John
You may already know about this. The development of a nicotine delivery
device that facilitated inhalation was developed on Java just after the
turn of the 20th century. Cloves, which contain the potent local
anesthetic eugenol, came to be mixed with dark tobaccos. Clove
cigarettes are today the major delivery device used in Indones:
Los Angeles Times March 21, 1986 SMOKE THICKENS OVER CLOVE CIGARETTE
INHALATION STUDY
By: DENNIS McLELLAN
The results of an industry-sponsored study, released this week, on the
possible toxic effects of smoking clove cigarettes show that clove
cigarette smoke is no more harmful to laboratory rats than smoke from
conventional cigarettes.
Scientists not connected with the study, however, caution that a
single study on rats does not provide conclusive evidence that the
pungent-smelling imported cigarettes from Indonesia do not cause lung
damage in humans.
The independent study, which was conducted by the Department of
Inhalation Toxicology at the Huntingdon Research Centre in Huntingdon,
England, is the first inhalation study made available to the public on
clove cigarettes (or kreteks), which have come under attack in the past
year for causing serious health problems and allegedly leading to the
death of one Orange County teen-ager.
The British inhalation study was funded by P. T. Djarum and House of
Sampoerna, both of Indonesia, although an industry spokesman said the
laboratory wasn't told who was backing the study. The two firms are the
largest manufacturers of clove cigarettes -- which contain 60% tobacco
and 40% ground cloves.
Cigarettes 'Vindicated'
"I think the study shows that clove cigarettes have been vindicated as
far as being guilty of what the critics have said they are guilty of:
that these things are much worse for you than non-clove cigarettes,"
said G. A. Avram, executive director of the Specialty Tobacco Council,
an organization representing the major manufacturers and importers of
clove cigarettes in the United States.
Avram, who released the results of the 119-page study at a news
conference in Washington, said the study "clearly establishes that
clove cigarettes do not cause acute respiratory distress or anesthetize
the lungs on the test animals." (Eugenol -- the major component of
cloves-- is used as a mild dental anesthetic; critics of clove
cigarette say the eugenol in the cigarettes numbs smokers' throats.)
The results of the British inhalation study differ sharply from those
of an as-yet-unpublished study conducted last year by the American
Health Foundation, which shows that eugenol can cause extensive lung
damage and may be lethal to laboratory animals when administered
directly into the lung via the trachea (in contrast to inhalation
studies, in which laboratory animals breathe smoke).
Another study by the American Health Foundation, however, supports the
findings of the British study: In that, an inhalation study, there were
no acute toxic effects among hamsters exposed to clove cigarette smoke,
according to Edmond LaVoie, associate division chief of environmental
carcinogens at the nonprofit, independent research foundation in
Valhalla, N.Y.
LaVoie added, however, that "one cannot discount the data obtained in
the intratracheal experiments because there are limitations in using
small rodents in inhalation experiments." The American Health
Foundation studies on clove cigarettes will be published soon in
Archives of Toxicology, a scientific journal.
In view of the findings in the British inhalation study, however,
Avram maintains that "the burden of proof has shifted and it's now up
to them (clove cigarette critics) to prove there is a problem with
clove cigarettes instead of clove cigarettes being put on the
defensive."
Robert Phalen, director of the air pollution health effects laboratory
at the College of Medicine at UC Irvine and author of "Inhalation
Studies," a professional reference book, observed that the inhalation
study "is important, but I'd say a single study is not definitive for
something that has widespread use."
Phalen added that "there's a segment of the population -- somewhere
around 5% -- that have very sensitive lungs. These people can
over-respond to a variety of chemicals when inhaling. The rat is not a
good model for those people."
Moreover, Phalen said, "You can never, in a small single animal study,
say that something is safe. Let's say clove cigarettes hypothetically
caused one smoker in a thousand to die. You could never detect that in
a study of human beings unless you had tens of thousands of people and
you couldn't detect that level of risk in a study using less than
several thousand animals."
"The conduct of a single study is suggestive but in no case convincing
evidence one way or the other unless the study is so designed as to be
essentially foolproof and these studies are so complicated that they
rarely can be made foolproof," said Dr. Tee L. Guidotti, professor of
occupational medicine at the University of Alberta Faculty of Medicine
in Edmonton, Canada, who has done research on clove cigarette
toxicity.
"We can't say anything about long-term health effects from a single
short-term study," Guidotti said. "We do know that the International
Agency for Research on Cancer, which is the international authority on
such matters, has concluded that eugenol is a possible human
carcinogen. The addition of a possibly harmful substance (eugenol) to
an already hazardous product (cigarettes) can only increase the risk
that much further."
Lawsuits Filed
In general, Guidotti added, clove cigarettes "have more tar, nicotine
and carbon monoxide than conventional cigarettes."
"I think it (Avram's assertion that clove cigarettes are as safe as
regular cigarettes) is bunk," said Eric Lampell, attorney for the two
Orange County families that have each filed $25-million lawsuits
against the makers, importers and sellers of clove cigarettes for
supplying their children with what they charge were "dangerous and
defective" cigarettes.
Anticipating possible criticism over having a vested interest in a
study examining his own product, Avram said the Huntingdon Research
Centre did not know until the study was completed that the sponsor,
Avram's North Carolina law firm, was representing two clove cigarette
manufacturers.
Avram said two more inhalation studies will be forthcoming soon from
the independent British contract research organization. "And," he said,
"the preliminary indications we're getting are that they are even more
encouraging from our point of view than this original one."
Avram was scheduled to present the inhalation study Thursday to a
state Senate committee in Maryland where legislators are considering a
bill to ban clove cigarettes. Missouri and Utah currently are
considering similar bills. Nevada and New Mexico already have banned
the imports, but a Florida judge declared unconstitutional a 3-week-old
law banning clove cigarettes in that state.
Reacted 'Hastily'
The Speciality Tobacco Council maintains that legislators have reacted
"hastily" in banning clove cigarettes "without taking time to obtain a
balanced appraisal on the issue."
The council was formed early last year in the wake of media reports on
the potential health hazards of smoking clove cigarettes, which have
been sold in the United States since 1970 but did not become popular
until the early 1980s. (Sales of the imports, according to Avram, have
dropped to about half of their peak of 150-170 million in 1984 as a
result of the controversy.)
Last March, Ron and Carole Cislaw of Costa Mesa filed a $25-million
lawsuit, claiming that the sellers, makers, and importers of clove
cigarettes were, among other things, negligent in supplying "dangerous
and defective" cigarettes. Their 17-year-old son Tim developed
shortness of breath shortly after smoking a clove cigarette and
eventually died of respiratory failure. A second $25-million lawsuit
was filed in July by a Buena Park woman whose 17-year-old allegedly
contracted a debilitating lung ailment after smoking clove cigarettes.
Last May, the U.S Centers for Disease Control reported 12 cases of
severe illness possibly associated with smoking clove cigarettes.
Symptoms in the 11 patients who were hospitalized, according to the CDC
report, included pulmonary edema (blood- or fluid-filled lungs),
bronchospasm (a constriction of the air passageway) and hemoptysis
(coughing up blood).
Minor symptoms reported to the CDC included nausea and vomiting,
increased incidence of respiratory tract infections, worsening of
chronic bronchitis and increased incidences and severity of asthma
attacks. Mild coughing up of blood, the report said, has been reported
with particular frequency. Preliminary Results
The CDC report, however, stressed that a cause-and-effect relationship
between clove cigarette smoking and the patients' illnesses has not
been proved.
When preliminary results of the the American Health Foundation
intratracheal study were obtained by The Times last June, the Specialty
Tobacco Council labeled the foundation's method of administering
eugenol via the trachea into the lungs of laboratory animals as an
"unsound scientific test."
"You might regard the intratracheal instillation (method) as a massive
overkill and it does not reflect the smoking of a (clove) cigarette,"
said Murray Senkus, a consultant for one of the major manufacturers of
clove cigarettes in Indonesia and a former director of research and
development for R. J. Reynolds Tobacco Co.
LaVoie responded by saying, "We gave them (the laboratory animals)
less than one-third the dose of eugenol which is delivered to the lungs
by one clove cigarette: less than one-third the amount of eugenol in
one clove cigarette kills 50% of the animals."
UC Irvine's Phalen said "intratracheal studies can be useful and
important in looking at the toxicity of something the lung has been
exposed to. However, it is not a definitive method of administration
for something that's inhaled. One of the principles of toxicology is to
expose animal subjects by the same route that one expects human
populations to be exposed."
In light of the results of the American Health Foundation's own
inhalation study on clove cigarettes, LaVoie said he is not surprised
by the results of the British inhalation study.
He maintained, however, that "because the rats used in the
(inhalation) studies are obligatory nose breathers -- they by nature
breathe through their nose -- only a very small portion of the smoke
components ever reach or become deposited in the lung. This is an
inherent deficiency of the animal model and I would say both models
(intratracheal instillation and inhalation) do not mimic the way humans
actively smoke."
More Studies Recommended
LaVoie said he could not say much about the British study because he
hasn't seen it. "I can say that no two-month inhalation study using
small rodents would convince me that these cigarette products are
safe."
LaVoie recommends conducting more inhalation studies that are "longer
term and possibly more sophisticated in order to bypass some of the
inherent differences in the inhalation of particulates observed with
small rodents vs. man."
"I think what they (Huntingdon Research Centre researchers) have done
is an appropriate beginning and I anxiously await both details on the
study and further studies to evaluate just how dangerous clove
cigarettes are," said LaVoie. "Like cigarettes, they do adversely
affect health, we just don't know how severe the degree."
As Guidotti said, "We'll be going back and forth for years on the
inhalation toxicology."
(end of article)
Rowdy Yates
Director
Scottish Drugs Training Project
Dept. of Applied Social Science
University of Stirling
Tel: +44 (0) 1786 - 467732 (office)
+44 (0) 1786 - 467737 (direct line)
Fax: +44 (0) 1786 - 467737
Mobile +44 (0) 7801 - 279 - 384
E-mail: [log in to unmask]
Home Page: http://www.stir.ac.uk/sdtp/
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