Human Toxicity, Environmental Impact and Legal Implications of

HUMAN TOXICITY, ENVIRONMENTAL IMPACT AND LEGAL IMPLICATIONS OF WATER FLUORIDATION
7.0 HUMAN TOXICITY TO FLUORIDE
Fluoride is a toxin and its mode of action occurs at both the cellular and
molecular levels causing significant enzyme inhibition involved in
biochemical, cellular and molecular processes. Along with other toxic effects,
fluoride is known to induce oxidative stress leading to excessive generation of
reactive oxygen species (ROS), lipid peroxidation, a decrease in the
glutathione(GSH)/oxidized glutathione (GSSH) ratio and alterations in
activities of antioxidant enzymes, as well as an inhibition of glycolysis thus
causing the depletion of cellular ATP and disturbances in cellular metabolism.
Furthermore fluoride changes the expression profile of apoptosis-related
genes and cause endoplasmic reticulum stress leading to inhibition of protein
synthesis. 311 The fluoride ion is a potent nucleophile in its desolvated state,
fluorine's high redox potential precludes the haloperoxidase-type mechanism
used in the metabolic incorporation of chloride and bromide ions. 312
The toxicity of fluoride is associated with its high chemical and biological
activity. Fluoride freely and rapidly migrates across the biological membranes,
primarily in the form of HF via passive non-ionic diffusion in response to
differences in the acidity of adjacent body fluid compartments.
After ingestion, fluoride is rapidly and virtually totally absorbed into the blood
and distributes between organs and tissues. On an average, approximately
50% of the fluoride ingested by our body each day is excreted through the
kidneys while the remaining fluoride accumulates in the bones, teeth, pineal
glands and other tissues. 313
The toxic fluoride effects include an induction of inflammatory reactions, cell
contractile responses, inhibition of protein synthesis and cell cycle progression,
oxidative stress and DNA damage. 314
Fluoride induced apoptosis (cell death) was demonstrated in the cells from
different organs and tissues including lungs, 315 , 316 , kidneys, 317 , 318 liver, 319 , 320
311 Natalia Ivanovna Agalakova, Gennadii Petrovich Gusev, Molecular mechanisms
of cytotoxicity and cell death induced by inorganic fluoride, Sechenov Institute of
Evolutionary Physiology and Biochemistry, Russian Academy of Sciences.
312 Dong C, Huang F, Deng H, Schaffrath C, Spencer JB, O'Hagan D, Naismith JH.
Crystal structure and mechanism of a bacterial fluorinating enzyme. Nature. 2004 Feb
5;427(6974):561-5.
313 G. M. Whitford, ―Intake and metabolism of fluoride‖, Advanced Dental Research,
vol. 8, pp. 5-14, 1994.
314 O. Barbier, L. Arreola-Mendoza, L. M. Del Razo, ―Molecular machanisms of fluoride
toxicity‖, Chemico-Biological Interactions, vol. 188, pp. 319-333, 2010.
315 E. V. Thrane, M. Refsnes, G. H. Thoresen, M. Lag, P. E. Schwarze, ―Fluoride-induced
apoptosis in epithelial lung cells involves activation of MAP kinases p38 and possibly
JNK‖, Toxicological Sciences, vol. 61, pp. 83-91, 2001.
316 M. Refsnes, P. E. Schwarze, J. A. Holme, M. Lag, ―Fluoride-induced apoptosis in
human epithelial lung cells (A549 cells): role of different G protein-linked signal
systems‖, Human and Experimental Toxicology, vol. 22, pp. 111-123, 2003.
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