FLUORINE

1. FLUORINE Created by: Josh Sugay and Paige Parker

2. Fluorine • Symbol: F • Atomic Number: 9 • Atomic Weight: 18.9984 • Group Number: 17 • Group Name: Halogen • Ground State Electron Configuration: • [He]2s22p5 • Oxidation State: -1 • It is the most electronegative and reactive of all elements.

3. In what form is Fluoride found? • Due to its high electronegativity, it does not naturally occur in the elemental state. • Instead it exists as the monovalent anion fluoride F-. • It forms soluble compounds with monovalent cations such as Na+ K+ and with multivalent cations such as Ca2+, Mg2+, and Al2+.

4. Where is Fluoride found in our body? • Fluoride is found mainly in our teeth and bone. • It can displace the OH group on hydroxyapatite crystals forming fluoroapatite which hardens tooth enamel and stabilizes bone mineral.

5. Absorption • 20-25% of fluoride is absorbed by the stomach.◦In the stomach, it depends on the formation of HF prior to its assimilation into the blood. Conditions of higher gastric acidity promote fluoride absorption from the stomach. • 75-80% is absorbed by the small intestine. ◦Absorption from the small intestine is pH-independent. The majority of fluoride absorption occurs in the small intestine via passive diffusion quite possibly through membrane channels.

6. Absorption & Antagonist • In the fasted state, fluoride in the form of fluoridated water or sodium fluoride tablets, the absorption is 100%. • However, when fluoride is found in food sources, or taken with food, the absorption varies from 50-80%. • Part of the reduction in fluoride absorption is caused by insoluble complex formation with cations in the alkaline small intestine, usually Ca2+ or Mg2+. • Aluminum from certain antacids has also been shown to form an insoluble complex.

7. Absorption • Dietary proteins contribute to high gastric acidity thus increasing fluoride absorption. • Dietary fats stimulate fluoride absorption from the stomach by delaying gastric emptying time.

8. Transport and Tissue Uptake • Absorbed fluoride enters the plasma where the concentration under usual intake ranges from 10-20μg/L. • It is quickly taken from the plasma into tissue in exchange with other anions (hydroxyl, citrate, and carbonate ions) • 95% of total body fluoride is found in bones and teeth.

9. Excretion • 90% of fluoride excretion occurs in the urine. • Only under heavy sweating is a considerable amount lost in sweat. • Some have suggested a homeostatic mechanism for fluoride by way of skeletal uptake and urinary excretion in order to prevent high amounts of fluoride in the plasma.

10. Fluoride’s involvement with Enzymes • Fluoride can activate enzymes by way of G-proteins as in the activation of adenylatecyclase and polyphosphoinositidephosphodiesterase which are involved in platelet activation

11. G protein activation and mediator release from human neutrophils and platelets after stimulation with sodium fluoride and receptor-mediated stimuli • C. BROM, J. BROM & W. KONIG. Immunology 1991: 73(3):287-292 • “It may be possible that NaF acts on a regulatory factor which enhances the exchange of GDP for GTP, as was recently isolated and characterized for rasP21 proteins.” • “Therefore, we conclude that the addition of NaF modulates the interaction between the thrombin receptor and the G proteins. It was postulated that two GTPases were stimulated by thrombin in membranes of human platelets. However, it may be also possible that different signal transduction pathways, including different G-proteins, are involved in the cell activation by NaF and thrombin.”

12. Adequate Intake (AI) for Fluoride

13. Tolerable Upper Intake Level (UL) for Fluoride

14. Dietary Sources of Fluoride

15. Fluoridation • Adding fluoride in the water. • Two main forms NaF and Hydrofluorosilicic acid, which is a waste product in fertilizer industries

16. History • From 1901 to 1933, fluoride, already a naturally occurring substance in water, was studied thoroughly, and it was determined to be safe and to have the ability to protect teeth enamel against decay, especially in children. • From 1933-1945 fluoridation was confirmed to be safe and efficient in fighting against dental caries and decay. Set an effective range of 0.7-1.2ppm. • Early 1960s fluoridation was occurring if 40 countries, protecting 300 million people. • For more than 50 years fluoridation has been responsible for reducing cavities as much as 60% in children and 35% in adults.

17. History • In 1989 the Centers of Disease Control and Prevention has set a goal of 75% of the US population to have fluoridation in communities by the year 2000. The current level is 62.1%. • In 1999 the Centers of Disease Control and Prevention put water fluoridation as one of the top 10 public health achievements in the 20th century Source: The Massachusetts Coalition for Oral Health

18. Controversy • Dental Fluorosis • Kidney Damage • Neural and Hormonal interferences

19. Dental Fluorosis • White spots to brown/black stains • Increased in porosity of enamel • Endoplasmic Reticulum(ER) stress on ameloblasts

20. Dental Fluorosis

21. Dental Fluorosis • Terms: ameloblasts – cells from which tooth enamel develops amelogenin – protein responsible for forming the matrix in which enamel is formed • Fluorosis – hypermineralization of enamel due to retention of amelogenin proteins by F. Thus the enamel does not mature and the surface and subsurface becomes porous. (Allen K, et al.) • A study by Kubota, et al. concluded that exposure to NaF induces ER stress response to both enamel proteins and ameloblasts. Ameloblasts are the most susceptible to high dosage exposure to fluorine.

22. Dental Fluorosis • 32% of American Children now have some form of dental fluorosis and 2%-4% have moderate to severe fluorosis (CDC 2005). • Rate of bone fractures among children with fluorosis is higher than bone fracture rate among children with no fluorosis (Alarcon-Herrera MT, et al.)

23. Kidney • Kidney is 2nd in having the most concentration of F in the body. Pineal gland has the most. • Kidneys of healthy adults excrete approximately 50% of an ingested dose of F. Individuals with kidney disease only excrete 10-20%. Thus, increasing susceptibility of F poisoning (Johnson, et al)

24. Kidney • Study in China detected evidence of kidney and liver disturbances in children drinking water with as little as 2ppm of F. • 210 children living in areas of 0.61-5.69ppm. • >2ppm were found to have high levels of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-GT in the urine which are indicators of kidney damage. Also high levels of lactic dehydrogenase in blood which is a marker for liver damage (Lui JL, et al).

25. Neural and Hormonal • Pineal gland contains the highest concentration of fluoride in the body ~300ppm. • Responsible for regulation of melatonin. Study in The Effect of Fluoride on the Physiology of the Pineal Gland shows that animals treated with fluoride have lower levels of circulating melatonin. Lead to earlier onset of puberty. Further investigations needed to apply to humans.

26. Neural and Hormonal • Hypothyroidism • Fluoride is used to treat hyperthyroidism with doses as low as 2mg/day. • Cause fatigue, muscle pains, weight gain, hair loss and increased LDL. • Secondary hyperparathyroidism (skeletal fluorosis)

27. "Up to now EPA, under the Safe Drinking Water Act, has regulated fluoride in order to prevent children from having teeth which looked like they had been chewing brown shoe polish and rocks... EPA in response to new studies, which only confirmed the old studies, and some flat out political preasure, has decided to raise the standard to 4 mg/L. This increase will allow 40% of all children to have teeth gross enough to gag a maggot."-Paul Price, EPA Drinking Water Analyst, October 31, 1985

28. Conclusion • Fluoridation in communities has made a huge impact in helping with dental health, though it needs to be monitored closely and revised to prevent fluoride toxicity.