Dr. Irwin Kash
School Health Advisory Committee
1555 Matthew Drive
Fort Myers, Florida 33907
Re: Lee County School Board's request for information on drinking water fluoridation

Dear Dr. Kash:

The Lee County School Board and its Health Advisory Committee arc to be commended for investigating the effects of fluoride ingestion. When the subject is controversial, as is fluoride or fluoridation, status quo may be easier but it is not scientific. Your decision to analyze data on both sides of the issue is a great example to set for the students. The following information describes my enlightenment of the subject, and it is offered in the hope it will aid your understanding of the advantages and disadvantages of water fluoridation.

Prior to 1982, my knowledge of fluoride was limited to television commercials saying it was good for my teeth. My expertise was not fluoride but the detection of neurotoxicity, which brought me to the Department of Psychiatry at Boston's Children's Hospital and Neuropathology at the Harvard Medical School. It was there that I met Dr. Jack Hein, Director of the Forsyth Dental Center and the scientist responsible for putting monofluorophosphate (MFP) into toothpaste. Dr. Hein was a student of Dr. Harold Hodge, the chief pharmacologist on the Manhattan Project who conducted the world renowned studies on fluoride (1) and started water fluoridation. Dr. Hein invited me to Forsyth to study the neurotoxic potential of materials that dentists use, starting with fluoride, and we set up the first toxicology department in any dental research institution in the world. I was made Head of the department, and Dr. Hodge moved to Boston and became a member of my department where he stayed until his death in 1990. Another Manhattan Project scientist and fluoride researcher, Dr. Ben Amdur, also joined the department.

My investigations of the neurotoxicity of fluoride started in 1987. Using a new computer pattern recognition system capable of a sensitivity and objectivity other behavioral measures did not possess, we studied an animal model first developed for the study of dental fluorosis. Frankly, we expected to find nothing. The results from the first experiment we thought must be wrong, so we kept repeating the study with more animals, different doses, sexes, ages and methods of administration. Like quicksand, every effort we made sank us further into the realization that brain function was impacted by fluoride. Scientific integrity dictated that we publish our results (2,3), but employed at a dental research institution made us weak in the knees to do so.

In our 1995 paper (2), we reported that brain function was vulnerable to fluoride, that the effects on behavior depended on the age at exposure and that fluoride accumulated in brain tissues. Rats exposed as adults displayed behavior-specific changes typical of cognitive deficits, whereas rats exposed prenatally had dispersed behaviors typical of hyperactivity. Brain histology was not examined, but the behavioral changes were consistent with those seen when hippocampal development is interrupted and memory problems emerge. Overall, we concluded that the rat study nagged potential for motor dysfunction, IQ deficits and/or learning disabilities in humans.

Criticisms of our study by dentists say that our results in rats are not relevant to humans because the doses we used were too high (75-125 ppm NaF in drinking water). These criticisms are without merit because our doses in rats produce a level of fluoride in the plasma equivalent to that found in humans drinking 5-10 ppm fluoride in water, or humane receiving some treatments for osteoporosis. This plasma level is exceeded ten times over one hour after children receive topical applications of some dental fluoride gels. Thus, humans are being exposed to levels of fluoride that we know alters behavior in rats. Perhaps dentists see no problem with this fact, but scientists involved with toxicity risk assessment will view it differently. The fluoride levels in the drinking water of our rats were not high, they were taken from the well known animal model developed for the study of dental fluorosis, a model used repeatedly by dental researchers for several years.

Other criticisms of equal absurdity have been expressed by dentists about our study. However, they are not important to dwell upon now because that first study was but one piece of an emerging picture. Soon after our study was published, we learned of two epidemiology studies from China showing IQ deficits in children over-exposed to fluoride via drinking water or soot from burning coal (4,5). Another epidemiological study I helped initiate in Boston found no association between behavior problems and dental fluorosis, but the lack of funds restricted experimental design which, in turn, limited detection of an association even if it existed (6). It has been well documented that tooth enamel defects occur more often in brain damaged and low IQ groups of children, and in fact, obvious enamel defects may be used as markers of not so obvious neurological problems (7). Since fluoride causes tooth enamel defects in the developing child, fluoride belongs in the behavioral spotlight.

A search of the medical literature uncovered case reports spanning 60 years on neurological effects in humans exposed to fluoride (8). A common theme in these reports was that fluoride exposure impaired memory and concentration and that it caused lethargy, headache, depression and confusion. Depression is not something to ignore because suicide occurs more frequently than expected in populations of fluoride workers (9). Headlines in newspapers today are a steady reminder that children are not immune to depression. The literature also revealed a case report of a 12-year-old boy that had convulsions precipitated by fluoridated drinking water ( 10). Alone, the report was anecdotal evidence. Coupled with unpublished information about a public health problem in Wallingford, CT, however, it assumed greater significance. Children living there near a stainless steel plant started having unexplained seizures when the plant released too much hydrogen fluoride (11). When the releases stopped, so did the seizures.

More recently, another laboratory investigation found that chronic exposure to fluoride (l ppm) in drinking water of rats compromised neuronal and cerebrovasculature integrity (blood brain barrier) and increased aluminum concentrations in brain tissues (12). Another study found that fluoride in drinking water of rats decreased membrane lipids important to proper brain function 13). Moreover, the latest studies have shown that fluoride accumulates in human and animal pineal glands where it impairs melatonin production (14,15), a finding critical when it is considered that melatonin is an agent that protects the central nervous system from radiation by scavenging free radicals ( 16). Finally, there is a recent study published which reports that silicofluorides in fluoridated drinking water increase levels of lead in children's blood, a risk factor that predicts higher crime rates, attention deficit disorder and learning disabilities ( 17).

Unfortunately, the link between fluoride and the brain does not end with the above mentioned studies. In 1993 while studying the neurotoxicity associated with the treatments of childhood leukemia, we demonstrated that the fluorinated steroid dexamethasone disrupted behavior in rats to a greater degree than did its nonfluorinated counterpart prednisolone (18,19). This finding prompted a clinical study of children treated for leukemia, where it was found that the fluorinated steroid was more detrimental to IQ than the nonfluorinated steroid (20). Greater deficits in reading comprehension, arithmetic calculation and short-term working memory were specifically identified. In short, this finding has fueled a growing concern about the contribution of fluorinated pharmaceuticals to the total body burden of fluoride.

As you discuss the benefits and risks of water fluoridation, it is imperative that the impact on total body burden of fluoride be considered. Total body burden experienced by children today is different from that of fifty years ago when fluoridation was promoted as a "safe and effective" means to protect against tooth decay. Children today are exposed to fluoride from their fruit juices, sodas, vegetables sprayed with pesticides, fluorinated pharmaceuticals, dietary supplements, toothpastes, dental sealants, and from the air especially near certain industries. In addition, many children are exposed to conditions that will interact with fluoride exposure and magnify harmful effects (i.e., exposure to lead, aluminum, cholinesterase-inhibiting pesticides, nutritional deficiencies, increased water consumption with exercise). Overall, fluoride exposures today are out of control, well beyond the dose touted as optimum for caries prevention.

In summary, there are no advantages to water fluoridation today. The risks far exceed the hoped for benefit. Dr. Hodge during the Manhattan Project requested funds from Col. Stafford L. Warren to do animal experimentation to determine central nervous system effects of fluoride (21). He did so because he had clinical evidence that the fluoride component of uranium hexafluoride caused "mental confusion, drowsiness and lassitude" among the workmen. Yet, he never got to do those studies, and because this information was classified, he never discussed his findings with me. Perhaps, however, this explains why he was so intensely interested in my fluoride studies up to the time of his death.

Therefore, in good conscience, I can only discourage the notion of fluoridating water supplies. The evidence against the safety of this public health policy keeps mounting; it is too compelling to ignore. However, proving harm takes a long but predictable path: ndustry complains, studies are criticized, and scientists are trashed. Do you have the time to wait while your children are at risk? The decision is yours.

Sincerely,
Phyllis J. Mullenix
Phyllis J. Mullenix, Ph.D.
Research Associate, Dept. of Psychiatry
Children's Hospital. Boston, MA

CC: The School District of Lee County (Board Member's Office) Kenneth Case

REFERENCES
1). U.S. Dept. of Energy, Pharmacology and Toxicology of Uranium Compounds, C. Voegtlin & H. C. Hodge, eds., Nat. Nuclear Energy Series, Manhattan Project Tech. Section, McGraw-Hill Book Co., NY, 1949.

2). Mullenix, P., Denbesten, P., Schunior, A., Kernan, W.J. Neurotoxicity of sodium fluoride in rats. Neurotoxicol. Teratol. 17:169-177, 1995.

3). Mullenix, P. J.: The computer pastern recognition system for study of spontaneous behavior of rats: A diagnostic tool for damage in the central nervous system? In: "Motor Activity and Movement Disorders. Research Issues and Applications." P. R. Sanberg, K. P. Ossenkopp and M. Kavaliers, eds., pp. 243-268, Humana Press, New Jersey, 1995.

4). Li, X. S., Zhi, J. L. and Gao, R. O. Effect of fluoride exposure on intelligence in children. Fluoride 28:189- 192, 1995.

5). Zhao, L.B., Liang, G. H., Zhang, D. N. and Wu, X. R. Effect of a high fluoride water supply on children's intelligence. Fluoride 29:190-192, 1996.

6). Morgan, L., Allred, E., Tavares, M., Bellinger, D. and Needleman, H. Investigation of the possible associations between fluorosis, fluoride exposure, and childhood behavior problems. Pediatrof Fluoride: a. Dent. 20:244-252, 1998.

7). Cohen, H. J. and Diner, H. The significance of developmental dental enamel defects in neurological diagnosis. Pediatrics 46:737-747, 1970.

8). Spittle,B. Psychopharmacology of Fluoride: a review. Int. Clin. Psychopharm. 9:79-82, 1994.

9). Grandjean, P., Olsen, H., Jensen, O.M., Juel, K. Cancer incidence and mortality in workers exposed to fluoride. J. N. Cancer Inst. 84:1903-1909, 1992.

10). Waldbott, G. L. Tetaniform convulsions precipitated by fluoridated drinking water. Confinia Neurologica 17:339-347, 1957.

11). Brown, D., personal communication, Connecticut Dept. of Public Health.

12) Varner, J. A., Jensen, K. F. Horvath, W. and Isaacson, R. L Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water alterations in neuronal and cerebrovascular integrity. Brain Res. 784:284-298, 1998.

13). Guan, Z.-Z., Wang, Y.-N., Xiao, K.-Q, Dai, D.-Y., Chen, Y.-H., Liu, J.-L., Sindelar, P. and Dallner, G. Influence of chronic fluorosis on membrane lipids in rat brain. Neurotoxicol. Teratol. 20:537-542, 1998.

14). Luke, J. Effect of fluoride on the physiology of the pineal gland. Caries Res. 28:204, 1994.

15). Luke, J. Effects of fluoride on the physiology of the pineal gland in the Mongolian Gerbil Meriones Unguiculatus. Fluoride 31:S24, 1998.

16). Mullenix, P. J.: Radiation protection in the developing central nervous system: Investigation of a biological approach. In: "Radioprotectors: Chemical, Biological and Clinical Perspective." E. A. Bump and K. Malaker, eds. CRC Press, Inc., Boca Raton, FL, 1997.

17). Masters, R. D. and Coplan, M. Water treatment with silicofluorides and lead toxicity. Inter. J. Env. Studies, in press.

18). Mullenix, P. J., Kernan, W. J., Schunior, A., Howes, A., Waber, D. P., Sallan, S. L. and Tarbell, N.J., Interactions of steroid, methotrexate and radiation determine neurotoxicity in an animal model to study therapy for childhood leukemia. Pediatr. Res. 35: 171- 178, 1994.

19). Mullenix, P.J., Fluoride and the brain: hidden "halo" effects. XXII Conf. Intern. Soc. Fluoride Res., 1998.

20). Waber, D. P., Carpentieri, S. C., Klar, N., Silverman, L. B., Schwenn, M., Hurwitz, C. A., Mullenix, P. J. and Sallan, S.E., Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone. In press, 1999.

21). Declassified letter. April 29, 1944. "Subject: Request for animal experimentation to determine central nervous system effects," from John L. Perry, Captain, Med. Corps, P.O. Box 287, Crittenden Station, Rochester, 7, N. Y. to Col. Stafford L. Warren, U. S. Engineer Office, Oak Ridge, TN (Thru The Area Engineer, Madison Square Area, N. Y.)

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