Monday, December 20, 2010

FDA Hearing on Mercury-Based Dental Fillings Pleases Both Sides of Debate

From Medscape Medical News

Robert Lowes

December 18, 2010 — An advisory panel to the US Food and Drug Administration (FDA) concluded this week that there are no huge scientific flaws in the agency's 2009 finding that mercury-based dental fillings, known as dental amalgam, are safe for adults and children aged 6 years and older.

However, at the end of its 2-day hearing, the agency's dental products panel recommended that the FDA look at more data — and the latest data — on the possible health risks that the filling material poses to pregnant women and their fetuses and to young children, particularly nursing infants whose mothers have these fillings. The panel also said the agency should consider adding warnings for these groups to the material's product instructions.

In one sense, the outcome of the hearing temporarily preserves the status quo for dental amalgam — so much so that the American Dental Association immediately issued a press release praising the expert panel's recommendations. The American Dental Association maintains that dental amalgam is safe and warrants no further regulation by the FDA as a medical device.

At the same time, the panel's quest for more scientific data about vulnerable populations acknowledged the concerns of dental amalgam opponents, who link mercury exposure to dozens of diseases ranging from autism to Alzheimer's disease. At high enough levels, mercury exposure can damage the brain and kidneys.

"We have to recognize that some patients should not have amalgam," said panel member Amid Ismail, BDS, DrPH, a professor and dean at the Kornberg School of Dentistry at Temple University in Philadelphia, Pennsylvania.

"There is really no place for mercury in children," added Suresh Kotagal, MD, a pediatric neurologist at the Mayo Clinic in Rochester, Minnesota. "The bottom line is, do no harm."

An attorney for the International Academy of Oral Medicine and Toxicology (IAOMT), which advocates mercury-free dentistry, told Medscape Medical News that he was encouraged by the consensus positions of the panel (no formal votes were taken).

"There was a lot of support that risk assessment needs to be done again," said Jim Love, the attorney for the group. "I thought it was a very constructive dialogue."

The FDA convened the hearing after the IAOMT and other antiamalgam groups and individuals petitioned the agency to reconsider its 2009 decision to reclassify the material from a lower-risk class I device to a moderate-risk class II device. That reclassification entailed revising product instructions to state in part that

* clinical studies have not established a causal link between dental amalgam and health problems for adults and children aged 6 years and older,
* the developing nervous systems of fetuses and young children "may be more sensitive to the neurotoxic effects of mercury vapour," and
* little or no clinical data are available regarding long-term health outcomes for fetuses, children younger than 6 years, and breast-fed infants.

The petitioners urged the agency to either ban dental amalgam, as Norway, Sweden, and Denmark already have done, or else reclassify it as a high-risk class III device with more restrictions on its use.

"Industry Will Go Crazy if That Reference Level Gets Moved"

By weight, dental amalgam is composed of roughly 40% to 50% liquid elemental mercury and a powdered alloy of mostly silver, copper, and tin. Much of the 2-day hearing focused on how much mercury is absorbed by people with these fillings, and what should be the reference exposure level (REL), or safety threshold, for the mercury vapor that the fillings release. Because mercury doses can be calculated from vapor exposure levels, an REL can establish a permissible dose. At the end, the advisory panel recommended that the agency take a second look at its positions on these issues.

The FDA currently holds that an individual with 7 to 10 amalgam fillings absorbs 1 to 5 μg of mercury per day. Amalgam opponents say this dose can be 4 times as high, meaning that tens of millions of people with these fillings are at risk for health problems, based on the current REL in place. The advisory panel's advice to the FDA is to study mercury doses for various population categories.

"We have virtually no data on fetuses," panel chairwoman Marjorie Jeffcoat, DMD, a professor at the University of Pennsylvania School of Dental Medicine, told Medscape Medical News. "It's important to subset out the different populations."

Also in dispute is the REL for mercury vapor. The FDA uses an REL of 0.3 μg/m3, set by the US Environmental Protection Agency (EPA). The EPA refers to this safety threshold as a "reference concentration" (RfC), which is an REL for inhaled, as opposed to swallowed, chemicals. This REL or RfC of 0.3 μg/m3 translates into a permissible dose that lies in the same range as the actual amalgam-derived dose assumed by the FDA.

The IAOMT told the panel that the REL for elemental mercury should be lower than 0.1 μg/m3 and cited a study it commissioned as proof. That study, whose lead author is Canadian biologist G. Mark Richardson, PhD, states that the EPA based its REL in part on studies of industrial workers exposed simultaneously to mercury and chlorine gas, with the gas acting to reduce mercury exposure, thus skewing the numbers. He notes that Health Canada, the Canadian equivalent of the US Department of Health and Human Services (and his former employer), set an REL of 0.06 μg/m3 by relying on studies free of this distortion.

The panel did not fully agree with Dr. Richardson's critique and called his chlorine gas argument a "red herring." Nevertheless, it advised the FDA to reexamine the scientific literature to reassess the REL and develop its own, noting that "the EPA RfC needs to be updated with the latest studies," according to an FDA hearing summary.

In essence, the panel wants the FDA to determine whether the REL really protects vulnerable populations, Dr. Jeffcoat told Medscape Medical News. "Tiny children can't speak for themselves," she said.

However, any lowering of the REL for elemental mercury has enormous consequences that extend far beyond the dentist's office, IAOMT attorney Jim Love told Medscape Medical News. The EPA, he said, uses this REL to regulate how much mercury that heavy industry can put into air and water, as well as to designate waste sites for its Superfund clean-up program. A lower REL means higher environmental protection costs — think billions of dollars — all around.

"Industry will go crazy if that reference level gets moved," said Love.

Need to Acknowledge Amalgam Benefits

The panel also revisited the question — raised in the FDA's 2009 deliberations — of whether clinical studies point to a causal relationship between dental amalgam and adverse health events. The panel reaffirmed that the literature at that time failed to do so, but only in terms of the general population. Again, it recommended that the agency continue to study the issue, particularly in terms of "susceptible subpopulations."

The panel grappled with how to best spell out the possible health risks of dental amalgam in the product instructions that dentists receive. It finally suggested adding warnings for young children, pregnant women, and individuals with metal allergies, and making the reference to limited scientific data about such individuals more explicit.

Panel members also stressed the need for dentists to discuss this information with patients. A number of individuals who spoke at the hearing complained that their dentists never mentioned mercury-associated risks for amalgam fillings, which they blamed for serious illnesses.

A model for warning language, incidentally, lies north of the border. Health Canada states on its Web site that although dental amalgam generally does not pose a health threat, the primary teeth of children should be filled with a nonmercury material when feasible. Pregnant women, individuals allergic to mercury, and those with impaired kidney function should avoid mercury-based fillings, according to Health Canada.

Tempering the panel's recommendations on Wednesday was an acknowledgment that amalgam's risks must be weighed against its benefits — namely, its superiority over tooth-colored composite fillings for restoring multiple surfaces, and its greater durability. In addition, although the use of amalgam has drastically declined during the last few decades as a result of patients choosing more cosmetically attractive alternatives, its lower price has made it the default material for poorer patients, who might not be able to afford more expensive fillings if amalgam were banned.

"It's nice for us to talk about risk and benefit and choice," said panel member Thomas Burbacher, PhD, a professor of environmental and occupational health sciences at the University of Washington in Seattle. "But if you don't have a choice, that discussion is meaningless."

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