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Fluoride is a developmental Nephrotoxin – coming to a Kidney near you


Abstract and Figures

Fluoride causes excess suffering and death by initiating and exacerbating kidney disease, which in turn causes a cascade of secondary, often fatal, diseases. This review demonstrates that proponents of water Fluoridation have attempted to suppress evidence of harm to the population at large and especially vulnerable groups with impaired renal function.
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Fluoride is a developmental Nephrotoxin
coming to a Kidney near you
Geoff N Pain
January 2017
Fluoride causes excess suffering and death by initiating and exacerbating kidney disease,
which in turn causes a cascade of secondary, often fatal, diseases. This review
demonstrates that proponents of water Fluoridation have attempted to suppress evidence of
harm to the population at large and especially vulnerable groups with impaired renal
Keywords: Aborigine, Apoptosis, Cancer, Caspase, Chronic Pain, Drinking Water, Enzyme,
Fluoridation, Fluoride, FSANZ, Hemodialysis, Hyperphosphaturea, Hypertension,
Hypophosphatemia, Iodine, Kidney, Mutagen, Nephrolithiasis, Nephrotoxin, NHMRC,
Osteomalacia, Osteitis Fibrosa, Osteosclerosis, Osteodystrophy, Public Health,
Pyelonephritis, Secondary Hyperparathyroidism, Suppression, Uremia
The myth that fluoride protects against tooth erosion persists despite the sophisticated
studies of leading experts in dentistry who have shown that high fluoride concentration
toothpaste does not work [Magalhães 2008]. Deliberate contamination of community drinking
water with industrial waste fluoride is a process called fluoridation, mass medication.
As noted on bags of this industrial waste, the vendors state quite clearly the human health
hazards and “target organs” of the poison including the heart, kidneys, bones, central
nervous system, gastrointestinal system and teeth.
This review focuses on the kidneys. Thousands of person years expended by eminent
scientists applying the best available technology has resulted in hundreds of peer-reviewed
scientific publications as outlined in the references, ignored by politicians and bureaucrats.
Fluoride is a Developmental Nephrotoxin
Nephrotoxin is not a term familiar to many people and some vested interests would like to
see that situation continue. It means a toxic agent or substance that inhibits, damages or
destroys the cells and/or tissues of the kidneys.
The link between fluoride and kidney disease has been known and confirmed in animal and
human studies since earlier than the 1890s [Hewelke 1890, Shortt 1937, Linsman 1943,
Isaacson 1997] and has even been admitted by early fluoridation proponents [Heyroth
This quote is typical of early warnings:
The question of the effect of water containing 1 ppm upon patients with severe impairment
of kidney function requires special consideration in view of the fact that radiologic evidence
of chronic fluorosis has been found in two persons with severe kidney disease who died at
the early ages of 22 and 23 years, respectively…” [Heyroth 1952].
Chronic renal failure induced by fluoride is well known in man as well as test animals and is
dose dependent [Roholm 1937, Bond 1952, Kawahara 1956, Ramseyer 1957, Manocha
1975, Waldbott 1978, Jolly 1980, Kour 1980, Reggabi 1984, Kessabi 1985, Lantz 1987,
Dote 2000, Harinarayan 2006, Xiong 2007].
There are a number of excellent reviews which cover the impact of fluoride on the kidney
and show the progression of fluoride toxicology understanding over time [Roholm 1937,
Jankauskas 1974, NRC 2006, Strunecka 2007, Connett 2009, Osvath 2009, Connett 2010,
Prystupa 2011, Waugh 2012, FFNZ 2014, Brockovich 2015] and the interested reader is
encouraged to follow online resources that are updated regularly [SLWEB] and especially
the database of the Fluoride Action Network [FAN 2017].
Recent work has confirmed that fluoride damages the kidneys of the foetus and suckling
mammal [Niu 2016]. Using mice, exposure of the mother to fluoride in drinking water was
found to produce a significant increase (p<0.05) in the malondialdehyde (MDA) content and
a significant decrease (p<0.05) in the catalase (CAT) activity of the pups. The CAT mRNA
level was increased (p<0.05) in the low and medium fluoride groups, compared with the
Experiments on human babies showed they retained 75.4 to 87.6% of the toxin and this
decreased significantly with age [Ekstrand 1994].
The World Health Organization is acutely aware that fluoride is a kidney toxin, recently citing
the finding that approximately 100,000 individuals in the Assam region in India have been
taken ill with kidney failure, stiff joints and anaemia as a result of high natural levels of
fluoride in the water [WHO 2015]. Similar results have been found in other parts of India
[Hindu 2017] and Sri Lanka [Dharmaratne 2015].
WHO ranks the toxicity of fluoride between that of Lead and Arsenic, both of which have
target values for ingestion of zero.
The consumption of tea is a major risk factor for kidney disease due to its high fluoride
content [Schmidt 1984, Cao 2001, Whyte 2006, Chandrajith 2007, Isbel 2010, Pehrsson
2011, Waugh 2016], however governments seem reluctant to warn of the tea hazard.
Perhaps mentioning the risks posed by the fluoride content of food and drink would make
people ponder the claimed “need” for water fluoridation [McLure 1949, Zhang L 2015].
In the United States it is recognized that “subsets of the population may be unusually
susceptible to the toxic effects of fluoride and its compounds. These populations include the
elderly, people with deficiencies of calcium, magnesium, and/or vitamin C, and people with
cardiovascular and kidney problems.” [CDC ATSDR 1993].
It was not until 2008 that the US National Kidney Foundation publicly recognized the fluoride
harm caused to sufferers of Chronic Kidney Disease (CKD) [NKF 2008] and it is interesting
that the NKF referred to a paper by Kidney Health Australia [KHA 2007].
It has been known for many decades that people with renal insufficiency have impaired renal
clearance of fluoride [Juncos 1972], accelerating the progress of other fluoride diseases.
In 1975 Sir Edward Dunlop warned against the risks of fluoridation, stating “Cases of kidney
disease are a special risk due to poor elimination of fluoride and consideration of thirst”
[Dunlop 1975].
Animal studies have shown damage to the kidneys directly caused by Fluoride [Battelle
Laboratories]. Early experimentation was performed by the University of Rochester as part of
the United States war effort, with kidney damage being reported after injection of beryllium
oxyfluoride or inhalation of uranium oxyfluoride in dogs [Bryson 2006]. Severe kidney
damage was found on autopsy of humans who inhaled uranium hexafluoride or hydrogen
fluoride [Mears 1945 cited in Bryson 2006].
Suffering and Deaths of Kidney Patients on Dialysis caused by Fluoride
People on kidney dialysis are particularly susceptible to the use of fluoridated water in the
dialysis machine which is supposed to clear their blood of toxins.
Bryson documents a case from 1962 of a woman who died suddenly after a dialysis session
that was reported without mention of the high fluoride content of the patient’s blood and
bone [Kretchmar 1962, Taves 1963, Bryson 2006].
Despite this early tragedy, papers appeared over the following decades highlighting damage
done by fluoride to dialysis patients through failure to eliminate the fluoride hazard [Taves
1965, Taves 1968, deVeber 1970, Posen 1971, Posen 1972, Jowsey 1972, Cordy 1974,
Johnson 1974, Anderson 1980, McIvor 1983, Gessner 1994, Tanimura 1994, Takahashi
1995, Frost 2013].
In 1979 a study of dialysis patients versus controls reported “Five of the six patients exposed
to fluoridated dialysate for an average of 23 months suffered bone pain and fractures, and
three of these patients had incapacitating symptoms. Bone biopsy specimens from five
patients exposed to fluoridated dialysate for more than 1 year were compared with those
from six patients of approximately the same age, duration of azotemia, and duration of
dialysis who were dialyzed using fluoride-free dialysate. The blood concentrations and ratios
of bone fluoride to calcium were significantly higher in patients exposed to fluoridated
dialysate. Although the severity of osteitis fibrosis was similar in the two groups, as reflected
by the percentage of bone surface undergoing osteoclastic resorption, osteomalacia was
significantly more severe in the fluoridated group. [Johnson 1979].
In 1979 1,000 gallons of 22 % hydrofluorosilicic acid were accidentally added to the
Annapolis, Maryland public water system, resulting in fluoride tap water levels of 30 to 50
ppm [McIvor 1983]. A dialysis unit served by this system treated water only with a softener to
prepare dialysate in the absence of deionizer or reverse osmosis. Two days after the
accident, 8 hemodialysis patients became ill with hypotension, nausea, substernal pain,
diarrhea, vomiting and itching. One patient died at home. Another patient was resuscitated
after a cardiopulmonary arrest that may have been the result of fluoride-induced
In 1993, patients on dialysis at the Chicago Medical Center were exposed to fluoridated
water, resulting in 3 deaths from cardiac arrest and harm to at least 9 others [Arnow 1994].
This incident involved human negligence because a water treatment system with completely
exhausted ion exchange resin in the deionization tanks was used.
The Government of New South Wales has published guidelines to help prevent further tragic
loss of life among dialysis patients, noting that fluoride can cause death in this vulnerable
group [NSW 2016].
Increased risk of Death and harm by fluoride from Anaesthetics
Inhalational drug exposure is a major risk to numerous organs, often causing death from
hyperthermia or neurological damage. Victims of fluoride induced malignant hyperthermia
suffer renal dysfunction [Dong-Cham Kim 2012].
The hepatic biotransformation of fluorocarbon anesthetics such as methoxyflurane to release
free serum fluoride, results in nephrotoxicity which has been intensively studied for almost 5
decades [Whitford 1971, Cousins 1972, 1973, Gottlieb 1974, Cousins 1976, Mazze 1976,
Frink 1992, Newman 1994, Conzen 1995, Higuchi 1995, Nishiyama 1996, Nuscheler 1996,
Eger-Il 1997, Hara 1998, Lochhead 1998, McGrath 1998, Akansel 1999, Groudine 1999,
Kasume 1999, Hase 2000, Obata 2000, Kusume 2009, Conzen 2002, Partanen 2002,
Abdel-Latif 2003, Al Sayed 2003, Jang 2005, Kharasch 2006, Rohm 2009].
Post-anesthesia peak plasma F- levels in afflicted humans exceeded 90 µmol/l [Cousins
1972, cited in Marier 1977].
The primary target organ apart from the heart and brain for most studies of the anaesthetic
fluoride hazard is the kidney - yet Australian health administrators are reluctant to discuss
the problem and its effects in public.
Vicious Cycle of Fluoride Kidney Damage and Diabetes
Patients with reduced glomerular filtration rates have a decreased ability to excrete fluoride
in the urine, leading to elevated serum fluoride levels, up to 5 times normal [Hanhijarvi 1975,
Seidenberg 1976] and development of dental and skeletal fluorosis even at normal
recommended limit of 0.7 to 1.2 mg/l [Call 1965, Juncos 1972, Groth 1973, Marier 1977,
Johnson 1979, Waterhouse 1980, Fisher 1981,Hanhijärvi 1981, Schiffl 1980, Arnala 1985,
Boivin 1985, Hileman 1988, Rao 1988, Fisher 1989, Pak 1989, Kraenzlin 1990, Tanimura
1994, Bansal 2006, Lyaruu 2008, Schiffl 2008, Itai 2010].
In the Netherlands, which banned water fluoridation many decades ago, the government
warned nephritic patients to restrict their total daily intake of fluoride to less than 1.5 mg per
day [NIHEP 1989]. This was based on one study that showed average retention of fluoride in
kidney patients of 65% compared to 20% in healthy patients. It was subsequently shown that
healthy patients retain 50% of their daily fluoride intake. Kidney patients are advised to avoid
promoted fluoridated dental such as toothpaste, gels and rinses [Torra 1998].
In Australia, health officials are not keen to talk about the fact that people with kidney
impairment have a lower margin of safety for fluoride intake. However, buried in little seen
documents, NHMRC Australian Drinking Water Guidelines 2004 and 2011, they state
Limited data indicate that their fluoride retention may be up to three times normal ” [ADWG].
Higher rates of kidney disease set up a vicious cycle as increased thirst and water
consumption and reduced fluoride elimination results in higher individual dosages and
increased risk of inflammatory symptoms and toxicity.
Fluoride toxicity is greater in diabetic mammals. In rats, fluoride reduces weight gain
compared to the effect in non-diabetic rats. Diabetic rats also develop fluoride induced
anaemia with lower red blood corpuscles and haemoglobin and have much higher levels of
alkaline phosphatase, indicating abnormal bone formation [Banu Priya 1997].
Impaired renal clearance of fluoride has been found in people with diabetes mellitus and
cardiac insufficiency [Hanhijarvi 1974].
Fluoride causes diabetes by reducing insulin production and insulin receptor function as
reviewed previously [Pain 2015b]. Diabetes is the leading cause of kidney failure, accounting
for 44% of all new cases of kidney failure in the USA in 2008 [NIDDK 2008].
Subjects with nephropathic diabetes can exhibit a polydipsia-polyurea syndrome that results
in increased intake of fluoride, along with greater-than-normal retention of a given fluoride
dosage [Marier 1975]. It was found that patients with polydipsia consume up to 6 times the
normal amount of water, massively increasing the toxic effects of fluoridation [Greenberg
Secondary hyperparathyroidism
Serum calcium deficiency caused by fluoride can induce secondary hyperparathyroidism
[Teotia 1973, Suketa 1983, Pettifor 1989, Lundy 1995, Fujita 2000, Gupta 2008, Gayathri
Secondary hyperparathyroidism can contribute to a number of diseases [Kurdi 2016].
degenerative neurological disease
diabetes mellitus
muscular dystrophy
colorectal carcinoma
Rickets and other bone diseases
Disfiguring tooth defects known as dental or enamel fluorosis, or enamel hypoplasia, is
hypomineralization of the enamel surface of the tooth caused by fluoride and occurs in
nearly half of fluoridated Americans.
Children with renal disease are known to suffer more severe dental fluorosis than children
without renal disease [Lucas 2005, Ibarra-Santana 2007].
Deliberate human experimentation comparing fluoride treated patients versus placebo
proved the destructive influence of fluoride on bone.
The scientists reported that in the fluoride-treated patients, “we observed osteoclasts
resorbing bone beneath osteoid seams, and fragments of osteoid isolated in the bone
marrow. This type of resorption beneath unmineralized bone matrix is often observed in
osteomalacia, particularly that caused by renal abnormalities and associated secondary
hyperparathyroidism.” [Lundy 1995 cited in Connett].
Fluoride induces severe bone disease in people with kidney failure [Morris 1965, Taves
1968, deVeber 1970, Posen 1971, Jowsey 1972, Cordy 1974, Johnson 1974]. High doses of
vitamin D were found to enhance the destructive influence of fluoride [Posen 1971].
The need to protect kidney patients from bone damage caused by fluoride was known and
well described in the 1960s as the following quote demonstrates:
within a year after starting dialysis the patient complained of chest pain and pain in the feet,
and the skeletal radiologic survey showed generalized demineralization and fractures of the
fifth through the eighth ribs posteriorly. In spite of a good appetite and a good intake of food,
his body weight decreased by 11kg. Because we had not seen such severe bone disease in
a patient while on relatively high concentrations of dialysate calcium when fluoride-free water
had been employed, we recommended in October, 1968, that a commercial mixed-bed
deionizer be installed to remove the fluoride. Bone resorption decreased and osteomalacia
improved, coincident with the lowering of dialysate, serum and bone concentrations of
fluoride… The excessive amounts of osteoid seen in the bone biopsy specimen and the
decrease in osteomalacia subsequent to correcting the deionizer operation are consistent
with a fluoride effect.” [Johnson 1974 cited in Connett].
Another research group reported “All 4 patients exposed to high-fluoride dialysate showed
excessive osteoid formation… Osteoid formation was 9 times greater in those exposed to
high-fluoride dialysate (1 ppm) than in those exposed to lower concentrations (0.095 ppm)…
The presence of increased amounts of osteoid tissue in patients exposed to high-F dialysate
is consistent with the observations of DeVeber and associates… Increased osteoid is
typically found in fluorosis, hence, ascribing our findings to an F effect seems reasonable.
There are several possible reasons for F causing increased osteoid. In vivo, excessive F can
result in increased bone production and failure of mineralization… It may be noteworthy that
4 of the 5 patients with the most disabling symptoms of bone pain, muscle weakness,
wasting and multiple spontaneous fractures were exposed to high-F dialysate. This would
suggest that prolonged exposure to F can contribute to the bone disease seen in long-term
hemodialysis… The use of F-free dialysate decreases the risk of severe morphologic
osteomalacia.” [Jowsey 1972 cited in Connett].
Osteomalacia is a bone-softening disease which makes bone more subject to fracture. It is a
well-established effect from excessive fluoride exposure and is often found in people with
skeletal fluorosis [Cohen-Salal 1996, Turner 1996, Cortet 2000, Harinarayan 2006].
Osteomalacia is a direct result of fluoride treatment [Cordy 1974, Boivin 1989].
People with renal failure can have a four-fold increase in skeletal fluoride content, and have
higher risk of spontaneous bone fractures, even at 1.0 ppm fluoride in drinking water [Reddy
1993, Cohen-Solal 1996, Turner 1996, Cortet 2000, Mathias 2000, Ayoob 2006, Bansal
2006, NRC 2006].
People with impaired kidneys have over 3,800 mg F/kg after only 15 years exposure [Health
Canada 1993]. Osteoid volume was increased over 20-fold in animals with renal deficiency
that received 15 or 50 ppm fluoride [Turner 1996].
Due to absence of adequate medical training, skeletal fluorosis is often mistaken for rickets,
renal osteodystrophy, osteosclerosis and hereditary osteopathies [Teotia 1998].
Osteosclerosis, osteopenia, and calcification of ligaments and tendons are common in end-
stage kidney disease [Applbaum 2010]. A bone biopsy series to assess the effects of trace
metals in 153 CKD patients treated with hemodialysis or peritoneal dialysis revealed that
increased fluoride was associated with poor mineralization and increased osteoid content
[Ng 2004].
Stress fractures have been induced in patients treated with fluoride [Orcel 1990].
As pointed out by numerous authors, renal osteodystrophy may be difficult to distinguish
from skeletal fluorosis on imaging studies. The mechanism of renal osteodystrophy
development is complex including calcium, phosphorus, parathyroid hormone and vitamin D
interactions [NKF 2008]. Sometimes the information is presented in languages other than
English [Noël 1985] and therefore specifically excluded and deliberately ignored by
governments in Australia, New Zealand and the United States in so-called “systematic
Defects in renal transepithelial transport of phosphate leads to a decrease in tubular re-
absorption of phosphate, hyperphosphaturea and persistent hypophosphatemia [Ando 2001,
Souza 2013].
Calcium regulation is maintained by parathyroid hormone (PTH), vitamin D, and calcitonin
through complex feedback. These compounds act primarily at bone, kidney, and
gastrointestinal sites.
Parathyroid Hormone (PTH) stimulates osteoclast activity and calcium is released from the
bone. PTH also acts on the kidneys to decrease urinary calcium excretion and increase an
intermediary that acts on the intestines to increase calcium absorption.
High bone turnover, with increased bone resorption, compromises bone strength, leading to
thinning of the bone structure, abnormal bone microarchitecture and reduced bone
mineralization. Fluoride exposure via drinking water results in elevated levels of alkaline
phosphatise (ALP), potassium, magnesium, calcium, and phosphate, and decreased levels
of thyroid hormone T3 and uric acid.
Calcification of soft tissues
Fluoride plays a crucial role in calcification of soft tissues by formation of fluoride doped
hydroxyapatite with devastating consequences including heart attack, stroke and cancer
[Hamuro 1972, Bonavita 1980, Suketa 1983, Jensen 1988, Hayes 1990, Murao 2000, Garcia
2003, Inkielewitz 2003, Applbaum 2010, Yang 2011, Zhang 2013, Pain 2015c].
Hydroxyapatite Disease is known to be associated with kidney damage.
Fluoridation of drinking water at 1.5mg/L (a concentration perversely recommended by the
WHO and more than double the level of 0.7 mg/l recently set by the Obama administration)
dramatically increased the incipient aortic calcification observed in rats with experimental
chronic kidney disease (CKD, 5/6-nephrectomy), fed a phosphate-rich fodder (1.2%
Phosphate). Fluoride further declined the remaining renal function of the CKD animals
[Martín-Pardillos 2014]. Aortic calcification in humans can lead to sudden death through
rupture, as previously reviewed [Pain 2016].
Bio-accumulation of Fluoride in the Kidney
Fluoride is a bio-accumulative toxin [Dunipace 1988]. Cows kidneys fluoride increased from
7 ppm to 43 ppm when deliberately fed fluoride contaminated grain containing 880 ppm F
dry weight. In comparison non-poisoned Guinea pig kidney contained only 0.06 ppm F wet
weight [McLure 1949].
The use of the artificial Fluoride radioactive
isotope 18F allows direct imaging of where the
Fluoride attaches to critical body sites. Each
black dot is formed by disintegration of a
fluorine atom releasing a high energy particle.
The figure at left [Gerety 2015] shows how the
body attempts to remove the toxin rapidly by
concentrating fluoride through the kidneys and
bladder. Note the sites of attack of the toxin.
The age/weight- based estimated absorbed
radiation doses (mGy/MBq) from intravenous
injection of Sodium Fluoride F 18 injection is
shown in the figure below. Note the high
concentration in the kidneys.
Fluoride causes Nephrolithiasis - Kidney Stones
Disturbance of ion balance by fluoride can lead to kidney stones [Jolly 1980, Juuti 1980,
Verma 1990, Singh 2001, Rathee 2004, Kurland 2009]. Calcium accumulation was found to
be remarkably increased by the addition of fluoride normal rat kidney epithelial cell line
(NRK-52E cells). The elevation of [Ca2+] was demonstrated to be due to calcium entry
through nifedipine-sensitive calcium channels [Murao 2000].
Kidney stones have been found in humans with over 500 ppm fluoride [Herman 1956,
Rathee 2004].
The 2007 NHMRC review did admit in passing that fluoride is a known cause of kidney stone
disease [NHMRC 2007].
Pyelonephritis cascade
Kidney stones can cause pyelonephritis by allowing bacteria to enter the kidney.
The people of Townsville were used as an experimental set for fluoridation from 1964, when
the rest of the Queensland population were not fluoridated. Townsville residents suffer
significantly higher rate of pyelonephritis [PHIDU 2005]. It is significant that Townsville was
chosen as the first location for the chronic kidney disease screening programme in Australia
in 2008 [SD 2008].
People with chronic pyelonephritis suffer a series of health problems including progressive
muscular weakness, fatigue, and increasingly severe pain [Fisher 1981].
In a postmortem study in Utah [Call 1965] the highest concentrations of fluorine were found
in those with chronic pyelonephritis. In chronic pyelonephritis there is commonly a defect of
water conservation with polyuria and polydipsia which can lead to skeletal fluorosis even
with low levels of fluoride in drinking water [Sauerbruun 1965]. People with advanced
bilateral pyelonephritis have skeletal fluoride content that can be 4 times that of similarly-
exposed persons with normal kidneys [Marier 1977, Mernagh 1977].
Pyelonephritis leads to a cascade of disaster including:
Increased vascular calcification
Reduced Bone Mineral Density
Increased Fracture Risk
Excess morbidity and mortality (polite word for death)
Death from fluoride induced chronic kidney disease is a major concern in countries like Sri
Lanka [Dharmaratne 2015] and India [Hindu 2017] as well as Australia.
Kidney Cancer caused by fluoride
Significantly higher rate of kidney cancer was found for females in fluoridated communities
[Hoover 1991, Takahashi 2001]. According to the US National Toxicology Program the
preponderance of evidence from laboratory in vitro studies indicate that fluoride is a
mutagenic compound. Many substances which are mutagens are also carcinogens. The
graph below highlights the effect of fluoridation on kidney cancer risk [Osmunson 2015].
Kidney failure induced by fluoride will increase the cancer rates throughout the body by the
accumulation of more fluoride [Pain 2015c]. In 2016 the US NTP announced that it was
conducting a new literature review in carcinogenicity of fluoride.
Mechanisms of fluoride damage to the Kidney
Human kidneys concentrate fluoride as much as 50-fold from plasma to urine [NRC 2006]
making kidney cells a target for fluoride toxicity [Hongslo 1980, Whitford 1996, Collins 2005].
As discussed for the neurotoxic mechanisms of fluoride destruction of the central nervous
system [Pain 2017], the nephrotoxic effects of fluoride appear to follow universal
mechanisms found in a wide variety of cells [Barbier 2010, Agalakova 2012].
The mechanisms of fluoride nephrotoxicity can be summarized under the following headings:
Mutation and abnormal embryo development with altered expression
Altered enzyme levels and enzyme inhibition
Oxidative stress with generation of reactive oxygen species and radicals
Apoptosis via mitochondria mediated and Caspase dependent pathways
Disruption of ion channels affecting pH, cation and anion balance
Physical damage from calcification including microcrystals and Kidney stones
Mutation and abnormal Embryo development with altered expression
Many studies have shown that exposure to F can cause morphological and functional
changes in the kidney [Siddiqui 1955, Kawahara 1956, Pindborg 1957, Lindemann 1959,
Taylor 1961, Singh 1963, Poulson 1965, Takagi 1982, Greenberg 1986,Turner 1989, Kapoor
1993, Varner 1998, Karaoz 2004, Bouaziz 2005, Shashi 2002, Zhang 2013].
Fluoride disrupts collagen synthesis in various organs including the kidney [Susheela 1981].
In the 1970s it was shown that hemodialysis with fluoridated water in chronic renal failure
induces activated osteoblasts to produce excessive osteoid in which the collagen fibrils are
disarrayed [Posen 1972, Lough 1975].
Electron microscopy has enabled much closer inspection of damage caused by fluoride
[Lough 1975, Bhatnagar 1998]. Fluoride causes expansion of renal tubules [Shashi 2002],
vacuolar degeneration, glomerular atrophy and necrosis, and disruption of the integrity of the
epithelium in renal tubules [Chattopadhyay 2011].
As found for humans, rodents largely prevent transfer of the fluoride toxin to their young via
milk. However immediately post weaning, the young mammal is vulnerable as indicated by
this quote re postweaning rats: “exposure resulted in increased kidney weight and
kidney/body weight ratio, profound diuresis, decreased urinary osmolality, and decreased
ability to concentrate urine during water deprivation. Urinary chloride excretion was
decreased for the first 2 days after NaF exposure, then increased in water-deprived rats 120
hr after treatment. Glucosuria and hematuria were present for 2 days after treatment with 48
mg/kg. Histological lesions were apparent in the proximal tubules of the treated Day 29 rats
[Daston 1985].
Early work suggested the possibility of a relationship between fluoride exposure and
increased excretion of albumin in the urine [Derryberry 1963, Kumar 1963].
Exposure to fluoride in drinking water produces statistically significant decrease in creatinine
clearance [Singla 1976].
Fluoride nephropathy results in decreased fluoride excretion and appearance of urinary B2
microglobulin [Cao 2001].
Fluoride inhibits DNA synthesis [Hellung-Larsen 1969] as well as protein synthesis [Holland
1979]. Accumulation of fluoride suppresses the synthesis of RNA in the kidney [Guan 1991].
A dose of 1mM sodium fluoride applied to human Embryonic Stem Cells (hESCs), disturbs
gene expression patterns during embryo differentiation by suppressing the expression of
endoderm markers while enhancing the expression of ectoderm, mesoderm and
osteogenesis markers [Fu 2016].
Proteomic analysis has opened up the possibility of gaining further insights in fluoride
nephrotoxicity [Xu 2005, Kobayashi 2009, Lu 2010, Carvalho 2013].
Recent proteomic analysis detected 37 serum proteins with altered expression as a result of
fluoride in drinking water given to rats [Wei 2016]. At present scientists have not identified all
the harms caused by this effect, with initial studies confined to fluorosis.
Mitochondria - prime targets for fluoride toxicity
As expected, much research on fluoride nephrotoxicity has focused on the damage done in
mitochondria [Radi 1993, Barbier 2010, Basha 2013]. Using cultured human kidney
collecting duct cells, morphological damage by fluoride was evident at 1mM concentration
with inhibition of Na-K-ATPase at 5mM [Cittanova 1996].
Crystalline deposits were observed in mitochondria treated with fluoride [Cittanova 1996].
Mitochondrial membrane microviscosity impairment caused by fluoride has been observed in
rat kidneys [Samanta 1016]. Work on fluoride-induced osteoblast apoptosis found it may
occur via the mitochondrial pathway (including endoplasmic reticulum stress pathway) and
death receptor pathway. Bcl-2 interacting mediator of cell death (Bim), Caspase 9, Caspase
14, B-cell lymphoma-2 (BCL2) and BAX increased with the doses of sodium fluoride in
osteoblasts [Zhang 2015].
Altered Enzyme Levels
Fluoride has long been known to interfere with numerous essential biological processes in
the kidney. Acetate activation was studied with homogenized kidney where fluoride inhibited
the reaction at a low concentration of 100 µM [Aisinger 1955].
Key enzymes involved in protein synthesis and cellular energy production are affected,
including Arginase [Tormanen 2003] and Adenyl cylcase [Zhou 1990].
Succinic dehydrogenase kidney enzyme activity has been known to be decreased by
fluoride nephrotoxicity for over 65 years [Slater 1962, William Sillivan 1962, Sullivan 1969,
Stachowski 2000] and showed a 47.8% decrease over the normal at 1 ppm in drinking water
[Sullivan 1969]. Inhibition involves one fluoride ion per enzyme molecule and is enhanced by
the presence of free phosphate, which led to the hypothesis that fluoride works at an iron
Cytochrome oxidase is inhibited by fluoride [Machoy 1981, Ogonski 1992 cited in
Stachowska 2000].
In 1973 it was observed that hemodialysis with fluoridated water was associated with an
elevation in serum alkaline phosphatase and an increase in renal osteodystrophy over a 2
year period [Nielsen 1973]. Fluoride used to be given as a treatment for osteoporosis,
however the elevated alkaline phosphatise was interpreted as a sign of damage to
osteoblasts and osteocytes [Krook 1998].
In kidney tissue of young pigs, lactate dehydrogenenase (LDH) activity was significantly
increased, whereas alkaline phosphatase (AKP) activity was significantly decreased,
accompanied by severe lesions caused by apoptosis [Zhan 2006].
Diabetic rats have much higher levels of alkaline phosphatase, indicating abnormal bone
formation [Banu Priya 1997].
Low levels of superoxide dismutase, glutathione reductase, and glutathione peroxidase are
found in renal tissues of F-treated rats [Birkner 2006, Bharti 2014].
Dose dependent fluoride damage has been demonstrated due to fluoride in drinking water at
concentrations as little as 2 ppm fluoride. Children drinking water with more than 2 ppm
fluoride were found to have increased levels of lactic dehydrogenase in their blood and
increased levels of N-acetyl-beta-glucosaminidase (NAG) and gamma-glutamyl transferase
in their urine [Liu 2005, Xiong 2007]. The level of dental fluorosis was dependent on the
amount of damage to the kidney [Xiong 2007].
Fluoride in drinking water and food interferes with Thyroid hormone control [Susheela 2005,
Singh 2014]. Iodothyronine deiodinase D1 is found in the kidney as well as the liver [Visser
2012] and is responsible for conversion of Thyroid hormone T4 to T3. Because of the iodine
dependence of the thyroid and parathyroid hormones, some Mexican States do not allow
consumption of iodized salt due to a fluoride concentration in water greater than 0.7 mg/L
[Ruiz-Payan 2005].
Oxidative stress
Fluoride is known to cause increased oxidative stress and lipid peroxidation in the kidney
[Guan 2000, Xue 2000, Karaoz 2004, Inkielewicz-Stepniak 2012]. Significantly high levels of
lipid peroxidation and catalase and low levels of reduced glutathione, superoxide dismutase,
glutathione reductase, and glutathione peroxidase are found in renal tissues of F-treated rats
[Birkner 2006, Bharti 2014].
Total phospholipid content significantly decreased in the kidney of rats treated with high
doses of fluoride and the main species influenced were phosphatidylethanolamine and
phosphatidylcholine. A significant decrease of ubiquinone in rat kidney was also observed
[Guan 2000].
Disruption of ion channels
Fluoride disrupts ion channels leading to Polyuria accompanied by an enhanced sodium
excretion and a decrease in osmolality [Hamuro 1972].
Increased diuresis and natriuresis led to the suggestion that fluoride alters renal function
primarily by inhibiting active chloride transport in the ascending limb of Henle’s loop [Roman
1977]. Urinary chloride excretion was decreased for the first 2 days after NaF exposure, then
increased in water-deprived rats 120 hr after treatment [Daston 1985].
Fluoride toxicity to the kidney has been shown to depend strongly on Na+ and Ca++
activities [Chandrajith 2011]. The Na-K-ATPase pump is a major target for fluoride toxicity in
Henle’s loop [Suketa 1977, Cittanova 2002].
Fluoride induced Polyuria was accompanied by significant increases in urinary K+, Na+,
Mg2+, Ca2+, and inorganic phosphate. A significant decrease in (Ca2+ Mg2+)-ATPase
activity is responsible for the increase in urinary Ca2+ [Suketa 1977]. Long-term fluoride
exposure causes reduced expression of the plasma membrane and endoplasmic reticulum
Ca++ pumps in the kidney [Borke 1999]. Cyclic AMP excretion decreased and urine volume
increased in rats given fluoride, showing that fluoride suppresses the antidiuretic hormone
vassopressin [Wallin 1977]. Caffeine appears to enhance kidney damage by fluoride [Birkner
Fluoride is well known to induce apoptosis or premature cell death [Xu 2002, Servais 2008,
Bai 2010, Song 2013, Yang 2013, Song 2014].
In a mechanism similar to the destruction of brain cells by fluoride, it induces the process of
apoptosis in renal tubules via activation of the Bax expression and Bcl-2 suppression in a
dose dependent manner. Osteopontin might have a protective role against this apoptosis [Xu
2006]. Recent work on genes associated with sodium fluoride-induced human osteoblast
apoptosis might also prove to be relevant to kidney destruction by fluoride [Zhang 2015].
Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated
pathways and DNA damage [Song 2013, 2014].
Treatment with NaF (2mM and above) markedly decreased the viability and proliferation
potential of hESCs and led to apoptosis via a ROS-independent and JNK-mediated pathway
[Fu 2016]. Fluoride-treated hESCs exhibited morphological and nuclear features typical of
apoptosis, including nuclear fragmentation, chromatin condensation, shrinkage and blebbing
of the plasma membrane, cytoplasmic vacuoles the formation of apoptotic bodies.
The kidneys of young pigs treated with fluoride caused severe renal histological changes as
well as increased renal cell apoptosis [Zhan 2006].
Fluoride toxicity enhanced by Aluminium with renal failure
Aluminium is known to work in toxic concert with fluoride through formation of complex ions
[Ittel 1992, Isaacson 1997, Varner 1998, Strunecka 2002, Ng 2004, ]. Together they increase
cytosolic Ca++ and cAMP in the kidney [Zhou 1990].
Ittel [1992] found that in rats with renal failure “Fluoride-treated, aluminum-loaded rats
accumulated a sevenfold larger amount of osteoid volume as compared to (the aluminum-
only group) and exhibited an increase in osteoid surface of a corresponding degree. As a
consequence of the severe osteoidosis, cancellous bone volume almost doubled in rats
exposed to fluoride and aluminium.” Subsequent studies by Varner of both the NaF and AlF3
treatment groups demonstrated glomerular hypercellularity and mesangial proliferation. For
the kidney deposition of protein was observed in the tubules. The overall Al content of the
kidneys in the AlF3 group was nearly double that found in the NaF and control groups
[Varner 1998].
The combined assault of Aluminium and Fluoride will increase the risk of Alzheimer’s
Disease [Tomljenovic 2011, Pain 2017]. The use of aluminium cooking utensils with
fluoridated water will increase the toxic hazard [Ileperuma 2009]. Similarly consumption of
aluminium preparations for relief of gastric upset will present a higher risk in fluoridated
Fluoride nephrotoxicity enhanced by Silicon
Hexafluorosilicate has been confirmed as a kidney poison [Dadej 1987, Haneke 2001]. The
deliberate addition of soluble silicon to the water supply presents an additional hazard that
has received little attention. Given the devastating effects of silicates in asbestosis and
silicosis, more research on what happens inside the human body to soluble and nanoparticle
silicates from fluoridation would seem to be a priority.
Fluoride nephrotoxicity enhanced by Tin and other Heavy Metals
Many consumers will remember seeing toothpaste containing Stannous Fluoride (Tin II
Fluoride) promoted in the mass media. They might not be aware of research published in
1981 showing that Fluoride renal toxicity is enhanced by Tin [Kessabi 1981]. Fluoride
toothpastes including Barium and Strontium have also been marketed, but little data has
been published on their toxicity in comparison to fluoride alone [Cohen-Solal 2002].
Genetic and racial differences in fluoride vulnerability of the kidney
Vulnerable groups that might be exposed to enhanced risk of kidney damage by fluoride
include those with a genetic and/or racial characteristic. Fluoride damage to American
Indians was studied quite early [Morris 1965]. In a later study it was reported that “A 40-year-
old American Indian woman with chronic pyelonephritis and renal failure complained of
progressive muscular weakness, fatigue, and increasingly severe pain in her ribs, low back,
and left hip. X-ray study of these areas showed evidence of osteosclerosis, compatible with
either renal osteodystrophy or skeletal fluorosis” [Fisher 1981].
Much variation in kidneys has been reported in comparing Caucasian and African Americans
[Zimanyi 2009]. High intake of fluoride provokes nephrolithiasis (kidney stones) in tribal
populations [Singh 2001].
Key proteins that could possibly regulate metabolism of water and F were identified in a
study that compared the profile of protein expression in kidney of A/J and 129P3/J mice
[Mousny 2008]. A/J mice are highly susceptible to dental fluorosis, while 129P3/J mice are
little affected, despite retaining more F in the body, which leads to higher femur and plasma
F concentrations [Everett 2002, Carvalho 2009, Buzalaf 2014]. This work has aided
understanding in genetic differences in humans in response to the fluoride toxin.
Aborigines in remote areas of Australia have much higher rates of renal disease, as well as
hypertension and cardiovascular disease, than non-Aboriginal Australians. Fluoride
exposure has been linked to hypertension [NKF 2004, Alexander 2006]. Aborigines had 30%
fewer glomeruli than non-Aborigines and their mean glomerular volume was 27% larger
indicating compensatory hypertrophy. Aboriginal people with a history of hypertension had
30% fewer glomeruli than those without and this is linked to low birthweight [Hoy 2006]. The
average current incidence of treated end-stage renal disease exceeds 1500 per million and
the age-adjusted rate is more than 20 times than that of non-Aboriginal Australians, whereas
the incidence approaches 3000 per million in some communities [Spencer 1998, McDonald
2003 cited in Hoy 2006]. Australian aborigines are suffering epidemic of cardiovascular
disease, type II diabetes, and hypertension.
Attempts to ameliorate Fluoride Nephrotoxicity
As noted for fluoride neurotoxicity [Pain 2017], many research groups have devoted effort to
determine if antioxidative, anti-inflammatory natural products or mineral supplements might
ameliorate fluoride nephrotoxicity [Xue 2000, Verma 2002, Blaszczyk 2008, Blaszczyk 2010,
Nabavi 2012, Yang 2013, Bharti 2014, Iano 2014, Zhang 2014,Trivedia 2015].
Levels of Glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase
(SOD) and malondialdehyde (MDA) are sometimes used to measure the effects, if any, of
attempted amelioration. Some limited success has been reported.
Australian experience of Suppression of fluoride Public Health information
A fascinating study demonstrating rampant corruption within the Australian Federal, State
and Territory government Health departments received evidence of 142 suppression events
in one year [Yazahmeidi 2007]. It found these governments most commonly hindered
research by sanitising, delaying or prohibiting publications. Researchers commonly believed
their work was targeted because it drew attention to failings in health services (48 %), the
health status of a vulnerable group (26%), or pointed to harm in the environment (11%). The
government agency seeking to suppress the health information mostly succeeded (87 %)
and the public was left uninformed or given a false impression.
Kidney Health Australia maintains 1.7 million residents over the age of 18 are estimated to
be suffering from some form of CKD, a stunning pandemic [KHA 2017]. Even worse is the
fact that in 2012 it was estimated a quarter of those Australians were undiagnosed
[Henderson 2012].
In 1991 the Australian National Health and Medical Research Council (NHMRC) stated “It
would not be surprising if there were some undetected cases of skeletal fluorosis in the
Australian population in individuals with pathological thirst disorders and/or impaired renal
function. However, the matter has not been systematically examined. This matter should be
the subject of careful and systematic review.”[NHMRC 1991]. The 1991 NHMRC
recommended autopsy data on Bone Fluoride levels be collected, looking for damage,
however none was commissioned. Early in 2006, before a tender had been let for a new
review of water fluoridation, the NHMRC commenced work on a “messaging strategy” to
promote fluoridation.
In 2006, the Australian Health Department advised the NHMRC with a copy to South
Australia Water [Drikas 2006] that it should include a health warning in a proposed brochure
promoting water fluoridation, saying “In terms of kidney impairment you could include a
comment to the effect that medical advice should be obtained as impairment leads to higher
retention of fluoride and reduces safety” [Cunliffe 2006]. In 2007 the NHMRC released the
final brochure with no kidney warning, after advice from a dentist from Adelaide University.
Stages of editing this promotional material are shown in the following figure, obtained under
Freedom of Information.
It is of great interest to study carefully the question put by one NHMRC employee:
“I think the statement regarding the impact of (sic) people with kidney impairment may get
people worrying that if they don’t know they have a kidney issue and drink tap water with
fluoride what sort of problems will it cause? When you say may be sensitive what
happens? I don’t know if there is a way to make this less of a worrying issue for people.”
[Drikas 2006].
Investigating fluoride’s cumulative effects was a specific requirement of the Tender to do the
2007 NHMRC fluoride review (known through FOI) but the NHMRC didn’t investigate or
In the request for tender document the NHMRC specified that effects on the kidney were to
be included in the review because “people with kidney impairment have a lower margin of
safety for fluoride intake. Limited data indicate that their fluoride retention may be up to three
times normal.” This sentence was derived from NHMRC’s Australian Drinking Water
The publicly released 2007 NHMRC review did not include the chapter on fluoride and the
kidney. It mentioned the word kidney just once in the context of acknowledging fluoride
contributing to kidney stones. It mentioned the word renal once in excluded studies.
The NHMRC in correspondence [NHMRC 2014] stated: “The NHMRC Systematic Review of
the Efficacy and Safety of Fluoridation (2007) does not discuss the possible link between
kidney disease and water fluoridation as the review focused on studies of the general
healthy population, not people with health conditions (general or oral) requiring specialised
advice. Most Australians have not seen that statement and many would be stunned.
The NHMRC received a number of independent submissions in its call for information from
people concerned about the nephrotoxicity of fluoride [FIA 2014, KHA 2014, Pain 2014] and
we await with interest to see how the NHMRC covers the topic in its final 2017 report.
Collusion across the Tasman
The Australian and New Zealand governments work closely to try to prop up the discredited
practice of water fluoridation. Both countries host companies that generate industrial fluoride
waste. One part of the strategy is the jointly administered organization Food Standards
Australia and New Zealand (FSANZ) that is currently recommending fluoride intake of up to
10 mg per day, and falsely claiming that fluoride is an essential nutrient.
It will be interesting to see whether FSANZ publishes submissions made as part of the
current review of its Nutritional Reference Value (NRV) for fluoride, as a number of
submissions raised the issue of kidney damage and vulnerability of the unborn, dialysis
patients and undiagnosed victims with kidney impairment.
The Australian Therapeutic Goods Administration (TGA) has sought legal advice over its
failure to act to protect the public from the harmful effects of fluoridated drinking water and is
fully aware of the extra risk to the kidney. The TGA has taken special interest in New
Zealand which is currently proposing to legislate to remove local community power to cease
fluoridation. The TGA receives funding from industry.
There is no “safe” dose of fluoride and most certainly no “optimal” concentration for disposal
of this industrial waste through public drinking water supplies.
It is criminal negligence to pretend that dental fluorosis is not an indicator of systemic
poisoning by fluoride. There is such a huge resource of science in humans, that reference to
animal studies is almost unnecessary. Therefore health officials have a moral duty to go
looking for the influence of fluoride on calcification, destruction and carcinogenesis of the
bones and soft tissues.
The damage to the kidneys is sufficient reason to immediately cease fluoridation and force
the waste producers to immobilize the toxin. But will politicians act to ban this unethical
[Awofeso 2012] practice and will bureaucrats confess to their sins?
Because citizens can no longer trust their governments or public servants, they use social
media to inform on another of the threat of fluoride to various organs, in this case the
Consumers are able to read analytical data, obtained under Freedom of Information law, that
shows fluoridation industrial waste, made in Australia or imported from New Zealand or
China, carries a host of inorganic sensitizers and carcinogens, many of which further
contribute to kidney disease.
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... Elevated and prolonged exposure to F − causes osteosclerosis and chronic renal failure (Balasooriya et al. 2019). Pain (2017) has also presented evidence of F − poisoning related to renal tubular dysfunction, leading to bone and kidney disease. Damaged kidneys accumulate more F − , which is detrimental to bones, kidneys, and other organs (Connett 2012). ...
Full-text available
Drinking water contaminated with As and F- is increasingly prevalent worldwide. Their coexistence can have negative effects due to antagonistic or synergistic mechanisms, ranging from cosmetic problems, such as skin lesions and teeth staining, to more severe abnormalities, such as cancer and neurotoxicity. Available technologies for concurrent removal include electrocoagulation ~ adsorption > membranes > chemical coagulation > , and among others, all of which have limitations despite their advantages. Nevertheless, the existence of competing ions such as silicon > phosphate > calcium ~ magnesium > sulfate > and nitrate affects the elimination efficiency. Mexico is one of the countries that is affected by As and F- contamination. Because only 10 of the 32 states have adequate removal technologies, more than 65% of the country is impacted by co-presence problems. Numerous reviews have been published concerning the elimination of As or F-. However, only a few studies have focused on the simultaneous removal. This critical review analyzes the new sources of contamination, simultaneous physicochemical behaviors, available technologies for the elimination of both species, and future trends. This highlights the need to implement technologies that work with actual contaminated water instead of aqueous solutions (55% of the works reviewed correspond to aqueous solutions). Similarly, it is necessary to migrate to the creation of pilot, pre-pilot, or prototype scale projects, because 77% of the existing studies correspond to lab-scale research.
... 73 Geoff pain clearly defined the fluoride as a developmental nephrotoxin in his recent technical report citing more than 350 research publications and reports. 82 Since kidney damage can be caused by fluoride, there can be a vicious cycle by which kidney damage causes more fluoride retention, which in turn furthers kidney damage. When the kidneys are severely impaired, the excretion of fluoride in the urine decreases and serum fluoride concentration further increases. ...
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This review covers nearly 100 years of studies on the toxicity of fluoride on human and animal kidneys. These studies reveal that there are direct adverse effects on the kidneys by excess fluoride, leading to kidney damage and dysfunction. With the exception of the pineal gland, the kidney is exposed to higher concentrations of fluoride than all other soft tissues. Therefore, exposure to higher concentrations of fluoride could contribute to kidney damage, ultimately leading to chronic kidney disease (CKD). Among major adverse effects on the kidneys from excessive consumption of fluoride are immediate effects on the tubular area of the kidneys, inhibiting the tubular reabsorption; changes in urinary ion excretion by the kidneys disruption of collagen biosynthesis in the body, causing damages to the kidneys and other organs; and inhibition of kidney enzymes, affecting the functioning of enzyme pathways. This review proposes that there is a direct correlation between CKD and the consumption of excess amounts of fluoride. Studies particularly show immediate adverse effects on the tubular area of human and animal kidneys leading to CKD due to the consumption of excess fluoride. Therefore, it is very important to conduct more investigations on toxicity studies of excess fluoride on the human kidney, including experiments using human kidney enzymes, to study more in depth the impact of excess fluoride on the human kidney. Further, the interference of excess fluoride on collagen synthesis in human body and its effect on human kidney should also be further investigated.
... Sodium fluoride (SF), a pollutant, is used as an insecticide and antihelminthic agent. 1,2 Fluoride can be present in the soil, water, and vegetation. It has been reported that chronic fluoride toxicity causes joint stiffness. ...
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The present study aimed to explore the efficiency of N-acetyl cysteine (NACC) or thymoquinone (TMQ) alone or in combination in the downregulation of inflammatory molecule expression and decreasing hepatic injury in response to sodium fluoride (SF). Sodium fluoride upregulated serum alanine and aspartate transferases activities, tumor necrosis factor α and hepatic malondialdehyde and nitric oxide levels, and the expression of cyclooxygenase 2, nuclear factor κB cell, and signal transducer and activator of transcription 3. In contrast, hepatic glutathione level, superoxide dismutase activity, and nuclear factor erythroid 2-related factor 2 expression were decreased. However, the concurrent treatment with antioxidants, alone or in combination, modulated the levels of these parameters. Histopathological examination revealed that SF treatment resulted in focal areas of massive hepatic degeneration and many degenerated hepatocytes, whereas the treatment with TMQ or NACC exhibited moderate improvement in cellular degeneration of the liver with many abnormal cells. Rats receiving a combination of TMQ and NACC showed marked improvement in cellular degeneration of liver with apparently normal hepatic architecture with very few degenerated hepatocytes. The results also revealed that the combination of TMQ and NACC is the most effective regimen in ameliorating SF toxicity, suggesting their efficacy against the toxicity of fluoride compounds. Their activities might be mediated via multiple molecular pathways.
... Fluoride is a nephrotoxin [Pain 2017c]. Urolithiasis kills thousands of people every year and many of the urinary stones contain significant Fluoride [Herman 1958] with correlation found between drinking water, serum and urine Fluoride levels and Fluoride content of the stones [Rathee 2004]. ...
Technical Report
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Green Tea is promoted as a healthy beverage yet few consumers are aware of the health risks caused by its Aluminium, Fluoride, Fluoroacetate, Heavy Metal, Oxalate and Polyphenol content.
... The mechanisms of fluoride toxicity can be summarized [Pain 2017a] under the following headings: ...
Technical Report
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Cataract blindness affects tens of millions of people, many of whom will never have access to lens replacement surgery. Fluoride from various sources including drinking water, tea, salt and drugs, enhances and stabilizes crystal growth of Hydroxyapatite within the eye. Fluoride is identified as the major risk for cataract and contributes to risk of other eye diseases including macular degeneration.
Technical Report
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Australia's National Health and Medical Research Council states that the only harm arising from water Fluoridation and total dietary Fluoride intake is Dental Fluorosis. This guide provides a quick reference to harms known by toxicologists to be caused by Fluoride, including those still under intensive research and recognized by other administrations.
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Blood is promptly affected by environmental pollutants and toxicants that can cause many metabolic disorders. The high level of fluoride acts as a potential pollutant, insecticide and rodenticide with very high toxicity, associated with the hematological damage. This study aimed to determine the toxicity of Sodium Fluoride on hematological parameters in Oryctolagus cunniculus. Twenty rabbits were acclimatized and divided in to control group and three experimental groups.Experimental group-I, II and III were treated with 10, 30 and 50 mg/kg body weight doses of Sodium Fluoride orally. Various blood parameters such as TEC, Hb, HCT, MCV, MCH, MCHC, TLC and PLT count were investigated. Result findings showed that values of blood indices in experimental groups were significantly lower than the control group. Oneway ANOVA was applied for statistical analysis. The outcomes of the current studies indicated the reduction in RBC counts (anemia), leukocyte count (leukocytopenia), monocytosis, eosinopenia, neutrophilia and thrombocytosis on fluoride intoxication. Hematological disruptions like microcytic hypochromic anemia and decreased leukocyte count may be linked to the inflammatory effects of Sodium Fluoride on lymphatic organs.
Technical Report
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Fluoride is a developmental neurotoxin that has been linked to human brain damage since the 1920s when Fluoride induced cretinism was investigated and confirmed with animal studies. With advances in imaging, chemical analytical techniques including proteomics, detailed molecular mechanisms of Fluoride damage to the brain, spinal cord and nerve networks have been investigated with ever increasing levels of detail. The current peer-reviewed scientific publication rate regarding Fluoride neurotoxicity is about one paper per week. This literature guide provides a snapshot of the science as easily obtained in early 2017, to help inform those interested in the depth of knowledge and where the ongoing studies are directed.
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Fluorosis induced by exposure to high level fluoride is quite widespread in the world. The manifestations of fluorosis include dental mottling, bone damage, and impaired malfunction of soft tissues. However, the molecular mechanism of fluorosis has not been clarified until now. To explore the underlying mechanisms of fluorosis and screen out serum biomarkers, we carried out a quantitative proteomics study to identify differentially expressed serum proteins in Wistar rats treated with sodium fluoride (NaF) by using a proteomics approach of isobaric tagging for relative and absolute quantitation (iTRAQ). We fed Wistar rats drinking water that had 50, 150, and 250 mg/L of dissolved NaF for 24 weeks. For the experimental duration, each rat was given an examination of the lower incisors to check for the condition of dental fluorosis (DF). By the end of the treatment, fluoride ion concentration in serum and lower incisors were detected. The results showed that NaF treatment can induce rat fluorosis. By iTRAQ analysis, a total of 37 differentially expressed serum proteins were identified between NaF-treated and control rats. These proteins were further analyzed by bioinformatics, out of which two proteins were validated by enzyme-linked immunoadsorbent assays (ELISA). The major proteins were involved in complement and coagulation cascade, inflammatory response, complement activation, defense response, and wound response, suggesting that inflammation and immune reactions may play a key role in fluorosis pathogenesis. These proteins may contribute to the understanding of the mechanism of fluoride toxicity, and may serve as potential biomarkers for fluorosis.
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Fluoride exposure to rats can alter system physiology and biochemistry and results in abnormal organ function. Mitochondria, the power house of the cell can be act as a marker to identify luoride mediated oxidative damage through changes of mitochondrial micro viscosity. Male albino rats were fed with 5 ppm, 10 ppm, 15ppm and 20 ppm sodium luoridated water to create diferent modes of luoride toxicity in rats to observe the luoride deposition level upon exposure, mitochondrial micro viscosity changes and organ histology alteration compared to control. The luoridated rats showed continuous increase in deposition level in liver, kidney, brain and testis. 20 ppm NaF exposure showed signiicant (P<0.001) decrease in mitochondrial membrane viscosity leading to alteration of energy production system. Necrotic haemolytic damages and presence of inlammatory cells were observed upon NaF exposure in rat liver and kidney tissues respectively. Similarly neuronal and spermatogonial degenerations were observed in rats brain and testicular cells exposed to luoride intoxication. All these above result describe the adverse efect of groundwater contaminants luoride be an environmental threat to animal kingdom.
Activities of various enzymes have been determined biochemically and histochemically in the liver and kidney of rats subjected for 10 months to fluoride concentration of 0 ppm (control), 10 ppm (Group 1) and 25 ppm (Group II) in drinking water. The activity of alkaline phosphatase and succinic dehydrogenase decreased appreciably. However, adenosine triphosphatase activity increased in liver and kidney of Grup II (25 ppm) animals. Lactic dehydrogenase activity also decreased but only in the kidney histochemically. The alterations in enzyme activities were very pronounced in proximal and distal convoluted tubules of the kidney. The biochemically determined activity of glutamic oxaloacetic transaminase increased slightly in the liver in Group II. The observations suggest that fluoride interferes with intracellular metabolism in liver and kidney.