Phyllis J. Mullenix, Ph.D.
P.O. Box 753
Andover, Massachusetts 0 1 8 10-3347
Tele. (978) 475-9196
FAX (978) 749-9447
June 17, 1999
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
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
page 2 (Mullenix letter to Lee County School Board Health Advisory Committee)
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
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 (1
l). 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).
page 3 (Mullenix letter to Lee County School Board Health Advisory Committee)
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:
industry 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.
Phyllis J. Mullenix
Phyllis J. Mullenix, Ph.D.
Research Associate, Dept. of Psychiatry
Children's Hospital. Boston, MA
C: The School District of Lee County (Board Member's Office)
page 4 (Mullenix letter to Lee County School Board Health Advisory Committee)
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,
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.
I 5). 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.)