Part 1
2007 Fluoride Abstracts
 
 

2007 Fluoride Abstracts. Part 1.

Abstracts for the following years:
Part 1 - mainly biochemistry and physiology (brain, hormonal, G-proteins, etc.)
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Report available free: HTML or PDF

Environ Health Perspect. 2007 Apr;115(4):643-647. Epub 2007 Jan 9.

Arsenic and Fluoride Exposure in Drinking Water: Children's IQ and Growth in Shanyin County, Shanxi Province, China.

Wang SX, Wang ZH, Cheng XT, Li J, Sang ZP, Zhang XD, Han LL, Qiao XY, Wu ZM, Wang ZQ.

Shanxi Institute for Prevention and Treatment of Endemic Disease, Linfen, Shanxi Province, People's Republic of China.

BACKGROUND: Recently, in a cross-sectional study of 201 children in Araihazar, Bangladesh, exposure to arsenic (As) in drinking water has been shown to lower the scores on tests that measure children's intellectual function before and after adjustment for sociodemographic features.
OBJECTIVES: We investigated the effects of As and fluoride exposure on children's intelligence and growth.
METHODS: We report the results of a study of 720 children between 8 and 12 years of age in rural villages in Shanyin county, Shanxi province, China. The children were exposed to As at concentrations of 142 +/- 106 mug/L (medium-As group) and 190 +/- 183 mug/L (high-As group) in drinking water compared with the control group that was exposed to low concentrations of As (2 +/- 3 mug/L) and low concentrations of fluoride (0.5 +/- 0.2 mg/L). A study group of children exposed to high concentrations of fluoride (8.3 +/- 1.9 mg/L) but low concentrations of As (3 +/- 3 mug/L) was also included because of the common occurrence of elevated concentrations of fluoride in groundwater in our study area. A standardized IQ (intelligence quotient) test was modified for children in rural China and was based on the classic Raven's test used to determine the effects of these exposures on children's intelligence. A standardized measurement procedure for weight, height, chest circumference, and lung capacity was used to determine the effects of these exposures on children's growth.
RESULTS: The mean IQ scores decreased from 105 +/- 15 for the control group, to 101 +/- 16 for the medium-As group (p < 0.05), and to 95 +/- 17 for the high-As group (p < 0.01). The mean IQ score for the high-fluoride group was 101 +/- 16 and significantly different from that of the control group (p < 0.05).
Children in the control group were taller than those in the high-fluoride group (p < 0.05); weighed more than the those in the high-As group (p < 0.05); and had higher lung capacity than those in the medium-As group (p < 0.05).
CONCLUSIONS: Children's intelligence and growth can be affected by high concentrations of As or fluoride. The IQ scores of the children in the high-As group were the lowest among the four groups we investigated. It is more significant that high concentrations of As affect children's intelligence. It indicates that arsenic exposure can affect children's intelligence and growth.

PMID: 17450237 [PubMed - as supplied by publisher]


PubMed abstract

J Occup Health. 2007 May;49(3):235-41.

Strong acute toxicity, severe hepatic damage, renal injury and abnormal serum electrolytes after intravenous administration of cadmium fluoride in rats.

Adachi K, Dote T, Dote E, Mitsui G, Kono K.

Department of Hygiene and Public Health, Osaka Medical College, Takatsuki City, Osaka, Japan. infinity_cab@yahoo.co.jp

Cadmium fluoride (CdF) is commonly used as an insulator for ulta high speed mass telecommunications equipment, and there is a considerable risk that industrial workers will inhale CdF particles. Despite the possibility that acute exposure can cause harmful systemic effects, there are no studies to date that address the health consequences of acute CdF exposure. This study therefore aimed to determine the acute lethal dose of CdF and its effects on various target organs, including the liver and kidney. We also determined the effect of CdF on serum electrolytes and acid-base balance. The effective lethal dose was determined and dose-response study was conducted after intravenous administration of CdF in rats. The 24 h LD(50) of CdF was determined to be 3.29 mg/kg. The dose-response study used doses of 1.34, 2.67, 4.01 mg/kg CdF. Saline or sodium fluoride solution were used for controles. Severe hepatocellular injury was induced at doses greater than 2.67 mg/kg, as demonstrated by AST and ALT activities greater than 1,500 IU/l in rats injected with a dose of 4.01 mg/kg. Acute renal failure was induced at doses greater than 2.67 mg/kg. Decreased serum Ca, increased serum K and metabolic acidosis were induced at a dose of 4.01 mg/kg. Decreased serum Ca was caused by exposure to ionized F. CdF has the strongest lethal and hepatic toxicity among all Cd containing compounds.

PMID: 17575404 [PubMed - in process]

Eur Rev Med Pharmacol Sci. 2007 Jul-Aug;11(4):211-24.

Neurofunctional effects of developmental sodium fluoride exposure in rats.

Bera I, Sabatini R, Auteri P, Flace P, Sisto G, Montagnani M, Potenza MA, Marasciulo FL, Carratu MR, Coluccia A, Borracci P, Tarullo A, Cagiano R.

Lucian Blaga University, Medical School, Sibiu, Romania.

Contrasting studies on the toxic effects of sodium fluoride (NaF) during developmental stages of Wistar rats, lead us to investigate the neurofunctional effects caused by its perinatal exposure, devoid of any overt sign of toxicity and/or gross malformation. NaF solution was administered to pregnant rats by intragastric gavage at a daily dose of 2.5 and 5.0 mg/kg from gestational day 0 to day 9 after parturition. Developmental NaF exposure caused sex and dose specific behavioural deficits which affected males more than females in the majority of the evaluated end-points. In particular, the perinatal exposure to NaF 5.0 mg/kg, significantly affected learning, memory, motor coordination and blood pressure only in male rats. Conversely, a lack of habituation upon the second presentation of the objects and failure in the ability to discriminate between the novel and the familiar object were observed only in NaF 5.0 mg/kg female rats. Finally, a significant impairment of sexual behaviour was observed in male rats at both NaF dose levels. The present data indicate that perinatal rat exposure to NaF results in long lasting functional sex-specific alterations which occur at fluoride levels approaching those experienced by offspring of mothers.

PMID: 17876956 [PubMed - indexed for MEDLINE]


PubMed Abstract

Biol Trace Elem Res. 2007 Sep;118(3):260-8.

Effect of long-term fluoride exposure on lipid peroxidation and histology of testes in first- and second-generation rats.

Oncü M, Kocak A, Karaoz E, Darici H, Savik E, Gultekin F.

Department of Histology and Embryology, Faculty of Medicine, Suleyman Demirel University, Morfoloji Binasi, Isparta 32040, Turkey. drmeraloncu@yahoo.com

This experiment was designed to investigate the histological and lipid peroxidation effects of chronic fluorosis on testes tissues of first- and second-generation rats. Sixteen virgin female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two groups: controls and fluoride-given group, each of which containing five rats. Pregnant rats in the fluoride-given group were exposed to a total dose of 30 mg/l sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/l of NaF throughout the gestation and lactation periods. After the lactation period, the young animals (first generation, F1) were exposed to the same dose of NaF in drinking water for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F1) were killed and testes tissues were taken for histopathological and biochemical analysis. The remaining eight female rats were mated with four males (2:1) for approximately 12 h to obtain second-generation rats. Six female were identified as pregnant and treated with similarly throughout the gestation and the lactation periods. After the lactation period, the young male animals (second generation, F2) were also treated in the same way for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F2) were killed and testes tissues were collected for histopathological and biochemical analysis. The rats in the control group were applied the same procedure without NaF administration. In biochemical analysis of the fluoride given F1 and F2 rats, it has been found that plasma fluoride levels and testes thiobarbituric acid reactive substance levels were significantly increased when compared with the control group. In F1 and F2 rats, similar histopathological changes were observed. In both groups, spermatogenesis was severely reduced. Spermatogonia and primary spermatocytes were normal, however, there was a widespread degeneration in other spermatogenic cell lines of the seminiferous epithelium. The histological structures of the Sertoli and interstitial Leydig cells were normally observed. It is concluded that chronic fluorosis exposure leads to a remarkable destruction in testes tissues of F1 and F2 rats via lipid peroxidation.

PMID: 17916930 [PubMed - indexed for MEDLINE]


PubMed Abstract

Anim Reprod Sci. 2007 Aug 6 [Epub ahead of print]

The influence of fluorides on mouse sperm capacitation.

Dvo?áková-Hortová K, Sandera M, Jursová M, Vašinová J, P?knicová J.

Department of Developmental Biology, Faculty of Science, Charles University, Vini?ná 7, 128 44 Prague 2, Czech Republic.

Increasing infertility, due to pathological changes on sperm, has become a serious issue. Eco-toxicological effect of rising concentration of fluorides can be enhanced in the presence of aluminium ions by forming fluorometallic complexes, analogues of phosphate groups that interfere with the activity of G-proteins and P-type ATPases, which are part of several signalling pathways during sperm maturation. In order for sperm to gain fertilizing ability, they must undergo in the female reproductive tract, capacitation that includes tyrosine phosphorylation and consequent actin polymerization. The present paper reports the findings of 3-month oral toxicity in mice of fluorides at the concentrations 0, 1, 10, and 100ppm and their synergic action with aluminium at dose of 10ppm. There were no mortalities, clinical signs of discomfort or body weight loss during the experiment. The analysis revealed, for the concentrations of 10 and 100ppm, abnormalities of spermatogenesis and ability of epididymal spermatozoa to capacitate in vitro, as the result of decreased sperm head tyrosine phosphorylation and actin polymerization. The enhancing overload caused by fluorides represents a potential factor, having an impact on function of sperm, hence contributing to a growing infertility in the human population.

PMID: 17884311 [PubMed - as supplied by publisher]


PubMed abstract

Toxicology. 2007 Jul 17;236(3):208-216. Epub 2007 Apr 24.

Effects of fluoride on the expression of NCAM, oxidative stress, and apoptosis in primary cultured hippocampal neurons.

Zhang M, Wang A, He W, He P, Xu B, Xia T, Chen X, Yang K.

MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji
Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030 Hubei, People's Republic of China; Institute of Occupational Diseases Control and Prevention, Tianjin Centers for Disease Control and Prevention, 76 Hualong Road, Tianjin 300011, People's Republic of China.

The mechanisms underlying the neurotoxicity of endemic fluorosis still remain unknown. To investigate the expression level of neural cell adhesion molecules (NCAM), oxidative stress, and apoptosis induced by fluoride, the primary rat hippocampal neurons were incubated with 20, 40, and 80mg/l sodium fluoride for 24h in vitro. The results showed that the cell survival rate in the 80mg/l fluoride-treated group was significantly lower than that of the control group. Forty and 80mg/l of fluoride induced significantly increased lactate dehydrogenase release, intracellular reactive oxygen species, and the percentage of apoptosis. Compared with control group, the malondialdehyde levels were significantly elevated while glutathione levels and glutathione peroxidase activities were decreased in all fluoride-treated groups, accompanied by the markedly reduced superoxide dismutase activity in 80mg/l fluoride-treated group. With respect to NCAM mRNA expression levels, a significant dose-dependent decrease was observed in 40 and 80mg/l fluoride-treated groups against the control group. In addition, as compared to the control group, the protein expression levels of NCAM-180 in 40 and 80mg/l fluoride-treated groups, NCAM-140 in all fluoride-treated groups, and NCAM-120 in the 80mg/l fluoride-treated group were significantly decreased. Our study herein suggested that fluoride could cause oxidative stress, apoptosis, and decreased mRNA and protein expression levels of NCAM in rat hippocampal neurons, contributing to the neurotoxicity induced by fluoride.

PMID: 17537562 [PubMed - as supplied by publisher]


PubMed abstract

Toxicol In Vitro. 2007 Apr 27; [Epub ahead of print]

Some characteristics of fluoride-induced cell death in rat thymocytes: Cytotoxicity of sodium fluoride.

Matsui H, Morimoto M, Horimoto K, Nishimura Y.

Laboratory of Cell Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.

Fluoride is found in the atmosphere, water, soil, coal, food, dental and industrial uses. There were some case reports concerning acute fluoride poisoning in workplaces and laboratories. However, there is limited information concerning the mechanism of fluoride-induced cell death. To study the cytotoxicity of fluoride, the effect of sodium fluoride (NaF) on rat thymocytes has been examined by using a flow cytometer with appropriate fluorescence probes for membrane and cellular parameters. The cytotoxicity of NaF under nominal Ca(2+)-free condition was significantly lower than that under control condition. NaF also increased intracellular Ca(2+) concentration. NaF significantly increased the population of shrunken cells and the cells positive to annexin V. Both are known to be parameters for early stage of apoptosis. However, NaF decreased the population of cells with hypodiploidal DNA, indicating that NaF apparently attenuated spontaneous apoptosis in rat thymocytes. It may be suggested that NaF induces necrosis, associated with some apoptotic characteristics.

PMID: 17544615 [PubMed - as supplied by publisher]


PubMed Abstract

Eur J Pharmacol. 2007 Oct 25 [Epub ahead of print]

Subchronic fluoride intake induces impairment in habituation and active avoidance tasks in rats.

Chioca LR, Raupp IM, Da Cunha C, Losso EM, Andreatini R.

Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná - UFPR, Centro Politécnico PO Box 19031, 81540-990 Curitiba, PR, Brazil.

Since clinical case reports suggest that sodium fluoride (NaF) intoxication may impair learning and memory, the objective of the present study was to evaluate the effects of NaF on two memory tasks: open-field habituation and two-way active avoidance. Adult male rats were exposed to NaF in drinking water at three concentrations for 30 days: 1.54 (control, tap water), 50 and 100 ppm NaF (corresponding to an intake of 0.10+/-0.005, 5.15+/-0.14, and 10.77+/-0.39 mg/kg of NaF, respectively). At day 30, the rats were placed in an open-field and retested after 24 h (test session) to measure habituation. In the two-way active avoidance task, another three groups of rats were trained in a 30-trial training session and tested again 24 h later (test session). Dental fluorosis was also evaluated. Habituation was impaired by 50 and 100 ppm, but not by 1.54 ppm NaF. Moreover, 100 ppm NaF reduced the number of avoidance responses in the active avoidance task. No locomotor impairment was observed. Mild dental fluorosis in rat incisor teeth was found in the 50 and 100 ppm NaF groups. Overall, these results suggest that moderate intoxication with sodium fluoride has potentially deleterious effects on learning and memory.

PMID: 18001709 [PubMed - as supplied by publisher]


PubMed abstract

Mayo Clin Proc. 2007 Jun;82(6):719-24.

Fluoride-related bone disease associated with habitual tea consumption.

Hallanger Johnson JE, Kearns AE, Doran PM, Khoo TK, Wermers RA.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.

Acquired osteosclerosis is a rare disorder of bone formation but an important consideration in adults with sclerotic bones or elevated bone density results. In such patients, malignancy, hepatitis C, and fluorosis should all be considered when making a diagnosis. We describe 4 patients evaluated at our Metabolic Bone Disease Clinic from May 1, 1997, to July 1, 2006, whose bone disorders resulted from chronic fluoride exposure due to excessive tea intake. Three of these patients had toxic serum fluoride levels (> 15 micromol/L). Although the clinical presentation of the patients varied, all 4 had an unexpectedly elevated spine bone mineral density that was proportionately higher than the bone mineral density at the hip. Other clinical features included gastrointestinal symptoms such as nausea, vomiting, and weight loss; lower extremity pain sometimes associated with stress fractures of the lower extremities; renal insufficiency; and elevated alkaline phosphatase levels. Readily available, tea often contains high levels of fluoride. Obsessive-compulsive drinking behaviors and renal insufficiency may predispose to excessive fluoride consumption and accumulation. The current cases show that fluoride-related bone disease is an important clinical consideration in patients with dense bones or gastrointestinal symptoms and a history of excessive tea consumption. Furthermore, fluoride excess should be considered in all patients with a history of excessive tea consumption, especially due to its insidious nature and nonspecific clinical presentation.

PMID: 17550752 [PubMed - indexed for MEDLINE]


No abstract available

Scand J Rheumatol. 2007 Mar-Apr;36(2):154-5.

Skeletal fluorosis mimicking seronegative arthritis.

Gupta R, Kumar AN, Bandhu S, Gupta S.

PMID: 17476625 [PubMed - indexed for MEDLINE]


Full paper at Science Direct

Experimental and Toxicologic Pathology, Volume 58, Issue 5, 26 April 2007, Pages 339-349

Oxidative stress induced by fluoride in adult mice and their suckling pups

Hanen Bouaziz (a), Françoise Croute (b), Tahia Boudawara (c), Jean Pierre Soleilhavoup (b) and Najiba Zeghal (a), Corresponding Author Contact Information, E-mail The Corresponding Author
a) Laboratoire de Physiologie Animale, Département des Sciences de la Vie, Faculté des Sciences de Sfax, Route de la Soukra-Km 3.5, 3018 Sfax BP 802, Tunisie
b) Laboratoire de Biologie Cellulaire et Pollution, Faculté de Médecine Purpan, Université Toulouse III, 37 Allées Jules Guesde, 31073 Toulouse, France
c) Laboratoire d’Histopathologie, CHU Habib Bourguiba – Sfax, Tunisie

To assess renal and liver damages in pregnant and lactating mice as well as in their suckling pups, Wistar female mice were given 500 ppm NaF (226 ppm F-) in drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. In the present work, we evaluated the effects of sodium fluoride on histopathological aspects of kidney, antioxidant status, lipid peroxidation levels and on the expression of four stress proteins (namely, the cytosolic heat shock proteins: HSP72, 73, 90 and the reticulum-associated GRP94).
Histological studies have shown many abnormalities in mothers and their pups. Biochemical results showed that lipid peroxidation increased in NaF-treated mice, as evidenced by high kidney and liver thiobarbituric acid reactive substance (TBARS) levels. Alteration of the antioxidant system was confirmed by the significant decline of serum total antioxidant status and of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in red blood cells. Besides, fluoride treatment induced a decrease in serum levels of non-enzymatic antioxidants such as uric acid and of some oligoelements: zinc and copper, known to be cofactors of superoxide dismutase (SOD-Cu–Zn). Compared to control group, the 72 kDa protein was found to be overexpressed in kidney of 14-day-old mice only. HSP90 expression in liver appeared moderately inhibited in mothers, but decreased significantly in their pups. No significant changes were detected in the expression of 94 kDa protein in both liver and kidney.
Results showed that fluoride given to dams led to an oxidative stress in mothers as well as in offspring able to induce enhanced lipid peroxidation levels and protein conformational changes, as suggested by stress protein (HSP, GRP) expression changes.


PubMed Abstract

Vet Pathol. 2007 Sep;44(5):703-6.

Spontaneously occurring alimentary osteofluorosis associated with proliferative gastroduodenopathy in rabbits.

Bock P, Peters M, Bagó Z, Wolf P, Thiele A, Baumgärtner W.

Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.

Growing rabbits from two rabbitries, fed with commercial concentrates and hay, developed painful thickenings of the extremities. Four rabbits from each farm were clinically examined and necropsied. All animals showed multiple moderate to severe osseous proliferations of extremities and mandibles and a mild to severe proliferative gastroduodenopathy. Histologically, periosteal and endosteal hyperostosis and a mild to severe proliferation of the gastric and duodenal mucosa were noted. Bone analyses revealed 12,700 and 15,000 microg fluoride per gram of bone ash in affected rabbits, compared with 550 microg fluoride in a control animal. A highly elevated fluoride content was found in concentrates. Vitamin A levels were moderately increased only in one concentrate, and copper levels were normal. Results indicate that alimentary fluoride intoxication caused prominent bony proliferations in the examined rabbits. Whether the proliferative gastroduodenopathy is related to the elevated fluoride intake or represents an incidentally occurring secondary disease remains to be determined.

PMID: 17846246 [PubMed - indexed for MEDLINE]


PubMed abstract

Biol Trace Elem Res. 2007 Apr;116(1):81-90.

Fluoride-induced oxidative stress of osteoblasts and protective effects of baicalein against fluoride toxicity.

Jin XQ, Xu H, Shi HY, Zhang JM, Zhang HQ.

College of Chemistry; College of Pharmacy, Jilin University, Changchun 130012, People's Republic of China.

The key role of osteoblasts in skeletal fluorosis makes the exploration of the possible mechanisms of the fluoride-induced oxidative stress of osteoblasts of great importance. In this article, the in vitro effects of fluoride on the oxidative stress of osteoblasts are presented. To study the inhibitory effect of baicalein on the oxidative stress of osteoblasts, the antioxidant activity of baicalein was evaluated for osteoblasts exposed to fluoride. Calvarial osteoblasts were prepared and respectively treated with alpha-MEM (5% calf serum) containing 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 20.0 mg/L fluoride for 48 h. Baicalein (10 mumol/L) was added to the cells for the same period of time as that of the fluoride treatment. Low concentrations of fluoride (0.5-2 mg F-/L) stimulated the mitochondrial activity of osteoblasts and produced significant reaction to the oxidative stress, whereas high concentrations of fluoride (>/=12 mg F-/L) inhibited cell proliferation and the activity of antioxidant enzymes. This suggests that the oxidative stress induced by low concentrations of fluoride might mediate or participate in the process of fluoride inducing the proliferation of osteoblasts. The viability of osteoblasts in the high concentrations of fluoride with the addition of 10 mumol/L baicalein (>/=12 mg/L) was higher than those of the same level of fluoride- treated groups without the addition of baicalein. The protective role of baicalein is obvious as an inhibitor of lipid peroxidation against the damage induced by the high concentration of fluoride.

PMID: 17634630 [PubMed - in process]


PubMed Abstract

J Anal Toxicol. 2007 Oct;31(8):526-33.

The tissue distribution of fluoride in a fatal case of self-poisoning.

Martínez MA, Ballesteros S, Piga FJ, Sánchez de la Torre C, Cubero CA.

National Institute of Toxicology and Forensic Sciences, Ministry of Justice, C/ Luis Cabrera 9, 28002 Madrid, Spain. ma.martinez@mju.es

The purpose of this paper is to report a case of fluoride poisoning along with a discussion of poisoning characteristics, analytical procedures, and a review of previous reports of fatal intoxications with analytical data. A case of suicidal ingestion of 40 mL of a rust removal agent containing hydrofluoric acid and ammonium fluoride by a 33-year-old white male is presented. He had an organic personality disorder with residual schizophrenia and previous suicide attempts with therapeutic drugs and cleaning products. At admission, he presented with a Glasgow coma score of 3, third degree atrioventricular block, and asystole. Resuscitation efforts were performed during which the patient suffered two episodes of ventricular fibrillation followed by asystole. In spite of advanced resuscitation efforts and the administration of calcium chloride, he died 2.5 h after the ingestion. Analytical data in the hospital showed calcium levels of 3.1 mg/dL and metabolic acidosis. Internal findings were erosive gastritis, brain edema, and pulmonary and hepatic congestion. Quantitation of fluoride was performed using an ion-selective electrode for the anion. Disposition of fluoride in the different tissues was as follows:
peripheral blood, 19.4 mg/L;
urine, 670 mg/L;
vitreous humor, 2.5 mg/L;
liver, 40.0 mg/kg;
kidney, 60.0 mg/kg;
lung, 17.5 mg/kg;
brain, 2.5 mg/kg;
spleen, 30.0 mg/kg;
bone, 0.5 mg/ kg; and
gastric content, 1120 mg/L (67 mg total).

Validation of the analytical method was performed using different spiked tissues, in a range of concentrations from 2.4 to 475 mg/L or mg/kg, and submitting them to dilution (1:25) to avoid the matrix effect and to bring these concentrations to the range of the aqueous calibration curve (0.19-19 mg/L). Limits of detection and quantitation were 0.02 and 0.1 mg/L, respectively. The linearity of the method, for all studies tissues, was excellent, with r(2) values of 0.999. Accuracy and precision were within 10.5% and 5.7%, respectively. Fluoride analyses using the ion selective electrode are simple, sensitive, and rapid. This report provides an extensive tissue distribution study of fluoride after a well documented case of acute poisoning. Based on the autopsy findings, patient history, toxicology results, and previously reported data the forensic pathologists ruled that the cause of death was due to a fluoride poisoning, and the manner of death was listed as suicide.

PMID: 17988468 [PubMed - indexed for MEDLINE]


PubMed Abstract

Bone. 2007 Dec;41(6):1036-44. Epub 2007 Aug 8.

Genetic background influences fluoride's effects on osteoclastogenesis.

Yan D, Gurumurthy A, Wright M, Pfeiler TW, Loboa EG, Everett ET.

Dental Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Excessive fluoride (F) can lead to abnormal bone biology. Numerous studies have focused on the anabolic action of F yet little is known regarding any action on osteoclastogenesis. Little is known regarding the influence of an individual's genetic background on the responses of bone cells to F. Four-week old C57BL/6J (B6) and C3H/HeJ (C3H) female mice were treated with NaF in the drinking water (0 ppm, 50 ppm and 100 ppm F ion) for 3 weeks. Bone marrow cells were harvested for osteoclastogenesis and hematopoietic colony-forming cell assays. Sera were analyzed for biochemical and bone markers. Femurs, tibiae, and lumbar vertebrae were subjected to microCT analysis. Tibiae and femurs were subjected to histology and biomechanical testing, respectively. The results demonstrated new actions of F on osteoclastogenesis and hematopoietic cell differentiation. Strain-specific responses were observed. The anabolic action of F was favored in B6 mice exhibiting dose-dependent increases in serum ALP activity (p<0.001); in proximal tibia trabecular and vertebral BMD (tibia at 50&100 ppm, p=0.001; vertebrae at 50 and 100 ppm, p=0.023&0.019, respectively); and decrease in intact PTH and sRANKL (p=0.045 and p<0.001, respectively). F treatment in B6 mice also resulted in increased numbers of CFU-GEMM colonies (p=0.025). Strain-specific accumulations in bone [F] were observed. For C3H mice, dose-dependent increases were observed in osteoclast potential (p<0.001), in situ trabecular osteoclast number (p=0.007), hematopoietic colony forming units (CFU-GEMM: p<0.001, CFU-GM: p=0.006, CFU-M: p<0.001), and serum markers for osteoclastogenesis (intact PTH: p=0.004, RANKL: p=0.022, TRAP5b: p<0.001). A concordant decrease in serum OPG (p=0.005) was also observed. Fluoride treatment had no significant effects on bone morphology, BMD, and serum PYD cross-links in C3H suggesting a lack of significant bone resorption. Mechanical properties were also unaltered in C3H. In conclusion, short term F treatment at physiological levels has strain-specific effects in mice. The expected anabolic effects were observed in B6 and novel actions hallmarked by enhanced osteoclastogenesis shifts in hematopoietic cell differentiation in the C3H strain.

PMID: 17936699 [PubMed - in process]


PubMed Abstract

Toxicology. 2007 Oct 23 [Epub ahead of print]

Formation of hydrogen fluoride by gamma and beta sterilisation in medical devices containing perfluoroheptane.

Zündorf J, Kremer S, Grüger T.

Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn, Germany.

Infusion of hexadecafluoroheptane, a liquid perfluorocarbon released from repaired Althane dialysers was found to be the most probable reason for the deaths of 53 dialysis patients reported in the year 2001. This study focuses on toxic decomposition products generated due to gamma and beta sterilisation of hexadecafluoroheptane. The responsible dialysers were sterilised with a maximum dose of 45kGy gamma irradiation. We investigated the influence of both 20-500kGy gamma and beta irradiation on perfluoroheptane. Analysis of the irradiated samples verified the decomposition of perfluoroheptane in dependence on the dose of irradiation. Beta irradiation resulted in a higher degree of decomposition than the same dose of gamma irradiation. As decomposition products, hydrogen fluoride, CO(2), and one saturated fluorinated hydrocarbon which could not be analysed exactly were identified. Even at 20kGy gamma irradiation hydrogen fluoride was detectable. Our results provide evidence that hydrogen fluoride is generated as a highly toxic decomposition product when perfluoroheptane is sterilised with gamma irradiation as it was applied on the affected dialysers. There is no evidence of other toxic degradation products especially perfluoroisobutylene. Therefore, hydrogen fluoride or the dissociated fluoride ions might act as a toxic agent when medical devices containing liquid perfluorocarbons are sterilised by irradiation.

PMID: 18053630 [PubMed - as supplied by publisher]


PubMed abstract

Hum Exp Toxicol. 2007 May;26(5):435-40.

Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats.

Leite Ade L, Santiago JF, Levy FM, Maria AG, Fernandes Mda S, Salvadori DM, Ribeiro DA, Buzalaf MA.

Department of Biological Sciences, Bauru Dental School, University of São Paulo, USP, 17012-901 Bauru, SP, Brazil.

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

PMID: 17623768 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17456401&query_hl=7&itool=pubmed_docsum

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2007 Feb;25(2):96-9.

[Effect of fluoride on expression of telomerase reverse transcriptase expression and proliferating cell nuclear antigen in germ cells of rats' testes]

[Article in Chinese]

Jiang Q, Song XK, Cui QH, Chen LJ.

Zhengzhou Prevention and Treatment Institute for Occupational Disease Zhengzhou 450053, China.

OBJECTIVE: To study the damages of fluoride on the male reproductive system in rat testes.
METHODS: A total of 30 male SD rats were randomly divided into control group, high, low dose fluorine treated groups, which were given normal saline, 20 mg/kg sodium fluoride, and 10mg/kg sodium fluoride respectively. After 39 days the change of the weight of rats and the number of sperms were observed. The change of telomerase reverse transcriptase(TERT) and proliferating cell nuclear antigen (PCNA) were observed by using in situ hybridization and radioimmunoassay respectively.
RESULTS: The weight was (273.39 +/- 20.68), (240.00 +/- 21.39) g in NaF treated groups, which was lower than that in control group(P < 0.05); The rate of TERT expression in germ cells of testes in NaF treated groups was (13.89 +/- 4.86)% and (6.33 +/- 4.42)% respectively, which was significantly lower than that in control group (P < 0.05). The rate of PCNA expression in germ cells of tests in NaF treated groups was (0.71 +/- 0.05)%, (0.60 +/- 0.08)% respectively, which also was significant lower than that in control group(P < 0.05). The number of sperms was (18.31 +/- 1.20)10(10)/L, (9.17 +/- 1.38)10(10)/L, which was lower than that in control group (P < 0.05).
CONCLUSION: Fluorine possibly damages the male reproductive system by reducing the expression of TERT and PCNA.

PMID: 17456401 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17440625&query_hl=1&itool=pubmed_docsum

Methods Find Exp Clin Pharmacol. 2007 Mar;29(2):93-9.

Effect of fluoride intoxication on the levels of intestinal antioxidants studied in rats.

Shanthakumari D, Srinivasalu S, Subramanian S.

Department of Biochemistry and Molecular Biology, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India. subbus2020@yahoo.co.in.

High concentration of fluorine is noxious to the health of humans and animals. Analysis of fluoride in water samples meant for human consumption in the Vellore District of Tamil Nadu, India, revealed its presence above the permissible limit (4.56 ppm). The present study was aimed to investigate the toxic effects of oral administration of the water sample that contains the highest fluoride content on the status of pathophysiological parameters and lipid peroxidation in experimental rats. A positive control group orally treated with 4.5 ppm of fluoride was also included in the study. The assay of pathophysiological enzymes and histological observations made on the stomach and intestinal tissue have revealed the toxic effects of fluoride intoxication. The observed increase in the levels of thiobarbituric acid reactive substances (TBARS) both in plasma and in intestinal epithelium, with a concomitant decrease in both enzymatic and nonenzymatic antioxidants in the plasma of experimental rats, revealed that the altered antioxidant status during fluoride intoxication may be due to increased free radical generation. (c) 2007 Prous Science. All rights reserved.

PMID: 17440625 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17459864&query_hl=7&itool=pubmed_docsum

J Vet Diagn Invest. 2007 May;19(3):305-8.

Sodium fluoride/copper naphthenate toxicosis in cattle.

Debey BM, Jacob B, Oehme FW, Imerman P.

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506. debey@vet.ksu.edu.

Fourteen cattle on a Kansas pasture died from ingestion of a wood preservative compound containing sodium fluoride and copper naphthenate. Clinical signs included depression, anorexia, ataxia, diarrhea, and recumbency. Grossly visible lesions included perirenal edema, pale kidneys, and forestomach ulceration. All 3 cows that had postmortem evaluations had extensive renal cortical tubular necrosis. Tissue concentrations of fluoride were slightly elevated above expected background levels, while copper tissue concentrations were not elevated. The findings indicated that the sodium fluoride caused renal tubular necrosis leading to renal failure. Copper naphthenate may have contributed to abomasal ulceration; however, tissue copper concentrations indicated that copper from the formulation was not appreciably absorbed from the gastrointestinal tract.

PMID: 17459864 [PubMed - in process]


PubMed Abstract

Community Dent Oral Epidemiol. 2007 Dec;35(6):479-88.

Fluoride intake and urinary excretion in 6- to 7-year-old children living in optimally, sub-optimally and non-fluoridated areas.

Maguire A, Zohouri FV, Hindmarch PN, Hatts J, Moynihan PJ.

School of Dental Sciences, University of Newcastle, Newcastle upon Tyne, UK.

Objectives: This study was designed to measure total intake, urinary excretion and estimated retention of fluoride in children under customary fluoride intake conditions, living in either fluoridated or low-fluoride areas of north-east England. Subsidiary aims were to investigate the relationships between the variables measured.
Methods: Using a randomized cluster design with schools as the sampling units, four schools from a non-fluoridated area and two from a fluoridated area were selected from the schools chosen to participate in the study. Fluoride intake from diet and toothbrushing was assessed using a 3-day food diary and fluoride analysis of expectorated saliva during toothbrushing. Samples of all foods and drinks consumed were measured for fluoride content using direct and indirect silicon-facilitated diffusion methods as appropriate. Urinary fluoride excretion and urine volume were measured over 24 h and estimation of fractional urinary fluoride excretion (FUFE) and fluoride retention made from collected data. Following descriptive analysis of variables, Pearson's correlations investigated relationships between fluoride content of home tap water, daily fluoride intake, excretion and retention.
Results: Thirty-three children completed the study: 18 receiving non-fluoridated water [mean = 0.08 (+/-0.03) mg F/l], nine sub-optimally fluoridated water [mean = 0.47 (+/-0.09) mg F/l] and six optimally fluoridated water [mean = 0.82 (+/-0.13) mg F/l] at the time of the study. Complete data on F intake, excretion and retention were available for 29 children. Mean fluoride intake from diet and toothpaste ranged from 0.031 (+/-0.025) mg/kg body weight (bw)/day for the low-fluoride area to 0.038 (+/-0.038) and 0.047(+/-0.008) mg/kg bw/day for sub-optimally and optimally fluoridated areas respectively. Contribution of toothpaste to total fluoride intake ranged from 3% to 93% with mean values of 57%, 35% and 47% for children receiving low, sub-optimally and optimally fluoridated water respectively. FUFE ranged from a mean of 32% (+/-13%) for the optimally fluoridated area to 44% (+/-33%) for the low-fluoride area. Fluoride retention was not correlated with the fluoride concentration of home water supply, but was strongly positively correlated (P < 0.001) with total daily fluoride intake.
Conclusions: In an industrialized country, total fluoride intake, urinary excretion and consequently fluoride retention no longer reflect residence in a community with a non-fluoridated or fluoridated water supply. Fluoride toothpaste contributes a significant proportion of total ingested fluoride in children, particularly in low-fluoride areas.

PMID: 18039290 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17439417&query_hl=1&itool=pubmed_docsum

Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):467-74.

Protective effects of vitamins C and e against endometrial damage and oxidative stress in fluoride intoxication.

Guney M, Oral B, Demirin H, Karahan N, Mungan T, Delibas N.

Department of Obstetrics and Gynecology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.

1. Fluoride (F) is an essential trace element that has protective effects against bone mineral loss. However, it becomes toxic at higher doses and induces some adverse effects on a number of physiological functions, including reproduction. The aims of this study were to examine F-induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of vitamins C and E against possible F-induced endometrial impairment in rats.
2. Rats were divided into three groups: control, F and F plus vitamins. The F group was given 100 mg/L orally for 60 days. Combined vitamins were also administered orally. Fluoride administration to control rats significantly increased endometrial malondialdehyde (MDA) but decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Endometrial glandular and stromal apoptosis were investigated by DNA nick end-labelling (TUNEL) method on each sample and the mean endometrial apoptotic index (AI) was calculated.
3. Vitamin administration with F treatment caused endometrial MDA to decrease, but SOD, GSH-Px and CAT activities to increase, all to significant levels. Vitamins showed a histopathological protection against F-induced endometrial damage. There was a significant difference in the AI between the groups. Lymphocyte and eosinophil infiltration in stroma in F-treated rats were more than those in the control and F + Vit groups.
4. It can be concluded that oxidative endometrial damage plays an important role in F-induced endometrial toxicity, and the modulation of oxidative stress with vitamins reduces F-induced endometrial damage both at the biochemical and histological levels.

PMID: 17439417 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17270411&query_hl=1&itool=pubmed_DocSum

Exp Toxicol Pathol. 2007 Apr;58(5):339-49. Epub 2007 Jan 30.

Oxidative stress induced by fluoride in adult mice and their suckling pups.

Bouaziz H, Croute F, Boudawara T, Soleilhavoup JP, Zeghal N.

Laboratoire de Physiologie Animale, Departement des Sciences de la Vie, Faculte des Sciences de Sfax, Route de la Soukra-Km 3.5, 3018 Sfax BP 802, Tunisie.

To assess renal and liver damages in pregnant and lactating mice as well as in their suckling pups, Wistar female mice were given 500 ppm NaF (226ppmF(-)) in drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. In the present work, we evaluated the effects of sodium fluoride on histopathological aspects of kidney, antioxidant status, lipid peroxidation levels and on the expression of four stress proteins (namely, the cytosolic heat shock proteins: HSP72, 73, 90 and the reticulum-associated GRP94). Histological studies have shown many abnormalities in mothers and their pups. Biochemical results showed that lipid peroxidation increased in NaF-treated mice, as evidenced by high kidney and liver thiobarbituric acid reactive substance (TBARS) levels. Alteration of the antioxidant system was confirmed by the significant decline of serum total antioxidant status and of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in red blood cells. Besides, fluoride treatment induced a decrease in serum levels of non-enzymatic antioxidants such as uric acid and of some oligoelements: zinc and copper, known to be cofactors of superoxide dismutase (SOD-Cu-Zn). Compared to control group, the 72kDa protein was found to be overexpressed in kidney of 14-day-old mice only. HSP90 expression in liver appeared moderately inhibited in mothers, but decreased significantly in their pups. No significant changes were detected in the expression of 94kDa protein in both liver and kidney. Results showed that fluoride given to dams led to an oxidative stress in mothers as well as in offspring able to induce enhanced lipid peroxidation levels and protein conformational changes, as suggested by stress protein (HSP, GRP) expression changes.

PMID: 17270411 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17318612&query_hl=1&itool=pubmed_DocSum

Naturwissenschaften. 2007 Feb 22; [Epub ahead of print]

Suppression of male reproduction in rats after exposure to sodium fluoride during early stages of development.

Reddy PS, Pushpalatha T, Reddy PS.

Department of Biotechnology, S.V. University, Tirupati, 517 502, India, reddy_1955@yahoo.co.in.

Sodium fluoride (NaF), a widespread natural pollutant was given to sperm-positive female rats throughout gestation and lactation at a dose of 4.5 and 9.0 ppm via drinking water. The neonates were allowed to grow up to 90 days on tap water, and then sperm parameters, testicular steroidogenic marker enzyme activity levels, and circulatory hormone levels were studied. The sperm count, sperm motility, sperm coiling (hypoosmotic swelling test), and sperm viability were decreased in experimental rats when compared with controls. The activity levels of testicular steroidogenic marker enzymes (3beta hydroxysteroid dehydrogenase and 17beta hydroxysteroid dehydrogenase) were significantly decreased in experimental animals indicating decreased steroidogenesis. The serum testosterone, follicle stimulating hormone and luteinizing hormone levels were also significantly altered in experimental animals. Our data indicate that exposure to NaF during gestation and lactation affects male reproduction in adult rats by decreasing spermatogenesis and steroidogenesis.

PMID: 17318612 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17227693&query_hl=148&itool=pubmed_docsum

Toxicology. 2007 Mar 7;231(2-3):215-23. Epub 2006 Dec 22.

Effect of fluoride intoxication on endometrial apoptosis and lipid peroxidation in rats: role of vitamins E and C.

Guney M, Oral B, Take G, Giray SG, Mungan T.

Department of Obstetrics and Gynecology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey. mguney@med.sdu.edu.tr

Fluoride is a strong, hard anion and cumulative toxic agent. The effect of fluoride intoxication on lipid peroxidation in endometrial tissue and the protective effects of combinations of vitamins E and C in rats were studied. Additionally, the apoptotic changes in endometrial tissue were examined. Experimental groups were as follows: control group; a group treated with 100 mg/l fluoride (F group); and a group treated with 100 mg/l fluoride plus vitamins E and C (F+Vit group). The F and F+Vit groups were treated orally with fluoride for 30 days. Vitamins E and C were injected simultaneously at doses of 50 mg/kg day i.m. and 20 mg/kg day body weight i.p. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick and labeling (TUNEL) method. Malondialdehyde (MDA) levels were determined in uterine tissue of rats. Fluoride caused a significant increase in MDA levels (an important marker of lipid peroxidation) in the fluoride group compared with the controls (p<0.05). Vitamins E and C significantly reduced the fluoride-induced lipid peroxidation in the F+Vit group compared with the F group (p<0.05). Diffuse apoptosis in glandular epithelium and stromal cells was found in endometrial tissues of F treated rats by TUNEL method. The severity of these lesions was reduced by the administration of vitamins. From these results, it can be concluded that subchronic fluoride administration causes endometrial apoptosis, and lipid peroxidation may be a molecular mechanism involved in fluoride-induced toxicity. Furthermore, treatment with a combination of vitamins E and C reduced endometrial apoptosis caused by fluoride.

PMID: 17227693 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17182085&query_hl=1&itool=pubmed_DocSum

Sci Total Environ. 2007 Feb 1;373(1):43-8. Epub 2006 Dec 19.

Osteosclerosis due to endemic fluorosis.

Tamer MN, Kale Koroglu B, Arslan C, Akdogan M, Koroglu M, Cam H, Yildiz M.

Suleyman Demirel University Medical School, Endocrinology and Metabolism Department, Isparta, Turkey. numantamer@hotmail.com

Endemic water borne fluorosis is a public health problem in Isparta, a city located in southern Turkey. In order to investigate the association between osteosclerosis and fluorosis, we retrospectively screened the results of lumbar spine and femur neck bone mineral density (BMD) of 1500 patients who were examined before, for any reason in between 2001-2003. Sixty nine patients (67 females and 2 males, mean age 52.6+/-10.2) with vertebra T-scores>or=+2 were found only except a patient with osteoid osteoma in the femur neck (femur T-score+6.64). Thirty-four of the patients could be reexamined with lateral vertebra BMD and investigated for fluorosis and the other etiologic causes of osteosclerosis. Of 34 patients, 14 had either mottled tooth enamel or urine fluoride level greater than 1.5 mg/l. Other etiologic causes were hypothyroidism (2), hypoparathyroidism (1), history of lumbar fracture (1), use of retinoids (1), vitamin D (7), oral calcium preparations (9), and bisphosphanates (3). Lateral lumbar vertebral T-score was greater than+2 in 12 patients (35.3%). Femur T-score was greater than+2 in 7 patients (20.6%). Fourteen patients (41.2%) had lateral vertebral or femur T-score>or=+2. Five (35.7%) of these patients had signs of fluorosis, as discussed before. Mean body mass index of individuals with fluorosis was 36.4+/-7.9 and this result was significantly higher than other osteosclerotic subjects (31.6+/-4.4). In conclusion we believe that approximately one third of the osteosclerosis in our region was due to endemic skeletal fluorosis and obesity may enhance this osteosclerotic type bone changes in endemic fluorosis.

PMID: 17182085 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17256094&query_hl=1&itool=pubmed_DocSum

Environ Geochem Health. 2007 Apr;29(2):83-102.

A health risk assessment for fluoride in Central Europe.

Fordyce FM, Vrana K, Zhovinsky E, Povoroznuk V, Toth G, Hope BC, Iljinsky U, Baker J.

British Geological Survey, West Mains Road, Edinburgh, EH9 3LA, UK, fmf@bgs.ac.uk.

Like many elements, fluorine (which generally occurs in nature as fluoride) is beneficial to human health in trace amounts, but can be toxic in excess. The links between low intakes of fluoride and dental protection are well known; however, fluoride is a powerful calcium-seeking element and can interfere with the calcified structure of bones and teeth in the human body at higher concentrations causing dental or skeletal fluorosis. One of the main exposure routes is via drinking water and the World Health Organisation currently sets water quality guidelines for the element. In Central Europe, groundwater resources that exceed the guideline value of 1.5 mg l(-1) are widespread and effects on health of high fluoride in water have been reported. The aim of the current project was to develop a geographic information system (GIS) to aid the identification of areas where high-fluoride waters and fluorosis may be a problem; hence, where water treatment technologies should be targeted. The development of the GIS was based upon the collation and digitisation of existing information relevant to fluoride risk in Ukraine, Moldova, Hungary and Slovakia assembled for the first time in a readily accessible form. In addition, geochemistry and health studies to examine in more detail the relationships between high-fluoride drinking waters and health effects in the population were carried out in Moldova and Ukraine demonstrating dental fluorosis prevalence rates of 60-90% in adolescents consuming water containing 2-7 mg l(-1) fluoride.

PMID: 17256094 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17419550&query_hl=1&itool=pubmed_docsum

Ann Anat. 2007;189(2):175-81.

Effect of fluoride ions on apatite crystal formation in rat hard tissues.

Kakei M, Sakae T, Yoshikawa M, Tamura N.

Division of Oral Anatomy, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan. m-kakei@dent.meikai.ac.jp

Fluoride is widely believed to be a useful chemical substance for preventing dental caries. However, the mechanism underlying crystal perforation in the tooth enamel and the effect of fluoride on hard tissues are unclear. To clarify the mechanism of the biological action of fluoride in the mineralization process, we examined the hard tissues of rats having received water containing a relatively low fluoride level. Electron microscopy revealed that fluoride ions could interrupt the crystal nucleation process, resulting in crystal perforation in the developing tooth enamel and the presence of amorphous minerals in bone crystals. Furthermore, the results of enzymatic analyses indicated that fluoride directly interfered with the synthesis of carbonic anhydrase by the enamel-forming cells, rather than being directly involved in the crystal formation. From the results, we would like to provide a possible mechanism of crystal perforation in the enamel induced by fluoride intake. Also, we would like to suggest that regardless of its amount, fluoride intake has harmful effects on both tooth and bone formation.

PMID: 17419550 [PubMed - in process]


PubMed abstract

J Vet Diagn Invest. 2007 May;19(3):305-8.

Sodium fluoride/copper naphthenate toxicosis in cattle.

DeBey BM, Jacob B, Oehme FW, Imerman P.

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA. debey@vet.ksu.edu

Fourteen cattle on a Kansas pasture died from ingestion of a wood preservative compound containing sodium fluoride and copper naphthenate. Clinical signs included depression, anorexia, ataxia, diarrhea, and recumbency. Grossly visible lesions included perirenal edema, pale kidneys, and forestomach ulceration. All 3 cows that had postmortem evaluations had extensive renal cortical tubular necrosis. Tissue concentrations of fluoride were slightly elevated above expected background levels, while copper tissue concentrations were not elevated. The findings indicated that the sodium fluoride caused renal tubular necrosis leading to renal failure. Copper naphthenate may have contributed to abomasal ulceration; however, tissue copper concentrations indicated that copper from the formulation was not appreciably absorbed from the gastrointestinal tract.

PMID: 17459864 [PubMed - indexed for MEDLINE]


No abstract available

Br Dent J. 2007 May 12;202(9):507-8.

Fluoride allergy.

Keanie H.

PMID: 17496835 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17393698&query_hl=1&itool=pubmed_DocSum

Zhonghua Zheng Xing Wai Ke Za Zhi. 2007 Jan;23(1):59-61.

[Apoptotic study on the effect of fluorine and selenium on the human hair follicle in vitro]

[Article in Chinese]

Tu JB, Yang ZQ, Xing Z, Xue Y, Liu XH.

Department of Oral and Maxillary Surgery, Stornatological College, Xi'an Jiao Tong University, Xi'an 710004, China.

OBJECTIVE: The aim of this study was to observe the human hair follical apoptosis status affected by fluorine and the antagonism effect by selenium in vitro.

METHODS: The single hair follicles were separated and cultured, then they were added in different concentrations of sodium fluoride and sodium selenite. Chosen the appropriate concentrations, they were divided into 7 groups. The TUNEL was used to investigate the apoptotic cells of different parts. The morphous of hair follicles was observed consecutively and electron microscope was used.

RESULTS: We found that in 1 mmol/L and 10 mmol/L sodium fluoride groups, when the human hair follicles in vitro were cultured on the 5th day, the apoptotic cells of outer root sheath (ORS), dermal sheath and hair papilla, hair bulb were obviously increased. But 0.01 mmol/L sodium selenite weakened the toxicity of 1 mmol/L sodium fluoride at the outer root sheath and hair bulb (P < 0.05).

CONCLUSIONS: Different concentrations of sodium fluoride had different effect on the growth of human hair follicle in vitro which were cultured on 5th day. Sodium fluoride of certain concentration could accelerate the apoptosis of human hair follicle in vitro. Sodium selenite of certain concentration could act antagonism to the toxicity of sodium fluoride.

PMID: 17393698 [PubMed - in process]


From Science Direct

Forensic Science International
Volume 167, Issue 1, 22 March 2007, Pages 49-52

Case report
Pathological demonstration of rapid involvement into the subcutaneous tissue in a case of fatal hydrofluoric acid burns

Maki Ohtani (a), Naoki Nishida (a), Takashi Chiba (a), Hajime Muto (b) and Naofumi Yoshioka (a)

a) Division of Forensic Sciences, Department of Social Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan
b) Environmental Research Center of Akita University, 1-1-1 Hondo, Akita 010-8543, Japan

We report an autopsy case of a man who suffered accidental chemical burns following exposure to 60% hydrofluoric acid. The extent of the burns covered about 30% of his body surface, and cardiopulmonary arrest occurred about 30 min after the exposure. At autopsy, the skin of the affected area showed greenish gray or black coloring with thin circumferential erythema, and this discoloration extended as far as the periosteum of the skull. However, such discoloration was not found on the mucosa of the airway or the gastrointestinal tract. Microscopically, severe liquefactive necrosis was already evident on the skin. Elastic fibers within the dermis were completely lost, and the entire wall of large vessels within the subcutaneous layer was already severely affected. Blood analysis in the emergency room showed hypocalcemia, and the levels of fluoride ions in the postmortem blood and urine showed extremely high values. However, fewer fluoride ions were detected from the lung tissue. The present case suggests that the hydrofluoric acid had immediately penetrated down into the deep layer of the skin, thereby involving the large vessels present within the subcutaneous layer. These pathological findings of the skin seen in the present case explain the mechanism behind the rapid dissemination of fluoride ions which entered the bloodstream from damaged arteries, resulting in the development of acute toxicity.


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Extremophiles. 2007 Mar;11(2):225-35. Epub 2006 Oct 28.

Comparative analysis of the protein folding activities of two chaperonin subunits of Thermococcus strain KS-1: the effects of beryllium fluoride.

Yoshida T, Iizuka R, Itami K, Yasunaga T, Sakuraba H, Ohshima T, Yohda M, Maruyama T.

Research Program for Marine Biology and Ecology, Extremobiosphere Research Center, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), 2-15 Natsushima-cho, Yokosuka, 237-0061, Japan, tyoshida@jamstec.go.jp.

We conducted a comparative analysis of the effects of beryllium fluoride (BeFx) on protein folding mediated by the alpha- and beta-subunit homooligomers (alpha16mer or beta16mer) from the hyperthermophilic archaeum Thermococcus strain KS-1. BeFx inhibited the ATPase activities of both alpha16mer and beta16mer with equal efficiency. This indicated that BeFx replaces the gamma-phosphate of chaperonin-bound ATP, thereby forming a stable chaperonin-ADP-BeFx complex. In the presence of ATP and BeFx, both of the two chaperonin subunits mediated green fluorescent protein (GFP) folding. Gel filtration chromatography revealed that the refolded GFP was retained by both chaperonins. Protease digestion and electron microscopic analyses showed that both chaperonin-ADP-BeFx complexes of the two subunits adopted a symmetric closed conformation with the built-in lids of both rings closed and that protein folding took place in their central cavities. These data indicated that basic protein folding mechanisms of alpha16mer and beta16mer are likely similar although there were some apparent differences. While beta16mer-mediated GFP refolding in the presence of ATP-BeFx that proceeded more rapidly than in the presence of ATP alone and reached a twofold higher plateau than that achieved with AMP-PNP, the folding mediated by the alpha16mer that proceeded with much lower yields. A mutant of alpha16mer, trapalpha, which traps the unfolded and partially folded substrate protein, did not affect the ATP-BeFx-dependent GFP folding by beta16mer but it suppressed that mediated by alpha16mer to the level of spontaneous folding. These results suggested that beta16mer differed from the alpha16mer in nucleotide binding affinity or the rate of nucleotide hydrolysis.

PMID: 17072688 [PubMed - in process]


PubMed abstract

Drug Chem Toxicol. 2007;30(3):263-81.

Vitamin E supplementation protects oxidative stress during arsenic and fluoride antagonism in male mice.

Mittal M, Flora SJ.

Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.

Arsenic and fluoride are common environmental contaminants. Coexposure to these elements can occur through groundwater. We investigated the effects of sodium meta arsenite (50 mg/L in drinking water) and sodium fluoride (50 mg/L in drinking water) individually and in combination. Biochemical parameters suggestive of alterations in heme synthesis pathway, oxidative stress in liver and kidneys, and concentration of essential metals in blood and soft tissues were studied in Swiss albino male mice given the chemicals for 3 weeks. The possible beneficial effect of vitamin E administration (25 mg/kg, oral, alternate days after arsenic/fluoride exposure) on the above variables was investigated. Exposure to arsenic or fluoride caused a significant depletion in blood delta-aminolevulinic acid dehydratase (ALAD) activity, platelet counts (PLT), and glutathione (GSH) level. Blood white blood cell (WBC) counts also decreased. These changes were accompanied by increased reactive oxygen species (ROS) levels. Arsenic and fluoride exposure led to a significant depletion of super oxide dismutase (SOD) activity with no effect on catalase and glutathione peroxidase (GPx) activities. Combined exposure to these toxicants had no synergistic effect on blood ALAD activity and WBC counts, and the effects seen appeared to result predominantly from arsenic. Hepatic catalase activity, on the other hand, increased significantly on exposure to arsenic and fluoride. There was only moderate antagonistic effect on arsenic and fluoride concentration in blood and liver, and kidney arsenic concentration was less pronounced during coexposure compared with arsenic alone. Interestingly, fluoride concentration showed less pronounced uptake during concomitant exposure compared with fluoride exposure alone. Vitamin E supplementation during coexposure to arsenic and fluoride provided only moderate recovery in the altered antioxidant enzymes and in depleting ROS level, but the altered essential metal concentration, particularly calcium level, responded more favorably to vitamin E administration. It can be concluded from the current study that (i) coadministration of arsenic and fluoride was less toxic to the animals compared with individual toxic effects of these toxicants, and (ii) vitamin E supplementation during coexposure had only limited additional beneficial effects in restoring altered biochemical variables, maintaining pro-oxidant/antioxidant balance, and reducing body arsenic store but plays a significant role in maintaining essential metal balance.

PMID: 17613011 [PubMed - in process]


PubMed abstract

Transplant Proc. 2007 Jun;39(5):1544-8.

Renal safety and extrahepatic defluorination of sevoflurane in hepatic transplantations.

Kanbak M, Karagoz AH, Erdem N, Oc B, Saricaoglu F, Ertas N, Berkkan A, Abbasoglu O, Aypar U.

Department of Anesthesiology and Reanimation, Hacettepe University Faculty of Medicine, Sihhiye, Ankara 06100, Turkey. mkanbak@hacettepe.edu.tr

BACKGROUND: The main metabolic pathway for defluorination of sevoflurane in the liver produces inorganic fluoride (Fl). The metabolism and effect of sevoflurane on the kidney is not clear during anhepatic phase in liver transplantation. The goal of the present study was to investigate the metabolism and renal effect of sevoflurane by measuring plasma and urine inorganic fluoride, urinary N-acetyl-glucosaminidase (NAG), and plasma creatinine levels in patients undergoing liver transplantations.
METHODS: After institutional approval and informed consent, we studied nine cases of orthotopic liver transplantation after anesthesia was induced with 5 mg . kg(-1) thiopental, 1 mug . kg(-1) fentanyl intravenously, the trachea was intubated after vecuronium bromide 0.1 mg . kg(-1). Anesthesia was maintained with sevoflurane (2%), O(2), and N(2)O at a total gas flow of 6 L . min(-1) using a semiclosed circle system with a sodalime canister. Blood and urine samples were obtained to measure plasma and urine fluoride concentrations and urinary NAG excretions before induction (P0), hourly during resection (P1, P2, P3), every 15 minutes during anhepatic phase (A1, A2, A3), hourly after reperfusion (neohepatic phase) (N1, N2, N3), and postoperative first hour (Po1). Preoperative (T0) and postoperative day 1 (T1), 3 (T3), 7 (T7) plasma blood urea nitrogen (BUN) and creatinine (Cr) levels were also recorded.
RESULTS: Mean duration of surgery was 9:06 +/- 0:09 hours. Mean inorganic fluoride concentrations in plasma were in the range of 0.71 +/- 0.30 to 28.73 +/- 3.31 mumole . L(-1). In P3, N1, N2, N3, increases in plasma inorganic fluoride concentrations were significant (P < .05) and reached a peak value at Po1. The mean urine inorganic fluoride concentrations were 12.49 +/- 2.04 to 256.7 +/- 49.62 mumole . L(-1). In A2, A3, N1, N2, and N3, mean urine inorganic fluoride concentrations were significantly increased (P < .05) and the peak value was observed at Po1. Mean NAG concentrations in urine varied (5.6 +/- 1.6 IU . L(-1) to 12.5 +/- 1.14 IU . L(-1)) and peak level was observed at 30 minutes of the anhepatic phase (A2), which did not exceed the normal values for urine NAG levels (1.5 to 6.1 U . L(-1)). No impairment was observed in serum BUN and creatinine levels at any time. While there was only a slight increase in NAG during anhepatic phase, there was no change in plasma F1.
CONCLUSIONS: Sevoflurane seemed to have minimal effect on kidney functions of BUN and Cr levels during liver transplantation. Although urine F1 and NAG levels increased during the anhepatic phase plasma F1, BUN, and Cr levels did not, suggesting that renal F1 production may occur in the absence of hepatic function. The renal effect of sevoflurane in chronic liver disease is controversial and must be investigated in further studies.

PMID: 17580185 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17403599&query_hl=1&itool=pubmed_DocSum

Pathophysiology. 2007 Mar 31; [Epub ahead of print]

A 43kD protein from the herb, Cajanus indicus L., protects against fluoride induced oxidative stress in mice erythrocytes.

Sinha M, Manna P, Sil PC.

Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata 700009, India.

Present study has been carried out to evaluate the protective and curative roles of a 43kD protein isolated from the herb Cajanus indicus L. on sodium fluoride (NaF) induced toxicity in mice erythrocytes. In the preventive study, mice were divided into five groups consisting of six in each for the experiments. Group I animals got water and used as normal controls, animals of groups II and IV were exposed to 600ppm fluoride in water for 7 days. Animals of group III were treated with the protein (2mg/kg body weight) intraperitoneally for 7 days followed by NaF treatment for next 7 days (600ppm). Animals of group V were treated with NaF (600ppm) followed by the protein treatment (2mg/kg body weight) for the same time as mentioned for group III. In the curative study, four groups of six mice were compared. Erythrocytes were isolated, and the antioxidant enzyme superoxide dismutase (SOD) as well as the levels of reduced and oxidized glutathione (GSH and GSSG), total thiols and lipid peroxidation end products were measured in those cells. There was a significant increase in lipid peroxidation along with a decrease in total thiols and SOD activity in the erythrocytes of NaF only and NaF bovine serum albumin treated animals. The 43kD protein treatment in animals either prior or post to fluoride administration normalized the levels of parameters measured and restored the SOD activity in mice erythrocytes. Data suggest that the 43kD protein possesses significant protective and curative activity against NaF induced oxidative stress in erythrocytes.

PMID: 17403599 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17194019&query_hl=1&itool=pubmed_DocSum

J Enzyme Inhib Med Chem. 2006 Oct;21(5):509-14.

Detection of sarin in plasma of rats after inhalation intoxication.

Bartosova L, Bielavska M, Bajgar J.

Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, Hradec Kralove, Czech Republic. bartosova@pmfhk.cz

Presently used methods for detection and diagnosis of the severity of intoxication with organophosphorus (OP) compounds are mostly those that quantify inhibition of blood cholinesterases. It was found that when plasma inhibited with OP compounds is incubated in the presence of a high concentration of fluoride ions, the organophosphate is released from the enzyme thus yielding a phosphofluoridate, which can be analyzed by gas chromatography and NP detection. In our study, the concentration of sarin released after fluoride ions were added to the plasma of sarin-poisoned rats was determined. Sarin amounts in plasma measured after refluoridation and plasma butyrylcholinesterase activity in ten rats, that were exposed to sarin vapors at concentration of 1.25 microg/L (E1 group) and 2.5 microg/L (E2 group) respectively, for 60 min. In the E2 group the concentration of sarin in plasma was nearly 2-fold higher than in the E1 group. These results correspond well with the concentrations of sarin vapors to which the animals were exposed. Both experimental groups of animals showed significant decreases in butyrylcholinesterase activity by more than 30%-36.4% (E1 group) and 47.0% (E2 group). The method of fluoride-induced reactivation provides a very good marker for monitoring sarin intoxication in laboratory animals determined previously mostly by ChE determination which does not allow any information on sarin amounts in plasma.

PMID: 17194019 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17190044&query_hl=1&itool=pubmed_DocSum

Gig Sanit. 2006 Nov-Dec;(6):8-11. Links

[Immunity and normal pharyngeal microflora in persons living in a technogenically exposed area]

[Article in Russian]

Kolenchukova OA, Savchenko AA.

The impact of industrial emissions of an aluminum plant of immunity and pharyngeal mucosal biocenosis were studied in healthy individuals living in the Sovetsky district. The effect of sodium fluoride in various concentrations on the activity of metabolic enzymes in the bacterial Staphylococcus epidermis cells isolated from the pharyngeal mucosa of the healthy individuals was also studied. The persons living in the Sovetsky district were found to have higher values of cellular immunity, an increase in the quantitative composition of the oral microflora being observed when its qualitative composition was worse. Various concentrations of sodium fluoride were ascertained to have a heterodirectional impact on microbial metabolism.

PMID: 17190044 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17190191&query_hl=1&itool=pubmed_DocSum

Biomed Environ Sci. 2006 Oct;19(5):375-9.

Combined effect of fluoride and arsenate on gene expression of osteoclast differentiation factor and osteoprotegerin.

Jia L, Jin TY.

Department of Toxicology, School of Public Health, Fudan University, Shanghai 200032, China. linjia_1978@yahoo.com

OBJECTIVE: To study the combined effect of fluoride and arsenate on the expression of SD rat osteoblastic osteoclast differentiation factor (ODF) mRNA and osteoprotegerin (OPG) mRNA.
METHODS: Osteoblasts were obtained by enzymatic isolation from newborn SD rats. A factorial experiment was performed. Osteoblasts were exposed to NaF (0.5 mmolF/L, 4 molF/L) and Na3AsH2 (12.5 micromolAs/L and 200 micromolAs/L) separately or F plus As and cultured for 48 h. The gene expression of osteoblastic ODF and OPG was observed by RT-PCR.
RESULTS: The expression of ODF mRNA increased in F0.5, F4 groups compared with control group and two groups of F0.5As200, F4As200 compared with As200 group, and decreased significantly in groups of F4Asl2.5, F0.5As200, and F4AS200. The expression of OPG mRNA decreased in groups of F4, As200, F4As12.5, F0.5AS200, and F4AS200.
CONCLUSION: The joint effect of fluoride and arsenate on the gene expression of ODF is antagonistic, while the combined effect on the gene expression of OPG is synergistic. F4, F4As12.5, and F0.5As200 promote bone resorption of rat osteoclasts, whereas F0.5As12.5 inhibits osteolytic effect of rat osteoclasts.

PMID: 17190191 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17308916&query_hl=1&itool=pubmed_DocSum

Int Arch Occup Environ Health. 2007 Feb 17; [Epub ahead of print]

Respiratory and ocular symptoms in workers exposed to potassium aluminium-tetrafluoride soldering flux.

Larsson B, Karlsson JE, Nielsen J.

Department of Rehabilitation Medicine, INR, Faculty of Health Sciences, 581 85, Linkoping, Sweden, britt.larsson@inr.liu.se.

BACKGROUND: Exposure to aluminium compounds, such as fluorides in gaseous and particulate form, places people who work in potrooms at risk for respiratory symptoms. Workers in potrooms, however, also are exposed to a number of other air contaminants. In this study, we present the first report of a dose-response relationship after exposure to potassium aluminium tetrafluoride (KAlF(4)) and the influence of smoking and atopy.
MATERIALS: All workers (308) from an industrial plant that used KAlF as soldering flux were invited to participate in the study. In all, 289 workers participated and 118 employees not exposed to chemicals in their professional work served as an unexposed group.
METHODS: In the first step, all subjects answered a questionnaire concerning respiratory symptoms and work history, and participated in a lung function examination. In a second step, all workers who reported work-related complaints from lower respiratory airways were invited to participate in medical examination, methacholine test, screening test of respiratory allergy, and skin prick test against KAlF(4).
RESULTS: The exposed subjects had more symptoms than the unexposed group; dry cough odds ratio (OR): 5.17 (confidence interval 1.79-15.0), stuffy nose: 2.3 (1.25-4.22), nose bleeding: 10.7 (3.26-35.3) and ocular symptoms 5.01 (1.92-13.1) except for chest tightening and wheezing, and shortness of breath. The symptoms appeared in a dose response-like manner although the ORs between high and low exposed were significant for only chest tightening and wheezing, 2.62 (1.30-5.26) and stuffy nose 2.1 (1.22-3.66). Smokers and atopics did not report more frequent work-related symptoms. Smokers were significantly less hyperreactive than non-smokers, indicating a healthy-worker effect. No one showed a positive skin prick test against KAlF(4).
CONCLUSION: In spite of exposure levels of KAlF(4 )well below the new Swedish threshold limit, value frequent respiratory and ocular symptoms were reported. No evidence of IgE mediated allergy was found.

PMID: 17308916 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17420053&query_hl=1&itool=pubmed_docsum

Neurotoxicology. 2007 Mar 1; [Epub ahead of print]

Confirmation of and explanations for elevated blood lead and other disorders in children exposed to water disinfection and fluoridation chemicals.

Coplan MJ, Patch SC, Masters RD, Bachman MS.

Intellequity Technology Services Natick, Massachusetts, United States.

Silicofluorides (SiFs), fluosilicic acid (FSA) and sodium fluosilicate (NaFSA), are used to fluoridate over 90% of US fluoridated municipal water supplies. Living in communities with silicofluoride treated water (SiFW) is associated with two neurotoxic effects: (1) Prevalence of children with elevated blood lead (PbB>10mug/dL) is about double that in non-fluoridated communities (Risk Ratio 2, chi(2)p<0.01). SiFW is associated with serious corrosion of lead-bearing brass plumbing, producing elevated water lead (PbW) at the faucet. New data refute the long-prevailing belief that PbW contributes little to children's blood lead (PbB), it is likely to contribute 50% or more. (2) SiFW has been shown to interfere with cholinergic function. Unlike the fully ionized state of fluoride (F-) in water treated with sodium fluoride (NaFW), the SiF anion, [SiF6]2- in SiFW releases F- in a complicated dissociation process. Small amounts of incompletely dissociated [SiF6]2- or low molecular weight (LMW) silicic acid (SA) oligomers may remain in SiFW. A German PhD study found that SiFW is a more powerful inhibitor of acetylcholinesterase (AChE) than NaFW. It is proposed here that SiFW induces protein mis-folding via a mechanism that would affect polypeptides in general, and explain dental fluorosis, a tooth enamel defect that is not merely "cosmetic" but a "canary in the mine" foretelling other adverse, albeit subtle, health and behavioral effects. Efforts to refute evidence of such effects are analyzed and rebutted. In 1999 and 2000, senior EPA personnel admitted they knew of no health effects studies of SiFs. In 2002 SiFs were nominated for NTP animal testing. In 2006 an NRC Fluoride Study Committee recommended such studies. It is not known at this writing whether any had begun.

PMID: 17420053 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17384028&query_hl=1&itool=pubmed_DocSum

J Dent Res. 2007 Apr;86(4):336-40.

Micromolar fluoride alters ameloblast lineage cells in vitro.

Yan Q, Zhang Y, Li W, Denbesten PK.

Department of Orofacial Sciences, University of California at San Francisco, 513 Parnassus Ave. S-704, San Francisco, CA 94143-0422, USA.

Fluorosed enamel is caused by exposure to fluoride during tooth formation. The objective of this study was to determine whether epithelial ameloblast-lineage cells, derived from the human enamel organ, are directly affected by micromolar concentrations of fluoride. Cells were cultured in the presence of fluoride, and proliferation was measured by BrdU incorporation. The effect of 0, 10, or 20 microM fluoride on apoptosis was determined by the flow cytometry apoptotic index. The effects of fluoride on gene expression were investigated by SuperArray microarray analysis and real-time PCR. Fluoride had a biphasic effect on cell proliferation, with enhanced proliferation at 16 microM, and reduced proliferation at greater than 1 mM F. Flow cytometry showed that both 10 microM and 20 microM NaF significantly increased the apoptotic index of ameloblast-lineage cells. There was no general effect of fluoride on gene expression. These results indicate multiple effects of micromolar fluoride on ameloblast-lineage cells.

PMID: 17384028 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17385439&query_hl=1&itool=pubmed_DocSum

Klin Lab Diagn. 2007 Jan;(1):22, 35-7.

[Impact of antioxidative therapy on the activity of salivary glutathione-dependent enzymes in patients with fluorosis]

[Article in Russian]

Gavriliuk LA, Stepko EA, Spinei IuG, Vartichan AI, Lysyi LT.

Fluorosis caused by long-term intake of high fluoride levels is characterized by clinical bone and tooth manifestations. The adverse impact of high fluoride intake was also observed in soft tissues. Although fluorosis is irreversible it could be prevented by appropriate and timely interventions through the understanding of the process at biochemical and molecular levels. Increased production of reactive oxygen forms and lipid peroxidation are considered to play an important role in the pathogenesis of chronic fluoride toxicity. Saliva is a biological fluid of the human organism may be a reflection of the metabolic state. Salivary indices are clinical diagnostic indicators. The purpose of this investigation was to comparatively study the salivary antioxidative defense system, including glutathione, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase in adult patients with fluorosis before and after complex antioxidative therapy. Analysis indicated that there was a negative correlation between the level of glutathione and the clinical characteristics of the disease in patients with fluorosis. There was a direct relationship between the activity of glutathione-S-transferase and the clinical manifestations in the patients. These results reflected dose-dependent fluoride intoxication and metabolic imbalance. The imbalanced salivary antioxidative defense system was in part corrected by complex antioxidative therapy.

PMID: 17385439 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17220054&query_hl=1&itool=pubmed_DocSum

Health Phys. 2007 Feb;92(2):157-69.

Radon and lung cancer risk: an extension of the mortality follow-up of the Newfoundland fluorspar cohort.

Villeneuve PJ, Morrison HI, Lane R.

Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada. paul.villeneuve@utoronto.ca

Radon is a well-recognized cause of lung cancer, and studies of underground miners have provided invaluable insights on the mechanisms of radon carcinogenesis. Given the dramatic decreases in occupational exposures and the latent interval between the time of exposure and the development of lung cancer, continued follow-up of these cohorts is needed to address uncertainties in risk estimates. Here, we report on the relationship between radon and lung cancer mortality in a cohort of 1,742 Newfoundland fluorspar miners between 1950 and 2001; follow-up has been extended 11 y from previous analyses. The standardized mortality ratio (SMR) was used to compare the mortality experience of the cohort to similarly aged Newfoundland males. Poisson regression methods were used to characterize the radon-lung cancer relationship with respect to: age at first exposure, attained age, time since last exposure, interactions with cigarette smoking, and exposure rate. In total, 191 lung cancers were observed among underground miners (SMR = 3.09; 95% CI = 2.66, 3.56). ERR/WLMs decreased with attained age and time since last exposure. An inverse dose-rate effect was observed, while age at first exposure was not associated with lung cancer risk. An important strength of this study is that the effects of gamma radiation, thoron, and radioactive dust, common exposures in other miner studies, can be ruled out because the source of radon was from water running through the mine. However, the results should be interpreted cautiously due to uncertainties associated with the estimation of radon exposure levels before ventilation was introduced into the mine, and the relatively small number of lung cancer deaths that precluded joint modeling of multiple risk factors.

PMID: 17220717 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17160492&query_hl=1&itool=pubmed_DocSum

Arch Environ Contam Toxicol. 2007 Feb;52(2):270-81. Epub 2006 Dec 7.

Animal health problems attributed to environmental contamination in lake Nakuru National Park, Kenya: a case study on heavy metal poisoning in the Waterbuck Kobus ellipsiprymnus defassa (Ruppel 1835).

Jumba IO, Kisia SM, Kock R.

Department of Chemistry, College of Biological and Physical Sciences, University of Nairobi, P.O. Box 30197 00100 Nairobi, Kenya. ijumba@uonbi.ac.ke

A study was conducted in which samples of soil, forage, as well as serum, bone, kidney, and liver of waterbuck were collected from Lake Nakuru National Park. The objective was to determine the ecosystem health status in order to establish the causes of animal health problems previously recorded in some sections of the Park. Trace element analysis in serum indicated occurrence of copper (Cu) deficiency in the north and eastern sections of the Park where mean values were marginal (range: 0.36-0.81, mean: 0.62 mg/l) compared to concentrations recorded in the western part of the Park (range: 0.69-1.48, mean: 1.22 mg/l). Bone analysis on dry matter basis (DM) indicated higher (p < 0.01) levels of cadmium (Cd, 0.437 mg/kg), fluoride (F, 3178 mg/kg), and lead (Pb, 20.62 mg/kg) in animals from the east compared to those from the west (0.002, 1492, 4.87 mg/kg, respectively), suggesting heavy exposure. In addition, samples from the east had much lower than normal calcium (Ca)-to-phosphorus (P) ratios (mean: 1.9:1) compared to those recorded in the west (2.2:1), suggesting poor bone mineralization. There was a higher concentration of Cd in the kidney (16.24 mg/kg, p < 0.05) and Pb in the liver (58.3 mg/kg, p < 0.01) in animals from the east compared to those in the west (12.92 and 36.2 mg/kg, respectively), but the converse was true of Cu. The liver Cu status was better in animals from the west with, concentrations (mean: 21.7 mg/kg) being about twice those recorded in the east (11.9 mg/kg DM). Forage analysis revealed prospects of Ca, P, and Cu deficiencies in the entire Park. However, in the northeastern section of the Park (measuring 50 ha) where waterbuck residence times are high, forage concentrations of Cd (0.31 mg/kg DM), molybdenum (Mo, 7.20 mg/kg DM), Pb (2.88 mg/kg DM), and zinc (Zn, 126 mg/kg DM) were an order of magnitude greater (p < 0.01) than the levels recorded in the rest of the Park (ranges: 0.133-0.165, 3.69-5.61, 0.485-0.621, 11.6-17.4 mg/kg DM, respectively). These disparities were attributed to a higher soil concentration of Cd (2.77 mg/kg DM), Pb (85.1 mg/k DM) and Zn (1414 mg/kg DM) in this section compared to the rest of the Park (ranges: 0.10-0.15, 5.02-6.26, 1.49-5.44 mg/kg DM, respectively), and strongly suggest heavy metal contamination as the source of animal health problems in the Park.

PMID: 17160492 [PubMed - indexed for MEDLINE]


PubMed abstract

Health Phys. 2007 Aug;93(2):113-9.

Estimating active bone marrow dose from occupational exposure to uranium at a former gaseous diffusion plant.

Anderson JL, Spitz HB, Yiin JH.

* Division of Surveillance, Hazard Evaluation, and Field Studies (DSHEFS), National Institute for Occupational Safety and Health (NIOSH), Cincinnati, OH 45226.

Active bone marrow absorbed doses were estimated for 581 workers as part of a nested case-control study of multiple myeloma mortality at the Oak Ridge Gaseous Diffusion Plant (K-25). Uranium urinalysis results obtained by fluorometric and gross alpha measurements were available for about 20% of the 581 study subjects. These data were used to determine intakes of uranium as a result of occupational exposure during operation of the K-25 facility. Uranium solubility was inferred from the observed urinary excretion rate, job titles, and department codes. Data suggest that most study subjects were exposed to uranyl fluoride, a relatively soluble uranium compound. The median cumulative bone marrow dose determined for subjects with bioassay data was 0.06 mGy with a geometric standard deviation of 4.48. Subjects without bioassay data were assigned cumulative bone marrow dose based upon job titles and department codes.

PMID: 17622815 [PubMed - in process]


PubMed abstract

Vopr Pitan. 2007;76(2):60-2.

[The diet, fortified with fluorine and its influence on strontium accumulation in bone tissue of animals]

[Article in Russian]

[No authors listed]

The research work was devoted to accumulation of strontium-90 (Sr-90) in bone tissue of animals (white rats) and its dependence on the diet, enriched with Fluorine (F). Totally each rat received 18,5 MBk of strontium-90. Insertion of rusks, fortified with sodium fluoride to the rats dietary intake, reduces accumulation of strontium-90 in bone tissue for 26% comparatively to control group of animals. Stimulation action of fluorine on hematopoietic function of irradiated animals were also determined.

PMID: 17561659 [PubMed - in process]


 

PubMed Abstract

Traffic. 2007 Jul 29; [Epub ahead of print]

Mucolipin-2 Localizes to the Arf6-Associated Pathway and Regulates Recycling of GPI-APs.

Karacsonyi C, Miguel AS, Puertollano R.

Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

In mammals, the mucolipin family includes three members mucolipin-1, mucolipin-2, and mucolipin-3 (MCOLN1-3). While mutations in MCOLN1 and MCOLN3 have been associated with mucolipidosis type IV and the varitint-waddler mouse phenotype, respectively, little is known about the function and cellular distribution of MCOLN2. Here we show that MCOLN2 traffics via the Arf6-associated pathway and colocalizes with major histocompatibility protein class I (MHCI) and glycosylphosphatidylinositol-anchored proteins (GPI-APs), such as CD59 in both vesicles and long tubular structures. Expression of a constitutive active Arf6 mutant, or activation of endogenous Arf6 by transfection with EFA6 or treatment with aluminum fluoride, caused accumulation of MCOLN2 in enlarged vacuoles that also contain MHCI and CD59. In addition, overexpression of MCOLN2 promoted efficient activation of Arf6 in vivo, thus suggesting that MCOLN2 may have a role in the traffic of cargo through the Arf6-associated pathway. In support of this we found that overexpression of a MCOLN2 inactive mutant decreases recycling of CD59 to the plasma membrane. Therefore, our results indicate that MCOLN2 localizes to the Arf6-regulated pathway and regulates sorting of GPI-APs.

PMID: 17662026 [PubMed - as supplied by publisher]


PubMed Abstract

J Biol Chem. 2007 Jul 19; [Epub ahead of print]

Activation of the diguanylate cyclase pleD by phosphorylation-mediated dimerization.

Paul R, Abel S, Wassmann P, Beck A, Heerklotz H, Jenal U.

Biozentrum, University of Basel, Basel CH-4056.

Diguanylate cyclases are key enzymes of second messenger signaling in bacteria. Their activity is responsible for the condensation of two GTP molecules into the signaling compound cyclic di-GMP. Despite their importance and abundance in bacteria, catalytic and regulatory mechanisms of this class of enzymes are poorly understood. In particular, it is not clear if oligomerization is required for catalysis and if it represents a level for activity control. To address this question we perform in vitro and in vivo analysis of the Caulobacter crescentus diguanylate cyclase PleD. PleD is a member of the response regulator family with two N-terminal receiver domains and a C-terminal diguanylate cyclase output domain. PleD is activated by phosphorylation but the structural changes inflicted upon activation of PleD are unknown. We show that PleD can be specifically activated by beryllium fluoride in vitro, resulting in dimerization and c-di-GMP synthesis. Cross-linking and fractionation experiments demonstrated that the DGC activity of PleD is contained entirely within the dimer fraction, confirming that the dimer represents the enzymatically active state of PleD. In contrast to the catalytic activity, allosteric feedback regulation of PleD is not affected by the activation status of the protein, indicating that activation by dimerization and product inhibition represent independent layers of DGC control. Finally, we present evidence that dimerization also serves to sequester activated PleD to the differentiating Caulobacter cell pole, implicating protein oligomerization in spatial control and providing a molecular explanation for the coupling of PleD activation and subcellular localization.

PMID: 17640875 [PubMed - as supplied by publisher]


PubMed abstract

Med Phys. 2007 Mar;34(3):1026-36.

Monte Carlo simulations of absorbed dose in a mouse phantom from 18-fluorine compounds.

Taschereau R, Chatziioannou AF.

The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 700 Westwood Boulevard, Los Angeles, California 90095, USA.

The purpose of this study was to calculate internal absorbed dose distribution in mice from pre-clinical small animal PET imaging procedures with fluorine-18 labeled compounds (18FDG, 18FLT, and fluoride ion). The GATE Monte Carlo software and a realistic, voxel-based mouse phantom that included a subcutaneous tumor were used to perform simulations. Discretized time-activity curves obtained from dynamic in vivo studies with each of the compounds were used to set the activity concentration in the simulations. For 18FDG, a realistic range of uptake ratios was considered for the heart and tumor. For each simulated time frame, the biodistribution of the radionuclide in the phantom was considered constant, and a sufficient number of decays were simulated to achieve low statistical uncertainty. Absorbed dose, which was scaled to take into account radioactive decay, integration with time, and changes in biological distribution was reported in mGy per MBq of administered activity for several organs and uptake scenarios. The mean absorbed dose ranged from a few mGy/MBq to hundreds of mGy/MBq. Major organs receive an absorbed dose in a range for which biological effects have been reported. The effects on a given investigation are hard to predict; however, investigators should be aware of potential perturbations especially when the studied organ receives high absorbed dose and when longitudinal imaging protocols are considered.

PMID: 17441249 [PubMed - indexed for MEDLINE]


 

 
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