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Study Links Clove Cigarettes Ingredient, Toxicity : Experiment Yields Scientific Data Blaming Eugenol for Lung Damage to Animals

Times Staff Writer

Preliminary results of an ongoing study of the possible toxic effects of smoking clove cigarettes show that eugenol--the major component of cloves--can be lethal to animals when administered directly into the lung, The Times has learned.

The independent study by the American Health Foundation in Valhalla, N.Y., provides the first scientific report that links eugenol with observations by physicians on the toxicity of the faddish, pungent-smelling imported cigarettes from Indonesia.

Between March, 1984, and May, 1985, the Centers for Disease Control in Atlanta reported, it recorded 12 cases of severe illness possibly associated with smoking clove cigarettes. (The CDC did not mention the case of Tim Cislaw, a 17-year-old Newport Harbor High School student who developed shortness of breath shortly after smoking a clove cigarette early last year and eventually died of respiratory failure. In March, Cislaw’s parents filed a $25-million lawsuit claiming that the sellers, makers and importers were, among other things, negligent in supplying “dangerous and defective” cigarettes.)

Symptoms in the 11 patients who were hospitalized, according to a CDC report, included pulmonary edema (blood- or fluid-filled lungs), bronchospasm (a constriction of the air passageway) and hemoptysis (coughing up blood).

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Minor symptoms reported to the CDC include nausea and vomiting, increased incidence of respiratory tract infections, worsening of chronic bronchitis and increased incidence and severity of asthma attacks. Mild coughing up of blood, the report noted, has been reported with particular frequency.

“In a laboratory setting we’ve shown that symptoms reported by individuals who smoked clove cigarettes--such as spitting up of blood and bronchopneumonia--can also be observed with animals that have been treated with eugenol,” said Edmond LaVoie, associate division chief of environmental carcinogens at the American Health Foundation, a nonprofit, independent research foundation funded primarily through the National Institutes of Health.

“We found extensive damage occurring to the lungs of the animals in which we have instilled various doses of eugenol,” LaVoie said. “This provides further evidence that the toxic effects reported for some individuals may be related to the smoking of clove cigarettes.”

LaVoie said the rats that died during the experiments generally died from hemorrhaging and a fluid build-up in the lungs. He declined to reveal what the lethal doses of eugenol are until the foundation has completed an additional study on other animals and has repeated its study on rats.

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The rodents in the study were given various doses of eugenol into the lung via the trachea, which LaVoie acknowledges is not the same as inhalation. Although the study also will include experiments on inhalation of eugenol, LaVoie said that administering eugenol through the trachea is “one of the most direct routes we have available for determining the possible toxic effects of a chemical in lung tissues for small rodents.

“The fact that we see such evident toxicity certainly raises a great deal of concern regarding the health effects of clove cigarettes.”

Dr. Sue Binder, a medical epidemiologist for the Center for Environmental Health at the Centers for Disease Control, acknowledged that “the findings that have been described to me suggest the symptoms of these animals are similar to what has been described in some of the cases that have been reported to us.”

But, she said, the study’s preliminary findings don’t “prove that the diseases observed in the cases reported to us are caused by smoking clove cigarettes.”

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“Animal experiments can be very useful in indicating possible toxic effects of chemicals in man,” she said, noting, however, that rodents may have different susceptibilities than man and that the way eugenol was administered in the study was through the trachea and not by inhalation of cigarette smoke.

“Therefore,” she said, “the results of these small animal experiments do not prove that eugenol caused the illness in our reported cases but suggest it may have been responsible.”

LaVoie agreed that the study does not prove that eugenol caused the illnesses reported to the CDC but, he said, “I think with the information in hand--the CDC report and the additional data we have--you’re getting to the point where there’s enough information where there may be an issue of responsibility and possibly liability. The health effects of clove cigarettes are being questioned.

“With regard to the possibility of a difference between administration through the trachea versus inhalation, when you see an acute toxic effect by tracheal administration one cannot ignore the likelihood that a similar effect is likely to occur by inhalation. In each instance you’re hitting the same target tissue.”

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Clove cigarettes--also known as kreteks-- have been sold in the United States since the late 1960s, but it wasn’t until about four years ago that they became a fad among young Southern Californians. The imports are now a nationwide phenomenon, with sales jumping from an estimated 15 million in 1980 to about 150 million in 1984, according to industry sources. (Clove cigarette sales still are relatively insignificant compared to the estimated 650 billion conventional cigarettes sold in the U.S. annually.)

Although considered by many smokers to be a low-tobacco substitute for conventional cigarettes, the imports actually contain about 60% tobacco and about 40% cloves--and almost twice as much tar and nicotine as moderate tar American cigarettes.

Eugenol, a chemical that serves as a weak anesthetic and has been used by dentists as a pain reliever, is listed on the Food and Drug Administration’s “Generally Recognized as Safe” list of substances. It is, however, only presumed safe when consumed orally in its unburned form. Little is known of its safety when burned in a cigarette.

“The reason why eugenol is generally recognized as safe is because it’s very non-toxic when taken orally as a spice in foods,” said LaVoie. “It wasn’t anticipated that when administered via the trachea it would be this toxic.”

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More Research Needed

Dr. Tee Guidotti, a professor of occupational medicine at the University of Alberta Faculty of Medicine in Edmonton, speculates in an FDA fact sheet released in May that it is possible that the burned eugenol or some byproducts created when other clove cigarette additives are burned may immobilize infection-fighting cells, allowing viruses and bacteria already present in the lungs to spread. There’s also the possibility, he said, that the eugenol or other ingredients have a toxic effect or can trigger an acute allergic reaction.

LaVoie acknowledged that “a lot more research has to be done, but right now to characterize the results we do have, they are unexpected and they are strikingly similar” to some of the reports by physicians.

“We know there is damage going on,” he said. “We know certain doses will kill animals and certain doses will damage the lung.”

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LaVoie declined to identify the federal government agency that initiated the study and said he will not do so until the study has been completed and the “hard facts” are available, possibly by the end of June.

“These results indicate that clove cigarettes are by no means a safe substitute for conventional cigarettes. The studies performed to date suggest that clove cigarettes are uniquely toxic and that their full adverse health effects have yet to be determined.

‘A Lot of Imponderables’

“I hope,” he added, “that people really consider not smoking these cigarettes until further toxicological studies are done. I can’t imagine that if the data holds up in additional studies that they would still be sold.”

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Panos Georgopulo, president of G.A. Georgopulo and Co., a New York clove cigarette importer, said he could not comment on the American Health Foundation’s preliminary findings because he hasn’t seen a report of the study. “We have to know how the tests were conducted and a lot of imponderables,” he said.

Georgopulo’s company is a member of the newly formed Specialty Tobacco Council, a trade association for the manufacturers and importers of specialty cigarettes.

The council was organized in the wake of media reports on the potential health hazards of smoking clove cigarettes and the filing of the Cislaw lawsuit.

Georgopulo said the council, which has hired a Los Angeles public relations firm, “was formed to more or less answer our detractors in an intelligent way and to overcome the hysteria that’s surrounding the issue. Most of the claims (of illness) have been circumstantial, and there’s really no proof.”

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Noting the widespread use of clove cigarettes in Indonesia, Georgopulo said, “We talked to some of our Indonesian customers, and they are astounded that they’re hearing all this bad publicity about this product.”

(Binder said the Centers for Disease Control is exploring the possibility of conducting a study of clove cigarettes in Indonesia).

‘Factual Information’

Charles Ecker, information director for the Specialty Tobacco Council, said the council’s “main item on the agenda is to develop an educational program to convey factual information on clove cigarettes.”

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Referring to a recent statewide ban of clove cigarettes in New Mexico, Ecker said, “We felt they have acted very hastily and taken a very drastic step before there is any scientific evidence” demonstrating a link between health problems and smoking clove cigarettes.

Although several other states are considering banning clove cigarette sales, a bill co-authored by California state Assemblyman Richard L. Mountjoy (R-Monrovia) falls short of calling for a ban of the imports in California.

The bill, AB 2559, which is currently in the Assembly Ways and Means Committee, calls for the state Department of Health Services to conduct a scientific study to determine if there is a causal relationship between smoking clove cigarettes and lung injuries and any other health problems.

Responding to the preliminary findings of the American Health Foundation study, Ecker said, “the study, as explained to me, does not accurately reflect the method upon which eugenol is inhaled. It sounds like they’re trying to make an honest attempt, but on first glance it looks like they’re comparing apples and oranges.”

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Dr. Frederick Schechter, the Whittier thoracic and cardiovascular surgeon who operated on Tim Cislaw and who co-authored the CDC report on clove cigarettes, disagreed.

Wealth of Scientific Studies

Schechter said the American Health Foundation study “forms the pathological basis for the findings in these children admitted into the hospital as well as explains the symptoms of those who called with complaints.”

He was referring to the nearly 200 phone calls he received from clove cigarette smokers after a story on the Cislaw case appeared in The Times last December.

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“The animal studies show that you can reproduce many of the microscopic characteristics of the damage done to the lungs in the hospitalized individuals,” Schechter said, adding that he has received permission from the Cislaw family to send slides of biopsies taken from Tim Cislaw’s diseased lungs to the American Health Foundation for comparison with lung tissues of the dead rats.

Since December, Schechter also has discovered a wealth of scientific studies that have been conducted on eugenol.

Eugenol, according to Schechter, has been documented to be toxic to cells and pharmacologically active on the central nervous system (eugenol and its derivatives are being developed as anti-epileptic agents). He said eugenol also is sensitizing (it can induce the development of an allergy against itself) and it has produced severe allergic reactions in dental patients, manifested by wheezing and shortness of breath.

“Here we have one product on the FDA’s ‘Generally Recognized as Safe list that is safe to ingest but is toxic in the airway. Up to now it was always presumed that the materials on the FDA ‘GRAS’ list, because they were considered safe for ingestion, were considered safe to be added to cigarettes for inhalation. This is the first time we have at least preliminary evidence that material from that list was shown not be to be safe for inhalation.”

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Schechter, one of the most outspoken critics of clove cigarettes, wants to see the Legislature ban the sale of clove cigarettes in California.

“If adults want to smoke them that’s one thing, but I think this is a teen-age habit, and I think the importers and retailers are preying on the gullibility of teen-agers. They’re allowing kids to be the guinea pigs--they’re field testing the cigarettes on the kids. We want clove cigarettes out of the country.”


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