Published on Monday, November 27, 2000 in the Los Angeles Times
Volunteers Ingest Pollutant in Drinking Water Study
by Marla Cone
 
Every morning for six months, 100 volunteers in San Bernardino are dutifully swallowing pills.

But these human volunteers--recruited by Loma Linda University Medical Center and paid $1,000 apiece--are not testing a new medication. The pills contain an industrial pollutant called perchlorate, a chemical found in rocket fuel.

The experiment, which is funded by aerospace giant Lockheed Martin, is designed to see whether perchlorate pollution is harmful to human health. The intent is to develop data that could influence the setting of national and state drinking-water standards.

The unusual research raises ethical questions about whether scientists should allow volunteers to ingest chemicals or pesticides in the quest to understand the dangers of environmental contaminants. Several small, industry-funded experiments on human volunteers have been conducted in recent years for some compounds, like perchlorate, where the risks of consuming low levels are poorly understood.

But the perchlorate test, which began in August, reportedly is the first large-scale study to use human volunteers to test a water pollutant.

Scientists who perform these human experiments compare them to clinical trials for drugs. In fact, perchlorate isn't just a pollutant; high doses are used, in rare cases, to treat hyperthyroidism.

But some medical ethicists say there is one big difference: People who test drugs are helping society find treatments for sick people. Consuming a pollutant has no medical benefits.

"These tests are inherently unethical," said Richard Wiles, research director of the Environmental Working Group, a national environmental group opposed to human clinical trials for pollutants.

In the perchlorate tests, the volunteers swallow up to 3 milligrams daily--83 times more than a person would get from drinking water containing the amount allowed by California's Department of Health Services.

At high doses, perchlorate can inhibit production of thyroid hormones. Normal thyroid function is critical in regulating the growth of fetuses and young children and the metabolism of adults.

But scientists are trying to figure out whether small doses like those found in water supplies in San Bernardino, Azusa, Santa Clarita, Riverside and other areas interfere with thyroid glands.

In animals, exposure to perchlorate alters thyroid hormones. But the human evidence about the effects of the water contaminant is mixed.

A study published this year shows that infants in the Lake Mead area of Arizona--where water contains perchlorate--are born with altered thyroid function. But other studies, in perchlorate-contaminated areas of Las Vegas and Chile, have shown no such effects.

"As an endocrinologist, this is of interest to me because clearly we don't know what the effects of the contaminant are on thyroid function," said Dr. Anthony Firek, who is directing the perchlorate study at Loma Linda University Medical Center. "I hope this [research] will help define the risks."

Pollutants Usually Tested on Animals

The volunteers in the Loma Linda test signed a consent form telling them that perchlorate "may affect the way the thyroid gland works." Half of the 100 volunteers eat perchlorate; half get a placebo.

Exposing human volunteers to industrial chemicals is a recent development, and still seems relatively rare.

Most pollutants are tested on lab animals. Also, epidemiology studies--which search for patterns of diseases in people who live in areas with polluted air or water--are commonplace.

But those studies have numerous limitations, so the only true way for scientists to reduce the uncertainty about a chemical is to give a dose to human volunteers, some experts say.

Concerned about recent examples of human testing of pesticides, the U.S. Environmental Protection Agency sought advice from its scientific advisory board. The panel, in a report issued in September, supported human testing on a limited scale but urged "the greatest degree of caution."

Two of the 12 scientists felt even stronger, advocating that the EPA refuse to consider all human tests. They called the studies dangerous and insufficient to judge the safety of pollutants, especially for children.

"This recommendation lays the groundwork for a flood of . . . research that should not be conducted and should not be accepted by the EPA for regulatory purposes," said Dr. Herb Needleman of the University of Pittsburgh School of Medicine and Dr. J. Routt Reigart of the Medical University of South Carolina.

No government agency regulates human experiments. But every institution has a review board that must approve each study before it can take place.

In the case of the Loma Linda study, the boards of three medical institutions approved the perchlorate tests, Firek said. In addition to Loma Linda, the study was approved by Boston University--which employs one of the researchers--and the Jerry L. Pettis Memorial VA Medical Center, where some of the tests are being done.

In 1997, a similar study by a private California laboratory, McLaren/Hart-ChemRisk, involved five volunteers drinking chromium 6. Chromium 6 is a known carcinogen when inhaled, though the risks when it's swallowed in water are unknown. The idea was to see how much chromium entered the bloodstream.

Also, a smaller perchlorate study, involving nine volunteers who drank it for seven weeks, was conducted at Brigham and Women's Hospital in Boston. The report, published in August, found no thyroid changes.

Firek said that if perchlorate were only a pollutant and not a drug, he would have declined to conduct the human tests. Perchlorate is used in rare cases to treat people with hyperthyroidism, at a very large daily dose of 200 to 1,200 milligrams.

"Because we have a track record with it since the 1950s, we know what the side effects are. We know what the risks are [at higher doses]. So then we can feel comfortable with doing a study like this," Firek said.

Precautions Being Taken in Study

The volunteers in the Loma Linda experiment undergo extensive medical testing to ensure that they face no threats while ingesting the compound. Included are monthly tests to measure their thyroid, liver and kidney functions.

If someone experiences any changes, he or she will stop taking the pills, according to the volunteers' consent forms.

Pregnant or nursing women are banned as volunteers, and all female volunteers must be sterile or post-menopausal.

Lockheed Martin's funding of the study was disclosed to the Loma Linda volunteers.

The company, according to the consent form, "is involved in the manufacture of products like rocket fuel which contain perchlorate, and therefore has an interest in the outcome of this study."

A former Lockheed plant is the likely cause of the contamination of water wells in San Bernardino County, according to the state Department of Health Services.

Representatives of Lockheed Martin did not return telephone calls seeking comment.

Concern about perchlorate in drinking water began in 1997, after a test was developed in California to enable the detection of small concentrations of the substance in water.

The EPA does not regulate perchlorate, but it has mounted a review to consider setting a standard.

The state Department of Health Services has set an "action level" that recommends shutdown of wells with water exceeding 18 parts per billion. Within a year, state officials are expected to recommend a more stringent public health goal.

Officials at the state Office of Environmental Health Hazard Assessment say they would consider the results of human tests in setting limits as long as they were published in peer-reviewed medical journals and met standards of scientific validity.

Nationwide perchlorate testing of water supplies begins next year.

In California, tests of 352 public water systems serving half of the state's population show that 51 contain perchlorate, including 20 that exceed the state's action level of 18 ppb, according to the state health agency. One well in San Bernardino County showed a level of more than 800 ppb.

The Environmental Working Group has campaigned against human testing since 1998, after learning that a California pesticide company--Amvac Chemical Corp. in Compton--hired a lab in England to feed insecticide to human volunteers.

Wondering About the Experiment's Safety

Though human testing is new and controversial when it comes to water pollutants and pesticides, it has been routinely used in air pollution experiments for more than half a century.

Researchers in several institutions--including the EPA--use smog chambers to expose volunteers to ozone, particulates and other air pollutants. Some of the tests are conducted on sensitive people: asthmatics and seniors.

The main difference is that smog and particulates are pervasive, so the volunteers are exposed to something they routinely breathe. Also, a contaminant that is ingested rather than inhaled is more likely to travel throughout the body.

A pioneer of smog chamber research, Dr. Henry Gong of Rancho Los Amigos Medical Center in Downey, said human studies must be conducted cautiously.

Gong said volunteers should be given only compounds that reflect what they are exposed to in the real world. Also, the health effects of the compounds should already be relatively well understood and there must be no irreversible effects, he said.

Gong said he is unfamiliar with perchlorate, but he wondered if enough is known about its long-term effects to conduct a safe human test.

"I would wonder about the ethics and the medical complications," Gong said. "Do we really know everything about this compound? Are all the effects reversible? You'd better know the consequences of that."

Copyright 2000 Los Angeles Times

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