Daily Archives: June 12, 2012

“NaF causes DNA damage in human diploid fibroblasts in culture”

Takeki Tsutsui, Nobuko Suzuki, Manabu Ohmori, Heiji Maizumi. Cytotoxicity, chromosome aberrations and unscheduled DNA synthesis in cultured human diploid fibroblasts induced by sodium fluoride. Mutation Research Letters. Volume 139, Issue 4, April 1984, Pages 193–198.

The effects of exposure of cultured human diploid fibroblasts (JHU-1 cells) to sodium fluoride have been studied with respect to cytotoxicity and induction of chromosome aberrations and unscheduled DNA synthesis (UDS) Cytotoxicity of NaF on JHU-1 cells, as determined by a decrease in colony-forming ability, linearly increased with increasing dose of NaF (50–150 μg/ml) or exposure time (1–24 h). Treatment of the cells with 50 μg/ml NaF for 24 h resulted in a lethality (∼70%) similar to that obtained with 100 μg/ml for 12 h. A linear increase in cytotoxicity was observed as a fraction of the product of NaF treatment time and dose. JHU-1 cells treated with 20–50 μg/ml NaF for 12 or 24 h were analyzed for chromosome aberrations. A significant increase in the frequency of chromosome aberrations at the chromatid level was observed in treated cells in a dose-dependent manner. For detection of UDS, confluent JHU-1 cells were cultured with medium containing low serum and then exposed to NaF in the presence of 10 mM hydroxyurea. Treatment with 100–400 μg NaF/ml for 4–24 h reproducibly elicited UDS in a dose-related fashion as determined by direct scintillation counting of [3H]thymidine incorporated into DNA during repair synthesis. These results suggest that NaF causes DNA damage in human diploid fibroblasts in culture.

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Fluoride disrupted ordered collagen fibrils

E.A. Al Omireeni, N.J. Siddiqi, A.S. Alhomida. Biochemical and histological studies on the effect of sodium fluoride on rat kidney collagen. Journal of Saudi Chemical Society. Volume 14, Issue 4, October 2010, Pages 413–416.

Abstract: The present study was carried out to study the effect of acute doses of sodium fluoride on the collagen content of the rat kidneys. Five groups of rats were studied: (i) control rats and (ii) rats divided into four subgroups according to the dose of NaF. Results showed that higher doses of sodium fluoride 10, 20 and 30 mg of NaF/kg body weight caused a significant decrease in the collagen content of the kidneys when compared to the control rats. Electron microscope studies supported these results and showed the sodium fluoride doses 10, 20 and 30 mg of NaF/kg body weight caused disruption of ordered collagen fibrils of the rat kidneys.

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Rat study evaluates reproductive effects of fluoride

The applicability of such studies to humans is debatable….

T.F.X. Collins, R.L. Sprando, M.E. Shackelford, T.N. Black, M.J. Ames, J.J. Welsh, M.F. Balmer, N. Olejnik, D.I. Ruggles. Developmental toxicity of sodium fluoride in rats. Food and Chemical Toxicology. Volume 33, Issue 11, November 1995, Pages 951–960.

Despite the chronic exposure of the US population to fluoridated drinking water since the 1940s, existing studies have been judged inadequate to determine any potential reproductive or developmental hazard. This study was conducted to determine the effects of sodium fluoride (NaF) on foetal development. Sperm-positive female rats were given 0, 10, 25, 100, 175 or 250 ppm NaF daily throughout gestation. They were dosed by drinking water to mimic human exposure to fluoridated water. No dose-related behavioural changes or maternal clinical signs were noted. Fluid consumption by females in the 175- and 250-ppm groups was significantly less than that of the control females. Because of this decreased fluid consumption, the daily amount of NaF ingested (0, 1.4, 3.9, 15.6, 24.7 and 25.1 mg/kg body weight) was less than expected at the two high levels. Feed consumption decreased significantly at 250 ppm, and body weights of pregnant females reflected feed consumption trends. The mean number of viable foetuses per female in all treated groups was similar to that of the control group. The significant decrease in the mean number of implants per litter in the 250-ppm group is probably linked to the lower mean number of corpora lutea in this group. The occurrence of in utero deaths was similar in the control and treated groups. Foetal growth (in terms of foetal body weight and crown-rump length) was not affected by NaF, despite the fact that the dams in the 250-ppm group ate significantly less feed and drank significantly less fluid. There was no dose-related increase in the number of external anomalies in foetuses due to NaF ingestion. At the doses given, NaF had no effect on the development of specific bones, including sternebrae. A significant increase was seen in the average number of foetuses with three or more skeletal variations in the 250-ppm group; the number of litters with foetuses with three or more skeletal variations was increased in the 250-ppm group also, but the increase was not significant. There was no dose-related effect of NaF on the incidence of soft tissue variations.

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Animal study on fluoride evaluated maternal and developmental toxicity

Jerrold J. Heindela, Hudson K. Batesb, Catherine J. Priceb, Melissa C. Marrb, Christina B. Myersb, Bernard A. Schwetza. Developmental Toxicity Evaluation of Sodium Fluoride Administered to Rats and Rabbits in Drinking Water. Fundamental and Applied Toxicology. Volume 30, Issue 2, April 1996, Pages 162–177.

Sodium fluoride (NaF; Cas No. 7681-49-4) is used in fluoridating municipal water supplies, resulting in chronic exposure of millions of people worldwide. Because of a lack of pertinent developmental toxicity studies in the literature, sodium fluoride was administeredad libitumin deionized/filtered drinking water (to mimic human exposure) to Sprague–Dawley-derived rats (26/group) on Gestation Days (GD) 6 through 15 at levels of 0, 50, 150, or 300 ppm and New Zealand White rabbits (26/group) on GD 6 through 19 at levels of 0, 100, 200, or 400 ppm. Higher concentrations via drinking water were not practicable due to the poor palatability of sodium fluoride. Drinking water (vehicle) contained less than 0.6 ppm sodium fluoride (limit of detection) and sodium fluoride content of the feed was 12.4 ppm fluoride (rats) and 15.6 ppm fluoride (rabbits). Maternal food, water, body weights, and clinical signs were recorded at regular intervals throughout these studies. Animals were killed on GD 20 (rats) or 30 (rabbits) and examined for implant status, fetal weight, sex, and morphological development. In the high-dose group of both studies there was an initial decreased maternal body weight gain which recovered over time and a decreased water consumption—attributed to decreased palatability. No clear clinical signs of toxicity were observed. Maternal exposure to sodium fluoride during organogenesis did not significantly affect the frequency of postimplantation loss, mean fetal body weight/litter, or external, visceral or skeletal malformations in either the rat or the rabbit. The NOAEL for maternal toxicity was 150 ppm sodium fluoride in drinking water (∼18 mg/kg/day) for rats, and 200 ppm (∼18 mg/kg/day) for rabbits. The NOAEL for developmental toxicity was ≥300 ppm sodium fluoride (∼27 mg/kg/day) for rats and ≥400 ppm (∼29 mg/kg/day) for rabbits administered during organogenesis in drinking water. The total exposure to fluoride (mg F/kg body weight/day from food and drinking water combined) in the mid- and high-dose groups for both species was >100-fold higher than the range at 0.014–0.08 mg F/kg/day estimated for a 70-kg person from food and fluoridated (1 ppm) drinking water.

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Silver brazing flux ingestion is fatal….due to fluoride

Tilleard, J. Fatal fluoride toxicity from silver brazing flux ingestion. Emergency Medicine. Volume 6, Issue 1, pages 12–16, March 1994

Aim: To describe a case of fluoride poisoning due to ingestion of silver brazing flux and review the pathophysiology and treatment of such ingestions.

Introduction: The dominant hazardous constituent of silver brazing flux is KHF2 (potassium hydrogen fluoride). This compound is toxic, corrosive and rapidly absorbed from the gastrointestinal tract to produce systemic fluoride toxicity.

Case report: A woman ingested an unknown amount of silver brazing flux and was brought to the Emergency Department hypotensive and obtunded. Despite vigorous resuscitation and electrolyte replacement she developed refractory ventricular fibrillation and died eight hours later in intensive care.

Discussion: Hydrogen fluoride and its salts are widely used in industrial and domestic products but poisoning by these agents is uncommon. Rapid absorption produces systemic fluoride toxicity. This generates hypocalcaemia, hypomagnesaemia and hyperkalaemia with death resulting from refractory ventricular arrhythmias. These chemicals are corrosive and may cause haemorrhage or perforation of the gastrointestinal tract.

Conclusion: Survival from such ingestions is rare. Early recognition and appropriate treatment are essential to optimise outcome.