Measuring the Effects of Malathion : Medfly war: More than 1,000 studies have been published on the pesticide, but they haven’t been able to settle the question of whether it poses a real health risk.

It was a simple experiment--crude, but undeniably direct.

Twelve convict-volunteers from an unidentified prison were placed inside three plywood-sealed solitary confinement cells and for the next 42 days, sprayed by a research assistant with a misty drizzle of malathion for two hours a day, seven days a week.

The American Cyanamid Co., the nation’s largest producer of the pesticide, had been under pressure to show the pesticide was safe for aerial spraying. This 1959 experiment, the company hoped, would help resolve the issue.

In the end, the scientists in their study found that apart from “some nasal irritation,� the prisoners showed no serious side effects.

Did the study prove malathion’s safety? Ask the few thousand scientists who have published since then a mountain’s worth of studies that have expanded the knowledge about malathion, but at the same time, buried it under a heap of new questions and uncertainties.

At the heart of the controversy over California’s war against the Mediterranean fruit fly is the gnawing confusion and dread about malathion.

More than 1,000 studies have been published on malathion, from the mundane (“Caution in the treatment of cheetahs with malathion�) to the esoteric (“Effect of malathion on nucleic acid synthesis in phytohemagglutinin-stimulated human lymphocytes�).

Researchers have prodded the bodies of workers accidentally exposed to enormous doses of malathion, scanned thousands of slides in search of cancer cells and fed malathion to humans, rats, ring-necked pheasants, mice, eastern oysters, rabbits and mallard ducks.

Nearly 40 years of research has produced broad areas of agreement between scientists and health experts, who generally hold that malathion in small doses poses no significant health risk to humans.

But that one key word--significant--has spawned a whirlwind of debate. Most research has detected no link between malathion and cancer and birth defects, but many of those studies are dogged by problems in method and interpretation that have kept them from convincing a skeptical public.

Concerns about potential long-term health hazards that may not be noticed for decades have driven the debate into a murky arena of unprovable charges and counter charges.

Even researchers who believe in malathion’s safety now concede that the issue may never be resolved.

“As long as those fleets of helicopters are flying, there are going to continue to be questions,� said Dr. James W. Stratton, an epidemiologist with the state Department of Health Services in charge of reviewing the health effects of malathion.

The stakes in the debate are high for both Southern California’s city dwellers and the farmers of the Central Valley, whose fields and orchard lie over the peaks of the Tehachapi Mountains.

Over half the country’s fresh fruits and vegetables are grown in Central Valley, and agriculture officials say it would be a crippling blow to their war against the Medfly if malathion was removed from their arsenal.

Malathion opponents counter that the potential danger of aerial spraying outweighs the benefits to agriculture.

Although spraying is now scheduled to end on Wednesday throughout Los Angeles and Orange counties (spraying will continue in 53 square miles of Riverside and San Bernardino counties), state officials concede that until new eradication techniques are developed, some spraying will still be required for new infestations. Even with the use of sterile Medflies, which are being released by the millions in Southern California to breed the pest out of existence, one or two malathion sprayings are still necessary for new outbreaks.

There has never been much question about the inherent danger of malathion, a member of a deadly family of chemicals known as organophosphates, some of which were produced by the Nazis during World War II as a military nerve gas.

The pesticide kills insects by inhibiting an enzyme, called acetyl cholinesterase, critical for the transmission of nerve signals. Unlike insects, mammals have an enzyme that breaks down malathion into largely harmless components, making it one of the safest pesticides available.

Scientists estimate a 180-pound man would have to eat about 2.9 ounces of malathion--about the same amount the state is using to spray an acre--to die.

Because of the high doses of malathion needed to induce toxic effects in humans, modern research has focused largely on potential hazards that have nothing to do with cholinesterase, such as cancer, birth defects and immune system alterations.

And within the last decade, research has turned up hints of some possible links between malathion and those health problems.

USC professor Kathleen E. Rodgers has conducted a series of studies on mice over the past decade that shows that at the cellular level malathion does alter the response of the immune system in mice.

Earlier this month, a state panel of health experts in charge of reviewing the scientific information on malathion reported that preliminary evidence suggests malathion causes genetic damage in laboratory cell cultures, animals and humans.

In both cases, researchers say too much is still unknown to say what their laboratory results mean in terms of actual health problems for humans.

Over the last decade, there have been enormous efforts to bridge the gap between the experimental and real worlds, although the results have been far from conclusive. The largest attempts have been two studies on birth defects that grew out of the 1,300-square-mile spraying campaign in Northern California from 1981 to 1982.

The first, conducted by the state Department of Health Services, involved an analysis of 77,000 children conceived during the Northern California infestation.

Using routine hospital discharge forms that recorded newborn deformities and the ZIP codes of the children’s mothers, researchers investigated any possible correlations between the deformities and aerial spraying.

Judith K. Grether, an epidemiologist with the state Department of Health Services and the primary author of the study published in 1987, said the search found no significant problems related to malathion spraying.

But the study had its shortcomings. Grether said up to 15% of the defects were probably misclassified by the physician because of the difficulty in diagnosing newborns. In addition, the study had no way of determining which outside factors could skew the results: How old were the mothers? Where did they work? Did they smoke? Did they use artificial sweeteners?

To improve on the Grether study, Duncan C. Thomas, a USC professor of biostatistics, was put in charge of a second study--this time armed with a unique survey of 7,450 women who were patients at Kaiser Permanente hospitals.

Low birth weight, spontaneous abortion, stillbirths and limb and gastrointestinal defects were correlated by computer with information on the mother’s race, education level, work conditions and other factors.

Thomas had the detailed medical and demographic information that Grether lacked, but his study was hobbled by the relatively small survey group.

Thomas found no serious problems caused by aerial spraying, but he conceded that because the number of total deformities was so small, he needed an enormous increase in defects above normal levels before he could establish a statistical link with malathion. In one case, he needed at least a 400% increase.

“We’re limited to looking for the big effect,� Thomas said in a recent interview. But he added: “I’m basically pretty reassured by this study.�

By far, the most controversial debate has been over malathion’s possible connection with cancer. At least five studies have been conducted since the late 1970s. The results have been hotly debated.

The first three studies were sponsored by the National Cancer Institute and conducted in 1978 and 1979. For nearly two years, groups of 50 rats and mice were fed near-lethal doses of malathion and malaoxon, a toxic chemical formed by the breakdown of malathion. The animals were then killed and slides made of various body tissues.

Pathologists scanned more than 15,000 slides in search of abnormal cells and finally concluded the chemicals were not carcinogenic.

The studies, however, had two weaknesses that left them open to question. To begin with, evaluating slides is a subjective process. Some cell anomalies can be subtle, and what one pathologists sees as normal may appear abnormal to another.

In addition, the abnormal clumps of cells occur naturally, making it difficult with so few animals to discern what is actually caused by the chemicals.

The three cancer institute studies were barely out a year when a scientist from the Frederick, Md., Cancer Research Facility, Melvin D. Reuber, announced that according to his viewing of the same slides, malathion is carcinogenic in rats and mice.

Reuber’s findings sparked an outcry, and he eventually resigned after a supervisor criticized him for “actions that negatively affected the economics of agriculture and rural communities in California and Wisconsin.�

As Reuber was finally ready to publish his findings in a scientific journal in 1985, officials from the National Cancer Institute and the National Toxicology Program decided to prepare their own study. The agencies embarked on a complete re-evaluation of the original slides and again decided that malathion and malaoxon are not carcinogenic.

But just three years later, the U.S. Environmental Protection Agency ordered a new series of cancer tests for malathion, largely because the tests were done under old laboratory guidelines, but also because of the previous controversy.

The new tests will take at least four years to complete.

Stratton, of the state Department of Health Services, said that regardless of the outcome, the debate over malathion’s safety has become so polarized and confused that it may never be completely resolved.

He said the very nature of science--its inability to discern every hazard and its incomplete grasp of what is dangerous to humans--makes it impossible to eliminate all doubt about malathion.

And each time the state’s helicopters take to the air, the fears and complaints only continue to mount.

Adelaide Nimitz, a leader of the community group Families Opposed to Chemical Urban Spraying, said her group has recorded more than 10,000 complaints, ranging from nausea and irritated eyes to miscarriages and poisoned animals. Protesters have warned about poisoned children and raged at a panel of state doctors, calling them “Nazis.�

Beleaguered Los Angeles County health officials, who have been branded as yes men for the agriculture industry, now say that after receiving a flood of complaints, there may be plausible connections between malathion and minor health problems, such as eye irritation and nausea.

Dr. Paul Papanek, chief of the county’s toxics epidemiology program, said science alone cannot resolve the questions that remain: What is the acceptable level of uncertainty? What is the acceptable risk? Is one sick person out of a million acceptable? One out of 10 million?

“It really boils down to a question of values, not science,� he said.