkins, at Philip Morris
presented details of their successful design of a "total recovery
smoking machine" in 1971 (9). A 1973 report from the British
Tobacco Research Laboratories describes the construction and
evaluation of equipment which permits the quantitative puff-by-
puff collection of smoke streams (2). Workers at the University of
Kentucky described in 1974 a smoke system which they used to
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recover at least 85% of C-14 labelled insecticide residues from
burning cigarettes (23). Marmor and Minnemeyer illustrated their
apparatus for material balance studies on a potential tobacco
additive in a 1975 publication (16). A group from BAT described
their current smoke recovery system at the 1990 TCRC (48).
Various methods for application of labelled compounds have been
studied and evaluated (2, 7, 21, 23, 25, 35). The consensus that
has emerged is that an injection procedure is most desirable. A
mechanical cigarette spiking apparatus was described by the
British Tobacco Research Council in 1973 (20). Jenkins described
what has been adopted as the standard methodology for preparation
of C-14 labelled cigarettes in 1975 (4). Some Swiss workers
described in 1984 a fully automatic, microprocessor controlled
spiking device (54).
EQUIPMENT
To accomplish the objectives of this proposal it will be necessary
to modify some existing equipment and to design and fabricate some
apparatus from scratch. The purchase of some new equipment will
also be necessary. Much of our current analytical instrumentation
can be used without modification. Total smoke recovery equipment
has been built and is available for use within the Research
Center. Most probably this apparatus will require modifications
for the proposed project's applications. As mentioned above,
sufficient precedent is available in the literature for guidance
in achieving the necessary design features. Specifically, there
will need to be means for the smoking of cigarettes under standard
FTC conditions with separate collection of particulate matter, gas
phase components, and volatiles from both main stream and side
stream smoke including a provision for puff-by-puff analysis.
The literature again serves as an ample source for guidance in the
design and construction of an appropriate device for spiking
cigarettes with the radioactively labelled~test articles. This
apparatus will require complete fabrication since none is commer-
cially available and no such device has previously been used in
the Research Center.
The full arsenal of our currently available state of-the-art
analytical instrumentation will be appropriately applied to the
proposed research. These techniques will include liquid scintil-
lation counting (LSC), gas chromatography (GC), GC/MS, GC/FTIR,
NMR, HPLC, and thin layer chromatography (TLC). In order to
accomplish the stated objectives of the proposed research, it will
be necessary to locate, separate, identify, and quantitate the
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radioactive precursors applied to the cigarettes and their
products formed upon smoking. However, no radioactivity specific
detectors are presently available for our HPLC, TLC, or GC
equipment. The most essential of the various detectors for this
application will be an HPLC flow cell radioactivity detector.
Such detectors are available from several vendors and are widely
used for applications analagous to those proposed here (55).
Purchase of an HPLC radioactivity detector has been requested for
the 1991 capital budget (56). A commercially available splitter
and flow proportional counter would provide useful radioactivity
detection capability for GC applications. However, the HPLC
application is expected to be the more useful technique and no
purchase of an additional GC detector is initially contemplated.
Similarly, a radioanalytic imaging system or linear analyzer for
direct quantitation of TLC data would be quite useful, but is not
considered initially essential.
TEST ARTICLES
The additive test articles will be selected from the three
categories consisting of: 1. current production ingredients; 2.
investigational paper and filter additives; and 3. synthetics of
current high interest. The Product Development Department (PD),
has indicated that some of the criteria they would use in priori-
tizing additive selection include usage levels, degree of
occurrence in our product range, and the presence or absence of
previously published data on a specific compound. The fate study
investigations will generate information relevant to a number of
practical manufacturing situations. Current PD project applica-
tions include investigations of paper and filter additives. The
proposed fate studies could address a variety of specific issues
which are associated with these investigations. The Lorillard
Toxicological Testing Program includes a spectrum of biological
tests on a large number of specific chemical entitities including
synthetics of high interest. The relevance of these data for
current or potential cigarette additives depends to a great extent
on the assumption that the bulk of the additive enters the smoke
streams chemically unchanged. The proposed additive fate studies
will generate data on the extent of intact additive survival in
support of this assumption, for all three categories of compounds.
Personnel within the Organic Chemistry Section, during the past
eight years, have routinely proposed and created strategies for
incorporating radioactive labels in a wide range of compounds for
use in metabolism studies. These radiolabelling syntheses have
7
been developed and executed under contract with the Research
Triangle Institute (RTI). In accordance with funds included for
this purpose in the 1990 budget, RTI is currently performing
labelling syntheses for fate studies. The same range of specific
activity and total activity used in preparing compounds for
metabolism studies is employed in preparing compounds for the
proposed fate studies. Specific activities up to a maximum of
about 200 mCi/mmole, with total activities of up to about 100 pCi
per cigarette will be used (57, 58, 59, 60). Possession, use, and
disposal of these modest amounts of radioactivity are within
current Research Center capabilities and will not require revision
of our North Carolina license to handle radioactive materials
(61).
The specific design of cigarettes to be used in the fate studies
can be a variable within the project. For example, it is possible
that the migration and equilibration behavior of additives will
vary with cigarette and filter construction. Whatever the
specific design and construction, cigarettes used in the studies
will need to be closely matched because of the well-documented
influence of their physical characteristics on the composition of
smoke streams (62, 63, 64). These characteristics will include
the temperature and humidity used for conditioning, the weight of
tobacco in the cigarettes, the cigarette circumference, degree of
ventilation, and resistance to draw. Standard smoking conditions
will be employed, i.e. 35 mL puffs of two second duration at a
rate of one puff per minute in an air flow of 2 liter per minute
to the standard butt length.
TECHNICAL APPROACH
Proposed project activities will follow a time line consisting of
four phases. Some activities within several different phases are
expected to be concurrent and/or continuing. Phase one includes
fabrication and optimization of the total smoke recovery apparatus
and a syringe-injection spiking device. These activities would be
initiated in late 1990 and early 1991. Test article selection and
prioritization as well as design of their labelling syntheses are
other phase one activities which were started during 1990.
Phase two includes beginning the execution of the rad'iolabelling
syntheses. Synthesis for one compound, namely citral dimethyl
acetal, is complete. Syntheses for two other compounds, namely
glycyrrhizic acid and (L)-(+)-tartaric acid, are in progress Go
during 1990 and will be completed during 1991. Schemes I, II, and W
III illustrate the synthetic routes used. Once the syringe- W
injection cigarette spiking device is in hand, the phase two I`1
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equilibration and migration studies for the first group of tobacco
additives can commence in 1991. Cigarettes will be impregnated
with the radiolabelled material via the syringe-spiking device and
then stored under standard conditions. At predetermined inter-
vals, cigarettes will be removed from the conditioning chamber and
cut into segments corresponding to the length of tobacco rod
consumed during a puff cycle. The paper and filter will be
removed for separate analyses. The migration and equilibration of
the additive in the various portions of the cigarettes will be
monitored over time by extraction from the individual parts,
followed by liquid scintillation counting.
Phase three experiments will consist of smoke transfer material
balance studies. These will commence after the smoke recovery
apparatus is optimized. Because of the dependence of a compound's
transfer to smoke streams upon its distribution within the ciga-
rette, equilibration information obtained as part of phase two
will be required for each of the selected additives prior to
performing the material balance studies on burning cigarettes (20,
21). The smoke transfer studies will be performed by smoking the
equilibrated test cigarettes under standard conditions in the
total smoke recovery device, and quantitating the material balance
of radioactivity in the various fractions by extraction and liquid
scintillation counting. These first phase three studies are
expected to begin later in 1991.
The fourth phase of experimentation will consist of quantitation
and identification of the radioactive chemicals which result when
the test cigarettes are smoked under standard conditions. The
amount of unchanged additive will be measured. The identification
and quantitation of any pyrolysis products will also be under-
taken. This will be accomplished by application of the most
appropriate analytical techniques including GC, GC/MS, GC/FTIR,
TLC, and HPLC with radioactivity detection. Based on phase two
migration data, it may be of interest to investigate additive
behavior on a puff-by-puff basis. This would also be a phase four
activity. Initial phase four chemical identification work is
expected to commence in 1991.
PERSONNEL
Two groups within the Research Department would participate in
this project. The proposed project's leader will be L. H. Gains.
The project leader's responsibilities will include overall
direction, coordination, and monitoring of project activities,
design of labelling syntheses, liaison with RTI, the radio-
labelling synthesis contract laboratory, and oral and written
communication of project progress. Also from the Organic
:
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