Fluoride: The Aging Factor

About the Author: Dr. John Yiamouyiannis was, until his death in the fall of 2000, the world's leading authority on the biological effects of fluoride. His formal education included a B.S. in biochemistry from the University of Chicago and a Ph.D in biochemistry from the University of Rhode Island. After a year of postdoctoral research at Western Reserve University Medical School, Yiamouyiannis went on to become biochemical editor at Chemical Abstracts Service, the world's largest chemical information center. It was at Chemical Abstracts Service, where Yiamouyiannis became interested in the damaging effects of fluoride.

Chapter 4 - Breaking Down the Body's Glue

All animals, including humans, are made up of cells. The cell, the basic unit of life, can be identified under a microscope by its outer membrane and a nucleus within the membrane.

Some cells are able to produce a protein called collagen. In this book, the term "collagen" refers to collagen as well as collagen-like proteins. This process occurs inside the cell. Little globules called vesicles carry the collagen from the inside of the cell to the cell membrane where it is released to the outside of the cell. There, the collagen thickens into fibers.

The five different types of cells capable of producing and releasing collagen in this way are:

fibroblasts, which produce collagen for the structural support of skin, tendons, ligaments and muscle;
chondroblasts, which produce collagen for the structual support of cartilage;
osteoblasts, which produce collagen for the structual foundation and framework upon which calcium and phosphate are deposited, giving rise to bone;
ameloblasts, which produce collagen for the structural foundation and framework upon which calcium and phosphate are deposited, giving rise to tooth enamel.
odontoblasts, which produce collagen for the structual foundation and framework upon which calcium and phosphate are deposited, giving rise to the inner part of the tooth. This material is called dentin.

Like other proteins, collagen is composed of amino acids linked together in a chain. However, collagen contains two additional amino acids, hydroxyproline and hydroxylysine, not found in other proteins. Thus when collagen breaks down, the hydroxyproline and hydroxylysine levels in the blood and urine increase.

Researchers from Harvard University and the National Institutes of Health knew in the 1960s that fluoride disrupted collagen synthesis. It was not until 1979-1981, however, that a new flurry of research activity in this area began.

In 1981, Dr. Kakuya Ishida of the Kanagawa Dental University in Japan reported the results of studies in which he fed laboratory animals 1 part per million fluoride in their drinking water and analyzed the urine for hydroxyproline. He found that urinary hydroxyproline levels increased in those animals. This indicates that as little as 1 part per million fluoride interferes with collagen metabolism and leads to its breakdown.

Dr. Marian Drozdz and co-workers from the Institute of Bioanalytical and Environmental Studies in Katowice, Poland found increased hydroxyproline and hydroxylysine levels in the blood and urine as well as a decrease in skin and lung collagen levels in rats fed 1 part per million fluoride in their drinking water.

Dr. Anna Put and co-workers from the Department of Pharmacology of the Pomorska Akademy of Medicine in Szczecin, Poland also found that fluoride increased hydroxyproline levels in urine.

Drs. A.K. Susheela, Y.D. Sharma and co-workers from the All-India Institute of Medical Sciences found that fluoride exposure disrupts the synthesis of collagen and leads to the breakdown of collagen in bone, tendon, muscle, skin, cartilage, lung, kidney, and trachea.

As already noted, small vesicles transport collagen from the inside of the cell to the outside of the cell. Drs. Harold Fleming and Val Greenfield of Yale University School of Medicine found a larger number of these vesicles in collagen forming cells (ameloblasts) in animals exposed to fluoride. This work was recently confirmed by S. Chen and D. Eisenmann of the University of Illinois, who also found a fluoride-induced increase of these granules in ameloblasts.

It appears that fluoride disruption of collagen synthesis in cells responsible for laying down collagen leads these cells to try to compensate for their inability to put out intact collagen by producing larger quantities of imperfect collagen and/or noncollagenous protein.

In 1983, Dr. John R. Farley and co-workers from Loma Linda University showed that treatment of bone cells with less than 1 part per million fluoride increased collagen formation by 50 percent. One year later, Dr. J.R. Smid and co-workers from the Department of Oral Biology at the University of Queensland in Australia found that fluoride ingestion led to an increase of noncollagen proteins as well as collagen proteins.

This is supported by the works of Drs. J.H. Bowes and M.M. Murray, Dr. Kh.A. Abishev and co-workers, and Dr. B.R. Bhussry who report a vastly higher protein content in teeth and bone damaged by fluoride. Clinical findings also show that new irregular bone growth is stimulated by fluoride.

The drawings below illustrate the effect of fluoride on collagen metabolism.

While collagen is made by many different types of cells and, under normal circumstances, is only mineralized in teeth and bones, the body obviously has some mechanism to mineralize the collagen of some tissues while leaving the collagen of other tissues, such as skin, ligaments, tendons, etc., unmineralized.

During the aging process, the body loses its ability to discriminate between which tissues should be mineralized and which tissues should not. As will be shown, consumption of fluoride results in the same loss of the body's ability to discriminate. In other words, mineralization of tissue, such as bone, which should be mineralized, is disrupted, and tendons, ligaments, muscles, and other soft tissue which should not be mineralized start to become mineralized as a result of fluoride exposure.

By interfering with collagen production, fluoride leads to the production of larger quantites of imperfect collagen and/or other types of protein and thus interferes with the body's normal regulation of collagen mineralization.

The type and array of collagen and collagen-related proteins made by the various collagen-producing cells determine whether or not the collagen framework will be mineralized. During the aging process, cumulative damage to these cells leads to the diseases attributed to "old age" - arthritis, arteriosclerosis, brittle bones, wrinkled skin, etc. Consumption of fluoride produces the same effects and results in the same diseases.

Fluoride probably acts by interfering with enzymes essential for setting up the proper conditions for producing intact collagen. Thus, as has already been indicated, larger amounts of imperfect or deformed collagen fibers are formed and the body's ability to regulate collagen formation and mineralization is hindered...

Chapter 6 - Aging the Bone: The Degenerative Effects of Skeletal Fluorosis

Now let's look at the bone. Unlike the ameloblasts, and odontoblasts of teeth whose regenerative activity stops after tooth development, osteoblasts continue to actively lay down collagen, and new bone formation continues to take place.

If a tooth breaks or fractures, you're out of luck. The damage cannot be repaired. However, if a bone breaks or fractures, osteoblasts lay down collagen to produce a framework for new bone formation to repair the damage.

Bone also has the ability to rejuvenate itself. As older bone is removed by bone scavenger cells called osteoclasts, osteoblasts lay down collagen to produce a framework for new bone formation to renew the skeletal structure.

Thus, damage to collagen production in bone can interfere with the normal processes of bone rejuvenation and repair throughout life.

Cartilage

The balls and sockets of bones are lined with a smooth, tough elastic substance called cartilage. Maintaining the integrity of cartilage depends largely upon the ability of cells called chondroblasts to lay down noncalcified collagen which is the major structural component of cartilage.

The Effect of Fluoride on Bone and Cartilage

Fluoride has been shown to interfere with collagen formation in osteoblasts and chondroblasts. If, as pointed out, increased production of imperfect collagen or collagen-like protein results in mineralization of tissues which should not be mineralized, and vice versa, one would expect a calcification of ligaments, cartilage, and tendons as well as the formation of poorly and overly mineralized bone. This is exactly what happens after exposure to fluoride.

In discussing their examination of tissues from patients exposed to fluoride, Drs. A. Singh and S.S. Jolly, world-renowned experts on the clinical effects of fluoride on bone, point out that:

- The most noticeable changes are detected in the spine with calcification of various spinal ligaments, resulting in pronounced bony outgrowths. The other bones show numerous spiky outgrowths especially in tendons (collagen-rich fibrous tissue which attach muscles to bone) and ligaments (collagen rich fibrous tissue which holds bones together). Under careful inspection, the bony outgrowths are found to consist of coarse, woven fibers which are largely uncalcified.

- Irregular bone is also laid down in joint sockets...

and interosseous membranes (membranes between bones in arms and legs).

- In more advanced cases of fluoride exposure, bones become held together by masses of new bone laid down in the joint socket, ligaments and tendons. This results in the locking up of joints and permanent inability of victims to move or flex their joints. Vertebrae become fused at many places. This results in the characteristic "hunch back" symptom of skeletal fluorosis.

- There is a low degree of remineralization of the bone itself, which is partly due to a wide seam of uncalcified osteoid (collagen).

In 1973, Dr. Jolly and co-workers presented radiological evidence of skeletal fluorosis which results in these bone deformities in parts of India where the drinking water contained as little as 0.7 parts per million fluoride, with the occurrence and severity increasing with increasing levels of fluoride in the drinking water.

In 1985, Dr. I. Arnala and co-workers of Kuopio University in Finland reported that: "The upper limit for fluoride concentration in drinking water that does not increase the amount of unmineralized bone is roughly 1.5 parts per million. ...We should however, recognize that it is difficult to give a strict value for a safe concentration in drinking water because individual susceptibility to fluoride varies."

In addition to fluoride-induced bone irregularities, one could expect that the fluoride-induced irregularities of the joint cartilage (which is normally smooth) would result in the irritation and inflammation commonly referred to as arthritis. One could also expect fluoride to cause an increase in the incidence of fractures and a decrease in the body's ability to heal bone breaks and bone fractures.

Clinical observations show that this is exactly what happens.

Arthritic Changes

Drs. Singh and Jolly point out that early symptoms of fluoride-induced damage to bones and cartilage start with "vague pains noted most frequently in the small joints of the spine. These cases are frequent in the endemic [local] areas and may be misdiagnosed as rheumatoid or osteoarthritis.

"In later stages, there is an obvious stiffness of the spine with limitation of movements, and still later, the development of kyphosis [hunch back].

"There is difficulty in walking, due partly to stiffness and limitation of the movements of various joints....

"Some patients complain of dyspnea, [difficulty in breathing] on exertion because of the rigidity of the thoracic cage."

Dr. Jolly and co-workers reported these symptoms in parts of India where the drinking water contains as little as 0.7 parts per million fluoride, the occurrence and severity increasing as the fluoride content in the drinking water increased.

In the United States, Dr. George Waldbott also diagnosed some of the early symptoms listed above, including arthritis and joint pains, as being due to the consumption of water fluoridated at 1 part per million. He was able to bring about a reversal in these symptoms by eliminating fluoridated water from the patients'diets. However, if left unattended, the degeneration leads to the advanced stages of arthritis and "old age."

Similar arthritic symptoms have been reported among people exposed to air-borne fluoride in Switzerland, Germany, Britain, United States, Canada, and North Africa. Dr. Yiamouyiannis was contacted by an independent British broadcasting company who consulted him concerning a problem they had found in a brick manufacturing area about 50 miles outside of London where they reported that over 90% of the population was suffering from arthritis induced by air-borne fluoride.

Dr.Waldbott noted the possibility of the age-accelerating effects of fluoride with respect to arthritis and stated:

"Among the elderly, arthritis of the spine is an especially common ailment that is customarily attributed to 'aging.' Since fluoride retention in bones increases as a person grows older, how can we disregard the possibility that this 'old age' disease might be linked with fluoride intake? For example ... [others have] described in detail X-ray changes encountered in skeletal fluorosis in North Africa, that are in every respect identical to those present in the arthritic spine of the elderly."

Breaks and Fractures

In 1978, Dr. J.A. Albright and co-workers from Yale University reported at the Annual Meeting of the Orthopedics Research Society that as little as 1 part per million fluoride decreases bone strength and elasticity.

In 1983, Dr. B. Uslu from Anadelu University School of Medicine in Eskisehir, Turkey reported that addition of fluoride to the drinking water of rats with fractured bones resulted in defective healing of the fracture due to disruption of collagen synthesis.

In 1978, the Journal of the American Medical Association published an editorial pointing out that "in several short-term studies, fluoride has been administered for treatment of involutional osteoporosis, alone or with supplemental calcium, vitamin D or both. No studies have demonstrated alleviation of fracture[s]. ... However, studies in humans have shown an increased incidence of... fractures. When high doses of fluorides have been given to animals receiving a diet that was otherwise unchanged, most studies have shown no change or a decrease in the strength of the bone." They also pointed out that administration of fluoride resulted in nonmineralized seams in bones, resulting in the disease called osteomalacia. These nonmineralized seams imply that breaks and fractures in the patients' bones would tend to heal more slowly.

It is ironic that anyone would ever think of treating osteoporosis (a disease in which the bones lose calcium) with fluoride, a substance which leads to decalcification of bone. In 1977, Dr. Jennifer Jowsey, one of the originators of fluoride therapy for osteoporosis, admitted that fluoride was leading to a greater degree of osteoporosis (demineralization) in some bones while leading to osteosclerosis (overmineralization) in others. In other words, fluoride treatment of osteoporosis "robs Peter to pay Paul" and leads to a general weakening of the bones.

In 1980, Dr. J.C. Robin and co-workers from the Roswell Park Memorial Institute confirmed the foolishness of using fluoride for the treatment of osteoporosis by publishing their results in the Journal of Medicine. According to the authors, "fluoride had no preventive effect. In some experiments there was even a deleterious effect of fluoride." They found fluoride accelerated the process of osteoporosis leading to a loss of calcium from the bone.

Claims that the amount of fluoride found in fluoridated water would help prevent osteoporosis have been studied epidemiologically. Researchers from the U.S. National Center for Health Statistics claimed to find no preventive effect, while researchers from the National Board of Health in Finland claim to find a preventive effect. However, the number of people examined in these two studies was far too small to yield statistically meaningful results. The studies of Drs. Singh and Jolly as well as the studies of Dr. I. Arnala and co-workers who report increases in unmineralized bone, are consistent with the finding of Dr. Robin that fluoride accelerates the process of osteoporosis.

In 1973, a report from the National Institute of Arthritis and Metabolic Diseases found 50 to 100% increases in the incidence of a disease called osteitis fibrosa among patients whose artificial kidney machines were run on fluoridated water. Osteitis fibrosa is a disease characterized by fibrous degeneration of the bone; it results in bone deformities and sometimes in fracture...

In a number of areas where people consume water containing 3 parts per million fluoride or more, calcification of the arteries has been clinically correlated with the fluoride-induced bone disorders described in Chapter 6. The indication again is that fibroblasts in the arterial cell walls are producing larger amounts of an imperfect collagen or collagen-like protein, resulting in hardening of the arteries or arteriosclerosis, the leading cause of death in the United States.

During aging, hardening of the arteries is probably due to disruption of collagen production, according to Dr. John Negalesko, director of the first year medical program at the Ohio State University Medical School and an expert in the field. Thus, fluoride, by disrupting the production of collagen and by stimulating the calcification of arteries, has speeded up another phase of the aging process...

Chapter 8: Fluoride & Genetic Damage

As pointed out in Chapter 4, all animals, including humans, are made up of cells. Each cell contains a nucleus, which is separated from the remainder of the cell by a nuclear membrane. Within the nucleus exist chromosomes, which contain DNA and protein. DNA is the body's master blueprint material. It is the genetic material that determines how the body is built. DNA specifies traits such as height, hair texture and color, number of fingers on each hand, blood type, and by means of its control of protein and enzyme synthesis, the susceptibility of the individual to various diseases.

Since maintaining the integrity of this master blueprint is so vital, the cell makes a "photocopy" of the DNA called RNA, so that the risk of damaging the DNA is minimized. This photocopy blueprint is taken to "construction sites" in the cell. These construction sites are called ribosomes. On these ribosomes, the RNA blueprint is used to direct the manufacture of proteins and enzymes, which, in turn, directly determine the structure, traits, and limiting capabilities of the body.

To further insure the integrity of DNA, the cell provides a group of enzymes called the DNA repair enzyme system which repairs DNA when damage is done to it. As people age, their DNA repair enzyme system slows down. This results in DNA damage which goes unrepaired and leads to cell damage or death. Damaged or dead cells may then put out products which in turn damage other cells, leading eventually to massive cell death and the degenerative loss of various tissues and organs in a snowballing cycle of aging > damage > aging ....

Serious consequences can also arise if the unrepaired DNA damage occurs in a cell which gives rise to a sperm or egg cell. In these cases, DNA damage in the defective egg or sperm cell will be replicated in every cell of the offspring's body and will lead to a birth defect. If the child with this birth defect survives to maturity and reproduces, this genetic deformity will be passed on from generation to generation. A decline in DNA repair activity with "age" is one of the reasons why the number of birth defects increases as maternal age increases.

Unrepaired damage of a segment of the DNA responsible for control of cell growth (brought about by a deficient DNA repair enzyme system) can lead to uncontrolled cell growth or tumors. Many tumors stop growing when they are contained by the cells around them. However, in some cases, tumor cells may release an enzyme, or may be induced by additional genetic damage to release an enzyme, which digests the surrounding cells. The result is an invasive or malignant tumor and is more commonly referred to as cancer.

An excellent example of a defective DNA repair enzyme system leading to cancer is provided by victims of a disease called xeroderma pigmentosum. These people suffer from an inherited deficiency of DNA repair enzyme activity and are known to succumb to cancer early in life as a result.

A decline in DNA repair activity with "age" is one of the primary reasons why the incidence of cancer among older people is so much higher than the cancer incidence among younger people. The defective DNA repair enzyme in patients with xeroderma pigmentosum accelerates the aging process to the extent that xeroderma pigmentosum patients in their 20's have the same cancer risk as "normal" people in their 80's.

Dr. Wolfgang Klein and co-workers at the Seibersdorf Research Center in Austria reported that 1 part per million fluoride inhibits DNA repair enzyme activity by 50%. Since fluoride inhibits DNA repair enzyme activity, fluoride should also be expected to lead to an increase in genetic or chromosome damage.

This has indeed been found to occur in numerous studies showing that fluoride in water, even at the concentration of 1 part per million, can cause chromosome damage.

The following table outlines the results of laboratory studies regarding the effect of fluoride on genetic damage in mammals.

*A prepublication copy of this paper was submitted as an exhibit in a court case in Pittsburgh (USA). During trial, it was brought out that the results showed that increasing fluoride contents in drinking water increased genetic damage in mouse testes cells. Before the paper was published these figures were altered so as to destroy the original figures showing a relation between fluoride and genetic damage (see Chapter 16).

One of the most relevant of these studies are those of Dr. Aly Mohamed, a geneticist at the University of Missouri. They show that one part per million fluoride in the drinking water of mice causes chromosomal damage. These studies also show that as the fluoride content of the water increases the degree of chromosomal damage increases in both testes and bone marrow. The results are presented in the following table:

(Click to enlarge table)

Chromosomes (and thus any chromosomal abnormalities that may occur) are only visible while the cell is dividing. Therefore, Dr. Mohamed studied bone marrow and testes cells since these cells divide rapidly.

Since the testes cells observed by Dr. Mohamed give rise to sperm cells which are passed on to future generations, genetic damage to these testes cells can lead to birth defects and other metabolic disorders which can be passed on from generation to generation.

Early studies regarding the ability of fluoride to cause chromosome damage were done on plants and insects and as a result drew little attention. However, since the basic structure, function, and repair of chromosomes is similar in plants, insects, and animals, substances like fluoride which cause genetic damage in plants and insects, will most likely cause genetic damage in animals-including man.

The following table outlines the results of laboratory studies regarding the effect of fluoride on genetic damage in plants and insects.

Drs. R.N. Mukherjee and F.H. Sobels from the University of Leiden in Holland found that fluoride increased the frequency of genetic damage in sperm cells which were produced by laboratory animals exposed to X-rays. It is evident, from their studies, that fluoride inhibited the repair of DNA damaged X-rays. The authors themselves concluded: "sodium fluoride resulted in a consistent and highly significant increase of the mutation [i.e. genetic damage] frequency. This effect is thought to result from interference with a repair process."

In agreement with Drs. Mukheijee and Sobels were Dr. S.I. Voroshilin and co-workers from the Russian Research Institute of Industrial Health and Occupational Diseases. From their studies they concluded: "It would seem to us that fluoride could cause some kind of disturbance in the enzymes that are related to the mechanisms of DNA repair and synthesis."

In 1981, Dr. A. Iarez and co-workers from the Department of Toxicology from Central University ofVenezuela in Caracas, reported that fluoride added to the drinking water of female rats produced birth defects in their offspring. Just one year later Drs. Rhuitao Zhang and Shunguang Zhang of the Changjian Institute of Marine Products found that fluoride caused birth defects in fish.

According to the June 16, 1976 issue of the San Diego Union, an experiment showed that 10% of the litters of female mice drinking tap water from Durham, North Carolina (fluoridated in 1962) contained at least one malformed baby. No birth defects were observed in mice drinking purified water. While this study in itself does not prove that fluoride was the cause, the effects of fluoride as determined by the investigators mentioned above certainly make fluoride a prime suspect.

Fluoride-Induced Cancer

The ability of fluoride to cause genetic damage is so well recognized that investigators are now trying to find ways to counteract its genetic damaging effects.

Substances like fluoride which cause genetic damage are called mutagenic substances and it is a well-accepted fact that substances which are mutagenic also tend to be carcinogenic, or cancer producing. In fact, this is exactly what has been found with regard to fluoride.

Dr. Takeki Tsutsui and co-workers of the Nippon Dental College in Japan showed that fluoride not only caused genetic damage but was also capable of transforming normal cells into cancer cells. The levels of fluoride used in this study were the same levels of fluoride that the U.S. National Cancer Institute suggested should be used to determine whether or not fluoridation of public water supplies causes cancer.

They found that cells treated with 34 and 45 parts per million fluoride produced cancer (fibrosarcoma) when injected under the skin of otherwise healthy adult hamsters. In contrast, they found that cells that were not treated with fluoride did not produce cancer.

This confirms the earlier U.S. National Cancer Institute sponsored studies done by Drs. Irwin Herskowitz and Isabel Norton. In 1963, these St. Louis University scientists showed that low levels of fluoride increased the incidence of melanotic tumors in fruit flies by 12 to 100% (see the following figure).

Similar types of transformations of normal cells to potentially cancerous cells have been observed in humans.

Dr. Danuta Jachimczak and co-workers from the Pomeranian Medical Academy in Poland reported that as little as 0.6 part per million fluoride produces chromosomal damage in human white blood cells. This study has received support from two other studies by Dr. R. Lin and co-workers from the Kumming Institute of Zoology and Dr. E.J. Thomson and co-workers from the Medical Research Council in Edinburgh, Scotland, who showed a 2-fold to 15-fold increase in chromosomal aberration rates at levels of 1.5 to 60 parts per million fluoride. The Thomson study suffers from the fact that the investigators administered another mutagenic substance to all the cells tested to measure other indexes of chromosomal activity.

Dr. Stephen Greenberg from the Chicago Medical School observed a disturbance of the DNA in white blood cells of animals treated with 5-10 ppm fluoride and observed other changes which he maintained were characteristic of cancer cells. In humans, Dr. Paul H. Duffey and co-workers from the Tucson Medical Center also found that fluoride transforms certain white blood cells into cells which appeared to be cancerous.

It is quite clear that fluoride causes genetic damage. The mechanism of action of fluoride cannot be exactly pinpointed because fluoride interferes with a number of physiological processes. Most evidence indicates that fluoride acts on the DNA repair enzyme system. This does not rule out the possibility that fluoride also interferes with DNA synthesis or that it may even act directly on the DNA itself. DNA is composed of two molecular strands held together by hydrogen bonds and fluoride is capable of disrupting these bonds. Such disruption would be expected to result in genetic damage directly and/or interference with DNA synthesis and DNA repair.

Furthermore, fluoride-induced genetic damage may also result from the general metabolic imbalance caused by fluoride selectively inhibiting certain enzymes.

The fact that fluoride has also been shown to cause cancer should not be surprising since it is almost universally accepted that cancer results from genetic damage.

In any event, the fact that fluoride disrupts DNA repair enzyme activity, the fact that fluoride causes genetic damage, and the fact that fluoride causes cancer shows again that fluoride is directly accelerating the aging process.

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Marian Drozdz, et al., "Studies on the Influence of Fluoride Compounds upon Connective Tissue Metabolism in Growing Rats. 11. Effect of Sodium Fluoride With and Without Simultaneous Exposure to Hydrogen Fluoride on Collagen Metabolism," J. Toxicol. Med., Volume 4, pp. 151-157 (1984).

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S. Chen and D. Eisenmann, "Calcium Shifts in Ameloblasts During Experimentally Altered Enamel Formation," Journal of Dental Research, Volume 6, p. 372 (1985).

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J.R. Smid, et al., "Effect of Long-Tbrm Administration of Fluoride on the Levels of EDTA-Soluble Protein and Gamma CarWxyglutamic Acid in Rat Incisor Teeth,"Journal ofDentalResearch, Volume 63, pp. 1061-1063 (1984).

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Jennifer Jowsey, Comments made at the 1977 National Convention of the American Association of the Advancement of Science in Denver, Colorado.

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Jennifer Madans, et al., "The Relationship between Hip Fracture and Water Fluoridation: An Analysis of National Data," American Journal of Public Health, Volume 73, pp. 296-298 (1983).

Olli Simonen and Ossi Laitinen, "Does Fluoridation of Drinking Water Prevent Bone Fragility and Osteoporosis?"Lancet (August 24,1985), pp. 432-434.

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P.E. Cordy, et al., "Bone Disease in Hemodialysis Patients with Particular Reference to the Effect of Fluoride in Study of Nutritional Requirements of Patients on Chronic Hemodialysis," National Institute of Arthritis and Metabolic Diseases, July 1973, pp. 28-59. [Distributed by the National Technical Information Service of the U.S. Department of Commerce]

[According to the April 23, 1980 issue of the Medical Tribune, page 7, it was found that even low doses of fluoride in osteoporosis treatment cause rheumatic and gastrointestinal adverse reactions. Severe vomiting occurred in two patients until fluoride levels were reduced to 3.7 to 7.5 mg per day.]

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Georgiana Jagiello and Ja-Shein Lin, "Sodium Fluoride as Potential Mutagen in Mammalian Eggs," Archives of Environmental Health, Volume 29, pp. 230-235(1974).

Danuta Jachimczak and Bogumila Skotarczak, "The Effect of Fluorine and Lead Ions on the Chromosomes of Human Leucocytes in Vitro." Genetica Polonica, Volume 19, No. 3, pp. 353-357 (1978).

George Martin, et al., "Lack of Cytogenetic Effect in Mice or Mutations in Salmonella Receiving Sodium Fluoride," Mutation Research, Volume 66, pp. 159-167 (1979).

A.A. Aliev and D.A.Babaev, "Cytogenetic Activity of Vitamins in Bone Marrow Cells of Rat Femurs in Sodium Fluoride-Induced Mutation Conditions," Tsitol. Genet., Volume 15, pp. 19-23 (1981).

A.A. Aliev, et al., "Effect of alpha-Ibeopherol on the Level of Chromosome Aberrations Induced by Sodium Fluoride in Rat Femur Bone Marrow Cells," Izv. Akad. Nauk Az. SSR Ser. Biol. Nauk., No. 1, pp. 17-20 (1981).

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Weishun He, et al., "Effect of Sodium Fluoride and Fluoroacetamide on Sister Chromatid Exchanges and Chromosome Aberrations in Cultured Red Muntjac Cells," Huanjing Kexue Xuebao, Volume 3, pp. 94-100 (1983).

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Thkeki Tsutsui, et al., "Cytotoxicity, Chromosome Aberrations and Unscheduled DNA Synthesis in Cultured Human Diploid Fibroblasts Induced by Sodium Fluoride," Mutation Research, Volume 139, pp. 193-198 (1984).

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E. Vogel, "Strong Antimutagenic Effects of Fluoride on Mutation Induction by Trenimon and 1-Phenyl-3, 3-Dimethyltriazene in Drosophila Melanogaster," Mutation Research, Volume 20, pp. 339-352 (1973).

S.S. Bale and G.E. Hart, "Cytogenetic and Genetic Effects of Fluoride on Barley. I. Comparative Study of the Effects of Sodium Fluoride and Hydrofluoric Acid on Seedling Root Tips," Canadian Journal of Genetics and Cytology, Volume 15, pp. 695-702 (1973).

S.S. Bale and G.E. Hart, "Cytogenetic and Genetic Effects of Fluoride on Barley. IL Effects of Treatments of Seedling Coleoptiles with Sodium Fluoride," Canadian Journal of Genetics and Cytology, Volume 15, pp. 703712(1973).

A.A. Aliev, et al., "Cytogenetic Effect of Sodium Fluoride Treatment ofAllium Fistulosurn L. Seeds," Izv. Akad. Nauk Az. SSR, Ser. Biol. Nauk, No. 2, pp. 8-10 (1982).

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Irwin Herskowitz & Isabel Norton, "Increased Incidence of Melanotic Tumors in Two Strains of Drosophila Melanogaster Following Treatment with Sodium Fluoride," Genetics, Volume 48, pp. 307-310 (1963).

Danuta Jachimzcak and Bogumila Skotarczak, "The Effect of Fluorine and Lead Ions on the Chromosomes of Human Leucocytes in Vitro," Genetica Polonica, Volume 19, No. 3, pp. 353-357 (1978).

Stephen Greenberg, "The Reaction of Mouse Leukocytes to Long-Term Fluoride Exposure," Anatomical Record, Volume 196, No. 2, pp. 266-267 (1980).

Stephen Greenberg, "Leukocyte Response in Young Mice Chronically Exposed to Fluoride," Fluoride, Volume 15, No. 3, pp. 119-123 (1982).

Paul Duffey, et al., "Giant Cells in Bone Marrows of Patients on High-Dose Fluoride Treatment," Annals of Internal Medicine, Volume 75, pp. 745--747 (1971).

Nobutake Kanematsu, "Genetic Toxicity of Biomaterial. DNA Damaging Effects of Sodium Fluoride and Other Fluoride Compounds," Japanese Journal of Oral Biology, Volume 27, pp. 372-374 (1985).

V. Ya. Nikiforova, "Mechanism of the Mutagenic Action of Fluoride," Tsitol. Genet., Volume 16, pp. 40-42 (1982).

L.S. Strochkova, et al., "Effect of Fluoride on Morphological and Metabolic Modifications in Hela Cell Culture," Tsitologiya, Volume 26, pp. 299-306 (1984).

Thshio Imai, et al., "Effects of Fluoride on Cell Growth of Two Human Cell Lines and on DNA and Protein Synthesis in Hela Cells," Acta Pharmacol. 7bxicol., Volume 52, pp. 8-11 (1983).

Kataoka Masayuki, "Effect of Sodium Fluoride on Blastogenesis in Mouse Lymphocytes with Special Reference to the Uptake on 3H-Thymidine, 3 H-Uridine, or 'H-Leucine," Shika Gakuho, Volume 84, pp. 229-251 (1984).

Chong Chang, "Effect of Fluoride on Nucleotides and Ribonucleic Acid In Germinating Corn Seedling Roots," Plant Physiology, Volume 43, No. 5, pp. 669-674 (1968).

V.I. Shepotinovsky and Z.I. Mikashinovich, "Metabolic Response of Leukocytes as an Indicator of Animal Individual Reaction to Stress and Injury-Induced Shock,"Byull. Eksp. Biol. Med., Volume 90, No. 10, pp. 420-422 (1980).

Armando Moucdcy, "Histochemical (Glycogen, RNA, and Lipids) Studies of the Liver Cells of Rats Treated with Potable Water Containing Sodium Fluoride in Various Concentrations," Rev. Fac. Odontol. Univ. Sao Paulo, Volume 6, No. 3, pp. 197-215 (1968).

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John Remington Graham and Dean Burk, "Editorial Essay," Fluoride, Volume 17, pp. 63-69 (1984).