Blood - Adverse Effects
Sodium fluoride


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Note: The following is a limited selection of abstracts from 1994 to present.
• Due to length, we present this as a separate section
• Click here to return to the 4-part
Blood section for fluorine & organofluorine pesticides.
• When time allows more information will be added.

Fluoride & Bone Damage: Published Data.


• TABLE 3a:
Average Serum Fluoride Levels Reported in Human Skeletal Fluorosis

• TABLE 3b:
Serum Fluoride Levels Causing Damage to Mineralized Tissues in Rats

• TABLE 3c:
Maximum Serum Fluoride Levels in Humans Living in < 1.9 ppm areas

• TABLE 7:
The Relationship of Water Fluoride to Serum Fluoride in Rats

Compiled by Michael Connett.
Submission to the National Research Council Committee
"Subcommittee on the Toxicologic Risk of Fluoride in Drinking Water; BEST-K-02-05-A".
January 29, 2004.
See letter for this submission


Effects of sodium fluoride on total serum protein levels and transaminase activity in rats.

Qujeq D, Laghaie B, Gholipour A, Solimani N, Hassenzadeh S.

Department of Biochemistry and Biophysics, Babol University of Medical Sciences, Iran.

Transaminase activity and serum total protein level were investigated in adult rats after oral treating with sodium fluoride at three doses, 10, 20 and 30 mg/kg daily for 90 days. After 90 days, the average total serum protein level of the rats in the treatment group decreased significantly compared with that in the control [1.9 +/- 0.1 (mean
+/- S.D., n = 140) vs. 3.1 +/- 0.2] mg/dl, P< 0.05. Serum transaminase activity in the treatment group increased compared with that in the control [5.3 +/- 0.4 (mean +/- S.D., n = 140) vs. 3.2 +/- 0.3] micromol/min per ml, P < 0.05.

PMID: 12109808 [PubMed - in process]

Full report available at

Fluoride 2001; 34(2):108-113

Effect of fluoride intoxication on lipid peroxidation and antitoxidant systems in rats

YM Shivarajashankara (a), AR Shivashankara (a), P Gopalakrishna Bhat (b), S Hanumanth Rao (c)

(a) YM Shivarajashankara, Dept. of Biochemistry, MR Medical Col-lege, Gulbarga-585 105, Karnataka, India; E-mail:;
(b) Dept. of Biochemistry, Kasturba Medical College, Manipal-576 119, Karnataka, India;
(c) Dept. of Biochemistry, KBN Institute of Medical Sciences, Gulbarga-585 104, Karnataka, India.

SUMMARY: The effect of fluoride intoxication on lipid peroxidation and anti-oxidant systems in the blood, brain, and liver of rats was studied. Twelve one-month-old albino rats were administered 100-ppm fluoride (as NaF) in their drinking water for four months. In the red blood cells the levels of malondial-dehyde (MDA) and glutathione (GSH) increased, along with the activity of glutathione peroxidase (GSH-Px), but the activity of superoxide dismutase (SOD) decreased. In the plasma the level of ascorbic acid increased while that of uric acid decreased. In the brain and liver, MDA and GSH levels increased, as did the activities of GSH-Px and glutathione S-transferase (GST). The level of ascorbic acid increased in the brain, but it decreased in the liver. These results suggest that fluoride enhances lipid peroxidation in the red blood cells, brain and liver of rats and causes increased or decreased enzyme activity associated with free radical metabolism.

Full report available at

Fluoride 2001; 34(2):132-138

Glutathione metabolism in rats exposed to high-fluoride water and effect of spirulina treatment

Toshi Kaushik (a), Radhey Shyam (b), Praveen Vats (b), Shoba Suri (b), MML Kumria (b), PC Sharma (a), Som Nath Singh (b)

(a) Dept. of Biotechnology, Chaudhary Charan Singh University, Meerut-250 004, India.
(b) For correspondence: Dr Som Nath Singh, Nutrition Division, Defence Institute of Physiology and Allied Sciences, Timarpur, Delhi-110 054, India. Email:

SUMMARY: Effects of high fluoride intake through water on glutathione and related enzymatic activities in blood and liver of albino rats were studied. Twenty four rats were divided into three groups of 8 each. Group I was given normal municipal supply water (fluoride content 0.55 ppm), Groups II and III were exposed to 12 ppm fluoride in water for 15 days. Group III was treated orally with Spirulina (200 mg/kg bwt), a functional food rich in protein, vitamins and minerals, for study of protective effects. After 15 days of exposure reduced and oxidised glutathione (GSH and GSSG), lipid peroxidation and enzymes, i.e. glutathione reductase (GR), glutathione peroxidase (GPx), gluta-thione S-transferase (GST), and y-glutamyl transpeptidase (y-GT) activities were measured in blood/erythrocytes and liver. There was a significant rise in blood GSSG level and a decrease in GSH/GSSG ratio, with increased lipid peroxidation in fluoride-exposed animals. A marked decrease in GR and GST activities and an increase in y-glutamyl transpeptidase activity were also noted in blood of fluoride exposed animals. In the liver no significant changes in these variables were observed. Results indicate oxidative stress during fluoride exposure. Spirulina treatment was beneficial to some extent as a rich source of the antioxidant vitamin y carotene.

Int J Occup Med Environ Health 2001;14(4):369-73

The effect of sodium fluoride on the adenine nucleotide pool in erythrocytes of Wistar rats.

Suska M.

Department of Biochemistry, Institute of Life Sciences, University of Szczecin, Poland.

The effect of sodium fluoride on the content of adenine nucleotides, adenine nucleotide pool and energy potential of erythrocytes was studied in male Wistar rats, depending on the dose and time of exposure. Sodium fluoride was administered for 4 and 8 weeks at 4 or 16 ppm through a gastric tube. The concentration of fluorine in serum, ATP, ADP and AMP content in blood and erythrocytes, adenine nucleotide pool and energy potential of erythrocytes were calculated. The results were expressed in SI units and compared statistically with Student's t-test (Statgraphics v. 5.0 software). A significant reduction in the content of ATP and ADP and an increase in the content of AMP in erythrocytes was found after 4 weeks of exposure to 4 or 16 ppm NaF. The adenine nucleotide pool and
energy potential were reduced with the smaller dose. After 8 weeks, the ADP content remained significantly reduced with the smaller dose, while the greater dose was associated with a higher energy potential of the cells. Correlations between serum concentration of fluorine, content of adenine nucleotides and adenine nucleotide pool in erythrocytes were noted in all study groups.

PMID: 11885920 [PubMed - indexed for MEDLINE]

Full report available at:

Fluoride 2001; 34(3):174-180

Influence of fluoride ions on Na+-H+ exchanger actvity in human red blood cells

J Bober (a,b), D Chlubek (a), E Kwiatkowska (c), K K dziersk (c), E Stachowska (a), P Wieczorek (a) E Byra (d), Z Machoy (a), E Herdzik (c)

(a) Department of Biochemistry and Chemistry. Pomeranian Academy of Medicine (PAM).
(b) For correspondence: Dept. of Biochem. and Chem., PAM, 70- 111 Szczecin, Al. Pow-stancow Wlkp.72, Poland.; E-mail:,
(c) Chair and Dept. of In-ternal Medicine,
(d) Main Laboratory, Clinical Hospital of PAM.

Summary: The influence of fluoride ion (F - ) at concentrations of 0.25 and 2.5 mM on intracellular pH and Na + -H + exchanger (NHE) activity in human red blood cells was investigated. Erythrocytes from 15 healthy individuals were examined. We found that F - caused a decrease in NHE activity and an increase in intracellular H + ion concentration (decrease of intracellular pH). marrow haematopoietic cells.

Am J Physiol Lung Cell Mol Physiol 2001 Dec;281(6):L1472-83

Mechanisms of sodium fluoride-induced endothelial cell barrier dysfunction: role of MLC phosphorylation.

Wang P, Verin AD, Birukova A, Gilbert-McClain LI, Jacobs K, Garcia JG.

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224-6801, USA.

NaF, a potent G protein activator and Ser/Thr phosphatase inhibitor, significantly increased albumin permeability and decreased transcellular electrical resistance (TER), indicating endothelial cell (EC) barrier impair
ment. EC barrier dysfunction induced by NaF was accompanied by the development of actin stress fibers, intercellular gap formation, and significant time-dependent increases in myosin light chain (MLC) phosphorylation. However, despite rapid, albeit transient, activation of Ca(2+)/calmodulin-dependent MLC kinase (MLCK), the specific MLCK inhibitor ML-7 failed to affect NaF-induced MLC phosphorylation, actin cytoskeletal rearrangement, and reductions in TER, suggesting a limited role of MLCK in NaF-induced EC activation. In contrast, strategies to reduce Rho (C3 exoenzyme or toxin B) or to inhibit Rho-associated kinase (Y-27632 or dominant/negative RhoK) dramatically reduced MLC phosphorylation and actin stress fiber formation and significantly attenuated NaF-induced EC barrier dysfunction. Consistent with this role for RhoK activity, NaF selectively inhibited myosin-specific phosphatase activity, whereas the total Ser/Thr phosphatase activity remained unchanged. These data strongly suggest that MLC phosphorylation, mediated primarily by RhoK, and not MLCK, participates in NaF-induced EC actin cytoskeletal changes and barrier dysfunction.

PMID: 11704544 [PubMed - indexed for MEDLINE]

Adv Exp Med Biol 2001;498:263-71

Alterations in g-protein-linked signal transduction in vascular smooth muscle in diabetes.

Anand-Srivastava MB, Wang R, Liu YY.

Department of Physiology, Faculty of Medicine, University of Montreal, Quebec, Canada.

The present studies were undertaken to determine the levels of stimulatory and inhibitory guanine nucleotide regulatory proteins (Gs and Gi respectively) and their relationship with adenylyl cyclase activity in aorta from 5-day streptozotocin-induced diabetic (STZ) rats. The levels of Gi alpha-2 as determined by immunoblotting techniques using AS/7 antibody were significantly decreased by about 60% in STZ as compared to control rats, whereas the levels of Gs alpha were not altered. In addition, the stimulatory effect of cholera toxin (CT) on GTP-sensitive adenylyl cyclase was not different in STZ as compared to control rats. On the other hand, the stimulatory effects of GTPgammaS, isoproterenol, glucagon, forskolin (FSK) and sodium fluoride on adenylyl cyclase were enhanced in STZ-rats. Furthermore, GTPgammaS inhibited FSK-stimulated adenylyl cyclase activity in a concentration-dependent manner (receptor independent functions of Gi) in control rats which was almost completely abolished in STZ rats. In addition, receptor-mediated inhibition of adenylyl cyclase by angiotensin II (AII), oxotremorine and atrial natriuretic peptide (ANP) was attenuated in STZ rats. These results suggest that the decreased expression of Gi alpha, but not of Gs alpha, may be responsible for the observed altered responsiveness of adenylyl cyclase to hormonal stimulation and inhibition in STZ-rats. It may thus be suggested that the decreased Gi activity may be one of the possible mechanisms responsible for the impaired vascular functions in diabetes.

PMID: 11900377 [PubMed - indexed for MEDLINE]

Full report available at:

Fluoride 2000; 33(3): 108-114

The influence of fluoride ions on the viability, reduction of NBT, cytolysis, degranulation, and phagocytosis of human and rabbit neutrophils

J Bober (,a,b), E Kucharsk (c), J Zawierta (a), Z Machoy (a), D Chlubek (a), K Ciechanowski (a)

(a) Chair and Department of Biochemistry, Pomeranian Academy of Medicine, Al. Powsta • ców Wlkp. 72, 70-111 Szczecin, Poland. E-mail: (Head: Asst Prof Dariusz Chlubek, MD, PhD).
(b) For correspondence: Joanna Bober, MD, PhD, same address.
(c) Chair and Department of Microbiology and Immunology, Pomeranian Academy of Medicine, Al. Powsta • ców Wlkp. 72, 70-111 Szczecin, Poland.

Summary: The influence of fluoride ion at concentrations of 10, 20, and 30 mmol/L on various properties of human and rabbit granulocytes was investigated. We found that fluoride ion inhibited phagocytes functions of rabbit granulocytes. It also decreased the viability of rabbit polymorphonuclear leukocytes (PMN) which was connected with increased degranulation. Fluoride ion activated mainly the oxygen-dependent bactericidal system in human neutrophils and the oxygen-independent one in rabbit neutrophils.

Full report available at:

Fluoride 2000; 33(4):168-173

The influence of sodium fluoride on the clonogenicity of human hematopoietic progenitor cells: preliminary report

Boguslaw Machaliski (a), Maria Zejmo, Iwona Stecewicz, Anna Machalinska, Zygmunt Machoy, Mariusz Z Ratajczak

(a) For Correspondence: Department of General Pathology, Pomeranian Academy of Medicine, Al. Powstaców Wlkp. 72, 70-111 Szczecin, Poland. E-mail:

SUMMARY: Since fluoride accumulates not only in bones but also in bone marrow cavities where hematopoiesis occurs, a preliminary study was under-taken of the potential toxicity of sodium fluoride (NaF) against early human myeloid (CFU-GM, Colony Forming Unit of Granulocyte-Macrophages) and erythroid (BFU-E, Burst Forming Unit of Erythrocytes) progenitors. CD34 + cells isolated from human umbilical cord blood were exposed for 30 and 120 min at 37 o C or 4 o C to increasing concentrations of NaF (0, 1, 10 and 50 mM). At 1 mM NaF, a detectable but not statistically significant stimulatory effect was observed in 7 of the 8 different sets of experiments. At 10 and 50 mM, however, NaF was significantly toxic against cord blood CFU-GM and BFU-E progenitors. Fluoride may therefore be potentially toxic toward early human hematopoietic cells.

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