Fluoride concerns surface once again
Research linking fluoride in drinking water to health problems could lead to regulatory changes

by Bette Hileman

Despite decades of adding fluoride to drinking water to protect teeth from decay, there are growing concerns about the efficacy and the safety of this practice. Spurred by new research on fluoride's health effects and at the request of the Environmental Protection Agency, the National Academies' National Research Council (NRC) has begun another review of the problems of water fluoridation.

On Aug. 12, NRC held a public meeting to review EPA's standards for fluoride in drinking water. Several witnesses defended the current standards and the practice of adding fluoride to drinking water to protect teeth. But some argued that the maximum contaminant level (MCL) of 4 mg of fluoride per liter allowed by EPA in drinking water presents health risks to the population and provides little, if any, benefit to teeth. They claimed, in particular, that EPA's MCL presents risks to bones and other organ systems.

In 1986, EPA set an MCL of 4 mg per L and a secondary MCL of 2 mg per L for fluoride in drinking water. A secondary standard is a goal that water systems should try to reach, but they cannot be fined if they fail to do so. In 1993, the NRC Board on Environmental Studies & Toxicology reviewed those standards and found them acceptable. Last year, EPA asked NRC to once again review the toxicological and exposure data on fluoride, especially new research, and determine whether the standards can still be considered acceptable for protecting the public from potential adverse effects of fluoride.

In its 1993 review, the NRC panel found inconsistencies in the fluoride database and gaps in knowledge. It recommended further research on fluoride intake, dental fluorosis (mottling of the teeth caused by excessive fluoride intake during tooth development), bone fractures related to fluoride accumulation, and carcinogenicity. It also advised that EPA's standards be reviewed when results of new research became available. Since 1993, many studies have been published on fluoride's effects on the nervous system and bone.

THE FORMAL CHARGE for the new NRC review is to examine the toxicological, epidemiological, clinical, and exposure data published on fluoride since 1993. At the recent public meeting held by NRC, Joyce M. Donohue, toxicologist in EPA's Office of Water, pointed out that the enforceable MCL of 4 mg per L was set to protect against crippling skeletal fluorosis, while the nonenforceable secondary MCL for fluoride was set at 2 mg per L to prevent dental fluorosis. "At 2 mg per L, the incidence of moderate dental fluorosis ranges from 0 to 15%," she said, "and there are distinct increases in severe dental fluorosis at levels above 2.5 mg per L." Teeth with severe fluorosis are heavily stained and pitted and susceptible to fracture, those with mild fluorosis have white opaque patches on small areas of the teeth, and those with moderate fluorosis have yellow or tan stains.

Donohue explained that if people consume a minimum of 20 mg of fluoride per day for 20 years, they can contract crippling skeletal fluorosis. To calculate the MCL, she said, 20 mg per day was divided by the average water intake of 2 L per day to get 10 mg per L, and this figure was divided by a safety factor of 2.5 to yield 4 mg per L. "I do not know the origin of the 2.5 safety factor. Now, EPA uses safety factors of 1, 3, and 10, not 2.5," she said. Safety factors establish a margin of safety to account for individual variability and species differences when extrapolating from animal to human data.

In calculating the fluoride standards, Donohue explained, EPA assumed that all fluoride exposure comes from drinking water, when in fact it also originates from food processed with fluoridated water, personal care products, food fertilized or treated with fluoride compounds, and supplements. "In setting standards for all other drinking water contaminants except barium, EPA has considered exposure from many different sources, not just water," she said.

Since the NRC review in 1993, research indicates that over the past decade people have had greater exposure to fluoride through personal care products and that the prevalence of dental fluorosis may have increased, Donohue said. Also, studies have raised questions about whether topical exposure to fluoride may prove much more important than systemic exposure in preventing dental caries, she said. (If the primary action of fluoride is topical, drinking fluoridated water would probably not be as important as fluoridated toothpaste in preventing tooth decay.) In addition, new research suggests that low levels of fluoride have developmental effects and effects on the brain, she said.

Although the NRC panel's formal charge does not include an examination of the benefits of fluoride, William R. Maas, director of the division of oral health at the Centers for Disease Control & Prevention, spoke for nearly an hour, defending water fluoridation. He attributed the sharp decline in dental caries experienced in the U.S. since the late 1940s to fluoridation and called it "an important public health achievement." In the U.S., 162 million people, or about 55% of the population, are drinking fluoridated water, yet only 1.3% of school children experience moderate or severe dental fluorosis, he said. Altogether, 22% of children have some degree of fluorosis, he explained.

Twelve-year-old children who have lived in areas with fluoridated drinking water all their lives have on average 1.6 fewer cavities than children with no exposure to fluoridation, Maas said. Put another way, 12-year-old children in fluoridated areas have an average of 4.25 decayed, missing, or filled tooth surfaces out of a total of 128 surfaces, while 12-year-old children in fluoridated areas have 2.81 cavities out of a possible 128. This represents a 39% reduction in decay from fluoridation, he said.

Paul Connett, a chemistry professor at St. Lawrence University, called the 39% reduction a vagary of comparing small numbers--a difference that may not be statistically significant. Connett noted that few countries in Western Europe fluoridate their drinking water. Overall, only 1 to 2% of Europe's population drinks fluoridated water, yet all European Union nations have experienced tooth decay reductions similar to those in the U.S. over the past 50 years. Therefore, it is illogical to attribute the decline in tooth decay in the U.S. to fluoridation, he said.

"Many people who drink water that meets the EPA standard may have some degree of skeletal fluorosis."

CONNETT ARGUED that EPA's MCL of 4 mg per L, or 4 ppm, puts people at risk for skeletal fluorosis. There are four stages of the disease, he said, and the standard is designed to prevent only the most severe stage. The first three stages are indistinguishable from arthritis unless a doctor performs a bone biopsy to determine the fluoride content.

"Drinking water with a 4-ppm fluoride content for 20 years yields bone fluoride levels of more than 6,000 ppm," Connett said. People with clinical phase I of skeletal fluorosis have been reported to have bone fluoride contents of 6,000 to 7,000 ppm, he explained. Therefore, "many people who drink water that meets the EPA standard may have some degree of skeletal fluorosis," he said. Those who drink more than the average of 2 L per day would be at particular risk, he said.

Connett said it is likely that many people who live in communities with moderate fluoride content in their water supplies (about 1 ppm, for example) experience preclinical skeletal fluorosis. Some individuals who have lived all their lives in areas with 1 ppm fluoride in the water supply have been found to have elevated levels of fluoride in their bone ash, he explained.

There is evidence from both human and animal studies that cortical bone with excessive levels of fluoride is more brittle and prone to fracture, Connett said. With the exception of vertebrae, most bones in the body are primarily cortical, including the femoral neck in the hip. Consequently, people who accumulate excessive levels of fluoride in their bones are probably more likely to experience a hip fracture, he said.

In 11 clinical trials over the past decade, people were given fluoride tablets (20 to 34 mg per day over 1 to 4 years) to treat osteoporosis, Connett said. The effects were the opposite of what researchers expected. In all of these studies, the group of patients who received the tablets had higher hip fracture rates than the control group patients, who were given a placebo.

"Many people will experience cumulative fluoride doses over their lifetimes from fluoridated water which exceed the cumulative doses that have caused increased hip fractures in clinical trials," he said. "For humans, exposure to 4 ppm fluoride in drinking water yields an average of 6,400 ppm fluoride in bone," and several clinical trials showed increased fracture rates when the bone concentration is as low as 3,800 ppm, he explained.

There is also new evidence that fluoride can have neurotoxic effects, Connett said. Phyllis J. Mullenix, then a toxicologist at the Forsyth Research Institute in Boston, examined the effect of sodium fluoride on rat behavior. In utero fluoride exposure caused hyperactivity in the rats, and those dosed after birth were hypoactive.

In another study, one group of rats drank water containing 1 ppm sodium fluoride, a second group drank water with 1 ppm aluminum fluoride, and a control group drank distilled water. In both treated groups, but not in the control group, the brains developed the type of b-amyloid deposits associated with senile dementia in humans, Connett said.

NRC's review of fluoride has broader ramifications than the fluoridation of water. It may influence EPA's decisions on the insecticide sulfuryl fluoride (SO2F2), a substitute for stratospheric-ozone-depleting methyl bromide. EPA is now in the process of deciding whether the temporary tolerance it granted for the postharvest fumigation of food with SO2F2 should be made permanent. SO2F2 leaves residues on walnuts and raisins that are metabolized to inorganic fluoride.

Because the NRC committee has just commenced its review of fluoride, it has not yet drawn any conclusions from the deliberations. It will hold another public meeting in November and plans to complete its review by November 2004.