Product Design
R&D Review on Menthol
Abstract
Special report compiles the chemistry and characteristics of menthol cigarettes and summarizes major R&D projects. States this report elucidates the current [1980] understanding of menthol and provides references to literature and internal reports.
User-Contributed Notes
Fields
- Author
- Daniel, Harry G. (PM R&D Planning Coordinator c. 1975-82)Research Professional
- Walk, E.M.
- Recipient
- Bourlas, Manuel "Manny" C. (PM Science and Technology VP )1994 Neuchatel, Switzerland. VP Environ & Oper Compl in 1993. VP Science & Technology from June 7, 1993 to May 24, 1994. Member of PM Ventilation Task Force. Reported to Steven Parrish, Senior Vice President, PM External Affairs 1994. Represented PM interest in international markets.
- *Burns, Ken (use Burns, Ken S.)Defense
- Daniel, Harry G. (PM R&D Planning Coordinator c. 1975-82)Research Professional
- Daylor, Frank L. (PM Gen. Products Development. Mgr., R&D)Was involved in flavor development for Philip Morris; worked for PM Research and Development in Products Development 1962-93.
- Fagan, Raymond (PM Principal Scientist c. 1968-83)Principal Scientist at Philip Morris Research Center in Richmond, Virginia, between around 1968-84.
- Farone, William Anthony, Ph.D. (PM Former Dir. of Applied Research, Anti-Tobacco Expert)Hired to make safer products and to find business alternatives outside the tobacco industry for PM.
- Gannon, Walter F., Ph.D. (PM New Product Development Dir.)Defense
- Gauvin, Paul N. (PM R&D)
- Geiszler, Willard (Philip Morris Research Center, 1975)Defense
- Haut, Steve (Former PM scientist)Did research with Vedpal Mali on removing nicotine from tobacco plants was told by Cathy Ellis to alter lab notebooks (B. Campf 6/2/94).
- Houck, W. G.Associate Professional
- *Ikeda, R. M. (use Ikeda, Robert M., Dr.)Associate Principal
- Johnston, Myron E., Jr. (PM Marketing researcher)
- *Kassman, A (use Kassman, Allen, Ph.D.)1997
- Kosakowski, Bernard (PM Research Center)Defense
- Maxwell, M.
- Meyer, L.
- Mutter, Walter (PM Research Manager)Defense
- Nepomuceno, J.
- O'Donohue, Cynthia H.Defense
- Osdene, Thomas Stefan, Ph.D. (Director of Science and Technology, Philip Morris [1986])Ph.D. in Organic Chemistry. Ten years of research when he started with PM in 1965. Worked in Chemical Research Division of PM 1965-66; Chemical and Biological Research Division 1966-69; Director of Research 1969-1984, also assumed independent position as Director of Research and Extramural Studies during these years; became Director of Science and Technology in 1984, reporting directly to Philip Morris USA Executive VP Mark Serrano. Involved with Center for Indoor Air Research (CIAR) 1988. Attended PM's Operation Downunder Conference in June, 1987. Retired 1993.
- Osmalov, Jerome "Jerry" S. (Joined PM in Dec. 1964 to work on filter development)
- Sanders, Edward B. (Ted), Ph.D. (PM Dir. of Chemical Research)Neuchatel, '99
- Seligman, Robert B. (PM VP of R&D c. 1976-82)Vice President of Research and Development at Philip Morris Richmond, VA 1976-1982. Reported to Senior Vice President of Operations. In 1982 transferred to tobacco technology group. Wanted to share ammonia and other tobacco technology with PM International companies.
- Spielberg, Howard L. (PM Research Professional)Research Professional
- Thompson, R.
- Watson, D. C.
- Watson, Frank H., III (PM)Associate Professional
- Wickham, J.E. (PM scientist)J.E. Wickham was a Philip Morris scientist. (PMI's Introduction to Privilege Log and Glossary of Names, Estate of Burl Butler v. PMI, et al, April 19, 1996)
- Wolf, Dr. ---Defense
- Hypothesis
- Mainstream constituent yieldsModification of selected mainstream smoke constituents in response to health concerns.
- Smoke constituent testingDevelopment of methods for measurement of gas and particulate yields in mainstream and sidestream smoke.
- Smoking psychology and behavior
- 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.
- Keyword
- Brand differences
- Consumer acceptability (Consumer preference)
- Cooling
- Depth of inhalation
- Flavor/ Taste (Attribute measure)
- Generally_Recognized_As_Safe
- Human testing
- Inhalation (Smoke inhalation)
- Irritation (Attribute measure)
- Low delivery (Reduced delivery)
- Menthol delivery (Smoke menthol, menthol yield)
- Mildness (Attribute measure)
- Puff count
- Safer cigarette
- Sensory response
- Smoothness/Harshness (Attribute measure)
- Strength attributes
- stress
- Brand switching
- Additive
- Humectants (Additives to maintain moisture)
- Mentha Arvensis (Mentha Arvensis Oil)
- Menthol
- Menthone
- Neomenthol
- Peppermint (Peppermint Oil)
- Tetraethylene glycol"Softener", better versus TEG
- Triacetin
- Smoke Constituent
- Menthol
- Nicotine
- Total particulate matter
- Design Component
- Aftercut
- Blended leaf (BL)
- Bright tobacco (Flue-cured tobacco)
- Burley tobacco
- Expanded tobacco (Puffed tobacco, ET)
- Plasticizer
- RCB (Reconstituted cast blend)Early PM @reconstituted_tobacco
- Reconstituted leaf (RL)PM @reconstituted_tobacco, c. 1970s-1980s
- Named Organization
- American Tobacco Company
- Axton Fisher
- Brown & Williamson Tobacco Corp.Brown & Williamson Tobacco Corp.
- Eastman Kodak Co. (Kodak) (Cigarette filter mfg from 1950s to 1994.)Manufacturers of quality control equipment for cigarette packaging
- Glidden
- Haarmann & Reimer Corp. (Supplier of tobacco extracts in 1993)supplier of tobacco extracts in 1993
- Home Testing Institute
- National Cancer Institute NCIDivision of Cancer Prevention and Control, National Cancer Institute located in Rockville, MD
- Takasago
- Research and Development
- Manufacturing Center
- 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.
- Subject
- CNS/Brain (Effects)
- Menthol (Additives)
- Receptors (Effects)
- Sensory Effects—Impact (Effects)
- Sensory Effects—Taste (Effects)
- Smoothness/Harshness (Effects)
- Target/Women (Target Groups)
- Target/Young Adults (Target Groups)
- Test/Animal Subject (Testing)
- Test/Consumer Preference (Testing)
- Test/Smoke Machine (Testing)
- Test/Toxicity (Testing)
- Transfer to Smoke (Measures)
- Brand
- Alpine
- Belair (BW)
- Benson & Hedges 100
- Benson & Hedges Lights 100 s
- Cambridge (PM)
- Eve
- Kent (Lorillard)
- Kool (BW (1933-2003)/RJR (2003-present))First Menthol cigarette line, released in 1933. Premium priced brand.
- L&M
- Marlboro (PM)
- Merit 100
- Merit 85
- Merit Menthol
- Montclair
- Newport (Lorillard)
- Pall Mall (ATC)
- Salem (RJR)
- Spring
- Vantage (RJR)
- Virginia Slims (PM)
- Virginia Slims Lights
Document Images
PHILIP MORRIS U,S,A,
R E S E A R C H C E N T E R
CHARGE NO. & TITLE:'
TYPE REPORT: OANNUAt OSEMIANNUAL Q COMPLETION Q SPECIAL
DATE : July 111, 1980
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REPORT TITLE:
D I STR'LBUTI ON :
R&D Review on Menthol
WR I TTEN BY ~~C ~l / L ~ Yl'11~U'ZJ
Ellen M. Walk
APPROVED BY
Harry G. Daniel,
Dr. R. Seligman Mr. K. Burns Mr. W. Mutter
Dr. W. Farone Mr. H. Daniel Ms. C. O'Donohue
Dr. W. Gannon Mr. F. Daylor Mr. J. Osmalov
Mr. L. Meyer Mr. P. Gauvin Dr. E_ Sanders
Dr. T. Osdene Dr. A. Kassman Mr. F. Watson
Mr. R. Thomson Mr. B. Kosakowski Mr. J. Wickham
Dr. 'S. 3ourlas Mr. W. Kuhn Dr. R. Fagan
KEYWORDS:
Dr. W. Geiszler Mr. H. Spielberg
Dr. S. Haut Mr. D. Watson
Mr. W. Houck Dr. A. Wo1f (Outside),
Dr. R. Ikeda
Mr. M. Johnston
Mr. M. Maxwell Day File (4)
Mr. J. Nepomuceno Central File (2) -.,
men[ho1 review, chemistry, toxicology, analytical methods,
suppliers, filler, filter, plasticizer, aging, consumer
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To:
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Fromt
Subject:
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PHILIP MORRIS U. S. A.
INTER-OFFICE CORRESPONDENCE
RICHMOND, VIRGINIA
Mr. H. G. Daniel Date: July 11, 1980
. M. Walk
R&D Review on Menthol
Attached is a compilation on the chemistry and behavior of menthol
in cigarettes, summarizing major areas in which work has been done
in Research and Development. Topics covered~include physiological
effects, methods of analysis, flavor and odor chemistry, coamiercial
suppliers and forms, application to filler, effect of plasticizers,
effect of aging, and consumer testing of menthol in cigarettes.
The objectives of the report are to allow identification of strength
and weaknesses in our knowledge of menthol, and to provide references
to literature sources, internal reports, and personnel specialized'in
the study of menthol.
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EMW:fs
Attachment
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cc: Dr. R. Seligman
Dr.
Dr.
Mr.
Dr.
Mr.
Dr.
Mr.
Mr.
Mr.
Mr.
Dr.
Mr.
Mr.
Mr.
Ms.
Mr. W.
W.
L.
T.
R.
M.
K.
H.
F.
P.
A.
B.
W.
W.
C.
J. Farone
Gannon
Meyer
Osdene
Thomson
Bourlas
Burns
Daniel
Daylor
Gauvin
Kassman
Kosakowski
Kuhn
Mutter
O'Donohue
Osmallov
Dr. E. Sanders
Mr. F. Watson
Mr. J. Wickham
Dr. R'. Fagan
Dr. W. Geiszler
Dr. S. Haut
Mr. W. Houck
Dr. R. Ikeda
Mr. Mi. Johnston
Mr. Mi. Maxwell
Mr. J. Nepomuceno
Mr. H. Spielberg
Mr. Di. Watson
Dr. A. Wolf (Outside)
Central' File (2),
Day Fille (4)
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ABSTRACT
INTRCDUCTION
HISTORY OF MENTHOL IN CIGARETTES
TABLE OF CONTENTS
Page No.
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1
PHYSIOLOGICAL EFFECTS OF MENTHOL
Stimulation of Cool Receptors
Analgesic Properties
Effect On The Sense of Taste
Toxicological Effects
ANALYTICAL METHODS FOR THE
DETERMINATION
OF MENTHOL
External and Internal Literature References
Details Of Analytical Procedures Currently
In Use At R&D,
Comparison Of Methods Between R&D and'
Manufacturing Center
CH'EMI STRY OF MENTHOL
Flavor And Odor Chemistry Of Menthol And Its Isomers
Reactivity Of Menthol
Synthesis Of Menthol
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CObIMER'CIAL MIXTURES OF MENTHOL
Suppliers And Forms Of Commercial Menthol
MENTHOL BEHAVIOR' IN CIGARETTES
Application Of Menthol To Filler
Effect Of Filter Plasticizers On Menthol Delivery
Effect Of Aging On Equilibration Of Menthol
Between Filler And Filter
Storage Effects
CONSUMER RESPONSE'TO MENTHOL CIGARETTES
Internal Testing
Outside Testing
Demographics Of Menthol Smokers
TABLES,AND F'IGURES
APPENDICES
REFERENCES
1
2
4
7
8
21
30
43
47
AB'STRAT'
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A summary of the chemistry and behavior of menthol in
cigarettes was compiled, covering major areas in which work has
been done in Research and Development. Topics covered include
physiological effects, methods of analysis, flavor and odor
chemistry, commercial suppliers and forms, application to filler,
effect of plasticizers, effect of aging, and'consumer testing of
menthol in cigarettes..
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INTRODUCT'I0N
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The purpose of this report is to summarize the work done in
Research and Development on the chemistry and behavior of menthol
in cigarettes. The objective i~s to identify strength and weak-
nesses in our knowledge of inenthol
and to provide references to
,
! literature sources, internal reports, and personhiel specialized in
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the study of menthol.
This review is based on the proceedings of a multidisciplinary
meeting on the subject of menthol held in 1979. Many thanks go to
the participants of that meeting for their assistance and for
i their contributions to the report.
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PHYSIOLOGICAL EFFECTS OF MENTHOL (R.\~FAGAN).
Stimulation of Cool Receptors--The primary effect of menthol
is to create a feeling of coolness. Iniactuality, it is an irritant,
increasing the circulation around an area and causing heating, but
the stimulation of cool receptors gives the resulting sensation of
.. _,., .. _... ... ., .. ..,. ,_. ~..-- _ _, v~. :
coolness.
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Analgesic Properties--65enthol also reduces pain and itching,
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whichimay account for some of its popularity in cigarettes ;
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Effect on the Sense of Taste- In experiments, with.cats, menthol
. . . t.~. ... .
has been shown to enhance the taste of salt, quinine, and alicoho1'.
Mixtures of these three substances individually with menthol,-_
applied to the cat's tongue cause the nerve controlling taste to
fire at a lower concentration than if the solution contains no
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menthol. Thefinvestigators maintain~ that menthol should enhance
the taste of sweet solutions as well.
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There is no literature on the effect of menthol on. human
.,0~j_.1;-Il;.' ~i^.~ 1.-`,..f,f: yt'~?C}~.,>Ltu
taste. It is uncertain whether results of cat~experiments{1apply to
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HISTORY OF MENTHOL IN CIGARETTES (R. FAGA'N)
Menthol was first introduced into cigarettes by a man named
Spud Hughes in 1924, and his patent was bought by Axton-Fisher in
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the early 1930's. It was promoted as a remedy' for tenseness,,
especially targeted
subsequently bought
trademark.
toward an aristocratic market. Philip Morris
Axton-Fisher in
and acquired the Spud
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Toxicological Effects--The oral
2000-300& mg/kg in the mouse and rat, and 800-1000 mg/kg in the cat,
which extrapolates to an oral!/ dose of 63-78 g in a 175-pound man
(i.e., relatively nontoxic). (-)-fwientholi is relatively more toxic
than (t)-menthol, which is more toxic than (+)-menthol. [Monoqraphs
on Fragrance Raw Materials; Reqistry of Toxic Effects of Chemical
Substances]. There is no evidence of carcinogenicity in mice and
Literature References (D. Watson)--Tables
and 2 list methods for the determination of menthol found in the
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rats for (±)-menthol, although
comparison to controls.
tion on (-)-menthol.)
No. 98', 1979]
As to cases
was one case of
membranes) in a
(There
[NCI
of extreme
years. The disease
purpura disappeared
a
slight weight reduction, was
is
seen in
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no specific carcinogenicity informa-
Carcinoqenes;is
sensitivity to
LDso
of (-)-menthol Is aroun&
Technical Report' Series,
ment'ho1 in humans, there
b1'eed!i~ng in skin and mucous
" ... *1,
menthol cigarettes about 15
to be directly related to menthol; the
when she smoked
came back when she resumed
nonmentholated cigarettes, and
smoking menthol cigarettes. .
ANALYTICAL METHODS FOR THE DETERMINATION OF h1ENTHOL
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pubilsnea cnemaca:i 1'1Lerature and~ln x&ll lnternal reports.
Alttlougn a variety of compounds nave been used as lnternal
standards, it is probable that only a few of them really meet the
requirements for structural relationship to menthol and desirable
behavior in a GC column (retention time, peak quality). Anetholie and
naphthalene seem to be very good internal standards.
appeared
purpura: (subcutaneous
woman who had smoked
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Details of Analytical Procedures Currently in Use at R&D (J.
Nepomucenol)--To: determine menthol in smoke, a: random sample of 32
cigarettes from 20 packs is taken. Fromithe same 20 packs, a random
sample of 20 cigarettes is also taken for the determination of menthol
in fillier and fiI!ter. These samples are stored in sealed 8 oz ,jars
until analysis.
The anal~ysis of TPM is a good approxi'mation for the amount of
menthol delivered in, smoke (about 99% of menthol assayed in whole
peak heights vs. concentrationy mg/ml)
- calculate sample concentrations from calibration curve (ratio o
- measure menthol/anetholle peak height ratios
- inject 2' NI aliquot into GC
- mix for 2 hrs on rotary extractor (this is the minimum time
found to be required to extract maximum amount of inenthol),
smoke shows up in TPM). The steps are as follows:
'. -
- smoke 32 cigarettes (8 ports, 4 cigarettes/port)
- combine pads from 2 ports in test tube
- extract with standard solution of cold 95%, EtOHI and anethole
(internal standard)'
To analyze for menthol in filter:
heights vs. concentration,, mg/ml) :n,;r,.-
- determine samplle concentration from, calibration curve (peak
- measure menthol, peak heights - , - Y :`.7 i R ' 'r:' . 'c i :
- inject'2 Nli aliquot into GC
- shaker extraction for 2 hrs
- break off filters from 20 cigarettes
- place 10 split filters in 125 ml. flask (2' replicates)
- add 25 ml of 95% EtOH
shaker extraction for 2 hrs
add 100 ml of 95% EtCH containing 0.5 mg anethole _
place filler and paper into 250 ml flask (2 replicates)
split papers ofl 10 tobacco rods
inject 2 NI aliquot into GC t *-..
determine sample concentration from standard ratio . ~;
calculate menthol/anethol'e ratios
To give an idea of the mean and
smoke, filler, arnd ff1!ter Table 3 has been
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Comparisoni of Methods Between, R&D and the Manufacturing Center
(D. Watson)--Tablie 4 summarizes the variations between the analytical
procedures used in R&D and~ the Manufacturing Center. Two differentt
internal standards are used': anethole and 2-undecanone (anethole Is
used' for everything except filters at R&D). The GC' columns are
chosen to elute the compounds of interest with little or no interf'er-
ence (it i's generally known what the possible interferences are for
PM products, but not for competitors').
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Flavor and Odor Chemistry of Menthol and Its Isomers--During the
CHEMDSTRY OF MENTHOL (S. HAUT) == --
process of developing a method, for extracting and purifying menthol
from the mint pl'ant, it was found that the menthol obtained from Prep
500 liquid chromatography did not smell as "minty" as various commer-
cial mentholi samples on the shelf. The question which arose was
whether the real flavor and od'or of menthol actually come from trace
quantities in the natural oili (for example, pulegol isomers) which
crystallize out with the menthol. These trace quantities would be
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separable from menthol by chromat'ography. T'y 6 '
The "peppermilnty"' components really seemed to -appear in the
non-polar fraction of the extract, which probably contained the
ketones and hydrocarbons of the -oil. A GC separation'of the oill'
2'-, . `G-~.. .
yielided~ menthol which appeared to be pure, but which had odor
- ?lISc . : . .- ... . .3 1 L/- -.-...-3 ~~ - -. .
characteristics different from the commercial sampl'es;~'` it ha& more
f of a camphor-like odor.
Aniexamination of aII the isomers of inenthol, was begun'(Fig.
n the normali oil, there is` (-)-menthol, neomentholl, menthorie, and
~-
isomenthone (4 of 12 isomers possible for mentholi and menthone). The
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absolute configuration of (-)-menthol, as derived by NMR', methods, is
also shown in Fig. 1.
Using (-)-menthol, it is possiblie to deri~ve any of the other
menthol isomers by falrly simple chemical means. If (-)-menthol is
subject to oxidation the (-)-menthone is produced. This compound can
be isomerized to (+)-i'somenthone. Fromiei'ther of these two ketones
the isomers (+)-isomenthol (+)-neomenthol, and (+)-neoisomenthol can
be obtained through the use of suitable reducing agents. Starting
with (±)-menthol, (+)-menthol can be separated, and from that other
isomers can be obtained by identicAl methods. A11, isomers can be
obtained, even if they do not exist naturally; the isomers originat-
ing from (-)-menthol have been prepared' in-house. It i'.s not known
what significance the optical rotation has on flavor characteristics,
but it should~ be noted that the optical rotation of the isomers
depends on which menthol isomer was the starting material. " s
The odor characteristics of the isomers are different, varying
with the orientation of the alkyl groups on the alcohol. (-)-Menthol
is somewhat pepperminty;
isomenthol is similar
(+)-neomenthol
is somewhat sweeter; - ('+)
to menthol, but is sol!id at room temperature
and has a lower vapor pressure.
odor unrel'ated to the others;
menthone is very pepperminty
characteristics to the liquid
(+)-Neoisomenthol has a musty closet
(:+)-isomenthone is also musty; (-)-
and sweet, giving the primary odor
-
chromatography extracts (-)-Menthol
was the only compound in large
properties;
enough quantities to exhibit cooliing
it is not known whether the others aliso exhibit cooling.
r
The primary method used in the isomer study foridentification,
and purity checks was HPLC [Internal Report #80-002] :`1 ' A11 were also
whichi is more efficient than the Hyprose columns that are normally
verified with GC using a Carbowax 1500 column [Internal Report #80-105]I,
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