Fluoride Action Network


BACKGROUND: Toxicity due to excess fluoride concentration in drinking water is of great concern in people who rely only on the ground water as their water source in many region of the world.

METHODS: We collected samples and examined the toxicity of fluoride in a population residing at Salem, Dharmapuri and Krishnagiri districts of Tamil Nadu, India and measured HDL bound enzyme (PON1), erythrocyte membrane bound enzymes (acetylcholinesterase, AChE) and adenosine 5′ triphosphatase (ATPases), plasma enzyme (butyrylcholinesterase, BChE) and rate limiting enzyme in heme biosynthesis (delta aminolevulinic acid dehydratase, ?-ALAD) activities.

RESULTS: In fluorosis patients, formation of lipid peroxidation product was more in erythrocytes than in plasma. The observation further revealed that there was 50% reduction in the activity of HDL bound anti atherogenic enzyme-paraoxonase (PON1). The activities of membrane bound and signaling enzymes (acetylcholinesterase – AChE and adenosine 5′ triphosphatase – ATPase) of erythrocyte were also diminished. These results suggested that there was defectiveness in the signaling and energy metabolism in fluorosis patients. Altered isoenzyme pattern of lactate dehydrogenase (LDH) in fluorosis samples was observed. Furthermore, the result suggested that both the heart (LDH 1) and liver (LDH 5) were most affected by fluoride toxicity. The study also provided reference values for tests which are used to predict the severity of fluoride toxicity.

CONCLUSION: The toxic effect of fluoride was due to the collective effects on vital protective system rather than single factor.


.. High fluoride content in ground and surface water is a serious ecological problem for many countries including Algeria, Argentina, Australia, Canada, China, India, Iran, Iraq, Japan, Kenya, New Zealand, Libya, Turkey, South Africa, Srilanka, Thailand and the United States [1].

… In this study, 3 districts of Tamil Nadu namely (i) Salem, (ii) Dharmapuri and (iii) Krishnagiri were selected based on the prevalence of high fluoride contaminated water in order to assess its toxicity in fluorosis patients.

… As blood plays a major role for the circulation of fluoride in human and animals, it has been reported that blood enzymes profile is altered in fluorosis conditions which in turn provoke other consequences [6,7]. Paraoxonase (PON1) is an important anti-atherogenic and antioxidant enzyme, closely bound with high-density lipoproteins (HDL) that inactivates numerous toxic pollutants [8]. Thus, PON1 has been considered as a significant biomarker for complications caused by toxic pollutants in human as well as aided to predict the intensity of exposure [8,9].

Apart from this, many blood enzymes have been reported as biomarkers for different pathological conditions caused by toxic pollutants. However, there is no detailed report on blood enzymes including PON1 as biomarkers and their altered concentrations in fluorosis conditions.

… The study subjects were categorized into 4 groups namely, group I (control), group II (mild), group III (moderate) and group IV (severe). Cases ailing from both skeletal and dental fluorosis were selected in this study. The personal characteristics, duration of fluoride exposure, medical history, family socioeconomic status and lifestyle information of the individual were collected using a predetermined questionnaire.

Of total 508 volunteers, 52 subjects were segregated into group I (28 males and 24 females; age 29 ± 11 y), 112 subjects into group II (76 males and 36 females; age 28 ± 7 y), 136 subjects into group III (78 males and 58 females; age 28 ± 7 y) and 208 subjects into group IV (112 males and 96 females; age 30 ± 11 y). Exclusion criteria were smoking, heart, liver / kidney disease, cancer, chronic inflammation, autoimmune and hematological disorders.

… Furthermore, the decreased activity of the membrane bound enzymes, AChE and ATPase indicates that prevalence of memory loss with lower IQ scores as well as defect in signaling and energy metabolism in fluorosis patients. ROC-AUC helped to predict the severity of the fluorosis and significant cutoff values as diagnostic parameters in fluorosis patients.

TABLE 1 – Effect of fluoride on biochemical parameters and enzymes. The concentration of serum fluoride in control, mild, moderate and severe category is summarized
TABLE 2 – Correlation result of serum fluoride, TBARS of plasma and erythrocyte on lipid profiles
TABLE 3 – Influence of various parameters on PON1, ARE and lactonase in fluorosis patients
TABLE 4 – Activity of membrane bound and pesticide scavenging enzymes in fluorosis patients
TABLE 5 – Diagnostic efficacies of selected parameters and its cut off values in fluorosis condition

Fig. 1 – Location of sample collection in fluorosis endemic areas of Tamil Nadu
Fig. 2 – LDH isoenzyme profile in control and fluorosis patients
Fig. 3 – Correlation result of fluoride, plasma and erythrocyte TBARS on various enzymatic activity
Fig. 4 – ROC plot for the RBC membrane bound enzymes in fluorosis condition
Fig. 5 – ROC plot for the esterase enzymes in fluorosis condition
Fig. 6 – Location of sample collection in fluorosis endemic areas of Tamil Nadu


[1] K.M.K. Kut, A. Sarswat, A. Srivastava, C.U. Pittman, D. Mohan, A review of fluoride in African groundwater and local remediation methods, Groundw. Sustain. Dev. 2 (2016) 190-212.

[6] A. Shashi, G. Meenakshi, Inhibitory effect of fluoride on Na+, K+ ATPase activity in human erythrocyte membrane, Biol. Trace Elem. Res. 168 (2015) 340-348.

[7] P. Pratheebaa, S. Dhivyalakshmi, P. Shankar, Fluoride toxicity in humans: Effect on serum and plasma enzyme levels in endemic areas of Krishnagiri district of Tamilnadu, India, J. Life Med. 1 (2013) 33-37.

[8] M. Araoud, F. Neffeti, W. Douki, M.F. Najjar, A. Kenani, Paraoxonase 1 correlates with butyrylcholinesterase and gamma glutamyl transferase in workers chronically exposed to pesticides, J. Occup. Health. 52 (2010) 383-388.

[9] L.G. Costa, R.J. Richter, W.F. Li, T. Cole, M. Guizzetti, C.E. Furlong, Paraoxonase (PON 1) as a biomarker of susceptibility for organophosphate toxicity, Biomarkers 8 (2003) 1-12.