Chemical & Engineering News
September 4, 2006

Fluoride Risks Are Still A Challenge
The controversy about the risks of fluoride is unlikely to be resolved soon, a meeting held in late July strongly suggests.

By Bette Hileman

Ever since fluoride was first added to water supplies in Grand Rapids, Mich., in 1945 to prevent tooth decay, the practice has been controversial. Some claim it does little or nothing to prevent tooth decay and is dangerous for health. Others, including most dentists and public health officials, say it significantly lowers rates of tooth decay and presents no important health risks. About two-thirds of the U.S. population drinks fluoridated water, and in recent years, when towns and cities across the country have held voter referenda on fluoridation, its use has been rejected about half the time.

The status of the long-running debate over fluoride use and exposure was the subject of a citizens' conference held at St. Lawrence University, Canton, N.Y., on July 28-30. The meeting was organized by Paul Connett, emeritus professor of chemistry at St. Lawrence and executive director of the Fluoride Action Network. Three members of the National Research Council (NRC) committee that wrote a fluoride report released in March 2006 spoke at the meeting. In addition, J. William Hirzy, an Environmental Protection Agency scientist, and Donald R. Taves, a retired toxicologist who did extensive research on fluoride at the University of Rochester, as well as several other scientists, participated.

The 450-page NRC report on fluoride did not evaluate the safety or benefits of water fluoridation, which generally involves the addition of hydrofluosilicic acid or sodium silicofluoride to drinking water at levels of about 1 mg/L, or 1 ppm. It did specifically address the current maximum level of natural fluoride EPA allows in drinking water-4 mg/L-and concluded unanimously that fluoride at that concentration harms teeth and bones.

Even though the NRC report did not directly address water fluoridation, many of its findings are relevant to the debate over the issue, said NRC committee members who spoke at the meeting. Panel member Hardy Limeback, who heads preventive dentistry at the University of Toronto, said a lifetime of fluoride ingestion in areas where the water is fluoridated at about 1 ppm can change the quality of dentin and bone and may increase fracture rates for both.

He described a study that measured the fluoride content of bones in Toronto, where drinking water is fluoridated, and Montreal, where it is not. The study found that the average level of fluoride in bone is 1,033 ppm in Toronto and 643 ppm in Montreal. (About half of ingested fluoride is stored in bone.) The Toronto bone samples had altered architecture, which decreased their resistance to compression, and higher density but less mineral, which increased their brittleness, he said. "The study shows that fluoride lowers compressive strength and resilience, or toughness, of bone."

Limeback also noted that moderate fluorosis, which involves yellow or brown mottling of teeth from excessive fluoride exposure, is occurring at rates as high as 30% in some fluoridated communities. Teeth with moderate fluorosis also have weaker dentin with increased tubule size, he said. "This may make adult teeth fracture more easily."

The apparent benefit of water fluoridation, reduced tooth decay, may simply be a function of delayed tooth eruption, Limeback said. It is well-known that permanent teeth take longer to erupt in children who drink fluoridated water, he observed. Studies comparing decay rates in fluoridated and nonfluoridated communities usually assess the mean number of decayed, missing, and filled surfaces (DMFS) in permanent teeth of 12-year-old children. For example, a study conducted in 1990 found that 12-year-old children in fluoridated areas of the U.S. had a mean DMFS score of 2.46, while those in nonfluoridated areas had a score of 2.97 ( J. Dental Res. 1990, 69 Special Issue, 723). However, "if you control for delayed tooth eruption, the study shows no benefit," Limeback said. "Take fluoride out of the water supply, and use the money spent for fluoridation to promote better public health."

NRC panel member Kathleen M. Thiessen, senior scientist at SENES Oak Ridge Inc., Center for Risk Analysis, presented clear evidence that water with about 1 mg/L of fluoride or more presents potential risks to the thyroid gland.

Animal studies show that fluoride doses of 3-6 mg/kg of body weight/day disrupt thyroid function, and if dietary iodine is insufficient, doses as low as 0.06-1 mg/kg/day suppress thyroid function, Thiessen said. Human studies also demonstrate that fluoride affects thyroid function because doses of 0.03-0.14 mg/kg/day relieve hyperthyroidism−overproduction of thyroid−in some patients, she said. Furthermore, some research indicates that as the concentration of fluoride in water goes up, the prevalence of goiter, which is a natural attempt of the body to compensate for underfunctioning of the thyroid gland, increases, she said.

"Many Americans are exposed to fluoride in the ranges associated with thyroid effects, especially for people with an iodine deficiency," Thiessen said. "The average adult exposure is around 0.03 mg/kg/day, and the levels of exposure at which one sees thyroid effects in some individuals with an iodine deficiency are right around that same range," she said. A low level of thyroid hormone can increase the risk of cardiac disease, high cholesterol, depression, and, in pregnant women, decreased intelligence of offspring, she said.

Kidney patients and diabetics are at special risk from fluoridated water because they tend to drink more liquid than healthy individuals, Thiessen explained. Bottle-fed infants are also at special risk if formula is mixed with fluoridated water, she said. Because people drink widely different amounts of fluoridated water and other sources of exposure vary, individuals in the U.S. are receiving vastly different doses of fluoride, she said. "Speaking as a scientist, based on the information I have looked at, with fluoridated water, we're dealing with uncontrolled and unmonitored exposures to an agent that is known to have adverse effects."

Fluoride at levels found in drinking water affects brain function in adults, said NRC panel member Robert L. Isaacson, emeritus psychology professor at the State University of New York, Binghamton. "The receptor cells in the brain can alter in response to toxins and fluoride or a lack of nutrients like oxygen."

Generally, fluoride impairs the brain's ability to perform signaling functions, with the consequence that "messages that are passed along the many pathways are likely to be incomplete or wrong," Isaacson said. One way fluoride interferes is by disrupting the creation and breakdown of neurofilaments in the axons of neurons. "Fluoride also interferes with both primary and secondary signaling in the nervous system," he said.

Fluoride may also increase the number of plaques and tangles in the brains of adults, which could contribute to dementia, Isaacson said. In several studies using rats, chronic exposure to sodium fluoride or aluminum fluoride in drinking water led to plaques and tangles in the rats' brains that are similar to the abnormalities found in Alzheimer's patients, he explained.

Furthermore, Isaacson said, it appears very likely that exposure to fluoride in the womb and throughout early life lowers intelligence. "Epidemiological studies suggest that fluoridation of drinking water decreases the number of children at the very bright end of the IQ spectrum and increases the number in the low IQ region."

"While a number of studies have not found any overall effect of maternal fluoride intake and the birth of children with Down syndrome," Isaacson said, "suspicions have long been raised by some studies that young mothers might be affected more than more mature mothers." Using data from a large-scale study conducted in the Atlanta area, children with Down syndrome were born at a substantially higher rate to mothers under the age of 30 when exposed to fluoride in drinking water than similar mothers where the water was not fluoridated, he explained. "On the basis of this study, if no drinking water were fluoridated in the country, there would be 200 to 500 fewer babies with Down syndrome born each year to young mothers. The prevention of these births would justify the conclusion that a no-effect-level does not exist for universal fluoridation."

As if the debate surrounding fluoridation weren't enough, now another fluoride compound has become controversial - sulfuryl fluoride, which is used as a fumigant to kill insects in food warehouses and processing plants. In 2004 and 2005, EPA approved rules for food uses of sulfuryl fluoride, trade named ProFume, as a substitute for methyl bromide, which is being phased out because it depletes the stratospheric ozone layer. Previously, sulfuryl fluoride was used only to kill termites in vacant structures. Fumigating food with the compound leaves fluoride residues that some consider dangerous. In June of this year, three activist organizations, the Fluoride Action Network, the Environmental Working Group, and Beyond Pesticides, filed a petition asking EPA to suspend all food uses of sulfuryl fluoride.

Michael Connett, project director for the Fluoride Action Network (and son of meeting organizer Paul Connett), explained why food uses of sulfuryl fluoride, which breaks down to free fluoride ion, pose health risks. In its rules for fumigating food with sulfuryl fluoride, EPA approved high fluoride ion residue limits, he said. These residue limits, or "tolerances," include 125 ppm for wheat flour, 75 ppm for oat flour and rolled oats, 45 ppm for barley, 900 ppm for powdered eggs, and 70 ppm for other processed foods.

Connett described how EPA derived the maximum limit of 4 mg/L for fluoride in drinking water in 1985, and how it later used the same assumptions in calculating residue limits for sulfuryl fluoride. When EPA set the 4 mg/L limit for water, it assumed that adults consume 2 L of water per day, he said. It also assumed that chronic exposure to fluoride causes only one adverse health effect, which is crippling skeletal fluorosis. It then derived a "safe" intake of 8 mg of fluoride per day from occupational studies showing that ingestion of 20 mg of fluoride per day over 20 years is the lowest dose that can cause crippling skeletal fluorosis. EPA applied a safety factor of 2.5 to this 20 mg to calculate the safe maximum intake.

Even though about 10% of children who drink water with a fluoride level of 4 mg/L develop severe dental fluorosis, which makes their teeth subject to decay, EPA decided this was a cosmetic effect, Connett said. And all other potential health effects of fluoride-on the brain, kidney, and thyroid gland, for example-were ignored, he explained.

To calculate residue limits for sulfuryl fluoride, Connett said, EPA then divided the 8 mg/day by the weight of an average man, 70 kg, to come up with what the agency calls a "reference dose"-a maximum fluoride dose that should not be exceeded-of 0.114 mg/kg of body weight/day. Although EPA in its original 2001 risk assessment for sulfuryl fluoride said this limit should not be exceeded by anyone in any age group, in the 2006 risk assessment, the agency moved the goal posts. The final limits for children in different age groups are higher than 0.114 mg/kg/day. EPA set the limits by dividing 8 mg by the average weight for each group: 7 kg for infants, 13 kg for children one to two years, 22 kg for children three to five years, and 40 kg for children six to 12 years.

Through this process, EPA came up with an allowable dose for infants that is 10 times higher than the adult dose, Connett said. It is just the opposite of what is encouraged by the 1996 Food Quality Protection Act, he observed. "The act encourages an additional safety factor for children to account for children's heightened susceptibility to environmental contaminants."

After setting these total doses, EPA then calculated sulfuryl fluoride residue limits, taking into account fluoride exposure from water and probable intakes of various foods, Connett said. This whole derivation of acceptable limits has now been called into question, however, by the 2006 NRC report on fluoride, which strongly criticizes the 4 mg/L maximum contaminant level for water and the assumptions used in deriving it, he explained. If EPA follows the advice of the NRC panel, it will have to set a lower maximum contaminant level for fluoride in drinking water, and as a consequence, it will have to set lower residue limits for sulfuryl fluoride as well.

In August, Dow AgroSciences, the maker of sulfuryl fluoride, wrote a letter to EPA, asking it not to suspend food uses of the fumigant, as requested by the Fluoride Action Network and other environmental groups. It requested that EPA take no action on sulfuryl fluoride until the agency's drinking water office studies the NRC report and possibly sets a new standard. So far, EPA has changed none of the residue limits. The use of sulfuryl fluoride on food is increasing across the U.S., Connett said.

At the meeting, Hirzy, a senior scientist in EPA's Office of Pollution Prevention & Toxics, called for congressional hearings to examine the reasons why EPA approved sulfuryl fluoride as a fumigant for foods. The hearings should also look into the benefits and risks of fluoridation, he said.

The last time Congress held full-fledged hearings on the topic was in the fall of 1977. At that time, the possibility that fluoridation might cause cancer was almost the only issue under discussion.

Hearings on water fluoridation and use of sulfuryl fluoride-if they lead to change in laws and regulations-could be one way to end the impasse in the seemingly unending fluoride battle. But Taves, who has been involved in fluoride research for 50 years, offered a different solution. Much of the debate now involves each side trying to cast doubt on the biases of the opposing side, he said. "I do not think we know enough, that is, have enough solid scientific evidence, to stop fluoridation," he said.

Therefore, a reasonable way forward would be to convince government officials to stop promoting fluoridation and use the money saved on promotion to do well-conducted, critical studies of both benefits and risks, Taves said. Studies of the benefits of fluoride need to be blind and avoid being confounded by delayed tooth eruption, he observed. "We can't rule out the possibility that bone fracture rates are lower with water fluoridated at the optimal level (about 1 mg/L)," he said. "If fluoridation were stopped first, there wouldn't be any way to compare different groups, those with and without exposure to fluoridated water."

Most of the attendees at the meeting disagreed with Taves' suggestion. "If EPA just did simple arithmetic in a risk assessment, it would have to come up with a standard for fluoride in drinking water of less than 1 mg/L," Paul Connett said.

The meeting adjourned with no clear strategy on how to make progress toward resolving the fluoride debate. With the exception of Taves, most of the participants would like to ban water fluoridation immediately and outlaw food uses of sulfuryl fluoride as well. But so far, they have won only minor skirmishes in the struggle-about half the state referenda when fluoridation comes up for a vote.

Few speakers discussed any possible benefits of fluoridation, so there was no meaningful dialogue between opposing sides. Before the meeting, organizer Paul Connett had invited William R. Maas, director of the Centers for Disease Control & Prevention (CDC) Division of Oral Health, to come to the conference and present the reasons why he believes it is still a good idea to fluoridate drinking water. In a letter written in June, Maas declined the invitation, saying CDC's views on the benefits of fluoridation can be viewed at www.cdc.gov/OralHealth/waterfluoridation/benefits.htm. The findings of the 2006 NRC report on fluoride "are consistent with our assessment that water is safe and healthy at the levels used for water fluoridation (0.7-1.2 mg/L)," Maas wrote.

As long as most public health professionals' views on the benefits and risks of fluoride remain diametrically opposed to the views of some researchers who study the potential health effects−even when they are both evaluating the same evidence−it is hard to imagine a near-term resolution of this controversy.