That fluoride causes genetic damage in vitro is generally acknowledged. Sodium fluoride has been found to be mutagenic. Most of the in vitro cytogenic studies carried out with sodium fluoride demonstrate that it induces chromosome aberrations and sister chromatid exchanges, mainly chromatid gaps and breaks.549550,551,552,553 While it is accepted that the fluoride concentrations used in the in vitro studies were many times higher than the level often present in drinking water, alarmingly however a significant increase in Sister Chromatid Exchange (SCE) rate has been reported in fluorosis patients 554,555.
SCE analysis is a very sensitive measure of chromosome damage induced by some DNA damaging agent.556 Results from Sajayan et al.557 support the observation that there is a significant increase in the frequencies of chromosome aberrations and SCE in communities exposed to high levels of fluoride. The lymphocytes of these residents were also more susceptible, to a clastogen such as Mitomycin-C, than the other populations and displayed a significant increase in chromosome aberrations.
SCE was significantly increased in gastric cancer (GA) and chronic atrophic gastritis (CAG) patients. It is suggested that the increased SCE in patients reflects a genomic instability that may be operative in gastric
carcinogenesis.558
549 U.S National Toxicology Program Technical Report Series No. 393. Sodium Fluoride (CAS No. 7681-94-4) in F344/N rats and B6C3F1 mice (drinking water studies).
550 Gadhia PK, Joseph S. Sodium fluoride induced chromosome aberrations and sister chromatid exchange in cultured human lymphocytes. Fluoride 1997; 30(3):153-6. 551 Tsutsui T, Suzuki N, Ohmori M. Sodium fluoride induced morphological and
neoplastic transformation, chromosome aberrations, sister chromatid exchanges and unscheduled DNA synthesis in cultured Syrian hamster embryo cells. Cancer Res 1984;44,938-41.
552 Thomson EJ, Kilanowski FM, Perry PE. The effect of fluoride on chromosome aberrations and sister chromatid exchange frequencies in cultured human lymphocytes. Mutat Res 1985;144:89-92.
553 Sajayan Joseph, PK Gadhiaa Sister Chromatid Exchange Frequency And
Chromosome Aberrations In Residents Of Fluoride Endemic Regions Of South Gujarat, Fluoride Vol. 33 No. 4 154-158 2000 Research Report
554 Sheth FJ, Multani AS, Chinoy NJ. Sister chromatid exchanges: A study in fluorotic individuals of North Gujarat. Fluoride 1994;27(4):215-9.
555 Evans HJ, O‘Riordan ML. Human peripheral blood lymphocytes for the
analysis of chromosome aberrations in mutagen tests. Mutat Res 1975; 31:135-48. 556 Perry P. Evans H J. Cytological dctcction of mutagcncarcinogcn
cxposurc bv sister chromatid exchangc. Nature 1975: 258: 121 -5.
557 Sajayan Joseph, PK Gadhiaa Sister Chromatid Exchange Frequency And
Chromosome Aberrations In Residents Of Fluoride Endemic Regions Of South Gujarat, Fluoride Vol. 33 No. 4 154-158 2000 Research Report
558 Alteration of sister chromatid exchange frequencies in gastric cancer and chronic atrophic gastritis patients with and without H pylori infection by Ali Karaman, Doğan Nasir Binici, Mehmet Eşref Kabalar, Hakan Dursun, Ali Kurt, World Journal of
A person with gastric carcinoma has abnormal cells in the stomach that multiply out of control. These cells can form tumours and spread to other parts of the body. Gastric carcinoma is a serious healthcare concern and the
second most frequent malignancy worldwide.559 Nowadays it is accepted
that environmental factors play a significant role in the development of the
disease.560
The fact that fluoride has been demonstrated to significantly increase the SCE rate in humans and that gastric cancer patients have also been demonstrated to have increased SCE, presents a considerable risk factor for the percentage of the population that are known to be suffering from fluorosis in Ireland.
It can be assumed therefore that individuals with fluorosis may be considered at risk of developing gastric cancers or chronic atrophic gastritis (inflammation of the lining of the stomach). Given the association, the presence of fluoride or silicofluoride compounds in drinking water cannot be excluded as a possible likely cause of such disease.
As alarming is the fact that fluoride has been shown to cause genetic damage at a level of 1ppm, the level which is usually considered as being safe in fluoridation schemes.561,562,563,564,565,566 Bale et al.567 reported that “cytological analyses indicated that these treatments produced chromosome abnormalities, including bridges with or without fragments, univalents, fragments and micronuclei. The production of a significantly higher percentage of chromosomal aberrations by simultaneous treatment with a low concentration of sodium fluoride and dimethyl sulfoxide over that produced by treatment with low concentration of sodium fluoride alone indicates that dimethyl sulfoxide can enhance the uptake of the mutagen and thereby increase the mutagenic effect”.
Gastroenterology (2008) Volume: 14, Issue: 16, Publisher: The WJG Press and Baishideng, Pages: 2534-2539
559 Roukos DH. Relevant prognostic factors in gastric Cancer. Ann Surg 2000; 232:719-20. 560 Kabat G, Ng S, Wynder E. Tobacco, alcohol intake & diet in relation to
adenocarcinoma of the esophagus & gastric cardia. Cancer Causes Control.1993;4: 123. 561 S. S. Bale, G. E. Hart, Studies On The Cytogenetic And Genetic Effects Of Fluoride On Barley.: Ii. The Effects Of Treatments Of Seedling Coleoptiles With Sodium Fluoride, Canadian Journal of Genetics and Cytology, 1973, 15:(4) 703-712, 10.1139/g73-084 562 Cancer Research 44:938-941 (1984) and Mutagenesis 1:(2) 157-167 (1986)
563 W. L. Gabler, et al., " Effect of Fluoride on the Kinetics of Superoxide Generation by Fluoride," Journal of Dental Research, Vol. 64, p. 281 (1985).
564 A. S. Kozlyuk, et al., " Immune Status of Children in Chemically Contaminated Environments," Zdravookhranenie, Issue 3, pp. 6-9 (1987).
565 D. J. Newell, "Fluoridation of Water Supplies and Cancer - An Association," Applied Statistics, Vol. 26, No. 2, pp. 125-135 (1977).
566 Robert N Hoover, Frank W Mckay, Joseph F Fraumeni Jr. Fluoridated Drinking water and the occurance of cancer, Journal of national cancer institute Vol 57 No 4 october 1976, 757-768
567 S. S. Bale, G. E. Hart, Studies On The Cytogenetic And Genetic Effects Of Fluoride On Barley.: Ii. The Effects Of Treatments Of Seedling Coleoptiles With Sodium Fluoride, Canadian Journal of Genetics and Cytology, 1973, 15:(4) 703-712, 10.1139/g73-084
There is further data that supports the idea that fluorides can induce genetic alterations. Evidence indicating biochemical interactions of fluoride with the genetic mechanisms of cell division is presented in the U.S. NRC report568 on fluoride in drinking water.
Early research indicating a link between fluoride in drinking water and Down syndrome found that there was a significant relationship between residents in a fluoridated community and an increased prevalence of Down syndrome in younger mothers.569,570,571
While this research remains disputed the connection between fluoridation and Down syndrome was supported by AW Burgstahler in 1966572, 1975573 and in 1997.574 A review by Takahashi presenting evidence that fluoridation is associated with a higher incidence of Down syndrome was published in 1998.575
One of the most authoritative studies with relevant data comes from a study of births of children born in two areas of Atlanta, Georgia, as reported in 1976 by Erickson et al. 576,577 Two different estimates of the number of children with Down syndrome and normal children were presented. One estimate of Down syndrome births was made by the examination of copies of birth certificates and the other was based on hospital records.
A re-examination of Erickson‘s data by Burgstahler showed an overall enhancement of Down‘s Down syndrome births to mothers from the fluoridated area. Later, in 1998, Takahashi did a fine grain analysis of data from a number of sources that included the corrected numbers from the 1966
568 National Research Council of the National Academies, FLUORIDE IN DRINKING WATER, A Scientific Review of EPA‘s Standards, Ch. 8. Effects on the Endocrine System, Pages 259-260
569 Rapaport I. Contribution a l'etude du mongolism. role pathogenique du fluor. Bulletin de 1'Academie Nationale Medecine (Paris) 140 525-531 1956.
570 Rapaport I. Nouvelles Recherches sur le mongolisme a propos du role
pathogenique du fluor. Bulletin de 1'Academie Nationale Medecine (Paris) 143 367- 370 1959.
571 Rapaport I. Oligophrenie mongolienne et caries dentaire. Revue de Stomatologie et de Chirurgie Maxillo-Faciale 64 207-218 1963
572 Burgstahler, A. W. (1966) Fluoridated water and Down‘s syndrome. Long abstract of a report of the 21st Conference of the International Society for Brain Research, Budapest.
573 Burgstahler AW. Fluoride and Down‘s Syndrome (Mongolism). (Editorial review). Fluoride 1975;8:1-11, 120
574 Burgstahler AW. Fluoridated water and Down‘s Syndrome. (Abstract). Fluoride, 1997;30:113.
575 Takahashi K. Fluoride-linked Down Syndrome births and their estimated occurrence due to water fluoridation. Fluoride 1998;31:61-73.
576 Erickson JD, Oakley GP, Flynt JW, Hay S. Water fluoridation and congenital
malformations: No association. Journal of the American Dental Association 93 981-984 1976; 95 476 1977.
577 Erickson JD. Down syndrome, water fluoridation, and maternal age. Teratology 21 177-180 1980.
Erickson report.578 In the Takahashi report a clear-cut relationship between fluoride exposure and the number of affected children was found in mothers 30 years of age and younger. While this study has been disputed a recent re- examination of the data by Professor L. Isaacson579, Binghamton Public Research University, New York and Professor Juan C. Molino580 found the same age-fluoride- Down syndrome birth effect using only data from hospital records.581
It is estimated that there are approximately 7,000 people in Ireland with Down syndrome, with one baby in every 546 births born with the congenital chromosomal anomaly.582 Many of the associated health conditions with Down syndrome are also linked to potential fluoride toxicity including thyroid, neurological problems and gastro-intestinal problems as well as childhood cancers.
It is important to clarify that the research does not conclude that water fluoridation is the cause itself of Down syndrome. The previous research indicated that exposure to fluoride through water fluoridation appeared to increase the incidence of mothers, thirty years of age or younger, to having a child with Down syndrome.
It may be, though it is unproven, that the increased risk association may exist through the interaction of fluoride in Homocysteine Metabolism. As noted previously in this report, it has been found that Homocysteine metabolism is a risk factor for Down syndrome (DS). Fluoride is known to be an inhibitor of enzymatic activity and research has identified fluoride as an inhibitor of homocysteine hydrolase.583 Inhibition of homocysteine hydrolase would result in cellular accumulation of homocysteine.584
578 Takahashi, K. (1998) Fluoride-linked Down syndrome births and their estimated occurrence due to water fluoridation. Fluoride, 31: 61-73.
579 Robert L. Isaacson, Emeritus, Distinguished Professor of Psychology Ph.D.,
Binghamton University, New York. Member, National Research Council committee on possible toxic effects of Fluoride in drinking water, 2004-2005. Former Director, Center for Neurobehavioral Sciences, Past President, International Behavioral Neuroscience Society (IBNS), Fellow: American Psychological Society, Fellow: IBNS, Member, American Physiologic Society and Visiting Lecturer for Minority Institution, Member Editorial Boards: Brain Research . Past service on several NIH and NIMH Review Panels and Committees, Chairman and member of several committees for the Society for Neuroscience, Member, NRC Committee for the evaluation of possible hazards of fluoride in drinking water.
580 Dr. Juan Carlos Molina is the Director of the Ferryra Research Institute at the University of Cordoba, Argentina, as well as holding his distinguished professor position there. He also is a visiting research professor at Binghamton University.
581 My Views on the Fluoridation of Water Robert L. Isaacson Distinguished Professor of Psychology Binghamton University (See Appendices)
582 Downs Syndrome Ireland Statistics
583 Mehdi S, Jarvi ET, Koehl JR, McCarthy JR, Bey P. The mechanism of inhibition of S- adenosyl-L-homocysteine hydrolase by fluorine-containing adenosine analogs. J Enzyme Inhib. 1990;4(1):1-13.
584Liu S, Wnuk S F, Yuan C, Robins M J, Borchardt R T, Adenosine-5'-carboxaldehyde: a potent inhibitor of S-adenosyl-L-homocysteine hydrolase, J. Med. Chem., 1993, 36
It is known that Down syndrome is most common in infants of women thirty five years or older and that the incidence of Down Syndrome increases with increasing maternal age. It has been documented that women in Ireland are having children at later ages, therefore the overall incidence of Down Syndrome is likely to increase.585 Generally Down syndrome occurs in 1 in 800 births and while Ireland may have a higher than average incidence of Down Syndrome, the significance of the relationship between fluoride exposure and homocysteine metabolism cannot be underestimated. Particularly when fluoride is a persistent toxic substance that poses a specific risk to human health and a toxin which demonstrates a linear accumulation in the human body over time.
It is medically plausible therefore, given that fluoride increases in the body in a linear fashion with age, that older women having higher exposure to fluoride with parallel increases in homocysteine levels, may subsequently have a greater risk of having children with Down syndrome.
It is interesting to note that other independent research has documented that there was a statistically notable increase in the incidence of Down syndrome worldwide for young mothers in the age group 20-24yrs and 25-29yrs between 1984-2002 compared to the period 1962-1983.586 The general consensus however, from current research, appears to be that the increased incidence of genetic abnormalities in infants appears to be linked to environmental exposures to some as yet unknown contaminant.
In acknowledging this, one must also be aware that fluoride has in the past forty years become one of the most widely available conmtaminants that is present in artificially elevated concentrations in fluoridated drinking water, processed foods and drinks prepared with treated water as well as cooked foods prepared with fluoridated water. As a consequence the daily intake and exposure of the population to fluoride is now considerably higher than that of previous generations.
It is remarkable, therefore, that to this author‘s knowledge, no clinical studies have been undertaken to establish the likelihood that water fluoridation, fluoride or in particular silicafluoride interactive compounds may be a contributory factor to the increase in the risk of congenital chromosomal anomaly. This is particularly alarming given that a recent study by Machalinski et al.587 reported that the four different human leukemic cell lines were susceptible to the effects of sodium hexafluorosilicicte. It is worth observing that there is a much higher incidence of kidney, bladder, colorectum, brain and leukaemia cancer in Ireland compared to the average worldwide (7), pp 883–887
585 Hock, E.G. Lindsjo, A Down Syndrome in Live Births by Single Year Maternal Age. 586 World Wide Incidence of Down Syndrome, Stephen G. Read, Learning Disability Research Unit, University of Huddersfield
587 Machaliński B, Baskiewicz-Masiuk M, Sadowska B, Machalinska M, Marchlewicz M, Wiszniewska B, et al. The influence of sodium fluoride and sodium hexafluorosilicicte on human leukemic cell lines: preliminary report. Fluoride 2003;36;231-40
statistics based on figures compiled for 182 countries588.
The importance of such studies cannot be overestimated as it is known that fluoride does cross the placenta from the mother's blood to the developing foetus.589 According to the Agency for Toxic Substances and Disease Registry USA Public Health Service ―it is not known whether fluoride causes birth defects in people or animals. Fluoride does cross the placenta from the mother's blood to the developing fetus. No experiments have studied developmental effects of fluoride using standard testing methods. Some animal studies have found developmental effects of fluoride”.
It is obvious that to continue with any policy that effects the population at large in such an uncontrolled manner as fluoridation of the nation‘s drinking water supply, and without adequate testing to conclusively demonstrate that there are no health impacts, is completely unacceptable.
588 Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, International Journal of Cancer Volume 127, Issue 12, pages 2893–2917, 15 December 2010 and National Cancer register of Ireland.
589 Toxicological Profile For Fluorides, Hydrogen Fluoride, And Fluorine, Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, April 1993
The significance of any association between fluoride, gastric carcinoma, peptic ulcers, homocysteine metabolism, genetic abnormalities or other critical diseases cannot be underestimated. These findings are of major significance demanding, in the interests of public health and safety, an immediate response from the State requiring the cessation of the water fluoridation policy without delay.