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.
"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The results of the British inhalation study differ sharply from those of an as-yet-unpublished study conducted last year by the American Health Foundation, which shows that eugenol can cause extensive lung damage and may be lethal to laboratory animals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."
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.
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.
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."
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."