I'm an unlikely fluoride activist. I've lived in a house with well water since 1994. In the distant past, I casually assumed that adding fluoride and chlorine to municipal water posed similar and negligible risks, due to their proximity on the periodic table of elements. I feel lucky that to date, I've had no apparent health problems from many years of drinking fluoridated water. I'm not a subscriber to Chemical and Engineering News, but I occasionally encounter this publication, as a mechanical engineer working on the North Slope oil fields of Alaska.
As I read the 9/06 article below, seeds of doubt were planted, and my curiosity piqued. As the issue surfaced in 2008 at the Fairbanks City Council chambers, research for testimony about the C&EN article revealed the need for a website like Fluoride Free Fairbanks. -Ed Davis
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Fluoride bioassay study under scrutiny
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A recent animal study by the National Toxicology Program that failed to give fluoride a totally clean bill of health is now being questioned as being maybe too lenient on the widely used tooth decay preventative. Also, a government panel appointed to assess the risks and benefits of human exposure to fluoride and to put the NTP study into broader perspective is apparently running into some problems and has delayed its final report. In addition, a Congressional committee is beginning to show concern about the NTP study.
In the two-year NTP bioassay, mice and rats were exposed to sodium fluoride in their drinking water at fluoride levels of 0, 11, 45, and 79 ppm. Last spring, the NTP staff and a technical review panel concluded that the study showed "equivocal" evidence that sodium fluoride caused osteosarcoma, a rare form of bone cancer, in male rats.
At the ACS national meeting in Washington, D.C., William L. Marcus, senior scientific advisor in the office of drinking water at the Environmental Protection Agency, stated that fluoride should perhaps have been placed in the next highest category, called "some evidence" of carcinogenic activity. (NTP has five categories for chemicals in tests for cancer in rodents: clear evidence, some evidence, equivocal evidence, no evidence, and inadequate study.)
Marcus gave a number of reasons for his doubts about NTP's conclusions. First, the level of fluoride the low- and mid-dose animals had in their drinking water was within an order of magnitude of what humans are exposed to when drinking water containing the EPA-established maximum level of 4 ppm fluoride. This is almost unheard of in animal bioassays. Usually, animal exposure is four to six orders of magnitude more than what humans receive.
Furthermore, at the end of the study, the high-dose animals had accumulated lower levels of fluoride in their bones (5300 to 6200 ppm) than do humans after drinking water with 4 ppm fluoride for at least 10 years (reported to be 7000 ppm). "This is the first time in my memory that [test] animals have lower concentrations of the carcinogen at the site of adverse effect than do humans," Marcus said.
"But the most disturbing part of the report was the repeated reference to the historical controls as having the same or higher numbers of cancers than the test groups," Marcus noted. In previous NTP studies of other chemicals both control and test animals received 0.7 to 1.2 mg fluoride per kg of body weight in their feed each day. (The fish meal that is put in standard lab chow for rodents contains high levels of fluoride.) In the fluoride study, the animals received daily doses of 0.2 mg of fluoride per kg of body weight from their feed. Consequently, the historical control animals used to evaluate the significance of tumors found in the fluoride study were actually a dosed group receiving fluoride sufficient to place them between the low- and mid-dose groups in the fluoride study. Thus the cancer incidences in historical controls, which often were used to downplay the significance of certain tumors in this study, should not have been employed at all for comparison purposes, Marcus said.
Furthermore, when the incidence of osteosarcomas found in historical controls (0.5%) and the incidence found in this study are plotted against fluoride levels, an approximate linear relationship is found. Because it is unusual to find such a clear dose-response curve, Marcus said, this too is a strong indication that fluoride caused the osteosarcomas.
Marcus was particularly concerned about what he calls the "systematic downgrading" of lesions found by the original contractor for the NTP study. The final report for the study was prepared by the NTP staff, but the testing itself was done by Battelle Columbus Laboratories under contract to NTP. A report prepared by Battelle was audited by a quality assurance contractor, and a separate group of pathologists reviewed the studies. In the process, a number of postive findings in the original Battelle report were downgraded. Slides first diagnosed as showing a rare form of liver cancer called hepatochlolangiocarcinoma were later said to indicate hepatoblastoma, another type of rare malignant lesion, and finally to show the far more common cancer hepatocarcinoma. These hepatocarcinomas were combined with the other hepatocarcinomas found in both treated and control animals, Marcus said.
In addition, dose-dependent oral lesions noted in the Battelle report were downgraded from dysplasia and metaplasia to degeneration. Some other liver carcinomas were eventually reclassified as n onmalignant lesions. Because of what he calls systematic downgrading of the slides, Marcus has written a memo to the director of the criteria and standards division in the office of drinking water asking that EPA assemble an independent board of pathologists to review the slides again.
John R. Bucher, who was in charge of the NTP study, says that it is very common for diagnoses determined by the original contractor to be changed during later review. The hepatochlolangiocarcinomas were not downgraded but, based on their predominant cell type, simply revised to hepatoblastomas, which are actually a more unusual lesion, Bucher says. Later, because the hepatoblastomas are hepatocarcinomas, they were included with the other hepatocarcinomas for purposes of statistical evaluation, he says.
Marcus agrees that it is not unusual for diagnoses of slides to be changed in NTP studies, but it is unusual for nearly all diagnoses that suggest a dose-response relationship to a chemical to be altered.
A number of other government officials who asked not to be identified also have told C&EN that they have concerns about the conclusions of the NTP study. They, too, believe that fluoride should have been placed in the "some evidence" category, in part because osteosarcoma is a very rare form of cancer in rodents.
A panel appointed by Frank E. Young, deputy assistant secretary for health, science, and environment at Health & Human Services, is currently in the process of preparing a report on the risks and benefits to humans from fluoride exposure. One or more of the panel members reportedly agree that fluoride should have been placed in a higher category in the NTP study. Originally, the report was scheduled for release in June, but it is now slated for November.
EPA is committed to reevaluating its 4-ppm standard for fluoride in drinking water. But it won't go ahead until after the HHS panel's report is complete. Before the end of the year, the Government operations Subcommittee on Human Resources & Intergovernmental Affairs chaired by Rep. Ted Weiss (D.-N.Y) will be reviewing the NTP study.
Sounded On Fluoride
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Original article still on-line
The current maximum level of fluoride that EPA allows in U.S. drinking water, 4 mg/L or 4 ppm, harms teeth and bones, says a report from the National Research Council released on March 22. About 200,000 people in the U.S. consume water with naturally occurring fluoride levels of 4 mg/L or higher.
On average, about 10% of children exposed to the maximum contaminant level develop severe dental fluorosis, a permanent condition characterized by discoloration and pitting of the teeth, explains John Doull, professor emeritus of pharmacology and toxicology at the University of Kansas Medical Center and chair of the committee that wrote the report. Children who drink water that meets EPA's secondary standard of 2 mg/L are at risk of a less severe form of dental fluorosis, involving only discoloration of the teeth, he says.
In addition, "a population with lifetime exposure to fluoride in water at concentrations of 4 mg/L or higher is likely to experience more bone fractures than groups exposed to 1 mg/L," Doull says. "Our committee unanimously concluded that EPA should lower the maximum contaminant level goal for fluoride in drinking water."
The report discusses a number of other adverse health effects that may be associated with excessive fluoride exposure but comes to no definitive conclusions. For example, it says that lifetime exposure to fluoride at 4 mg/L can lead to bone fluoride levels associated with the most severe stages of skeletal fluorosis, a painful disease that resembles arthritis. The report also describes studies that find IQ deficits in children in high-fluoride areas. More research is needed, however, to determine if fluoride is indeed causing skeletal fluorosis or lower intelligence, the report says.
The NRC committee did not specifically examine the health risks or possible benefits of water artificially fluoridated at 0.7 to 1.2 mg/L and consumed by more than 160 million Americans.
EPA should use the information in the report to do a new risk assessment and set new fluoride standards, says committee member Charles Poole, associate professor of epidemiology at the University of North Carolina's School of Public Health.
Also on March 22, the Environmental Working Group released a study on infants' exposure to fluoride. In 1997, the Institute of Medicine set a safe upper limit of 0.7 mg of fluoride per day for children under six months of age. EWG found that in 25 of the 28 largest cities in the U.S., at least 15% of formula-fed infants are exposed to excessive levels of fluoride, mostly from tap water used to make infant formula. For example, 61% of the formula-fed babies in Boston ingest too much fluoride. "Communities should move to reduce the fluoride concentration in drinking water to a level that will protect infants," says EWG Senior Vice President Richard Wiles.
Risks Are Still A Challenge
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Original article still on-line
The controversy about the risks of fluoride is unlikely to be resolved soon, a meeting held in late July strongly suggests.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.
FLUORIDE REALLY ALL THAT SAFE?
Original article still on-line
"The Fluoride Deception" reads like a whodunit. There are conspiracies, cover-ups, human casualties, and broken careers. The prime suspects in this toxic thriller are compounds of fluoride; the coconspirators represent industry, the military, and the public health community. At the book's ending, the suspect chemicals are not proven guilty beyond a reasonable doubt, but we are left with compelling evidence that powerful interests with high financial stakes have colluded to prematurely close honest discussion and investigation into fluoride toxicity.
Christopher Bryson has woven together an impressive body of evidence that brings into question the near universally held view in the medical and public health communities that fluoridation of public water supplies at current levels (about 1 ppm) is unambiguously safe and does not involve any serious health or environmental trade-offs. Bryson conducted extensive interviews, read many scientific papers, and burrowed through archival sources (there are more than 100 pages of reference notes) to make his argument that fluoride toxicity, even at the levels found in public water supplies, is not a closed case. Some private interests, he alleges, will seek to destroy careers to ensure that scientific studies that raise doubts about the safety of fluoride never get funded--or if they do, never get published.
Few people of prominence will stand up and contest the issue of the safety of fluoride compounds, Bryson claims. One exception is Arvid Carlsson, a Swedish pharmacologist who shared the 2000 Nobel Prize in Physiology or Medicine. In a postscript to the book, Carlsson writes: "Fluoride is a pharmacologically very active compound with an action on a variety of enzymes and tissues in the body already in low concentrations. In concentrations not far above those recommended it has overt toxic actions." Carlsson was one of the scientists who helped persuade the Swedish Parliament to ban fluoridation of drinking water in that country.
The book summarizes 50 years of fluoride uses in steel, aluminum, phosphate, gasoline, uranium enrichment, refrigerants, and plastics. Bryson shows how fluoride became the "lifeblood of the modern industrial economy." Notwithstanding fluoride's broad industrial applications, its airborne emissions, and its toxic by-products, the public's awareness of fluoride comes primarily from its uses in drinking water, toothpaste, and preadolescent fluoride treatments as a prophylaxis against dental cavities.
There are many resemblances between the history of fluoride regulation and that of other toxic substances. The exigencies of World War II blinded public health regulators to medical reports of occupational hazards from fluoride exposure in those industries where compounds of fluoride were used or produced. The U.S government did not take kindly to lawsuits filed by farmers for gaseous fluoride damage to their families, their cattle, and their crops, an unintended by-product of nuclear weapons facilities during the Manhattan Project. Postwar economic growth served as a convenient excuse to ignore evidence that communities were exposed to unhealthy levels of airborne fluoride emissions.
But what is distinguishable about fluoride politics is the connection between this ion and the prevention of dental cavities. Bryson shows us how fluoride's dental applications were skillfully used by corporate stakeholders in their campaign to derail more stringent air and occupational standards for industrial fluoride emissions. Similarly, defense lawyers exploited the positive side of fluoride to protect companies from worker-injury suits.
AS THE SAYING GOES in the public health community, adopting an antifluoridation position is a career breaker. This is illustrated in the book by the case of Phyllis Mullenix, a neurotoxicologist hired by the Forsyth Dental Center in Boston to investigate materials used in dentistry. Mullenix found evidence of fluoride neurotoxicity in experimental rats. Mullenix showed that with chronic exposure, the fluoride ion could cross the blood-brain barrier. Moreover, when fluoridated water was fed to pregnant rats, she found the offspring exhibited behavior resembling hyperactivity.
Mullenix recalls the response of a Forsyth administrator to her findings: "You are going against what the dentists and everybody have been publishing for 50 years, that this [fluoride] is safe and effective. You must be wrong. ... You are jeopardizing the entire support of this entire institution. If you publish these studies, NIDR [the National Institute of Dental Research] is not going to fund any more research at Forsyth." Her studies were published in Neurotoxicology & Teratology. But within days after the paper's acceptance, her contract with Forsyth was not renewed.
Bryson's investigations into fluoride science led him to a 1962 unpublished study conducted at Kettering Laboratory at the University of Cincinnati, which he found in the basement archive of the laboratory. An industry group contributed nearly half-a-million dollars for a series of toxicological studies that they believed would help them against worker claims of crippling skeletal fluorosis--thickening and fusing of spinal vertebrae.
In one of the key experiments, 42 beagle dogs were exposed to calcium fluoride dust for six hours a day, five days a week--simulating human occupational exposure. According to the results of the study, calcium fluoride damaged the lungs and lymph nodes of the dogs. If released, the study could have provided the critical evidence needed to raise the industrial standard on fluoride emission limitations.
"The Kettering data pointed an arrow directly at the heart of key modern industrial enterprises, where the extraordinary incidence of emphysema in workers potentially 'dwarfed' even the silicosis crisis of the 1930s," Bryston writes. He quotes one toxicologist who was given the long-suppressed study data, who said, "The fact that the Kettering data were not published or made available is a crime against American workers--with profound health consequences for the rest of the nation."
The positive spin of this unpublished report was that the university researchers did not manipulate the science to give the sponsors what they wanted to hear. Scientists refused to fudge the data or give the study a proindustry interpretation. However, there is also a negative spin. The academic investigator at the University of Cincinnati either chose not to or lacked the contractual rights to publish the results. According to Mullenix, "The Kettering Laboratory's long-ago suppression of the dog study helped to perpetuate a cover-up of fluoride's potential for harm as an air pollutant."
Even today there are no legal constraints against the suppression of scientific data from privately funded studies. Recently, New York State Attorney General Eliot Spitzer filed suit against a major pharmaceutical company, charging that it had suppressed clinical trial data that was valuable to the medical community on a drug used to treat adolescent depression. A small group of prominent journals have adopted a policy that they will not publish studies unless the authors affirm their control over the data and publication. Some members of the medical community are calling for a public database on clinical trials, so that data unfavorable to a sponsor will not be suppressed.
In 1993, the National Academy of Sciences (NAS) issued a report on the health effects of ingested fluoride. The study supported the Environmental Protection Agency's fluoride drinking water standard of 4 mg per L as an "interim standard." It recommended additional research on bone strength, bone fractures, and carcinogenicity. NAS began a second study on fluoride toxicity in November 2002 to review the new scientific literature, as the academy considers the aggregate exposure one can get from all sources of fluoride, including drinking water, food, toothpaste, and dental rinses.
Although most of the book focuses on inorganic fluoride salts, it concludes with an epilogue citing the potential dangers presented by another branch of fluorine compounds--perfluorocarbons. Used in products like Scotchguard and Teflon, these molecules come with their own set of reactivities and toxicities. EPA is taking formal action against DuPont for failing to report birth defects among babies born to female workers who were exposed to perfluorooctanoic acid, a chemical used in its manufacture of Teflon. So there is still plenty of life left in fluoride science and politics.
"The Fluoride Deception" will leave any open-minded readers feeling uneasy about the acceptable levels of fluoride in drinking water, as well as the cumulative sources from dental hygiene products. But the deeper lessons of this story, going back to classified military research during World War II, are the book's insights into the threats to open inquiry in public health and environmental science. Premature closure of debate in science undercuts one of its unique features--a feature that distinguishes it from other forms of fixing belief--namely, science's self-correcting function. Without a scientific culture that supports reexamination of "no risk" results, however strongly held, we may find our public health and environmental policies resting on weak or faulty foundations, which can prolong our blindness to preventable illnesses.
Sheldon Krimsky is a professor of urban and environmental policy and planning at Tufts University. He does science policy research and is the author of "Science in the Private Interest.
Fluoride Concerns Surface Once Again
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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.
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.
& Engineering News
& Engineering News
The controversy over fluoridation of water supplies has raged ever since fluoride was first introduced into the drinking water of Grand Rapids, Mich., in 1945. Proponents of fluoridation say it prevents tooth decay and presents absolutely no health risks. Detractors say it causes, or may cause, serious damage to the health of some people. Many also question its effectiveness. For 43 years, there seems to have been no middle ground between the two points of view. "Neither side has given the other one rational moment," explains Jacqueline M. Warren, senior staff attorney with the Natural Resources Defense Council.
U.S. policy makers have had to make other scientific decisions, such as choices about pesticide regulation, that involve the careful balancing of risks and benefits and about which information probably is even more complex. But none has aroused acrimony quite like the fluoridation question. There is hardly any individual interested in the issue who can be classified as neutral, hardly an expert in the field who seems not to be adamantly pro- or antifluoridation. Neither side seems willing to listen to the other. Neither seems able to engage the other in constructive debate.
On the surface this seems surprising. The goal of fluoridation is unarguably worthy. Since U.S. communities began fluoridation in 1945, the prevalence of dental caries has decreased dramatically. The average number of decayed, missing, and filled permanent teeth in U.S. school age children has declined from an estimated seven to about three, according to a national survey released by the National Institute of Dental Research (NIDR) in June.
Why, then, is this issue so polarized?
According to Edward Groth III, an associate technical director of Consumers Union who wrote his Ph.D. thesis in biology on the fluoridation controversy in 1973, pro- and antifluoridationists approach the issue from completely different perspectives. "Proponents see it as a simple public health measure, effective and safe, which they need to ‘sell’ to the public, almost like a box of soap. Opponents tend to be much more concerned with risks than with benefits, and view fluoridation the same way society views many other ‘environmental hazards’—granting that the risks may be small and uncertain, they believe society’s attitude should be ‘better safe than sorry. Since any risks fluoridation may present are imposed involuntarily when a water supply is fluoridated, those risks-even if they are tiny or unsubstantiated—tend to provoke a disproportionate amount of outrage."
Indeed, anyone looking closely at the fluoridation debate can discern several separate subdebates, most with more than two distinct positions. Regarding fluoridation’s benefits, proponents, such as the American Dental Association (ADA), claim it reduces the incidence of tooth decay 40 to 65% wherever it is used.
Many proponents also insist dogmatically that there is absolutely no evidence that fluoridation has had, or ever could have, harmful effects of any kind on anyone. Some argue that because most natural drinking water contains 0.1 to 0.2 ppm fluoride and nearly all food has traces of fluoride, human beings are adapted to it. For many years, they have also claimed that fluoridation may reduce the incidence and severity of osteoporosis-decreased bone density in old age. Other proponents admit there are a number of recognized potential risks, but they believe there has been enough research of good enough quality to show that these risks are very remote and that the large benefits justify society’s taking those risks.
For many opponents of fluoridation, the overriding issue is a moral one of personal rights. These critics oppose fluoridation for ethical reasons. They view it as a form of medication, imposed on the public in violation of individual choice. Given that there are several other ways for people who want fluoride to consume it (for instance, in pills, mouthwashes, toothpaste, fluoridated bottled water), those who place a high value on freedom of choice argue that the state has no right to force them to consume fluoride.
Other opponents of fluoridation claim that fluoridation causes cancer, birth defects, and a large number of other ills. Such claims are frequently made by unscientific activists, who cannot support them with scientific references. But here, too, there are other less extreme opponents who argue that research has not adequately answered most of the critical questions about potential risks. Such critics, many of whom are scientists, cite hundreds of papers published in reputable journals, a collectively large body of evidence of potential hazards that, at a minimum, demands objective assessment. From the start, they also have questioned the benefits of fluoridation, claiming that its effects on tooth decay are nonexistent or greatly exaggerated.
Yet another niche in the debate has lately been filled by environmentalists, who resist being called "antifluoridation" but whose arguments tend to support the opponents. In 1986, the Natural Resources Defense Council (NRDC), one of the U.S.’s pre-eminent environmental advocacy organizations, filed a lawsuit against the Environmental Protection Agency (EPA), seeking to block the agency’s proposed relaxation of drinking water standards for fluoride in natural waters. NRDC argued that EPA had inadequately considered the likely effects of fluoride on susceptible subsets of the overall population, had over looked a great deal of scientific literature that suggested possible harm, and had not adequately evaluated a full range of possible hazards on which the evidence is incomplete or unconvincing. At best, NRDC asserted, EPA had no scientific basis for its action and more research is needed.
In general, environmental advocates believe fluoride should be investigated in the same manner many other environmental pollutants have been studied in recent years. The range of total human intake from air, water, and food must be assessed, they say’. The effects on the most susceptible individuals and the levels at which these effects begin to occur should be determined. Extensive epidemiological studies should be done to see if fluoride is causing cancer or any other more subtle health effects in the general population.
Very little of the research advocated by the environmentalists has ever been done in this country and not much of it has been done anywhere else either. Since the early 1960s, most studies on the long-term effects of chronic exposure to fluoride on human biological systems other than teeth have been carried out in foreign countries.
Current status of fluoridation
Fluoridation of water supplies is largely confined to the English-speaking countries, the Soviet Union, and some Latin American nations. Of the estimated 250 million people in the world who drink artificially fluoridated water (usually fluoridated at 1 ppm), 120 million live in the U.S. (50% of the U.S. population), about 50 million in Brazil (33% of its population), and 40 million in the Soviet Union (15% of its population). Nine percent of the U.K.’s population drinks fluoridated water, two thirds of Australia’s and New Zealand’s, and 50% of Canada’s. However, less than 1% of the population of continental Western Europe has artificially fluoridated water. For 10 years, the Netherlands tried fluoridation and gave it up in 1976 for legal reasons. (Many citizens claimed that the government had no right to add fluoride, which they considered a medicine, to the water supply, and a number of doctors observed strong hypersensitivity reactions to fluoridated water in some people.) It also was tried and then abandoned in a few towns in West Germany for legal and health reasons.
In the U.S., fluoridation is endorsed almost universally by medical and dental associations and by many scientific bodies. The American Medical Association, ADA, the U.S. Public Health Service (PHS), and every Surgeon General since the early 1950s have agreed that water fluoridated at levels of about 1 ppm is a cheap, effective, and perfectly safe way to reduce cavities.
Outside the U.S., a number of scientific groups and individuals have decided fluoridation is not safe. In France, the Chief Council of Public Health rejected fluoridation in 1980 because of doubts about whether it harms human health. The minister for the environment in Denmark recommended in 1977 that fluoridation not be allowed primarily because no adequate studies had been carried out on its long-term effects on human organ systems other than teeth and because not enough studies had been done on the effects of fluoride discharges on freshwater ecosystems. In 1978, the West German Association of Gas & Water Experts rejected fluoridation for legal reasons and because "the so-called optimal fluoride concentration of 1 mg per L is close to the dose at which long-term damage [to the human body] is to be expected."
The battle lines between pro- and antifluoridationists in the U.S. used to be very clear, with the medical and dental establishment and a great many public health officials and scientists on one side and a number of other scientists, private citizens, and members of extreme right wing groups (such as the John Birch Society and the Ku Klux Klan, who claimed fluoridation was a communist plot) on the other. Most of those who spoke out against fluoridation were, according to profluoridationists, either members of one of these radical groups or irrational, fanatic, unscientific, and fraudulent, even if they had legitimate scientific credentials.
Now, however, the lines are not so clearly drawn. Zev Remba, the Washington Bureau editor of AGD Impact, the publication of the Academy of General Dentistry (a group of 28,000 dentists dedicated to promoting the continuing education of general practitioners), described the situation in an editorial last year: "Today ... the antifluoridation movement has found supporters on the left as well as the right, particularly among groups dedicated to safeguarding the environment. And as the base of support broadens, community fluoridation appears to be losing ground. In about 60% of 2000 referenda held in the U.S. since 1950, fluoridation has been voted down. A 1985 poll by the American Dental Association found that 36% of the 255 [planned or existing] fluoridation programs surveyed had been cancelled," primarily because they were rejected in referenda.
Last year, the Commissioner for the Department of Health in New York State, David Axelrod, decided to turn the department’s emphasis away from fluoridation of water supplies and toward the use of topical sealants and fluoride rinses for school children. The department is still in favor of fluoridating water supplies, but is no longer funding it.
Even now fluoridation remains an issue in many cities across the U.S. Since 1983, referenda have been held on the question in well over 60 communities. In more than half of these, the majority of the people voted against fluoridation. Some referenda are held in cities without fluoridation in order to decide whether to initiate it. Others are called by opponents of fluoridation in cities where it already exists in order to terminate it. ADA and NIDR carry on a continuous campaign to persuade state legislatures to pass laws making fluoridation mandatory in all communities. So far only eight states have passed such laws, but dozens of proposed similar laws have been defeated.
Fluoridation is becoming more of an issue in developing nations as their tooth decay rates rise with the increasing use of sugar and processed food. Countries such as Brazil are now deciding whether to expand fluoridation or initiate it. In May, an international conference was held in Porto Alegre, Brazil, to assess the benefits and risks of fluoridation and help the authorities evaluate the question.
If more diverse interest groups are increasingly skeptical of fluoridation, what are the reasons? Is fluoridation just as effective as it appeared to be in the past? Have scientists uncovered new evidence of real health risks?
Benefits: a changing assessment
Originally, it was thought that the fluoride ion prevented tooth decay solely by being incorporated in tooth enamel as the teeth formed in childhood. Fluoride ingested in water or food is absorbed into the bloodstream. Part of it is excreted and the remainder is deposited in the bones and teeth. The proportion of fluoroapatite in the hydroxyapatite of developing tooth enamel is then increased:
Ca10(PO4)6(OH)2 + 2F- ‡ Ca10(PO4)6F2 + 2OH-
Fluoroapatite is less easily dissolved by mouth acids than hydroxyapatite and therefore more resistant to decay.
But today dental researchers believe two other mechanisms are just as important or more so. A number of factors, including fluoride ion, influence a constant exchange of ions across tooth surfaces. Bacteria in the mouth convert sugar to acids, which cause demineralization of tooth surfaces. Demineralization and remineralization take place constantly on the surface. When the pH of the surface drops, calcium and phosphate ions pass from the enamel into the plaque, but if the pH becomes neutral, these ions may redeposit themselves into the enamel. Fluoride ions in the plaque inhibit the bacterial conversion of sugar to acids and thereby help maintain higher pH levels, allowing remineralization to occur. Therefore, the fluoride ions in saliva and plaque may be just as important in preventing tooth decay as the ions in blood-and perhaps just as easily provided by toothpaste as water.
A third mechanism by which fluoride may prevent decay involves incorporation of fluoride into the remineralizing enamel surface, making it more resistant to decay.
For many years, most dentists believed that fluoridation of water supplies reduced tooth decay about 50 to 65%. These figures were based primarily on four studies during the early years of fluoridation: in Grand Rapids, Mich.; Newburgh. N.Y.; Evanston, Ill.; and Brantford, Ont. But a great deal of evidence indicates that water fluoridation reduces dental caries much less. In fact, some research suggests little or no reduction at all.
Alan S. Gray, former director of the Division of Dental Health Services for the British Columbia Ministry of Health, finds, for example, that the average number of decayed, missing, and filled permanent teeth in British Columbia, where only 11% of the population uses fluoridated water, is lower than in parts of Canada where 40 to 70% of the people drink fluoridated water. School districts in the province with the highest percentage of children with no tooth decay are totally unfluoridated. These differences could, of course, be caused by factors other than fluoridation.
Tooth decay is a complicated process, influenced by many factors, including diet, oral hygiene, dental care, genetic predisposition, geochemical factors, and possibly other trace elements, such as strontium, as well as fluoride in the water supply. Additional factors that may affect decay rates are the use of fluoridated toothpastes or topical rinses and the presence of fluorides in foods. Most people whose diet includes little sugar and few processed foods have very low rates of tooth decay. In those few developing countries in which only small amounts of sucrose and refined foods are eaten, decay rates are often lower than in the developed nations. And if other factors are equal, districts in the developed world where the socioeconomic status is higher generally have less decay.
Therefore, comparisons between fluoridated and unfluoridated districts that don’t adequately take such factors into account can be readily confounded. None of the early epidemiological studies controlled very well for most nonfluoride variables, so many scientists today have come to regard them as only part of the evidence one must consider to assess the size of fluoridation’s benefits.
One recent development that bears on the question is the widespread observation that tooth decay rates in the U.S., Canada, New Zealand, Australia, and in all countries of Western Europe have declined greatly during the past 40 years. Mark Diesendorf, an applied mathematician and health researcher in the Human Sciences Program at Australian National University and an expert in research design, has found, by comparing results from about 24 studies of unfluoridated districts in eight countries, that reductions in dental caries are just as great in nonfluoridated as in fluoridated areas. In Queensland, which is primarily unfluoridated, the rate of tooth decay is as low’ as it is in the fluoridated districts of Australia.
Diesendorf concludes from such data that fluoridation of water supplies may not be nearly so important in preventing tooth decay as many authorities believe. Some of the decline in dental caries in unfluoridated areas might be explained by the introduction of fluoride toothpaste. tablets, and mouthrinses, he says, but decay rates began to fall in many of the nonfluoridated regions long before these were available. He believes that changes in nutrition, oral hygiene, and possibly the immune status of the population may explain part of the decline.
A number of researchers in the U.S. have reported similar findings. Stanley B. Heifetz and coworkers at NIDR note in the April issue of the Journal of the American Dental Association that "the current reported decline in caries in the U.S. and other Western industrialized countries has been observed in both fluoridated and nonfluoridated communities, with percentage reductions in each community apparently about the same."
Robert L. Glass of Forsyth Dental Center, Boston, noted that in 1965, after more than 20 years of fluoridation, counts of decayed, missing, and filled permanent teeth for Grand Rapids, Mich., and Newburgh, N.Y., were only minimally different from the average for the entire U.S., which then was about 33%.. fluoridated. Because he had expected nonfluoridated areas to have higher decay rates than fluoridated ones, and to therefore raise the average for the entire U.S., he concluded that the U.S. average had not been determined correctly. It is also plausible, however, that the effects of fluoridation had been overstated, or perhaps that Grand Rapids and Newburgh had exceptionally high levels of decay before fluoridation began.
Other recent reports indicate that fluoridated areas have lower decay rates than unfluoridated areas, but by much less than the alleged 50 to 60% difference. A 1983 study of tooth decay in 10 cities by the Robert Wood Johnson Foundation and Rand Corp. found that fluoridated cities have roughly one third less decay, which means that average 12-year-olds in fluoridated cities have about 0.6 fewer cavities than those in nonfluoridated cities. Gray points out that decay reductions of even 33%. taking place today, when average base decay rates are at such a historically low level, do not mean as much as they did in the past.
Research conducted in the 1930s and 1940s in the U.S. showed that the incidence of dental caries was reduced most effectively where the natural fluoride level of the water supply was 1 ppm or above. But five studies in India, Sweden, Japan, the U.S., and New Zealand do not support this trend. In the Japanese study, for example, children in an area with 0.3 to 0.4 ppm fluoride in the water have the lowest decay rates; above and below this range, caries prevalence increases rapidly. These results contradict a central tenet of the fluoridation theory-that the ideal fluoride level, producing low decay rates with minimal damage to the teeth, is about 1 ppm.
At NIDR, officials are reassessing the decay reductions that can be attributed to fluoridated water. Herschel S. Horowitz, formerly chief of the clinical trials section of the caries prevention and research program, says that recent studies suggest that reductions are not so large as the 50 to 60% indicated by early studies. NIDR scientists are trying to determine what they call a "new baseline." Whatever the ultimate result, a consensus seems to have emerged that the promise of "two thirds less tooth decay" with fluoridation is no longer realistic, if indeed it ever was.
In a similar vein, the economic benefits of fluoridation appear to have been exaggerated. NIDR states that every dollar spent on fluoridation, which costs only 20 to 50 cents per person per year, reduces dental costs $50. NIDR assumes that fluoridation reduces cavities some fixed percent, such as 40%, and then multiplies the total number of cavities theoretically prevented by the average cost of filling one cavity. But when the actual costs of dental care delivered in similar cities are compared, residents of fluoridated cities seem to reap no economic benefit from fluoridation. In one study, reported in a February 1972 article in the Journal of the American Dental Association, the cost of dental care in five unfluoridated cities in Illinois was compared with costs in five similar cities with naturally fluoridated water. Even though dentists’ fees and the nature of treatments in the two groups of cities did not differ significantly, the cost per patient and the average number of visits to the dentist per year were greater in the fluoridated communities.
Proponents also are trying to show that fluoride can be used to alleviate the symptoms of osteoporosis, and therefore that people living in fluoridated areas may be helped by the excess fluoride they are accumulating in their bones. Because excess fluoride produces osteosclerosis (denser bones), patients in numerous clinical trials have been given and are still being given large doses of fluoride (60 to 80 mg per day) as treatment for osteoporosis. So far this method has produced no definitive beneficial results. In a 1987 review of fluoride therapy for osteoporosis, Louis V. Avioli, professor at the Washington University School of Medicine, concludes: "Sodium fluoride therapy is accompanied by so many medical complications and side effects that it is hardly worth exploring in depth as a therapeutic mode for postmenopausal osteoporosis, since it fails to decrease the propensity toward hip fractures and increases the incidence of stress fractures in the extremities." FDA has not approved the use of fluoride for osteoporosis.
Health risks: more questions than answers
The physiological effects of fluoride on the human body range from those about which there is a great deal of scientific information to those that are less certain, but about which there is some credible evidence, to those that are almost purely speculative. Even the effects for which there is good information are controversial. Some scientists define them as health effects, but others consider them as merely cosmetic or conditions without negative implications for health.
More than any other area of fluoride research, scientific debate over potential health hazards has been polarized by the political controversy over fluoridation. Does a study show adverse effects? Is certain evidence relevant to an assessment of the safety of fluoridation at 1 ppm? The answers experts give differ, depending on whether the experts favor or oppose fluoridation. The political schism over the measure has dominated scientific discourse on the topic, almost totally blocking consensus over what the evidence of adverse effects means-or in some cases, even over whether such evidence exists.
The effects of fluoridation that have been studied the most are dental fluorosis (mottling of teeth), skeletal fluorosis, kidney disease, hypersensitivity reactions, enzyme effects, genetic mutations, birth defects, and cancer. The information about dental fluorosis is clearest and least controversial. Knowledge of skeletal fluorosis is extensive, but not at all complete. The information about fluoride and kidneys is partly established and, in part, almost purely speculative owing to a lack of research. Hypersensitivity reactions have been studied thoroughly by only a few investigators and many important issues remain unresolved. Birth defects and cancer have been much discussed, but evidence in these areas is the most uncertain.
Though profluoridation statements almost always claim that all risks have been fully investigated and found to be groundless, in fact a number of important unanswered questions remain about each of these health risk areas. The 1977 National Academy of Sciences report "Drinking Water and Health" recommends research in 11 different areas. Even though more than a decade has passed, research in only three health effects areas, dental fluorosis, cancer, and birth defects, has been funded by the federal agencies responsible for research on fluoride (PHS and EPA).
The fluoride ion is unusual among trace elements in water or food because the same range of human exposure to fluoride ion that can produce beneficial physiological effects can also produce harmful effects. For most trace elements, such as chromium, manganese, and zinc, beneficial and harmful ranges of exposure differ greatly.
In 1962, PHS set fluoride levels of 0.7 to 1.2 ppm in drinking water as the ideal range to prevent dental caries with minimal dental fluorosis. The tower level was suggested for hot climates and progressively higher levels were prescribed for cooler regions, because average water consumption varies with temperature. Natural fluoride levels exceeding twice the ideal for the climate, PHS said, constituted grounds for rejection of the water supply, but it had no power to force communities to remove excess fluoride.
In 1975, EPA took over PHS’s responsibility for regulating contaminants in drinking water and, in 1986, relaxed the maximum contaminant level to 4 ppm for all climates. Communities that add fluoride to drinking water still do so according to the old PHS formula. But communities with naturally fluoridated water are not required to remove fluoride unless the level exceeds 4 ppm. Some of the potential adverse health effects, however, may occur at levels of about 1 ppm and above and are both more pronounced and more widespread at levels near 4 ppm.
In humans, 98%. of the fluoride ingested in water is absorbed into the blood from the gastrointestinal tract. The fluoride diffuses to the body’s cellular tissues and most of it is deposited in the bones and teeth or excreted by the kidneys. The aorta is the only other tissue that normally accumulates significant amounts of fluoride, mainly in calcified deposits. The amount stored in bones and teeth varies depending on the age of the subject. According to NIDR’s Heifetz and Horowitz, in children more than 50% of an ingested dose of fluoride may be deposited in bone, but in adults only about 10% is stored there. As with teeth, fluoride is deposited in bone by simple ionic exchange with the hydroxyl groups of hydroxyapatite. It also is removed from bone, though at a slower rate than it is deposited. If the intake remains constant, the level of fluoride in the bones increases linearly with age.
The most obvious and common effect of fluoride on humans is dental fluorosis. This occurs only if children drink fluoridated water, receive fluoride supplements, or ingest significant fluoride from other sources (like toothpaste) during the years of tooth formation. In excessive amounts, fluoride interferes with the normal function of the enamel-producing cells in the jaw, called ameloblasts, in laying down amelogen matrix and in the mineralization of this enamel matrix. (Amelogen is a collagenlike material that forms the structural foundation and framework upon which calcium and phosphate are deposited, giving rise to tooth enamel.)
The late H. Trendley Dean, a dental surgeon at PHS, defined five degrees of dental fluorosis: questionable, very mild, mild, moderate, and severe. In the questionable form, evidence of fluorosis is uncertain; in the very mild form, teeth have small white specks; in the mild form, teeth have chalky white areas; in the moderate form, they may have yellowand brown stains; in the severe form, depending on the amount of fluoride ingested, they are pitted, brittle, and susceptible to fracture. Severe fluorosis not only produces unattractive teeth but also may increase the risk of tooth loss because it destroys parts of the protective enamel.
According to a recent study conducted by NIDR in areas with different concentrations of naturally occurring fluoride in their water supplies, 2% of the children developed moderate or severe fluorosis and about 12% developed very mild and mild fluorosis at 1 ppm-the level of fluoride that NIDR considers ideal. But at 4 ppm, the maximum fluoride level EPA now allows in the U.S., 7%, had moderate and 23% severe dental fluorosis (approximately the same total fraction of objectionable fluorosis Dean noted in the 1930s in 4-ppm areas). Since this study was very limited, the percents of fluorosis may not be representative of the country as a whole.
But if the fraction of children subject to moderate and severe dental fluorosis is anywhere near 1 or 2% in most areas with 1 ppm fluoride, a great many children are at risk of developing disfiguring degrees of fluorosis, And, of course, a large fraction of children in the 4-ppm areas would develop noticeable fluorosis. To avoid dental fluorosis, "children under five years of age should drink water diluted with a fluoride-free source in communities with 4 ppm fluoride," NIDR’s Horowitz says.
There seems to be little controversy over what levels of fluoride in water cause moderate and severe dental fluorosis. Scientists disagree, however, about whether moderate to severe dental fluorosis is a health effect. This may seem like an academic issue, but under the Safe Drinking Water Act, EPA is required to set recommended maximum contaminant levels (RMCLs) that will prevent known or anticipated adverse health effects with an adequate margin of safety and to set the maximum contaminant levels as close to the RMCLs as is feasible. (The RMCLs are unenforceable goals; the maximum contaminant levels are enforceable standards.) A special committee convened by the Surgeon General in 1983 to guide EPA in setting its fluoride standard wrote in the first draft of its report that moderate to severe dental fluorosis per se is a health effect. The second draft, presented to the Surgeon General in September 1983, said that moderate to severe dental fluorosis is only a cosmetic effect-the position long held by political advocates of fluoridation. This rationale allowed EPA to ignore dental fluorosis in setting the RMCL for fluoride.
One solidly established concept in environmental health is that the effects of toxic agents fall on a continuum of biological change, ranging from undetectable effects at the lowest levels of exposure to severe health damage at very high doses. As exposure to an agent increases, the first detectable effect may be a subtle biochemical change, such as a decrease in the activity of an enzyme. At somewhat higher doses, measurable changes in some physiological functions may occur, but these often are not linked to clear symptoms or adverse effects, and may not be harmful. But as dosage increases, adverse effects begin to appear-at first mild ones, then moderate ones, and finally severe ones.
Most environmental health experts believe that the subtlest detectable effects-those with no outward symptoms, which are not clearly harmful-should be considered "precursors" of more serious effects. By this logic, people who show such subtle changes should be considered at risk for more serious effects if exposure continues.
Skeletal fluorosis, a complicated illness caused by the accumulation of too much fluoride in the bones, has a number of stages. The first two stages are preclinical-that is, the patient feels no symptoms but changes have taken place in the body. In the first preclinical stage, biochemical abnormalities occur in the blood and in bone composition; in the second, histological changes can be observed in the bone in biopsies. Some experts call these changes harmful because they are precursors of more serious conditions. Others say they are harmless.
In the early clinical stage of skeletal fluorosis, symptoms include pains in the bones and joints; sensations of burning, pricking, and tingling in the limbs; muscle weakness; chronic fatigue; and gastrointestinal disorders and reduced appetite. During this phase, changes in the pelvis and spinal column can be detected on x-rays. The bone has both a more prominent and more blurred structure.
In the second clinical stage, pains in the bones become constant and some of the ligaments begin to calcify. Osteoporosis may occur in the long bones, and early symptoms of osteosclerosis (a condition in which the bones become more dense and have abnormal crystalline structure) are present. Bony spurs may also appear on the limb bones, especially around the knee, the elbow, and on the surface of tibia and ulna.
In advanced skeletal fluorosis, called crippling skeletal fluorosis, the extremities become weak and moving the joints is difficult. The vertebrae partially fuse together, crippling the patient.
Most experts in skeletal fluorosis agree that ingestion of 20 mg of fluoride a day for 20 years or more can cause crippling skeletal fluorosis. Doses as low as 2 to 5 mg per day can cause the preclinical and earlier clinical stages.
The situation is complicated because the risk of skeletal fluorosis depends on more than the level of fluoride in the water. It also depends on nutritional status, intake of vitamin D and protein, absolute amount of calcium and ratio of calcium to magnesium in drinking water, and other factors.
In parts of India, China, Africa, Japan, and the Middle Fast, large numbers of people have skeletal fluorosis from drinking naturally fluoridated water. In India about a million people have this disease. Most of the victims live in areas where the water fluoride level is 2 ppm or above, but some cases are found in communities with natural fluoride levels below 1 ppm.
In the U.S., more than a dozen cases of skeletal fluorosis have been reported. Some have occurred at high fluoride levels, others at levels lower than 4 ppm when aggravating conditions were present, such as diabetes or impaired kidney function.
In setting the recommended maximum contaminant level for fluoride in drinking water in 1986, EPA considered only crippling skeletal fluorosis as a health effect and established little or no margin of safety, even for this disease. (A margin of safety is a difference between the maximum contaminant level and the level at which health effects first occur in the most susceptible individuals.) According to a Department of Agriculture survey, about 3% of the U.S. population drinks 4 L or more or water per day. Therefore, about 3 % of the people who live in areas where the water contains the natural fluoride level of 4 ppm allowed by EPA -- such as certain communities in Texas or South Carolina -- are ingesting at least 16 mg of fluoride a day, not including the fluoride they derive from other sources, such as toothpaste, food, or air.
Also, because a more or less constant percent of intake is accumulated in bone, persons who consume 8 mg a day for 50 years accumulate about the same amount of fluoride in their bones as those who consume 20 mg a day for 20 years. Therefore, for people who drink 2 L or more per day of water with 4 ppm fluoride throughout their lives, there appears to be no margin of safety even for crippling fluorosis. In its regulations for most other drinking water contaminants, EPA has included safety factors of 10 to 100 and has calculated intakes in terms of a lifetime—that is, 70 years instead of 20.
Joseph A. Cotruvo, director of the criteria and standards division
of EPA’s Office of Drinking Water, says the fact that so few people
in the U.S. have actually developed crippling skeletal fluorosis
indicates that fluoride levels found in U.S. water are safe and
that there is therefore an observed margin of safety. But critics
of EPA’s standard speculate that there probably have been many more
cases of fluorosis-even crippling fluorosis-than the few reported
in the literature because most doctors in the U.S. have not studied
the disease and do not know how to diagnose it.
Those who ingest much less than 20 mg of fluoride per day may still be at risk of developing less severe stages of skeletal fluorosis, such as preclinical forms or the subcrippling clinical stages. In its final report, the Surgeon General’s panel said that radiologic changes have been found in bone when fluoride exposure has been about 5 mg per day. Nearly all of those drinking water containing 4 ppm of fluoride and about 3% of the more than 124 million people whose water contains only 1 ppm would have intakes as high as this. It is not known, however, what fraction of those with low-level radiologic changes would suffer joint pains or other clinically obvious adverse health effects. In his landmark study of skeletal fluorosis in cryolite workers in the 1930s, the Danish scientist Kaj Roholm found that some of those with stage I of clinical skeletal fluorosis suffered joint pains and stiffness.
Although skeletal fluorosis has been studied intensely in other countries for more than 40 years, virtually no research has been done in the U.S. to determine how many people are afflicted with the earlier stages of the disease, particularly the preclinical stages. Because some of the clinical symptoms mimic arthritis, the first two clinical phases of skeletal fluorosis could be easily misdiagnosed. Skeletal fluorosis is not even discussed in most medical texts under the effects of fluoride; indeed, a number of texts say the condition is almost nonexistent in the U.S. Even if a doctor is aware of the disease, the early stages are difficult to diagnose.
The possibility that fluoride might cause skeletal abnormalities in children’s bones is of particular concern. In its April 1983 draft report, the Surgeon General’s committee wrote that moderate and severe dental fluorosis in children may be accompanied by skeletal changes. Although this statement was omitted from the final report in September 1983, the committee did urge more research into the skeletal effects of fluoride, particularly in children. It wrote: "The effects of various levels of fluoride intake on rapidly developing bone in young children are not well understood. Also, the modifying effects of total intake, length of exposure, other nutritional factors, and debilitating illness are not well understood." Since the committee’s report was written, PHS and EPA have undertaken no research in this area.
PHS has conducted several studies that it claims show that fluoride levels found in U.S. water supplies have had no clearly adverse effects on bones. But the majority of these studies either included a study population too small to detect rare effects or excluded people who would be most likely to suffer from skeletal fluorosis, such as those with kidney disease.
EPA’s approach to subtle, preclinical effects of fluoride on the skeleton differs from its usual approach to other environmental agents. For instance, when EPA assessed the health hazards of lead, it made an extraordinary effort to connect the observable effects of low-level exposure (inhibition of certain blood enzymes) with the known adverse effects of slightly higher exposure (decreased synthesis of hemoglobin, anemia, and possible neurotoxic effects). When it set its standard for lead in air, EPA argued that to prevent more serious effects, it needed to limit the more subtle biochemical changes that lead was provoking in millions of children.
By contrast, EPA’s assessment of fluoride in water took an almost opposite tack. By defining the most severe known hazard, crippling skeletal fluorosis, as the only effect it was concerned with preventing, EPA dismissed all degrees of fluoride-induced changes in bones less drastic than crippling fluorosis as not being health concerns.
Because fluoride causes denser bones (osteosclerosis), a number of researchers have compared fluoridated and nonfluoridated areas to see if the incidence and severity of osteoporosis is lower in fluoridated areas. A small number of studies in the past 25 years have reported a lower incidence of hip fractures in areas with fluoridated water, compared with nearby areas with low-fluoride water. For example. a recent report, comparing two towns in Finland, prompted widespread media stories that fluoridation is beneficial to the bones of the elderly, as well as to teeth. But a larger number of well-designed studies have found no evidence of a beneficial effect on osteoporosis. However, some of the profluoridation literature states as a fact that fluoridation will help prevent osteoporosis.
Two areas are of concern in regard to fluoride and kidneys. First, a fairly substantial body of research indicates that people with kidney dysfunction are at increased risk of developing some degree of skeletal fluorosis. Second, a small and inconclusive amount of research suggests that fluoride may actually cause or aggravate kidney disease.
D. Raja Reddy of the Gandhi Medical College in India claims, for example, that "patients suffering from chronic kidney diseases and those with transplanted kidneys do excrete fluoride, though in small quantities, but they are more vulnerable to osteofluorosis and even neurological complications than others." In its final report, the Surgeon General’s 1983 committee notes, "As renal function declines, due either to diseases or with aging, plasma and bone fluoride content both increase."
The National Kidney Foundation in its "Position Paper on Fluoridation-1980" also expresses concern about fluoride retention in kidney patients. It cautions doctors "to monitor the fluoride intake of patients with chronic renal impairment, but stops short of recommending the use of fluoride-free drinking water for all patients with kidney disease. It does recommend, however, that dialysis patients use fluoride-free water for their treatments.
Studies show that children with moderately impaired renal function (such as those who have diabetes insipidus), are at some risk of skeletal changes from consumption of fluoridated water, even if the fluoride level is no higher than 1 ppm. A number of researchers have found high concentrations of fluoride in the bones of patients who suffer from kidney disease and have found symptoms of skeletal fluorosis in some of these patients. However, there has been no systematic survey of people with impaired kidney function to determine how many actually suffer a degree of skeletal fluorosis that is clearly detrimental to their health.
Several animal studies suggest that fluoride may have direct adverse effects on the kidneys. For instance, cytological and enzyme changes have been found in the kidneys of squirrel monkeys drinking water with 5 ppm fluoride. It is not known how the changes affect kidney function in monkeys, nor is it known whether humans would suffer similar changes from relatively low levels of fluoride in drinking water. Impaired renal function, however, has been reported to be more common in areas of endemic skeletal fluorosis.
Just as a few people react idiosyncratically to almost anything, some people may have adverse reactions to fluoride whether contained in pills or water. Some individuals seem to be hypersensitive to fluoride pills or drops containing 1 mg or less as well as to fluoride toothpaste. The 1983 edition of the "Physicians Desk Reference" states: "In hypersensitive individuals, fluorides occasionally cause skin eruptions, such as atopic dermatitis, eczema, or urticaria. Gastric distress, headache, and weakness have also been reported. These hypersensitivity reactions usually disappear promptly after discontinuation of the fluoride." (This information was omitted from later editions of the reference.)
Many of those who agree that some people are hypersensitive to fluoride pills, drops, or mouth rinses deny that anyone could be hypersensitive to fluoridated water, even though just as much or more fluoride is contained in an average person’s daily intake of such water (the average water intake of 1 to 2 L has 1 to 2 mg of fluoride) as is contained in the standard pills (0.5 to 1 mg).
Some doctors call such hypersensitive reactions allergies. The American Academy of Allergy. however, defines allergies very narrowly-"quantitatively abnormal responses mediated by specific immunologic mechanisms, and therefore by specific antibodies or by certain sensitized cells (lymphocytes)." According to this definition, the academy says. allergies to fluorides do not exist.
Hans Moolenburgh, a Dutch physician who has studied hypersensitive reactions to fluoride, believes the reactions can be explained as effects of a toxic agent rather than as allergies. In large doses, everyone reacts to fluoride. A small fraction of the population, he says, reacts to much lower levels of fluoride.
The late George L. Waldbott, founder and chief of allergy clinics in four Detroit hospitals and noted antifluoridation activist and author, reported treating at least 500 patients who he concluded reacted negatively to fluoridated water. The symptoms included muscular weakness, chronic fatigue, excessive thirst, headaches, skin rashes, joint pains, digestive upsets, tingling in the extremities, and loss of mental acuity. Waldbott used double-blind tests to determine whether fluoride was the cause of symptoms in many of his cases. In each of these patients, the symptoms disappeared when the fluoride was taken away without the patient’s knowledge and reappeared when it was given again, but not with the administration of other possible agents.
Other investigators have reported similar cases. Reuben Feltman and George Kosel. then researchers at Passaic General Hospital in New Jersey, found that 1% of their subjects. who were children and pregnant women, reacted adversely to daily pills containing 1.0 to 1.2 mg of fluoride. The reactions, which affected the skin and gastrointestinal and nervous systems, disappeared when the fluoride was discontinued without the patients’ knowledge.
Moolenburgh, G. W. Grimbergen, and a number of other Dutch doctors performed double-blind experiments on patients who became ill after fluoridation began in the Netherlands. By using coded bottles of drinking water, some fluoridated and some not, the physicians showed that the symptoms were caused by fluoride, rather than some other factor.
Moreover, a report by the British Royal College of Physicians states that some patients receiving 9 mg of fluoride per day for osteoporosis suffered adverse side effects. This is about the same intake some would have in areas where the water fluoride level is 2 ppm.
Because the number of studies has been small, it is not known with certainty what fraction of the population may be hypersensitive to fluoride. Since all of the reported symptoms can be caused by other factors, reactions to fluoride could go undiagnosed unless a physician was looking specifically for fluoride sensitivity.
Enzyme and mutagenic effects
Sodium fluoride is used in many in-vitro studies to block the action of enzymes. in part because it can interfere with so many different enzymes.
One way the fluoride ion serves as an enzyme inhibitor in the lab is by acting on the GTP-binding proteins (or G-proteins). Fluoride ion also may disrupt enzymes by forming strong hydrogen bonds with amides. Fluoride switches off an enzyme by attacking its weakest links-the delicately balanced network of hydrogen bonds surrounding the active site. In some enzymes, the fluoride ion attaches itself to the atom at the heart of the enzyme and then disrupts the active site by attracting groups that can form strong hydrogen bonds to itself. Eventually, this inactivates the enzyme by changing its molecular conformation.
Because enzymes mediate most of the biochemical processes essential to life, any environmental agent that can affect a wide range of enzymes could, at least In theory, have a wide variety of effects on an organism’s health. For that reason alone, potential effects of fluoride on enzymes are of great interest. In addition, as has been discussed earlier, effects on enzymes are often the first detectable biological changes produced In an organism exposed to a toxic agent, just as enzyme changes in the heme biosynthetic pathway precede the onset of lead-induced anemia, Detailed knowledge of fluoride’s effects on a number of human enzymes could lead to an array of sensitive tests for the earliest signs of possible harm from excessive intake of this element and more precise identification of individuals who are at risk.
Studies on enzyme preparations in test tubes. however, don’t necessarily predict what will happen in living humans. In at least 11 in-vivo animal studies, fluoride has been shown to influence enzyme activity. In some tests, enzyme activity was depressed; in others, it was stimulated, In addition, one study indicates a transient decrease in human serum enzyme activity associated with the advent of water fluoridation. But there have been few other studies to measure the effects of typical levels of fluoride intake on enzyme activity in people.
Some scientists believe that interference with enzyme activity is the major mechanism by which fluoride exerts physiological effects. Certain changes in enzyme activity can be minor, easily repaired by the body. But others could be the first signs of more serious alterations that would take place with continued exposure to fluoride.
Just as the fluoride ion may disrupt enzymes with its ability to form strong hydrogen bonds, it may also disrupt DNA by interfering with its hydrogen bonding. The evidence for this mechanism consists of theoretical calculations, however, and some scientists, such as George R. Martin, chief of the laboratory of developmental biology and anomalies at NIDR, do not find it at all convincing.
A great many lab tests have been performed to measure the possible mutagenicity of the fluoride ion. The results are contradictory and often very confusing. Some of the positive mutagenicity tests involve very high concentrations of fluoride ion, so high that they would not be found anywhere in the human body. Others involve levels comparable to those in drinking water. However, the important consideration is not fluoride levels found in drinking water, but levels found in the human body. Geoffrey E. Smith, dental surgeon from Melbourne, Australia, says that when bones lose fluoride, localized high concentrations may result.
For example, in 1982, Aly H. Mohamed and Mary E. Chandler of the University of Missouri in Kansas City reported that 1 to 200 ppm fluoride in drinking water induced changes in a dose-dependent manner in bone marrow cell chromosomes and spermatocytes of living mice. In 1978, Danuta Jachimczak of the Pomeranian Medical Academy in Szezecin, Poland, showed that fluoride levels as low as 1 ppm caused changes in the chromosomes of human leukocytes in vitro.
Even if all the mutagenicity tests were positive, this would not prove fluoride is a mutagen in humans. But scientists consider a chemical a more likely mutagen if several types of lab tests are positive
John R. Bucher of the National Institute of Environmental Health Sciences says that tests in his lab show sodium fluoride mutagenic for cultured lymphoma cells derived from mice. He notes that a number of similar studies have been published by other investigators. Because most carcinogens are also mutagens, evidence of mutagenicity also bears on the issue of fluoride’s potential for carcinogenicity. Bucher’s results do not prove sodium fluoride is a carcinogen, but do "point out the need to test the chemical in the two-year rodent bioassay, which we are doing," he explains.
Because he believes that epidemiological studies show that fluoride has no effect on birth defects and cancer, Martin says he is not concerned about the positive mutagenicity studies. John S. Small, information specialist at NIDR who has a similar view of the epidemiology studies, calls the mutagenicity question a "used-up issue."
Very little work has been done on fluoride’s potential mutagenicity in humans, In one study involving only six patients receiving fluoride treatment for osteoporosis, inhibition of DNA repair was observed in one patient. But no firm conclusions can be drawn from such limited research, and more intensive research simply has not been pursued.
If the fluoride ion is a mutagen, it may be capable of causing birth defects in humans. Few studies have been done in this area. During the 1950s, Ionel Rapaport, a researcher at the Psychiatric Institute of the University of Wisconsin who specialized in the epidemiology of mental disorders, found that babies born in areas of North Dakota, South Dakota, Illinois, and Wisconsin with natural fluoride in drinking water had twice the incidence of Down’s syndrome as those born in fluoride-free areas. However, a few more recent surveys have shown a smaller or no relation between water fluoridation and Down’s syndrome.
In 1976, J. David Erickson, an epidemiologist at the Centers for Disease Control, looked at the rates of overall birth defects in the fluoridated and unfluoridated counties around Atlanta and also at national birth defect data supplied by the National Cleft Lip & Palate Intelligence Service (NCLPIS). Like Rapaport, he recorded a higher rate of Down’s syndrome births among younger mothers in the fluoridated areas around Atlanta, but he found no substantial overall differences in the birth defect rates that form a consistent pattern for the metropolitan Atlanta anti the NCLPIS data. However, many’ of the mothers in the Atlanta area counties had been exposed to fluoridation for only a few years and the NCLPIS data indicated substantial underreporting of birth defects. Clearly, there is need for more work in this area.
Two types of research have been done to determine if fluoride causes cancer-lab studies of animals and human epidemiology studies. Neither kind of research has shown clearly that fluoride is a carcinogen in animals or humans, But the studies have not been extensive enough to show’ that it clearly is not a carcinogen.
A few animal bioassays on fluoride in the 1950s produced contradictory and inconclusive evidence on the ion’s potential to cause or accelerate cancer. In 1977, Congress requested that the National Institutes of Health conduct large-scale animal tests of fluoride for carcinogenicity. In the first chronic test, certain rats in both the control and dosed groups became ill and died at an early age, probably because their feed, highly purified to remove fluoride, ‘was deficient in certain essential trace elements. The study on 360 mice and rats was done over again ‘with a different feed. Results are scheduled to be available in 1990. Because of its well-established effects on many enzymes in vitro, Groth suggests that fluoride also should probably be tested for cocarcinogenicity (ability to act as a promoter of cancer) in animals. But no such research is now under way.
Groth: science cannot say how much uncertainty we should tolerate
Cancer epidemiology studies are probably the most controversial issue in the fluoride debate. In the 1950s, PHS did some general mortality studies of crude overall death rates from all causes. It found no excess mortality from cancer or other causes in naturally fluoridated areas, compared with areas without fluoride in water.
In 1977, biochemist John Yiamouyiannis, president of the Safe Water Foundation (a citizens group opposed to fluoridation), and Dean Burk, retired after working for 35 years as a biochemist at the National Cancer Institute, published a study comparing cancer mortality rates from the 10 largest U.S. cities with fluoridated water with mortality rates from 10 of the largest cities with nonfluoridated water. Before 1952, when fluoridation had not yet begun in most of these cities, the cancer death rates rose together. After 1952, the death rates for people over 45 in the cities with nonfluoridated water were 4 to 5% lower than those for the cities with fluoridated water. In England, Sir Richard Doll and Leo Kinlen of Oxford University and Peter D. Oldham and D. John Newell of the Royal Statistical Society at about the same time completed studies that show no excess of cancer mortality in those same cities in the U.S. with fluoridated water.
The National Research Council (NRC) reviewed this discrepancy in 1977 and concluded that the conflicting results could be explained in large part by the different data sets and different analytical approaches used by the investigators. According to the NRC analysis, the margin of possible error in the most sensitive cancer study is about three cancer deaths per 100,000 people or 4000 possible excess or fewer cancer deaths per year among the 130 million individuals drinking fluoridated water in the U.S.
A June article in the Proceedings of the Pennsylvania Academy of Science by attorney John R. Graham, Burk, and Pierre J. Morin, former scientific adviser for the minister of environment in Quebec, also reviews this controversy. It concludes that, compared with the unfluoridated cities, there is an excess of 20 to 30 cancer deaths per 100,000 people who live in the major fluoridated cities of the U.S. for at least 15 to 20 years.
Several investigators have looked for a more specific relationship between stomach cancer and fluoridation. The hypothesis is that fluoride would be more likely to cause stomach cancer than any other type because fluoride in the stomach forms hydrofluoric acid, a powerful irritant that is mutagenic in several in-vitro lab tests. In 1978. CDC’s Erickson, after correcting for age, race, and sex, found the death rate from cancer of the digestive system was 9% higher in cities with fluoridated water. However, when he subtracted all subjects with Asian and Hispanic surnames and corrected for education and population density, the excess disappeared.
The Knox report, a comprehensive review of most fluoride cancer studies that was completed in 1985 by the Royal College of Physicians in England. concludes that there is no convincing evidence that cancer death rates are higher in areas with fluoridated water. Thus, as with most environmental agents that have been studied for their effects on cancer, the results for fluoride are still inconclusive.
Values influence the choice
Even if all evidence from fluoride research indicated that the risks are slight, not everyone would agree that it is proper to fluoridate water supplies. Obviously, there is never enough time or money to investigate all the scientific questions, and some research results will always be equivocal. And, at least in environmental health, it is, of course, impossible for science to establish anything with absolute certainty.
The decision to fluoridate a community’s water or not boils down to a matter of values Scientific evidence can make the choice more clearcut, more rational, but the choice can’t be made purely on the basis of scientific evidence. So long as there is uncertainty about risk from fluoridation, some people will not want to accept that risk, And others who favor fluoridation will demand proof of harm beyond a reasonable doubt before they reject it According to Groth, "A scientific assessment cannot say what degree of adverse effects is acceptable in return for the expected benefits. . . . It cannot say how much uncertainty we should tolerate in estimates of hazards when more than 100 million people are exposed to lifelong ingestion of fluoridated water. Those decisions are value judgments, and scientists’ values are no better than everyone else's.
If the risks could be shown to be minuscule beyond a reasonable doubt, it still might make no sense to fluoridate water supplies if the benefits are also small. Perhaps the best approach is, as Groth suggests, not to make the issue whether to fluoridate public water supplies or not. Such an approach allows for no compromise: A water supply is either fluoridated or it is not. Perhaps a better question for policy makers, scientists, and citizens to address is: "What is the best way to promote dental health?" he says. Fluoridation might well be part of the answer, Groth suggests. But communities should simultaneously examine the pros and cons of a variety of other approaches, too. That way, the characteristic all-or-nothing, fight-to-the-finish political battle over fluoridation might someday truly become a historical curiosity.
Original article still on-line
Ask any dentist whether fluoridated water helps prevent tooth decay, and in all likelihood they will reply that the difference between those who drink it and those who don't is like night and day. Comparative studies have shown that, on average, the incidence of tooth decay among children in fluoridated communities is 15–50% less than it is in nonfluoridated communities. Yet after more than 60 years since the first intentional fluoridation of a public drinking water supply in Grand Rapids, Mich., the benefits and risks of fluoridation continue to be debated.
No other public health controversy has been so long-running and so divided, with each side refusing to listen to the other, R. Allan Freeze and Jay H. Lehr note in their book "The Fluoride Wars: How a Modest Public Health Measure Became America's Longest-Running Political Melodrama." Advocates of fluoridation say it prevents dental cavities with no health risks. Those opposed question the benefits of fluoridation and say it leads to dental fluorosis, a cosmetic condition in which teeth become mottled, as well as other health problems such as crippling skeletal fluorosis and even cancer.
The authors do an excellent job tracing the history of fluoridated drinking water, from the early 1900s when high levels of fluoride in water were first linked to brown stained teeth to the first intentional fluoridation of a public water supply in 1945. The book then follows the path of fluoridation in the U.S. until 2000, using various cities as case studies.
What started out in Grand Rapids with little opposition soon turned into the "longest running circus in town," the authors write. Fluoridation referenda popped up in cities across the U.S., and pro- and antifluoridation forces battled at town hall meetings. In most cases, "votes ended up within a point or two of 50:50."
The book is entertaining and easy to read, chock-full of interesting people and stories, beginning with the mystery of brown stained teeth in Naples, Italy, and Colorado Springs, Colo., at the dawn of the 20th century.
Fast forward 30 years to the company-owned town of Bauxite, Ark., home to a mining subsidiary of the Aluminum Co. of America (Alcoa). Children who drank water from the town's two wells also developed the mysterious mottled teeth. The book describes how Alcoa's chief chemist, H. V. Churchill, solved the mystery in 1931 when he detected high levels of fluoride in the town's water.
Churchill, however, was careful not to make a correlation between fluoride and mottled teeth, presumably to absolve Alcoa from blame, the authors note. Instead, Churchill wrote that no correlation could be made because detecting fluoride in water is "fraught with difficulty."
The book then turns to the National Institutes of Health, which was celebrating its first anniversary in 1931. The chief scientist of its Dental Research Section, H. Trendley Dean, was on a mission to find out whether fluoride was the sole cause of mottled teeth. He was also assigned to determine whether there was a threshold below which mottling does not occur and, ironically, to examine the costs of removing fluoride from water.
By the mid-1930s, Dean had determined that there was a clear relationship between mottled teeth and fluoride in drinking water. He also concluded that fluoride begins to blemish teeth at levels above 1 ppm.
It became increasingly clear that patients afflicted with mottled teeth suffered tooth decay less frequently than those without the condition. The authors describe how Dean became obsessed with this observation and by 1937 had shifted his work "from the role of fluoride in mottling to the role of fluoride in caries protection." It wouldn't be long before the idea of adding fluoride to water supplies that do not have enough was born.
Grand Rapids was chosen to be the first city to have its water fluoridated, in a trial carried out by the Public Health Service in 1945. After much consideration, the level of fluoride was set at 1 ppm, the value still used today by roughly two-thirds of all municipal water works in the U.S. The remaining one-third do not add fluoride.
Concerns over fluoridation are still voiced loudly today. Although some of them are far-fetched, others do have merit, the authors acknowledge. For example, antifluoridationists often point to the fact that dental cavities have decreased in both fluoridated and nonfluoridated communities in recent years. In earlier years, "on average, children in fluoridated communities experienced 50% less tooth decay than their cousins in nonfluoridated communities," Freeze and Lehr note. Today, some studies suggest that the difference could be as low as 15%.
The authors and many profluoridationists attribute the decline in tooth decay in nonfluoridated communities to the increase in fluoride exposure from sources other than drinking water, such as fluoridated toothpastes, processed foods and beverages, and air.
Evidence of such exposure brings the reader to an important question: Is the current fluoride dose of 1 ppm in public drinking water too high? Freeze and Lehr note that in 1986 the Environmental Protection Agency set the maximum safe dose of fluoride at 4 ppm, on the basis that cosmetic problems are not adverse health effects. The agency also set a secondary "nonenforceable standard established for aesthetic reasons" of 2 ppm. Many antifluoridationists argue that the combined exposure to fluoride from all sources brings current exposure levels dangerously close to the 4-ppm level.
A documented rise in dental fluorosis in children from fluoridated communities supports that contention. Freeze and Lehr point out that in a study Dean conducted in 1940, the prevalence of the condition was 13.6%. In contrast, a study conducted by the Ontario Ministry of Health in the late 1990s, reported a 51.3% prevalence. Most of those cases are in the very mild to mild categories, although the prevalence of moderate to severe cases is not insignificant, they add.
Crippling skeletal fluorosis, on the other hand, is extremely rare in the U.S. According to the book, only five cases have been documented in the U.S. in the past 35 years. Nonetheless, the World Health Organization estimates that more than 1 million people in India and China, where drinking water naturally contains 20 to 30 ppm fluoride, suffer from the disease.
Antifluoridationists continue to claim a link between fluoride and cancer. They point to studies dating back as far as 1950 that showed an increased rate of tumor growth in mice exposed to fluoride, even though those studies have been refuted by the scientific and medical communities.
The book gives pretty convincing evidence that fluoride is responsible for the near eradication of dental cavities and that it doesn't cause cancer at current exposure levels. But it probably contains too much detail for most readers about the makeup of teeth and how fluoride protects them.
Numerous reviews of water fluoridation have been published over the years, but most of them have failed to give equal treatment to both sides of the argument. "The Fluoride Wars" is one of the few that provides both sides of the controversy; however, most readers will find the book biased in favor of fluoridation.
If balance is truly what the authors aimed to achieve with this book, they should have avoided statements like, "Overall, the pro-fluoridation movement is the clear winner on the credibility front," or "there seems little doubt, based on current scientific and medical understanding, that fluoridation does more good than harm." They should have let the readers decide for themselves.
Throughout the book, profluoridationists come across as traditional, mainstream scientists who tried to keep the controversy on rational ground and whose views are endorsed by the medical and dental establishments. Antifluoridationists, on the other hand, are portrayed as conspiracy theorists, alarmists, fringe scientists, crackpots, or coming from grassroots organizations that view the medical establishment with disdain.
Although Freeze and Lehr acknowledge that a few respected scientists have adopted antifluoride views, they maintain that those scientists are in the minority. They describe opposition as living in a "strange but alluring world of fluoridation conspiracy theory." An entire chapter is devoted to fluorophobia and those conspiracy theories.
One leading conspiracy theory is that the aluminum industry lobbied hard for fluoridation so that it would create a market for the significant amount of fluoride waste it produces during the electrolytic process to make aluminum. Indeed, as the authors point out, "there was a period between 1957 and 1968 when Alcoa sold sodium fluoride to cities for the fluoridation of their water supplies."
Readers learn next that the phosphate fertilizer industry also generates large amounts of fluoride waste and actually priced Alcoa out of the fluoride market in the late 1960s. Since then, most of the fluoride added to water has come from the fertilizer industry.
Another conspiracy theory antifluoridationists often cite is that fluoridation of drinking water was used to cover up the hazards of toxic hydrogen fluoride gas emitted from industrial sources like aluminum smelters. According to the argument, if people are convinced that fluoride in drinking water is safe, it won't be hard to convince them that it is also safe to breathe the chemical in the air, thus giving industry the green light to emit higher amounts of the gas. Today, hydrogen fluoride emissions are well regulated.
The authors save the most bizarre theory for last—that the government is using fluoride in drinking water to control the minds of the population. "Let's face it. If you believe the mind-control arguments, you qualify as a true-blue, bona fide conspiracy lover," they write.
Although "The Fluoride Wars" is biased toward profluoridation, the authors should be commended for providing all of the facts of the controversy in one place. Their call for both sides to get together to study the health issues with reason and respect is also a worthwhile goal because, as they point out, perhaps then "this long-standing and somewhat silly dispute could finally be laid to rest."
Britt E. Erickson is an associate editor in the government and policy group of C&EN.