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Fluoride readily accumulates in the human pineal gland590,591,592, by old age the pineal gland has a higher fluoride content than either bone, teeth or enamel.593

The main pineal hormone is melatonin. Melatonin has strong antioxidant effects with a particular role in the protection of nuclear and mitochondrial DNA. Preliminary evidence suggests that melatonin may help strengthen the immune system. Melatonin also helps control the timing and release of female reproductive hormones. Animal studies suggest that melatonin may be effective for treating Alzheimer's disease and in the mechanisms of learning and memory. 594,595,596,597

Pineal fluoride concentrations significantly correlate with pineal calcium. In fact, calcification of the developing enamel organs and the pineal gland occur concurrently. This could affect pineal metabolism in much the same way that high local concentrations of fluoride in the developing enamel organ affect ameloblast function (the structural development of enamel).598 There is consequently a risk for bottle-fed babies who ingest milk formula made up from fluoridated water that fluoride will accumulate in the child's pineal gland. This is particularly significant given that large amounts of calcification have been demonstrated in the pineals of young children.599,600,601,602,603

590 Luke J. (1997). The Effect of Fluoride on the Physiology of the Pineal Gland. Ph.D. Thesis. University of Surrey, Guildford.

591 Ongkana, Nutcharin; Zhao, Xiao-zhen; Tohno, Setsuko; High Accumulation of Calcium and Phosphorus in the Pineal Bodies with Aging Biological Trace Element Research, Volume 119, Number 2, November 2007 , pp. 120-127(8)

592 Luke, Jennifer. "Fluoride Deposition in the Aged Human Pineal Gland". Caries Res 2991 (35): 125–28. Retrieved 2009-05-20.

593 Michotte Y, Lowenthal A, Knaepen L, Collard M, Massart DL: A morphological and chemical study of calcification of the pineal gland. J Neurol 1977;215:209-219.

594 Hardeland, RüDiger (2005). "Antioxidative Protection by Melatonin: Multiplicity of Mechanisms from Radical Detoxification to Radical Avoidance". Endocrine 27 (2): 119–30

595 Reiter, Russel J.; Acuña-Castroviejo, Dario; Tan, DUN-Xian; Burkhardt, Susanne (2006). "Free Radical-Mediated Molecular Damage". Annals of the New York Academy of Sciences 939: 200–15

596 Pappolla, MA; Sos, M; Omar, RA; Bick, RJ; Hickson-Bick, DL; Reiter, RJ;

Efthimiopoulos, S; Robakis, NK (1997). "Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide". The Journal of neuroscience : the official journal of the Society for Neuroscience 17 (5): 1683–90

597 Larson, John; Jessen, Ruth E.; Uz, Tolga; Arslan, Ahmet D.; Kurtuncu, Murat; Imbesi, Marta; Manev, Hari (2006). "Impaired hippocampal long-term potentiation in

melatonin MT2 receptor-deficient mice". Neuroscience Letters 393 (1): 23–6 598 Luke J. (2001). Fluoride deposition in the aged human pineal gland. School of Biological Sciences, University of Surrey, Guildford, UK, Department of Obstetrics and Gynaecology, The Royal London Hospital, Caries Research 35:125-128.

599 Cooper ERA: The human pineal gland and pineal cysts. J Anat (Lond) 1932;67:28- 46.

After finding that the pineal gland is a major target for fluoride accumulation in humans, Luke J (2001) conducted preliminary animal experiments to determine if the accumulated fluoride could impact the functioning of the gland - particularly the gland's regulation of melatonin. Luke found that animals treated with fluoride had lower levels of circulating melatonin, as reflected by reduced levels of melatonin metabolites in the animals' urine. This reduced level of circulating melatonin was accompanied by an earlier onset of puberty in the fluoride-treated female animals. Luke summarized her human and animal findings as follows: "In conclusion, the human pineal gland contains the highest concentration of fluoride in the body. Fluoride is associated with depressed pineal melatonin synthesis by prepubertal gerbils and an accelerated onset of sexual maturation in the female gerbil. The results strengthen the hypothesis that the pineal has a role in the timing of the onset of puberty. Whether or not fluoride interferes with pineal function in humans requires further investigation." 604

This risk was further acknowledged by the U.S. National Research Council in their statement that ―recent information on the role of the pineal organ in humans suggests that any agent that affects pineal function could affect human health in a variety of ways, including effects on sexual maturation, calcium metabolism, parathyroid function, postmenopausal osteoporosis, cancer, and psychiatric disease.‖605

The potential consequences of disturbances to functions of the pineal gland and resultant human health impacts from increased absorption of fluoride through dietary intake from water fluoridation cannot be underestimated. The first step in assessing a health risk by a substance to humans is the identification of its harmful effects on animals. A health risk to humans is assessed using results from human epidemiological studies in conjunction with results from animal studies. The Newburgh-Kingston Study (Schlesinger et al., 1956) identified that bone defects, anaemia and earlier female menstruation occur more often in children living in the fluoridated Newburgh than in non- fluoridated Kingston community.606 Limited animal studies examining how

fluoride affects the timing of the onset of sexual maturation suggest that fluoride inhibited pineal melatonin synthesis up until the time of sexual 600 Wurtman RJ: The pineal gland; in Endocrine Pathology. Baltimore, Williams &

Wilkins, 1968, pp 117-132.

601 Kerényi NA, Sarkar K: The postnatal transformation of the pineal gland. Acta Morphol Acad Sci Hung 1968; 16:223-236.

602 Tapp E, Huxley M: The weight and degree of calcification of the pineal gland. J Pathol 197 1; 105:31-39

603 Doskocil M: Development of concrements in the human pineal body. Folia Morphol (Praha) 1984;32:16-26.

604 Luke J. (2001). Fluoride deposition in the aged human pineal gland. School of Biological Sciences, University of Surrey, Guildford, UK, Department of Obstetrics and Gynaecology, The Royal London Hospital, Caries Research 35:125-128.

605 National Research Council. (2006). Fluoride in Drinking Water: A Scientific Review of EPA's Standards. National Academies Press, Washington D.C. p221-22

606 Newburgh-Kingston caries-fluorine study. XIII. Pediatric findings after ten years. J Am Dent Assoc. 1956 Mar;52(3):296-306. Schlesinger ER,Overton DE,Chase

maturation resulting in an accelerated onset of puberty in females. 607The U.S Agency for Toxic Substances and Disease Registry similarly reported that fluoride was reported to affect negatively some endocrine organs, particularly the thyroid, in animal studies.608 Camargo reported609 that with Grandidierella lutosa and lignorum estuarine amphipods female fecundity was shown to be the most sensitive endpoint in a 90 day life-cycle test, with a maximum acceptable toxic concentration (MATC) of 4.15 mg F-/L. It is noticeable that below this value it was observed that fluoride was stimulating female fecundity (stimulating reproductive fertility).610,611 Consequently there is scientific evidence to show that fluoride acts as an endocrine disruptor in the aquatic environment as well as on human female reproduction.

Early sexual maturation has both physiological and psychological consequences in humans. For girls, it is also associated with an increased risk of certain cancers in later life.612,613 The implication therefore of fluoride exposure for long-term health or the environment cannot be overlooked. It is important to be aware that many of the man-made substances that are listed as known endocrine disruptors by the European Commission‘s ‗Community Strategy for Endocrine Disruptors‘ (COM (1999)706), are fluoridated compounds. Fluoridated compounds form the basic building block of many insecticides and pesticides. Fluoridated elastomers are used in the plastics and silicon industries.

Fluoride is used because of its high chemical and biological reactivity. It is plausible that increased exposure to fluoride through water fluoridation may result in the creation of fluoride interactive xenobiotic compounds which are metabolised in the body and act as endocrine disruptors. A key therefore to limiting the effect of possible endocrine disruptors in the environment may be to limit the availability of fluoride or fluorsilicic compounds.

sis, secretion, transport, binding, action or elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, development and/or behaviour.614,615 Stated differently, such compounds

607 Luke J A, The Effect of Fluoride on the Physiology of the Pineal Gland, PhD dissertation School of Biological Sciences, University of Surrey, 1997

608 ATSDR (Agency for Toxic Substances and Disease Registry) (2001) Toxicological profile for fluoride. US Department of Health and Human Services, Atlanta, Georgia. 609 Camargo, J.A. Fluoride toxicity to aquatic organisms: a review. Chemosphere. 2003 Jan;50(3):251-64.

610 Connell, A.D., Airey, D.D., 1982. The chronic effects of fluoride on the estuarine amphipods Grandidierella lutosa and G. lignorum. Water Res. 16, 1313–1317. 611 McClurg, T.P., 1984. Effects of fluoride, cadmium and mercury on the estuarine prawn Penaeus indicus. Water SA 10, 40–45.

612 Reproductive History and Breast Cancer Risk, Factsheet, U.S National Cancer Institute, National Institutes of Health, Department of Health and Human Services. 613 Freedman DS, Khan LK, Serdula MK, Dietz WH, Srinivasan SR, and Berenson GS, Relation of Age at Menarche to Race, Time Period, and Anthropometric Dimensions: The Bogalusa Heart Study, Pediatrics 2002; 110:e43

614 Toxicological Profile for Fluorides, Hydrogen Fluoride, and Fluorine, U.S. Agency for Toxic Substances and Disease Registry, Dept Of Health & Human Services, 2003

may cause toxicities that are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, for example, metabolic, sexual, immune and neurobehavioural function.616

Such compounds are also thought to be involved in inducing breast, testicular and prostate cancers, as well as endometriosis.617,618,619

There is some data to suggest that fluoride does adversely affect some endocrine glands. An increase in serum thyronine levels, in the absence of changes in triiodothyronine and thyroid stimulating hormone levels, was observed in individuals living in areas of India with high fluoride levels in the drinking water.620

It is noteworthy that as, far back as 1991, the U.S. Public Health Service recommended that further research be undertaken including the conducting of analytical epidemiological studies to determine the relationship, if any, among fluoride intake, fluoride bone levels, diet and body levels of nutrients such as calcium. It was also recommended that research on bone fractures be carried out as well as studies on the reproductive toxicity of fluoride using various dose levels including the minimally toxic maternal dose. Further studies were also recommended to investigate whether or not fluoride is genotoxic.621

It is rather disturbing, given the implications for human health, that similar recommendations were made in the York Review (2001), raised again in the NRC review published in 2006, and once more by the SCHER review in 2010. As yet, to my knowledge, no such research has commenced.

340.3. U.S. Environmental Protection Agency.

616 Toxicological Profile for Fluorides, Hydrogen Fluoride, and Fluorine, U.S. Agency for Toxic Substances and Disease Registry, Dept Of Health & Human Services, 2003 617 Berger GS. 1994. Epidemiology of endometriosis. In: Berger GS, ed. Endometriosis: Advanced management and surgical techniques. New York, NY: Springer-Verlag. 618 Giwercman A, Carlsen E, Keiding N, et al. 1993. Evidence for increasing incidence of abnormalities of the human testis: A review. Environ Health Perspect Suppl 101(2):65-71.

619 Hoel DG, Davis DL, Miller AB, et al. 1992. Trends in cancer mortality in 15 industrialized countries, 1969-1986. J Natl Cancer Inst 84(5):313-320.

620 Michael M, Barot VV, Chinoy NJ. 1996. Investigations of soft tissue functions in fluorotic individuals of north Gujarat. Fluoride 29(2):63-71.

621Report of the Ad Hoc Subcommittee on Fluoride, Public Health Service
 Department Of Health And Human Services, February 1991.

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