November 9, 1994 Contact: Robert Irion (408/459-2495)

LEAD-POISONING THERAPY MAY POSE HIDDEN RISKS, ACCORDING TO PRELIMINARY RESEARCH

FOR IMMEDIATE RELEASE

SANTA CRUZ, CA--A drug commonly used to treat lead poisoning may increase the amount of lead absorbed from the gastrointestinal tract into other parts of the body, according to a pilot study on twelve adult men.

The study's authors are proposing research on a larger scale using people with moderate cases of lead poisoning. Meanwhile, they urge doctors to keep patients in lead-clean places while giving them the drug. Otherwise, the patients' bodies might absorb additional lead and store it in bones or vulnerable organs, which can cause long-term harm.

"It's common sense that when you treat people for lead exposure, you shouldn't return them to the same environment during treatment," says principal author Donald Smith, assistant research toxicologist at the University of California, Santa Cruz. "This study provides preliminary evidence that we should justifiably be concerned when that happens--and the reality is that it may happen."

Smith and his coworkers published their results in the October 1994 issue of the journal Environmental Research. His coauthors were pediatricians Morri Markowitz and John Rosen of the Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, New York, and two colleagues in the environmental toxicology program at UC Santa Cruz: earth sciences professor Russell Flegal and technician Jonathan Crick. Smith also is affiliated with the department of laboratory medicine at UC San Francisco.

The team examined "succimer," now considered the safest drug to treat lead poisoning. The McNeil Consumer Products Company sells succimer under the trade name CHEMET. Like other chemicals used for lead poisoning, succimer clamps onto lead and other toxic metals and allows patients to excrete them. However, it is not clear whether succimer also moves lead from the blood, stomach, or intestines to other parts of the body, such as the skeleton and the brain. That transfer of lead is the primary concern with EDTA, another lead-poisoning treatment. If that occurs with succimer as well, it would compromise the effectiveness of the drug--especially for children, who are most susceptible to lead's insidious behavioral and neurological effects.

In the study, each participant ingested a tiny amount of a nonradioactive isotope of lead, followed by one dose of either the drug or a placebo. The researchers took several blood samples and collected urine and feces from the volunteers for about 26 hours. Measurements sensitive to one part per 10 billion allowed the team to trace the levels of the lead isotope in the samples.

The research team found two hints that succimer did cause the men to absorb some lead through their gastrointestinal tracts. First, those who took the drug excreted more lead isotope in their urine but less in their feces, on average, than those who got a placebo. Second, when the researchers added up all of the lead isotope from each person's blood and excretions, they accounted for less lead, on average, from the people who took succimer. Smith suggests that the missing lead isotope went elsewhere in their bodies, rather than staying in the blood or being excreted.

Smith cautions that several factors make this research preliminary. The size of the study--three groups of four men each-- produced results that were not statistically robust. Rather, the data pointed to trends among the groups. Doctors using succimer on lead- exposed patients give the drug for up to several weeks, rather than in one dose. Further, the study's volunteers had low levels of lead in their blood, whereas patients who receive succimer have five to ten times as much. Even so, the researchers found their pilot study compelling enough to request funds for a larger physiological study on children who receive succimer for lead poisoning.

In 1991, the U.S. Food and Drug Administration approved succimer for use on children whose lead levels exceed 45 micrograms of lead per deciliter of whole blood (45 ug/dL). However, medical researchers suspect that lead can cause subtle harm at levels of 10 ug/dL or even lower. Scientists are striving to weigh the medical and financial costs of lead-poisoning therapy against its benefits for children with moderate lead levels--in the range of 25 to 40 ug/dL. A major new study funded by the National Institutes of Health will examine whether succimer helps these children by reducing behavioral and neurological lead toxicity. A parallel study, involving Smith and Flegal, will use monkeys to explore the same questions under controlled conditions. The study also will trace succimer's effects on the monkeys' bodies: Does it carry lead to the brain, liver, kidneys, skeleton, or elsewhere?

"These studies are trying to evaluate the benefit of treatment at lower blood-lead levels," Smith says. "However, for all children, the focus should remain on removing the sources of lead exposure, especially when they are being treated for lead poisoning." Those sources are not always readily apparent, Smith notes. Even in obvious cases, such as old lead-based paint in a home, the financial resources to remove the lead often do not exist.

Editor's note: You may reach Donald Smith at (408) 459-5041 or at .

This release is also available on UC NewsWire, the University of California's electronic news service. To access by modem, dial (209) 244-6971.

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