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Introduction. Aluminium production is characterized by the accumulation of impurities of various toxic and chemical compositions in the air of working areas, the predominant among which are fluoride compounds. The accumulation of fluorides in the body causes the development of osteoarticular and associated systemic pathology. The aim of the study was to evaluate the hygienic and medico-biological features of toxic liver damage in the conditions of chronic fluoride intoxication of the body. Material and methods. The hygienic working conditions of the workers of the primary professions in aluminium production were evaluated. The analysis of hepatobiliary dysfunction based on clinical and instrumental methods was carried out in 263 subjects with fluoride intoxication and a comparison group of 116 persons. Experimental studies of the morpho-functional liver state in modelling chronic fluoride intoxication were carried out based on toxicological, biochemical, pathomorphological methods with histological analysis of tissues. The toxic properties of sodium fluoride were studied in 117 white laboratory male rats with its peroral route intake into the body. Results. The qualitative composition of the air in the working areas in the electrolysis building was analyzed. The prevalence of pathological disorders of the biliary tract in metallurgists engaged in aluminium production was assessed. Clinical studies revealed a significant prevalence of toxic fluoride hepatopathy, fatty hepatosis, cholecystitis and other disorders in the group of patients with chronic fluoride intoxication. The harmful effect of sodium fluoride on hepatocytes, vessels of the portal tract was shown in an experiment. Hyperfunction of the reticuloendothelial system, Kupffer cell proliferation, irreversible destruction of hepatocytes, necrosis against the background of severe dystrophy, and decreased synthetic activity of the liver were determined. Conclusion. The structure of occupational diseases in the workers engaged in the aluminium production is dominated by hepatobiliary pathology caused by toxic liver damage with fluoride confirmed by experimental data on destructive violations of its morphostructure. Contribution: Yadykina T.K. — the concept and design of the study, collection and processing of material, statistical processing, writing a text; Mikhailova N.N. — the concept and design of the study, editing; Bugaeva M.S. — collection and processing of material; Gorokhova L.G. – collection and processing of material, statistical processing; Kislitsyna V.V. — collection and processing of material; Danilov I.P. — collection and processing of material; Kochergina T.V. — collection of literature data. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version. Conclusion of the Biomedical Ethics Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases: the clinical study was carried out with the informed consent of the subjects and complies with the ethical standards of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, developed in accordance with the Declaration of Helsinki by the World Association “Ethical Principles for Conducting Scientific Research with Human Participation” as amended in 2013 and “Rules of Clinical Practice in the Russian Federation” approved by the Order of the Ministry of Health of the Russian Federation No. 266 dated June 19, 2003 Research Institute for Complex Problems of Hygiene and Occupational Diseases. The study did not infringe on the rights and did not endanger the subjects. The experimental study on rats was carried out in accordance with the international rules “Guide for the Care and Use of Laboratory Animals” (Strasbourg, 1986) and the “Rules of laboratory practice in the Russian Federation (GLP)” (approved by order of the Ministry of Health of the Russian Federation dated 19.06.2003, No. 267). Acknowledgement. The study had no sponsorship. Conflict of interest. The authors declare no conflict of interest.

Connection of work with scientific plans, topics. The work was performed in accordance with the research plan of the Kharkiv Medical Academy of Postgraduate Education of the Ministry of Health of Ukraine and is a fragment of research work of the Department of Clinical Pathophysiology, Topographic Anatomy and Operative Surgery "Pathophysiological mechanisms of radiotoxins on the body and principles of early diagnosis 2017–2021). SUMMARY. One of the important medical and biological problems is to elucidate the physiological and molecular mechanisms of the impact of harmful environmental factors on the body, including fluorine and its compounds, in particular sodium fluoride [1]. Solving this problem is of great theoretical and practical importance for understanding the intracellular defense mechanisms of the organism. Close attention to various aspects of the biological effects of fluoride on the body is due to the significant distribution of this halogen in nature. At physiological concentrations, it is necessary for normal growth and development of the organism, where it performs its specific metabolic function. Any changes in the external and internal environment are accompanied by changes in the function of the endocrine glands, which leads to certain changes in metabolism and energy. It is known that hormonal insufficiency is accompanied by a decrease in the body's resistance to various adverse factors, including physical, biological, chemical. Disturbance of hormone balance and functioning of endocrine organs and systems entails profound changes in metabolic processes and immunobiological reactivity of the organism, weakening of adaptive-protective mechanisms in support of homeostatic function [2,3]. It is important to study the effects of subchronic fluoride intake, which can in a relatively short time cause various intracellular and systemic disorders in the body.

The objective of the study was to evaluate the intracellular cyclase cascade under the conditions of chronic fluoride intoxication in white rats of the Wistar population. Materials and methods. The study was conducted from 2009 to 2014 in the Department of Biochemistry and vivarium of Kharkiv National Medical University MOH, Kharkiv, Ukraine. The study was performed on white rats of the Wistar population. In these rats, we administered intragastric, in the morning, on an empty stomach, a solution of sodium fluoride at a rate of 20 mg/kg of body weight. In this way, the development of fluoride intoxication was simulated. The duration of oral administration of the drug was 1.5 months. The intracellular metabolism was assessed in plasma, liver, kidneys, spleen, and brain cortex. The energy components of the adenylate cyclase system, adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), inorganic phosphorus and ions of Mg2+, guanylate cyclase, phosphodiesterase, were measured. The organs and tissues content of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and absorption of Са2+ by the liver membranes microsomes and synaptosomes of the brain were also determined. Results. The increase in the content of cAMP and a decrease in the level of cGMP were observed in the blood plasma of animals, whereas a decrease in the concentration of cAMP and an increase in the amount of cGMP were observed in the liver, kidneys and spleen. In the cerebral cortex, a decrease in adenylate cyclase activity and cAMP content has been established. At the same time, the activity of guanylate cyclase, phosphodiesterase, and cGMP content increased. Conclusions. Analysis of the absorption of Са2+ membranes by macrosomes of the liver and brain synaptosomes revealed a decrease in basal and К+– stimulated absorption of calcium ions by membrane preparations of nerve cells. In the liver, the К+-stimulated and basal absorption of Са2+ ions was significantly less than in the brain.

Introduction. Certain regions in Europe and Ukraine have high concentration of fluorides in drinking waters. Highly developed agriculture can result in increased concentration of nitrates in ground and drinking waters. Therefore, their combined excessive intake with food and water is not excluded. The objective of the study was to determine the influence of combined nitrate-fluoride intoxication on concentration of different fractions of glycosaminoglycans (GAG) and L-hydroxyproline concentration in gastric mucosa of rats. Materials and methods. Chronic intoxications were induced by intragastric injection of sodium fluoride in a dose of 10 mg/kg, sodium nitrate in a dose of 500 mg/kg and their combination during 30 days. Concentration of GAG was determined by carbazole method. To evaluate concentrations of different fractions of GAG we used the method of differential precipitation with ethanol. For L-Hydroxyproline concentration estimation, we used Hydroxyproline Colorimetric Assay Kit (BioVision K555-100). Results. The total concentration of GAG decreases during chronic fluoride and nitrate intoxications, but increases during combined intoxication. Concentration of Heparin/Heparan GAG fraction and Keratan/Dermatan GAG fraction drops during nitrate and fluoride intoxications, but increases during combined intoxication. Chondroitin GAG fraction shows no statistically significant changes during fluoride intoxication, but increases during combined and nitrate intoxications. Concentration of L-hydroxyproline increases in all studied groups. Conclusions. We established that chronic excessive fluoride or nitrate intake can cause oxidative and nitrosative stress-depended collagen degradation, simultaneously decreasing the concentration of anti-inflammatory GAG. Combined intoxication leads to even more severe connective tissue degradation, but subsequently activates compensatory mechanisms through increase in concentration of anti-inflammatory GAG.

The aim of the study was to assess the state of receptor binding parameters under the action of sodium fluoride on the organism under model conditions for the intoxication formation. Material and methods. The experimental part of the work was performed on 16 white rats of the Wistar population. Internal organs and tissues were subjected to the study of the state of receptor binding parameters of labeled C1, C2 serotonin, α1, α2, β-adreno, D2-dopamine and glucocorticoid type II receptor agonists and antagonists in various regions of the brain and liver. The functional activity of the receptors was assessed by affinity and the number of binding sites and ligands. Results. The study of the effect of sodium fluoride on the kinetic characteristics of the adrenoreceptors of the membrane fractions of liver cells and the cerebral cortex showed similar dynamic changes in the parameters of receptor binding of both α1-adreno- and β1-adrenoreceptors. The effect of sodium fluoride was manifested in a decrease in the affinity of the radioligand for α2-adrenoreceptors and an increase in the number of binding sites for this type of receptors. Similar dynamics of the kinetic characteristics of α2-adrenoreceptors was found in the cerebellum. The number of binding sites for β1-adrenoreceptors increased, while their affinity for ligands decreased. In the brainstem, there was a decrease in the affinity of the D2-receptors for ligands and the number of binding sites. Under conditions of subtoxic effect of sodium fluoride on white rats, a decrease in the affinity of radioligands for C2-receptors and the number of their binding sites in the cerebral cortex was observed. Conclusions. The results of the study show that under the conditions of the formation of fluoride intoxication, structural and functional disorders of the receptor apparatus occur, which confirms the leading role in the development of this pathology of the state of biological membranes. Changes in the kinetic characteristics of adrenaline (α1, α2, β1), serotonin (C1, C2), dopamine (D2) and glucocorticoid receptors confirm the polytropic nature of the action of sodium fluoride on organs, systems and functions of the body.

This study aims to present an accessible and sustainable proposal for development and evaluation of a activated carbon/CeO2 filter matrix for water defluoridation, with potential application in Brazilian regions and abroad with high fluorosis (dental and skeletal) incidence. Using a soft chemistry process, microwave assisted hydrothermal rout, cerium (VI) oxide nanostructures (ceria, CeO2) and its composites (activated carbon/CeO2 with 0%, 1%, 10% and 20% of CeO2) were prepared, using coconut (Cocos nucifera L.), from using coconut residue (Cocos nucifera L.), from the agribusiness in the interior of Paraiba. All synthesis, were proceeded at 120 °C, with different time intervals (1, 5, 15, 30 and 60 minutes, for the CeO2 obtention; and 30 minutes for composites – activated carbon/ CeO2). The structural, thermodynamic, morphological and adsorptive (fluorine) properties, were analyzed by X-ray diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDX), Infrared spectroscopy (IR), Thermogravimetric analysis (TGA), BET adsorption method, high resolution transmission electron microscopy (HR-TEM), high resolution scanning electron microscope (HR-SEM), respectively. The phase of the cerium oxide was determined by XRD analysis with planes ((1 1 1), (2 0 0), (0 2 2), (3 1 1), (2 2 2) and (4 0 0), in accordance with the cards JCPDS 34-0394), and the presence of the composite deposition was confirmed by EDX analysis. BET results showed for the best sample a surface area of (261 m2. g-1) for ceria particles, synthesized for 5 minutes. Microscopic analyzes (HR-SEM and HR-TEM) confirmed these results, presenting particle clusters of the order of 5nm, which justified its use for the composites production. Analyzes of fluoride concentration (direct and indirect methods), in composites obtaining, on a laboratory scale, were performed in triplicate with mean ± deviation and Tukey test with significant differences (p

The aim of the research is to study influence of combined nitrate-fluoride intoxication on the production of peroxynitrite (ONOO-) and superoxide anion radical (O2•-) in gastric mucosa of rats. Material and methods. We carried out experiments on 52 mature rats. Intoxication was modeled by intragastric administration of sodium fluoride and nitrate in a dose of 10 mg/kg and 500 mg/kg respectively. Total production of O2•-, ONOO- and concentration of thiobarbituric acid reactants (TBA-reactants) was determined in 10% homogenate of gastric mucosa. Results. We observed the highest ONOO- production from fluoride intoxication, while O2•- production was the highest under combined intoxication. The TBA-reactant concentration was the highest in fluoride intoxication group. Conclusion. Combined nitrate-fluoride intoxication intensifies lipid peroxidation by increased production of both O2•- and ONOO-.

The effect of small subtoxical doses of sodium fluoride on the activity of hepatocytes' microsoms on 30 Wistar rats' populations was studied in subacute experiments. The results indicate the disorder of mitochondrial respiratory activity of rats' hepatocytes during prolonged fluoride intoxication. Identified changes can be explained by the initiation of sodium fluoride free radical reactions and lipid peroxidation, whose products are the factors damaging membranes, including mitochondrial, where localized respiratory chain. Increased activity of the mitochondrial NADH-coenzymeQ-oxidoreductase action in the case of sodium fluoride at a dose 1/100 LD50, can probably be seen as a defensive response

В условиях непрерывного воздействия неблагоприятных факторов окружающей и производственной среды на человека особую актуальность приобретает изучение механизмов, поддерживающих гомеостаз организма. Длительное поступление фторидов в организм приводит к формированию хронической фтористой интоксикации, патогенез которой вызывает многочисленные споры и дискуссии. До сих пор недостаточно внимания уделяется изучению висцеральной патологии, обусловленной нарушениями иммунного статуса в условиях воздействия на организм соединений фтора. Практически отсутствуют исследования по изучению иммунной реактивности, определяющей морфофункциональный характер ответной реакции печени на ранних стадиях развития фтористой интоксикации. Цель работы изучение действий патофизиологических механизмов иммунной реактивности печени при субхроническом действии на организм соединений фтора. Методика. Опыты проведены на 210 лабораторных крысахсамцах массой 180220 г., разделенных на 2 группы: контрольную (n80) и группу животных с субхроническим действием фторида натрия (n130). Экспериментальные животные в течение 12 нед имели свободный доступ к водному раствору фторида натрия (концентрация 10 мг/л, что составляет суточную дозу фтора 1,2 мг/кг массы тела). Для изучения иммунологических и биохимических показателей забирали кровь из хвостовой вены через 1, 3, 6, 9, 12 нед от начала эксперимента. Для оценки состояния гуморального звена иммунитета определяли уровень сывороточных иммуноглобулинов (IgA, IgG, IgM) иммуноферментным анализом с помощью наборов реактивов ЗАО ВекторБест (Новосибирск). Уровень сывороточных цитокинов: TNF, IL1, 2, 4, 6, 10 определяли на анализаторе Multiskan EX методом иммуноферментного анализа с использованием наборов Вектор Бест (Новосибирск). Подсчет общего количества лейкоцитов произведен классическим способом в камере Горяева, анализ лейкоцитарной формулы в окрашенных мазках периферической крови. Метаболические изменения оценивали по активности ферментов в ткани печени: щелочной фосфатазы (ЩФ), аланин и аспартатаминотрансфераз (АЛТ, АСТ), лактатдегидрогеназы (ЛДГ), гаммаглутамилтранспептидазы (ГТ). Активность ферментов определяли унифицированными методами с помощью наборов реактивов ЗАО ВекторБест (Новосибирск) на фотометре PM750 (Германия). Гистологические исследования печени осуществляли после декапитации крыс, проводимой под эфирным наркозом. Результаты. Показано, что субхроническое воздействие фторида натрия сопровождается формированием внутриклеточных и внутрисосудистых повреждений печени. Активация медиаторов воспаления и развитие иммунологических нарушений в динамике эксперимента способствуют формированию системной воспалительной реакции, которая приводит к появлению стойких морфологических нарушений в печени и изменению активности ферментов основных метаболических путей. Заключение. Полученные результаты могут быть использованы при разработке и проведении профилактических мероприятий в условиях воздействия на организм высоких концентраций фтора с последовательным применением детоксикационной, иммуномодуляторной и органопротекторной коррекции., Studying mechanisms, which maintain the body homeostasis, is particularly important in the conditions of continuous impact of adverse environmental and manufacturing factors. Longterm exposure to fluorides leads to chronic fluoric intoxication, the pathogenesis of which is a subject of multiple controversy and discussions. Not enough attention is still paid to elucidating the visceral pathology associated with fluorineinduced immune disorders. There are virtually no studies of immune reactions that define the morphofunctional nature of the liver response to early stages of fluoric intoxication. Aim. To study pathophysiological mechanisms of hepatic immune reactivity in subchronic exposure of the body to fluorine compounds. Methods. Experiments were performed on 210 male rats weighing 180220 g. The animals were divided into two groups: 1) control (n80) and 2) subchronic exposure to sodium fluoride (n130). The rats had free access to a 10 mg/l aqueous solution of sodium fluoride (daily dose, 1.2 mg/kg body weight) for 12 weeks. Blood was withdrawn from the caudal vein at 1, 3, 6, 9, and 12 weeks of the experiment for immunological and biochemical tests. Histological study of the liver was performed after decapitation of rats under ether anesthesia. Results. The subchronic exposure to sodium fluoride was associated with intracellular and intravascular damage of the liver. Activation of inflammatory mediators and development of immunological disorders during the experiment contributed to a systemic inflammatory reaction, which resulted in persistent morphological injuries of the liver and changes in enzyme activities in major metabolic pathways. Conclusion. The study results can be used for development and implementation of preventive measures against the effects of high fluorine concentrations, which would include a successive use of detoxification, immunomodulation and organ protection., №3 (2019)

Hydrofluoric acid (HF) is a colorless and odorless solution of the hydrogen fluoride in water. It is used in some household products. The rapid onset of severe toxicity and death after the ingestion of HF is not reported often. Also, there is no reported fatal pediatric case after HF ingestion. In this case report, we present a 3.5-year-old girls who unintentionally drunk a rust remover that contained 8% HF. She died in a short period as a result of refractory ventricular fibrillation, which was developed due to fluoride intoxication.

Graphical abstract, Highlights • Sodium fluoride toxicity in Oryctolagus cunniculus and resulting fluctuations in hematological profile. • Dose pattern for 5 rabbits in each group 1. Control group without dose, Experimental group I with 10 mg/kg, Experimental group II with 30 mg/kg, Experimental group III with 50 mg/kg. • Leucocytosis and anemia was observed in affected animals., Blood is promptly affected by environmental pollutants and toxicants that can cause many metabolic disorders. The high level of fluoride acts as a potential pollutant, insecticide and rodenticide with very high toxicity, associated with the hematological damage. This study aimed to determine the toxicity of Sodium Fluoride on hematological parameters in Oryctolagus cunniculus. Twenty rabbits were acclimatized and divided in to control group and three experimental groups.Experimental group-I, II and III were treated with 10, 30 and 50 mg/kg body weight doses of Sodium Fluoride orally. Various blood parameters such as TEC, Hb, HCT, MCV, MCH, MCHC, TLC and PLT count were investigated. Result findings showed that values of blood indices in experimental groups were significantly lower than the control group. Oneway ANOVA was applied for statistical analysis. The outcomes of the current studies indicated the reduction in RBC counts (anemia), leukocyte count (leukocytopenia), monocytosis, eosinopenia, neutrophilia and thrombocytosis on fluoride intoxication. Hematological disruptions like microcytic hypochromic anemia and decreased leukocyte count may be linked to the inflammatory effects of Sodium Fluoride on lymphatic organs.

In this study, we report the concentrations of four trace elements in muscle and kidney tissues of sheep grown in an area with endemic fluorosis. Fifteen 3- to 4-year-old fluorotic sheep were selected for the study. Ten age-matched sheep with no sign of fluorosis were used as the control group. The animals were killed in a slaughterhouse in the village of Doğubeyazıt, located in the Ağrı province of Eastern Turkey, where kidney and muscle tissue samples were surgically obtained to be analyzed for copper, zinc, nickel, and iron. In muscle tissue of the fluorotic sheep, the copper levels were higher than those of the control group (p 0.05). In the case of zinc, its levels were significantly higher in the controls than in the sheep with fluorosis (p 0.01). No statistically significant differences were found in the muscle contents of nickel and zinc (p 0.05). Compared to controls, the concentrations of zinc (0.01), iron (p 0.05), and nickel (p 0.05) were significantly higher in kidney tissues of fluorotic sheep, but there were no significant differences of the copper levels (p 0.05). These results suggest that fluorosis significantly alters the mineral metabolism in muscle and kidney resulting in higher levels of mineral accumulation and excretion caused by fluoride intoxication. Further research shall focus on the enzymatic and metabolic activities of these and other trace elements.

Increased exposure to fluorine-containing compounds leads to accumulation of fluorides in hard tissues of bones and teeth, which may result in numerous skeletal and dental disorders. This study evaluates the influence of methionine and vitamin E on fluoride concentration in bones and teeth of rats subjected to long-term exposure to sodium fluoride in drinking water. The study was conducted in 30 3-month-old female Wistar FL rats. The animals were divided into five groups, six rats per group. The control group consisted of rats receiving only distilled water as drinking water. All other groups received NaF in the amount of 10 mg/kg of body mass/day in their drinking water. In addition, respective animal groups received: NaF + Met group--10 mg of methionine/kg of body mass/day, NaF + Met + E group--10 mg of methionine/kg of body mass/day and 3 mg of vitamin E (tocopheroli acetas)/rat/day and NaF + E group--3 mg of vitamin E/rat/day. Femoral bones and incisor teeth were collected for the study, and the fluoride concentration was determined using a fluoride ion-selective electrode. Fluoride concentration in both bones and teeth was found to be higher in the NaF and NaF + Met groups compared to the control group. In groups NaF + Met + E and NaF + E, the study material contained much lower fluoride concentration compared to the NaF group, while the effect was more prominent in the NaF + E group. The results of the studies indicate that methionine and vitamin E have opposite effects on accumulation of fluorides in hard tissue in rats. By stimulating fluoride accumulation, methionine reduces the adverse effect of fluorides on soft tissue, while vitamin E, which prevents excessive accumulation of fluorides in bones and teeth, protects these tissues from fluorosis. Therefore, it seems that combined application of both compounds would be optimal for the prevention of the adverse effects of chronic fluoride intoxication.

The study was initiated by the sudden uncontrolled release of airborne fluorides in 2005 into the environment from aluminium smelter factory that caused damage of vegetation. Samples of corn leaves and corn male flower heads with visible symptoms of fluoride intoxication had been collected in autumn 2005. Increased contents of total fluoride, which exceeded the maximum allowable content of fluorine in feeding stuffs, including meadow grass, were detected. During continuation of the study some commercially available herbal teas and plants used for preparing herbal teas infusions, collected in the field in 2010, were investigated to investigate possible uptake of fluoride from the soil. Nettle (Urtica dioica) has been found to be a promising passive bioindicator for monitoring phytotoxic effects of fluoride in the soil on the vegetation. Good correlation between labile free fluoride in the soil and total fluoride in the nettle has been found, while total fluoride in the soil, soil pH and the dominant wind direction were also proven as important factors influencing the uptake of fluoride by the nettle.

We studied chronic fluoride intoxication in 10 villages of Udaipur receiving F emissions from phosphate fertilizer factories. Although fluoride remained below permissible limit in most of the drinking water samples, the incidence of fluorosis in adults as well as in children was surprisingly high. Khemli appeared to be the most affected village (with48% cases) where, about 93% of 2 h air samples contained fluoride above 2.0 μg m(-3) and crops and vegetable F ranged from 27.5 to 143.4 μg g(-1). Concentrations of fluoride and inorganic P in urine showed asynchrony and were well linked with prevalence of fluorosis. The study indicated that air-borne fluoride was the major factor for higher prevalence of fluorosis in these rural areas.

We examined the effects of fluoride intoxication on certain blood plasma biochemical indices in rats. Fortyeight adult female Wistar rats weighing 123-142 g were divided into eight groups: two control groups (0 and 28 days) and six experimental groups, namely sham-injected animals (vehicle), injected with pineal proteins (PP) and melatonin (Mel), intoxicated with fluoride (F), and also F+PP and F+Mel groups. Fluoride (150 ppm, per os administration with drinking water), melatonin (10 mg/kg, i.p.), and PP (100 μg/kg, i.p.) were administered daily for 28 days. Blood samples were collected at the end of experiments to estimate plasma [Na+] and [K+], alkaline phosphatase (ALP) activity, and levels of glucose and proteins in different animal groups. The plasma [K+] and [Na+], and ALP activity were significantly (P < 0.05) elevated in F-treated animals, as compared with others. Administration of PP and Mel in F-treated rats caused significant (P < < 0.05) reduction of [Na+], [K+], and ALP levels. Interestingly, PP and Mel administrations resulted in noticeable (P < 0.05) increases in the plasma glucose level in F-intoxicated animals, as compared to other groups. These findings convincingly indicate that PP and Mel exert ameliorative effects on fluoride-induced adverse changes in certain biochemical parameters in rats.

Tea trees (Camellia sinensis), abundant in fluoride, selectively absorb F from the soil and air in the surrounding, and accumulate mainly in the tea leaves in the form of Al and F complex. Long-term consumption of high fluoride tea could result in chronic fluoride intoxication. This review summarized those data of the fluoride content in various tea commodities, and estimated the risk of fluorosis caused by high fluoride tea commodities. We also introduced fluorosis caused by tea from case reports, epidemiology observations and animal models. Fluorosis was easily misdiagnosed and over-looked and people made little acquaintance in the high fluoride in some tea commodities. So it is the time to pay more attentions on the over-looked safety problem of tea and tea products and some measures should be taken to the fluorosis caused by tea. Large-scale epidemiological investigations and further studies on tea-type fluorosis are in need for those tea-drinking areas. In addition, it is urgent that governmental and international agencies adopt safe standards of fluoride content in tea commodities.

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 ug fluoride per gram of bone ash in affected rabbits, compared with 550 ug 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.

Hydrofluorosis in humans and domestic animals is a worldwide health problem and caused by a prolonged period of fluoride exposure through drinking of fluoride contaminated water. But in recent years, due to rapid industrialization in India, diverse serious health problems among industrial workers and residents and domestic animals living in the industrial areas due to fluoride pollution are on the rise. A number of coal-burning and industrial activities such as power-generating stations, welding operations and the manufacturing or production of steel, iron, aluminum, zinc, phosphorus, chemical fertilizers, bricks, glass, plastic, cement, and hydrofluoric acid are generally discharging fluoride in both gaseous and particulate/dust forms into surrounding environments which create a industrial fluoride pollution and are an important cause of occupational exposure to fluoride in several countries including India. An industrial emitted fluoride contaminates not only surrounding soil, air, and water but also vegetation, crops and many other biotic communities on which man and animals are generally dependants for food. Long- time of inhalation or ingestion of industrial fluoride also causes serious health problems in the forms of industrial and neighborhood fluorosis. In India, whatever research works conducted so far on the chronic industrial fluoride intoxication or poisoning (industrial and neighborhood fluorosis) in man and various species of domestic animals due to a prolonged period of industrial fluoride exposure or pollution (contamination) are critically reviewed in the present communication. Simultaneously, we are also focused the various bio-indicators and bio-markers for chronic industrial fluoride intoxication or pollution.

Fluoride content in black tea in various commodities, packages, and preparation processess was assayed and its safety evaluated. A fluoride ion selective electrode method was used to determine the fluoride content in 20 tea samples, in various black tea commodities, namely stick-shaped, granular, and canned or bottled tea beverage, originally produced in India, Sri Lanka, China, Japan and UK, and milk–tea after addition of milk and sugar. The fluoride content of 5 stick-shaped black teas was 96.9–148 mg/kg, that of 8 granular black tea was 139–223 mg/kg, and that of 3 canned or bottled beverage black tea beverages was 0.70–0.96 mg/l, respectively. Neither the bagged black tea paper nor the addition of milk and sugar affected the ionic fluoride level within the tea. These results suggest that, for heavy black tea drinkers, the fluoride intake in areas with drinking water fluoridation, and also other probable sources of fluoride, may approach or reach the level of risk from chronic fluoride intoxication.

Objective: Chronic fluoride intoxication or fluorosis is a worldwide health problem in humans and animals. The present research work was aimed to assess the status of copper, zinc, cobalt, manganese, magnesium, calcium and phosphorus in blood of fluorotic cattle in brackish water zone of Punjab. Methods: The present study was conducted in villages of district Muktsar, a brackish water zone, of Punjab state. Cattle (n=103) showing signs of dental lesions or lameness, from the villages with water fluoride concentration more than 1 ppm, were selected for the study whereas cattle (n=98) from villages with water fluoride concentration less than 1 ppm and with no clinical signs served as control. Blood samples were collected from both the groups and were analysed for minerals.Results: Significantly (P

A chronic fluoride intoxication in the form of dental and skeletal fluorosis has been observed in tribal subjects and domestic animals (cattle and buffalo) of twelve villages; Badoda, Bhavanpura, Devala, Dhunda, Ghanta, Katisor, Khalil, Bhagela, Masona, Munged, Pindawal and Ramgarh of Dungarpur district of Rajasthan (India), where mean fluoride concentration in drinking water sources varied between 1.5 to 5.0 mg/L. The greatest prevalence of dental fluorosis in children and adult subjects was found at 3.5 and 3.7 mg/L fluoride concentration, whereas in calves and mature animals at 2.9 and 3.5 mg/L, respectively. The highest prevalence of skeletal fluorosis, 57.0% in tribes and 58.6% in animals, has been observed at 5.0 and 4.8 mg/L fluoride concentrations, respectively. Some observations pertaining to other deformities and radiological in fluorotic cases have also been focussed.

Thyroid function was examined in 165 workers of electrolysis shops of aluminum production with more or less expressed signs of chronic fluoride intoxication (fluorosis) by radioimmunoassay of hormones and the test of 13II absorption by the thyroid. The detected thyroid abnormalities were characterized by a moderate reduction of iodine-absorbing function of the thyroid, low T3 with normal T4 level, and a slight increase of TTH concentration. These changes augmented with longer service and fluorosis progress. Hence, the syndrome of low T3 and reduced absorption of 1311 may be considered as diagnostic signs of fluorosis. In case of toxic involvement of the liver in fluorosis patients, low T3 syndrome is observed much more frequently: in 75.6% cases. Liver abnormalities evidently lead to disorders in the peripheral conversion of T4 in T3, occurring primarily in liver parenchyma. Indirect effect of fluorine on the enzymatic system of deiodination cannot be ruled out as well.

Endemic fluorosis was detected in 31 villages in the Dhar district of Madhya Pradesh, Central India. Out of the 109 drinking water sources that were analyzed, about 67 % were found to contain high concentration of fluoride above the permissible level of 1.0 mg/l. Dental fluorosis among the primary school children in the age between 8 and 15 served as primary indicator for fluoride intoxication among the children. Urinary fluoride levels among the adults were found to be correlated with drinking water fluoride in 10 villages affected by fluoride. Intervention in the form of alternate safe water supply in five villages showed significant reduction in the urinary fluoride concentration when compared to the control village. Urinary fluoride serves as an excellent marker for assessing the effectiveness of intervention program in the fluoride-affected villages.

Fluoride is an essential trace element for human beings and animals; however, high level of fluoride in drinking water is harmful to the living system. Chronic fluoride intoxication causes damages to osseous tissue (teeth and bone) and soft tissues (liver, kidney, brain, etc.). Liver and kidney are the target organs markedly attacked by excessive amount of fluoride. High doses of fluoride intake lead to changes of structure, function, and metabolism in liver and kidney.

Analysis of soil, fodder and water samples collected from some localities of Udaipur district, Rajasthan, India revealed high fluoride concentrations indicating the areas endemic for fluoride pollution. Concentration of micro and macro minerals was estimated in blood samples collected from cattle reared in these localities, and with clinical lesions suggestive of chronic fluoride toxicity. In comparison to healthy controls, zinc, copper and manganese levels were significantly (p < 0.05) lower, while cobalt and magnesium concentrations were significantly (p < 0.05) higher in fluoride-intoxicated cattle. Results of the present study suggested that interaction of fluoride with other minerals possibly played a role in pathogenesis of chronic fluoride intoxication.

Fluoride is a widespread, non‐biodegradable and relatively persistent pollutant, which at low levels of contamination causes serious health problems difficult to cure. Fluoride pollution in India is mainly due to natural sources reported so far. Its concentration in waters is much higher than the recommended values by different authorities. More than half a million people are affected by the disease called fluorosis, which is due to chronic fluoride intoxication. This paper describes the problems of fluoride pollution and its health hazards in India. It also suggests approaches for the study of industrial fluoride intoxication.

SummaryYoung male rats (~200 g) were employed to study the distribution of parenterally administered inert and radiolabeled fluoride. Animals receiving 25 mg of fluoride/kg body weight did not live...

Effects of airborne fluoride on industrial health are discussed with regard to acute and chronic effects. Injuries to lungs and skin from acute exposures are described. Chronic effects are discussed with regard to industrial sources of fluoride and air concentrations vs. urinary concentrations of fluoride. An extensive literature review is presented in the form of a table showing responses in man exposed to industrial airborne fluorides. Osteosclerosis is discussed with regard to the fluoride air standard, bone fluoride, and air fluoride concentrations. Occupational exposures to fluoride are also discussed with regard to arthritis, shortness of breath, asthma, upper respiratory infections, chronic respiratory disease, effects on kidneys, effects on pregnancy, and indices of fluoride intoxication. A table is presented showing references to studies on responses in neighborhood residents exposed to fluoride emissions. (HLW)

The literature has shown overwhelmingly that fluoride used for dental prophylaxis presents minimal risks if used appropriately. However, there is an increasing potential for ingestion of toxic doses of fluoride because of the increasing use of pleasant-tasting fluoride products. The ADA has recommended that no more than 120 mg fluoride (264 mg NaF) be dispensed at any one time. As with any medication, fluoride preparations should be prescribed in child-resistant containers, and patients or parents (or both) should be instructed as to the proper daily treatment regimens and the potential for toxic overdoses. Possibly the greatest risk of fluoride intoxication relates to the concentrated fluoride preparations used for professionally applied fluoride treatment (Table 3). Therefore, patients receiving professional topical fluoride treatments should have well-fitting trays with the minimal amount of fluoride necessary to contact the teeth. These patients should be provided with a saliva ejection system, and they should never be left unobserved during the topical application. Health professionals should be aware of the potential toxic effects of fluoride in addition to the well-known caries preventive effects. It is necessary to know how to calculate the amount of fluoride ingested and the emergency treatment recommended to prevent toxic effects in suspected overdose cases.

Twenty-four male patients with genuvalgum deformity drawn from an area of endemic fluorosis in Andhra Pradesh, India, were investigated clinically, radiologically, and biochemically. All had evidence of spinal osteosclerosis along with extensive osteoporotic changes in the bones of the extremities. Levels of serum calcium, phosphorus, and alkaline-phosphatase activity were normal. It is concluded that deficiency of several nutrients may modify and aggravate the toxic effects of chronic fluoride intoxication. Hormones may play a part in the causation of the syndrome.

Marked peaking of the T waves later recognized as being due to hyperkalemia was noted in a patient with acute fluoride intoxication before developing refractory ventricular fibrillation. Such T wave changes have not been previously described in fluoride intoxication and should alert one to the presence of hyperkalemia complicating this condition, the presence of which may herald the onset of lethal ventricular arrhythmias.

Fluoride renal clearance (CF) was studied in young healthy subjects with standard clearance technique following administration of 3 mg F as a 30-min constant infusion. High urinary flow rates were induced and experiments were performed under both urinary alkaline and acidic conditions. The data showed that a high urinary flow resulted in maximum fluoride clearance. High water diuresis may therefore be an important part in the treatment of acute fluoride intoxication.

Fluoride concentrations were determined in human bones in order to establish whether bone fluoride levels could be indicative of a chronic exposure to a fluoride contaminated environment. The bone samples studied were mainly obtained from thirteen post mortem examinations. In ten of these cases, the persons involved had lived in rural areas, free of any fluoride pollution (reference cases). In the other three cases, the individuals involved had lived for many years in the neighborhood of a fluoride emitting plant. In addition, an analysis was also performed on a bone fragment procured by a 71-year-old woman who underwent an arthroplastic reconstruction of the hip. This patient also had a previous history of chronic fluoride intoxication. The fluoride concentrations measured in the four suspected cases were within the limits indicated by the reference cases. As such they were not directly indicative of a chronic exposure to industrial fluoride pollution.

Publisher Summary Fluorosis is considered chronic fluoride intoxication in humans and animals. This chapter discusses ossifications and calcifications of muscle and tendon insertions in human industrial fluorosis. Four types of human fluorosis have been categorized: (1) endemic fluorosis, (2) wine fluorosis, (3) neighborhood fluorosis, and (4) industrial fluorosis. Human fluorosis is characterized by three phenomena—namely, (1) periostosis with formation of exophytes, with ossifications of ligaments, muscle insertions, and joint capsules, (2) endostosis, and (3) sclerosis of the spongiosa. In advance stages, the x-rays of the spine show an extreme marble-like sclerosis of the bones with ossification of the longitudinal ligaments. In addition, the formation of outgrowths and spurs at the muscular insertions and ossifications of the ligaments of the pelvic floor is also reported. Different phenomena are found especially on the periosteal surface such as subperiosteal fibrous bone formation, sometimes with transformation into lamellar bone and ossification of inserting periosteal fibers with transformation into lamellar bone. The chapter also discusses some of the scanning-electron-microscopic findings (SEM) that are based on examinations of bones of three persons in different stages of industrial fluorosis.