Temporal trends of suspect- and target-per/polyfluoroalkyl substances (PFAS), extractable organic fluorine (EOF) and total fluorine (TF) in pooled serum from first-time mothers in Uppsala, Sweden, 1996-2017.

A combined method for quantitative analysis, along with suspect and non-target screening of per- and polyfluoroalkyl substances (PFAS) was developed using ultra-high pressure liquid chromatography-ultra-high resolution (Orbitrap) mass spectrometry. The method was applied together with measurements of total- and extractable organofluorine (TF and EOF, respectively), to pooled serum samples from 1996-2017 from first-time mothers living in the county of Uppsala, Sweden, some of which (i.e. 148 of 472 women sampled 1996-2012) were exposed to drinking water contaminated with perfluorohexane sulfonate (PFHxS) and other PFAS until mid-2012. Declining trends were observed for all target PFAS as well as TF, with homologue-dependent differences in year of onset of decline. Only 33% of samples displayed detectable EOF, and amongst these samples the percentage of EOF explained by target PFAS declined significantly (-3.5% per year) over the entire study period. This finding corroborates prior observations in Germany after the year 2000, and may reflect increasing exposure to novel PFAS which have not yet been identified. Suspect screening revealed the presence of perfluoro-4-ethylcyclohexanesulfonate (PFECHS), which displayed declining trends since the year 2000. Non-target time trend screening revealed 3 unidentified features with time trends matching PFHxS. These features require further investigation, but may represent contaminants which co-occurred with PFHxS in the contaminated drinking water.

Health risk assessment of fluorine in fertilizers from a fluorine contaminated region based on the oral bioaccessibility determined by Biomimetic Whole Digestion-Plasma in-vitro Method (BWDPM).

Due to potential adverse effects of excessive fluorine (F), interests regarding considerable accumulation of F in agricultural soils from application of fertilizers are increasing continually. However, less detailed information of hazard and risk of F in fertilizers to human directly by hand-to-mouth pathway can be obtained. Herein, the bioaccessibility of F (Fbio) in fertilizers is determined by Biomimetic Whole Digestion-Plasma in-vitro Method (BWDPM), which is developed to detect the behaviour of bioaccessible F in both the whole digestive system and plasma for the first time. Observations of higher Fbio in small intestinal phases (4.35-56.33%), large intestine (1.01-40.52%) and plasma (8.07-66.70%) yielded them as the major phases which are faced with higher exposure risk of F. Compared with phosphate fertilizer, more bioaccessible F was observed in compound fertilizer. Some studied factors, such as sweat and food, yield insignificant influences on Fbio, whereas can affect the exposure estimations of F considerably. Exposure risks based on Fbio of fertilizers should be highly concerned, especially the occupational exposure to local farmers. In a word, more explicit and realistic information of the potential risk of F on human health could be obtained by the introduction of Fbio.

Translating from lab-use to household: Dual-functional upconversion nanoprobes for solar-powered photothermal fluorosis diagnosis.

Due to the serious symptoms of brittle bones and endocrine disorders, the common disease fluorosis diminishes quality of life. With the aim of developing probes for both laboratory and household fluorosis diagnosis, in this study we rationally designed a novel dual-functional gallic acid-Fe(III) complex-modified upconversion nanoprobe (DF-UCNP) with simultaneous upconversion luminescence (UCL) and photothermal (PT) conversion capacities. The nanoprobe was feasible for UCL fluorine (F-) detection with a low detection limit of ∼20 nM and a broad linear range of 0-50 µM, as well as UCL fluorosis diagnosis both in vitro and in vivo for lab-use. Furthermore, by utilizing gathered solar irradiation as a PT excitation source and a digital thermometer as a signal reader, the nanoprobe possessed outstanding PT detection capacities for F- with a detection limit of ∼100 nM. Based on this nanoprobe and an accessional self-developed Android application, a household PT kit for fluorosis diagnosis was also constructed. This work provides a new method for rapid laboratory fluorosis diagnosis without a cumbersome determination process as well as household fluorosis diagnosis without requiring specific instruments.

Calcium Intake and Nutritional Adequacy in Spanish Children: The ANIVA Study.

Calcium is an important nutrient for child development. The main objective of this study was to assess calcium intake and its adequacy with dietary reference intake (DRI) in Spanish children. The ANIVA (Antropometría y Nutrición Infantil de Valencia) study is a descriptive cross-sectional study. During two academic years 2013-2014 and 2014-2015, 1176 schoolchildren aged 6-9 years were selected from 14 primary schools in Valencia (Spain). Three-day food records were used to assess dietary intake, completed by parents/guardian. Anthropometric data (weight and height) were evaluated in all subjects. Nutritional intake was compared to estimated average requirements (EARs) and adequate intake (AI) values to determine nutritional adequacy. A percentage of 25.77% had inadequate calcium intake, and a significantly higher prevalence was observed in girls (p = 0.006). Adequate calcium intake showed a positive association with the height z-score (p = 0.032). When assessing dietary patterns, schoolchildren with adequate calcium intakes had better nutritional adequacy in all nutrients, except cholesterol (p = 0.086) and fluorine (p = 0.503). These results suggest a public health problem that must be addressed through nutrition education programs to increase intake of calcium-rich food and to correct the associated dietary pattern.

Fe- and Ln-DOTAm-F12 Are Effective Paramagnetic Fluorine Contrast Agents for MRI in Water and Blood.

A series of fluorinated macrocyclic complexes, M-DOTAm-F12, where M is LaIII, EuIII, GdIII, TbIII, DyIII, HoIII, ErIII, TmIII, YbIII, and FeII, was synthesized, and their potential as fluorine magnetic resonance imaging (MRI) contrast agents was evaluated. The high water solubility of these complexes and the presence of a single fluorine NMR signal, two necessary parameters for in vivo MRI, are substantial advantages over currently used organic polyfluorocarbons and other reported paramagnetic 19F probes. Importantly, the sensitivity of the paramagnetic probes on a per fluorine basis is at least 1 order of magnitude higher than that of diamagnetic organic probes. This increased sensitivity is due to a substantial-up to 100-fold-decrease in the longitudinal relaxation time (T1) of the fluorine nuclei. The shorter T1 allows for a greater number of scans to be obtained in an equivalent time frame. The sensitivity of the fluorine probes is proportional to the T2/T1 ratio. In water, the optimal metal complexes for imaging applications are those containing HoIII and FeII, and to a lesser extent TmIII and YbIII. Whereas T1 of the lanthanide complexes are little affected by blood, the T2 are notably shorter in blood than in water. The sensitivity of Ln-DOTAm-F12 complexes is lower in blood than in water, such that the most sensitive complex in water, HoIII-DOTAm-F12, could not be detected in blood. TmIII yielded the most sensitive lanthanide fluorine probe in blood. Notably, the relaxation times of the fluorine nuclei of FeII-DOTAm-F12 are similar in water and in blood. That complex has the highest T2/T1 ratio (0.57) and the lowest limit of detection (300 µM) in blood. The combination of high water solubility, single fluorine signal, and high T2/T1 of M-DOTAm-F12 facilitates the acquisition of three-dimensional magnetic resonance images.

Perfluoroalkyl substances in the blood of wild rats and mice from 47 prefectures in Japan: use of samples from nationwide specimen bank.

Numerous studies have reported on the global distribution, persistence, fate, and toxicity of perfluoroalkyl and polyfluoroalkyl substances (PFASs). However, studies on PFASs in terrestrial mammals are scarce. Rats can be good sentinels of human exposure to toxicants because of their habitat, which is in close proximity to humans. Furthermore, exposure data measured for rats can be directly applied for risk assessment because many toxicological studies use rodent models. In this study, a nationwide survey of PFASs in the blood of wild rats as well as surface water samples collected from rats' habitats from 47 prefectures in Japan was conducted. In addition to known PFASs, combustion ion chromatography technique was used for analysis of total fluorine concentrations in the blood of rats. In total, 216 blood samples representing three species of wild rats (house rat, Norway rats, and field mice) were analyzed for 23 PFASs. Perfluorooctanesulfonate (PFOS; concentration range <0.05-148 ng/mL), perfluorooctane sulfonamide (PFOSA; <0.1-157), perfluorododecanoate (<0.05-5.8), perfluoroundecanoate (PFUnDA; <0.05-51), perfluorodecanoate (PFDA; <0.05-9.7), perfluorononanoate (PFNA; <0.05-249), and perfluorooctanoate (PFOA) (<0.05-60) were detected >80 % of the blood samples. Concentrations of several PFASs in rat blood were similar to those reported for humans. PFSAs (mainly PFOS) accounted for 45 % of total PFASs, whereas perfluoroalkyl carboxylates (PFCAs), especially PFUnDA and PFNA, accounted for 20 and 10 % of total PFASs, respectively. In water samples, PFCAs were the predominant compounds with PFOA and PFNA found in >90 % of the samples. There were strong correlations (p < 0.001 to p < 0.05) between human population density and levels of PFOS, PFNA, PFOA, and PFOSA in wild rat blood.

Detections of commercial fluorosurfactants in Hong Kong marine environment and human blood: a pilot study.

Previously, much of the perfluoroalkyl and polyfluoroalkyl substance (PFAS) research has focused on perfluoroalkyl carboxylates (PFCAs) or perfluoroalkane sulfonates (PFSAs). Recent studies indicate that known PFCAs and PFSAs accounted for 5-95% of the organofluorine (OF) in human and wild rat blood samples suggesting that a relatively large proportion of OF remained unknown. Until recently, some studies reported commercially available compounds such as polyfluoroalkyl phosphate diesters (diPAPs) and fluorotelomer sulfonates (FTSAs) in human blood and sludge samples. The present investigation is a pilot study aiming at surveying some newly identified PFASs such as diPAPs, FTSAs, and perfluorinated phosphinates (PFPiAs) in different environmental samples including surface water, sediment, sewage treatment plant influent and effluent, sludge, benthic worm, and human blood from Hong Kong. DiPAPs (6:2, 6:2/8:2, and 8:2) were detected in some of the samples at part-per-billion (ppb) levels in sludge, sub ppb levels in influent and effluent, sediment, worm, and human blood samples, and sub part-per-trillion (ppt) levels in surface waters. Sub ppt to ppb levels of 6:2 and 8:2 FTSAs were observed in worm, surface water, and human blood samples. PFPiAs were only observed in worm samples. The detected "new PFASs" accounted for a minor proportion (less than 5%) of the total PFASs in benthic worm and human blood, but up to 95% in sewage sludge samples from Hong Kong. This is the first report of commercial fluorosurfactants (PFPiAs, diPAPs, and FTSAs) in the samples from the environment and human blood in Hong Kong; further information on the distribution, fate, and transport of "new PFASs" in other Asian cities, as well as toxicity, is needed for further assessing the human exposure and risk.

Myeloperoxidase activity and its corresponding mRNA expression as well as gene polymorphism in the population living in the coal-burning endemic fluorosis area in Guizhou of China.

The myeloperoxidase (MPO) activity and its corresponding mRNA expression as well as gene polymorphism were investigated in the population who live in the endemic fluorosis area. In the study, 150 people were selected from the coal-burning endemic fluorosis area and 150 normal persons from the non-fluorosis area in Guizhou province of China. The blood samples were collected from these people. The activity of MPO in the plasma was determined by spectrophotometer; the expression of MPO mRNA was measured by employing real-time polymerase chain reaction; DNAs were extracted from the leucocytes in blood and five SNP genotypes of MPO promoter gene detected by a multiplex genotyping method, adapter-ligation-mediated allele-specific amplification. The results showed that the MPO activity and its corresponding mRNA in blood were significantly increased in the population living in the area of fluorosis. The different genotype frequencies of MPO, including -1228G/A, -585T/C, -463G/A, and -163C/T, and the three haplotypes with higher frequencies, including -163C-463G-585T-1228G-1276T, -163C-463G-585T-1228G-1276C, and -163C-463G-585T-1228A-1276T, were significantly associated with fluorosis. The results indicated that the elevated activity of MPO induced by endemic fluorosis may be connected in mechanism to the stimulated expression of MPO mRNA and the changed gene polymorphism.

Análise proteômica em fígado de ratos submetidos à exposição crônica ao flúor / Proteomic analysis of liver in rats chronically exposed to fluoride

O recente desenvolvimento de técnicas proteômicas tem permitido a análise do perfil proteico completo dos sistemas biológicos, permitindo um melhor entendimento da fisiologia normal do organismo, bem como dos mecanismos de doenças, descoberta de biomarcadores para detecção precoce de doenças, identificação de novas terapias e descobertas de fármacos. No presente trabalho, a análise proteômica foi usada para auxiliar no entendimento dos mecanismos moleculares envolvidos na intoxicação induzida pelo fluoretono fígado de ratos e definir biomarcadores potenciais de toxicidade. Três grupos de ratos Wistar machos recém-desmamados (21 dias de vida) foram tratados ad libitum com água de beber contendo 0 (controle), 5 ou 50 mg/L de fluoreto, por 60 dias (n=6/grupo). Os animais foram eutanasiados e o fígado e o soro foram coletados. O fígado foi dividido em lobos, sendo que o esquerdo foi destinado à dosagem de fluoreto (eletrodo íon-sensível, após difusão facilitada por hexametildisiloxano), o direito à análise histológica (hematoxilina e eosina) e o mediano, à análise proteômica (eletroforese bidimensional associada a LC-MS/MS). Os dados foram analisados por ANOVA e teste de Tukey (p<0,05). Foi possível detectar uma dose-resposta em relação à ingestão para os níveis de fluoreto presentes no soro e no fígado houve diferença significativa entre os grupos que receberam 5 e 50 mg/L de fluoreto. A análise morfométrica histológica não revelou alterações nas estruturas celulares e exame o morfológico indicou inclusões lipídicas nos grupos 5 mg/L e 50 mg/L de fluoreto, mais intensas no último. A análise quantitativa de intensidade (software ImageMaster 2D-Platinum v 7.0), comparando a porcentagem de alteração de volume do spot protéico, revelou que 33, 44 e 29 spots aumentaram ou diminuíram sua expressão nos grupos controle X 5 mg/L, controle X 50 mg/L e 5 mg/L X 50 mg/L de fluoreto, respectivamente. Além disto, foram encontradas 18, 1 e 5 spots exclusivos nos grupos...

The recent development of proteomic techniques allowed the analysis of the whole proteomic profile of the biological systems, allowing the comprehension of the normal physiology, as well as of the mechanisms underlying diseases. It has also made easier the discovery of biomarkers of diseases, as well as the identification of new therapies and drugs. In the present study, proteomic analysis was used as a tool to help understanding the molecular mechanisms underlying chronic fluoride toxicity in rat liver and also to define potential biomarkers of toxicity. Three groups of weanling male Wistarrats (21 days) were treated ad libitum with drinking water containing 0 (control), 5 or 50 mg/L fluoride for 60 days (n=6/group). After euthanasia, liver and serum were collected. The liver was divided into lobes. The left lobe was used for fluoride analysis (ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion). The right lobe was used for histological analysis (hematoxylin and eosine) while the median was used for proteomic analysis (2D-PAGE associated with LC-MS/MS). Data were analysed by ANOVA and Tukeys test, (p<0.05). A dose-response relationship was observed for serum fluoride levels. In liver, a significant increase in fluoride levels was observed in the 50 mg/L group when compared with the 5 mg/L group. Morphometric analysis did not reveal alterations in the cellular structures. The morphological exam revealed macrovesicular lipid droplets in the 5 and 50 mg/L groups which were more intense in the later. Quantitative intensity analysis (software ImageMaster 2D-Platinum v 7.0) comparing the percentage of alteration of volume of protein spots revealed 33, 44 and 29 protein spots that had increase or decrease in expression in the groups control X 5 mg/L, control X 50 mg/L and 5 mg/L X 50 mg/L, respectively. In addition, 18, 1 and 5 protein spots were detected exclusively in groups control, 5 mg/L and 50 mg/L, respectively. From the...

Análise proteômica em rim de ratos submetidos à exposição aguda de flúor / Proteomic analysis in kdney of rats submitted to acute fluoride treatments

O flúor é comprovadamente um agente terapêutico contra a cárie dentária, porém, quando consumido de maneira inadequada pode causar reações indesejáveis, tanto crônicas como agudas. A proteômica é uma ferramenta que permite analisar o perfil proteico completo dos sistemas biológicos, permitindo um melhor entendimento da fisiologia normal do organismo, bem como dos mecanismos de doenças, descoberta de biomarcadores para detecção precoce de doenças, identificação de novas terapias e descobertas de fármacos. Assim, o presente estudo teve como trabalho realizar um estudo proteômico diferencial em amostras de tecido renal de ratos submetidos à intoxicação aguda por fluoreto. Para isso, 27 animais, receberam desde o desmame água deionizada e ração AIN-93 por 50 dias. Ao completarem 75 dias de vida, e, após jejum por 12 horas, os animais receberam via gástrica as seguintes doses agudas de F: 0 (controle), 50 e 100 mgF/Kg peso corporal. Após 2 horas foram, os animais foram anestesiados e tiveram o sangue e os rins coletados. Inicialmente foi realizada a dosagem de flúor no plasma e tecidos renais, após difusão facilitada por hexamethyldisiloxano. Em um segundo momento, as proteínas do tecido renal foram extraídas e submetidas à eletroforese bidimensional. Os géis obtidos foram analisados através do software ImageMaster 2D-platinum v. 7.0. Os spots que se apresentaram diferencialmente expressos foram submetidos à identificação por espectrometria de massas. As proteínas identificadas foram classificadas em 5 categorias funcionais. A categoria metabolismo e energia reuniu a maior parte das proteínas (40%), seguida pelas categorias de transporte e processos celulares com 20% e 13% respectivamente. Na categoria estrutura e organização estrutural, que reúne proteínas com funções relacionadas ao citoesqueleto e membrana celular, foram identificadas 17% das proteínas. Por fim, os 10% restantes das proteínas...

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, if consumed in high concentrations, it can cause side effects as dental fluorosis, skeletal fluorosis and, in extreme situations, death. The recent development of proteomic techniques has allowed the analysis of the entire protein profile of biological systems, contributing to the understanding of the normal physiology of the organism, as well as the mechanisms of diseases and the investigation of biomarkers for their early detection, identification of new therapies and drugs. This study used proteomic techniques to analyze the differential protein expression in kidney of rats submitted to acute fluoride treatments. Three groups of five 75-day-old Wistar rats received, by gastric gavage, the following single doses of fluoride: 0 (control), 50 and 100 mgF/Kg body weight. After the treatments, the animals were killed and the left kidney and plasma were collected for fluoride analysis. For proteomic analysis, the right kidney was collected. Fluoride in plasma and renal tissues was analyzed with the electrode, after hexamethyldisiloxanefacilitated diffusion. Proteins from kidney were profiled by two-dimensional gel electrophoresis. Gels from control and treated groups were digitalized using the ImageScanner III and analyzed with ImageMaster 2D Platinum version 7.0 for statistical differences (ANOVA, p <0.05). The proteins identified were classified into five functional categories. The category of metabolism and energy had the majority of the proteins (40%), followed by the categories of /"transport/" and cell processes, with 20% and 13% of the proteins, respectively. In the category /"structure and cell organization, which brings together proteins with functions related to the cytoskeleton and plasma membrane were identified 17% of the protein. Finally, 10% of the proteins belonged to the category /"information...

Comparison of total fluorine, extractable organic fluorine and perfluorinated compounds in the blood of wild and pefluorooctanoate (PFOA)-exposed rats: evidence for the presence of other organofluorine compounds.

The widespread occurrence and environmental persistence of perfluorinated compounds (PFCs) received worldwide attention recently. Exhaustive analysis of all fluorinated compounds in an environmental sample can be daunting because of the constraints in the availability of analytical standards and extraction methods. Combustion ion chromatographic technique for trace fluorine analysis was used to assess the concentrations of known PFCs (e.g., PFOS, PFOA) and total fluorine (TF) in the blood of wild rats collected from Japan. The technique was further validated using tissues from PFOA-exposed rats. Six PFCs (PFOS, PFOSA, PFUnDA, PFDA, PFNA, and PFOA) were detected in all of the wild rat blood samples. Concentrations of extractable organic fluorine (EOF) in fraction 1 (Fr1; MTBE extraction) of wild rats ranged 60.9-134 ng F mL(-1), while those in fraction 2 (Fr2; hexane) were below LOQ (32 ng F mL(-1)); TF concentrations in the blood of wild rats ranged from 59.9-192 ng F mL(-1). The contribution of known PFCs in EOF-Fr1 (MTBE) varied from 9% to 89% (56% on average), and known PFC concentrations in TF content were less than 25%. In contrast, TF concentrations in the blood of PFOA-exposed rats ranged from 46900 to 111,000 ng F mL(-1), with PFOA contributing over 90% of TF. A comparison of results from the samples analyzed in this study and the literature revealed three distinct groups with PFOA/known PFC and TF levels (i.e., wild rats and general population, occupationally exposed workers, and PFOA-exposed laboratory rats). The mass balance analysis of the different forms of fluorine in blood suggested the presence of other forms of organic fluorine in addition to known PFCs.

Perfluorinated compounds and total and extractable organic fluorine in human blood samples from China.

An improved extraction (ion pairing) and cleanup (ENVI-carb and solid phase extraction) method was developed for analysis of perfluorinated compounds (PFCs) in human whole blood samples from China. Ten PFCs including PFOS, PFHxS, PFOSA, PFDoDA, PFUnDA, PFDA, PFNA, PFOA, PFHpA, and PFHxA were detected in the blood samples (n=30) from five cities (Jintan, Nanjing, Guiyang, Beijing, and Shenyang). PFOS was found to be the dominant PFC ranging from 0.446-83.1 ng/mL. Total fluorine (TF) and extractable organic fluorine (EOF) also were measured in the blood samples using combustion ion chromatography for fluorine. Analysis of known PFCs and extractable organic fluorine showed that known PFCs could account for >70% of EOF in samples from Beijing, Shenyang, and Guiyang, whereas known PFCs could only account for approximately 30% of EOF in samples from Jintan. Results of the present study indicated the presence of substantial amounts of unidentified organic fluorine in human blood samples from Jintan. Characterization and identification of these unidentified fluorinated compounds will be instructive.

90-day oral gavage toxicity study of 8-2 fluorotelomer alcohol in rats.

8-2 fluorotelomer alcohol is a fluorinated chemical intermediate used to manufacture specialty polymers and surfactants. The potential subchronic toxicity and the reversibility of the effects of this chemical were evaluated following approximately 90 days of oral gavage dosing to Crl:CD(SD)IGS BR rats. A complete toxicological profile, including neurobehavioral assessments and hepatic beta-oxidation, were conducted at selected intervals and a group of rats was included for a 90-day postdosing recovery period. Dose levels tested were 0 (control), 1, 5, 25, and 125 mg/kg. No test-substance-related mortality occurred at any dose level. Rats at 125 mg/kg developed striated teeth, such that these animals were switched to ground chow at 77 days. No treatment-related alterations in body weight, food consumption, neurobehavioral parameters, or hematology/clinical chemistry were found. Hepatic beta-oxidation was increased in males at 125 mg/kg and in females at 25 and 125 mg/kg. In both males and females, plasma fluorine levels were increased at 125 mg/kg and urinary fluorine was elevated at > or =5 mg/kg. Degeneration/disorganization of enamel organ ameloblast cells was observed at 125 mg/kg in males, but not females. Liver weight increases accompanied by focal hepatic necrosis were observed at both 25 and 125 mg/kg, and chronic progressive nephrotoxicity occurred in female rats at 125 mg/kg. With the exception of hepatocellular necrosis in males at 125 mg/kg and the increased incidence and severity of chronic progressive nephropathy in females at 125 mg/kg, all other changes showed evidence of reversibility. The no-observed-adverse-effect level was 5 mg/kg.

Metabolismo e distribuição do flúor em ovinos jovens tratados cronicamente com fluoreto de sódio / Metabolism and distribution of fluor in lambs chronically treated with sodium fluoride

Este estudo teve por objetivo avaliar o metabolismo do flúor (F) em ovinos. Para tanto, utilizaram-se 12 animais, com cinco meses de idade, os quais receberam como dieta base 3 por cento do peso vivo de feno de alfafa e água ad libitum. Os animais foram divididos e constituíram um grupo Controle, que recebeu apenas sal iodado (5g de NaCl/animal + 0,2mg I/kg matéria seca) e, um grupo Tratado, que recebeu sal iodado adicionado de fluoreto de sódio (4,7mg F/kg de peso corporal). Esses sais foram administrados via sonda oro-esofágica, diariamente por um período de 150 dias. Para análise de F, coletaram-se amostras de sangue, urina e fezes e, ao fim do período experimental, após a eutanásia dos animais, coletou-se a glândula pineal e amostras de osso. Também nesta ocasião, coletou-se uma amostra de rim para exame histopatológico. Analisando-se os teores séricos, urinários e ósseos de F, verificou-se que foram significativamente superiores nos animais Tratados em relação aos Controles. Quanto ao F contido na glândula pineal, não houve diferença significativa entre os grupos. Na análise histológica do rim, não foram observadas alterações. Conclui-se que a administração crônica de flúor induz ao acúmulo desse elemento nos ossos, mesmo havendo um alto teor de cálcio na alimentação e esse acúmulo parece não ser nocivo aos animais. Em ovinos, a capacidade orgânica de acúmulo ósseo e excreção urinária do flúor é diferente de outras espécies animais.

The objective of the present study was to evaluate fluorine metabolism in growing lambs. Twelve 5-month-old male lambs maintained on alfalfa hay (3 percent BW) and non-fluorinated water ad libitum were used. Animals were allocated into Control, receiving 5g NaCl/animal/day + 0.2mg I/kg dry matter) and Treated group, receiving the same treatment plus sodium fluoride (4.7mg F/kg body weight). Mineral treatment was given by gavage, daily for 150 days. Blood, urine and fecal samples were collected during and the end of the experiment. At the end of treatment period animals were euthanized and kidney, pineal and bone samples were collected. Urine F was higher in treated animals throughout the experiment. Bone F levels were also increased in treated animals; pineal F content however, was not different between groups. Kidney histology revealed no differences. It is concluded that chronic F administration induces accumulation of the element in the skeleton. However such fact appears not to be detrimental to animals. Rates of F accumulation in bone and urine excretion obtained in other species can not be used in growing lambs.

Trace analysis of total fluorine in human blood using combustion ion chromatography for fluorine: a mass balance approach for the determination of known and unknown organofluorine compounds.

The number of perfluorochemicals (PFCs) that have been found in biological and environmental matrices is increasing as analytical standards and methods evolve. Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) constitute only a fraction of the total suite of PFCs found in environmental and biological matrices. A robust method and approach is needed to evaluate the mass of fluorinated compounds in biological matrices. In this study, we developed a method to measure total fluorine (TF) and organic fluorine (TOF) in human blood matrices using combustion ion chromatography (CIC). Blood matrices (whole blood, serum, and plasma) were analyzed in bulk to determine TF. An aliquot of the blood was also extracted with organic solvents such as methyl-tert-butyl ether (MTBE) and hexane, and organic and aqueous extracts were separated, to fractionate organofluorines from inorganic fluorine. The organic layer was analyzed for TF by CIC, and for known PFCs by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). PFCs measured by HPLC-MS/MS accounted for >80% of the TF in the organic fraction. The aqueous fraction contained inorganic fluorine and other non-extractable organofluorines. However, in the bulk sample, fluoride and non-extractable organofluorines accounted for >70% of the TF in blood samples from the general population. In occupationally exposed individuals, known organofluorines accounted for a major proportion of the TF. These results suggest the existence of yet uncharacterized fluorine fraction in human blood. Further studies are needed to characterize the aqueous fraction that contains inorganic fluorine and non-extractable forms of fluorine.

The effect of a temporal change in ingestion rates of fluorine (F) in soil on the concentration of F in serum and bone of young sheep.

AIM: To determine the changes in concentrations of fluorine (F) in serum and bone of young sheep given a high intake of F, as F in soil, followed by a low intake of F, to simulate the varying intakes experienced by grazing sheep. METHODS: Sixty autumn-born, weaned, mixed-sex lambs were randomly divided into two groups (n=30). One group (Control) was fed a low-F (12 mg/kg dry matter; DM) lucerne/ grain diet for 345 days, while the other group (High soil-F) was fed a high-F (224 mg/kg DM) lucerne/grain diet containing 10% soil for 94 days and then a low-F diet for a further 251 days. Blood samples were collected on Days 1, 32, 94, 108, 153, 214, 280 and 345, to determine concentrations of F in serum. Groups of five or six animals from each group were killed on Days 1, 94, 153, 214, 280 and 345, to collect radii and humeri for determination of F content. The sheep were weighed at about 6-8-weekly intervals. RESULTS: Initial liveweight of the sheep was 22.1 (standard error (SE) 1.12) kg and the mean liveweight gains were 270 (SE 22.1) and 170 (SE 12.4) g/day from Days 1 to 94 and 95 to 330, respectively. The mean initial (Day 1) concentration of F in serum was 0.03 (SE 0.005) mg/L, and this changed very little for animals on the low-F diet. In sheep on the high soil-F diet, the concentration of F in serum reached 0.38 (SE 0.021) mg/L at Day 94 but after being placed on the low-F diet concentrations decreased to 0.04 (SE 0.006) mg/L after 14 days (Day 108) and then remained at about this low level for the remainder of the duration of the study. The mean concentrations of F in the humerus and radius of the lambs at Day 1 were 161 (SE 19.4) and 159 (SE 20.4) mg/kg DM, respectively, which increased to 2,784 (SE 80.6) and 1,805 (SE 51.5) mg/kg DM, respectively, at Day 94 in lambs fed the high soil-F diet, then decreased to 1,075 (SE 58.1) and 1,064 (SE 61.6) mg/kg DM at Day 153, and then progressively increased to 1,669 (SE 57.7) and 1,312 (SE 30.8) mg/kg DM at Day 345. CONCLUSIONS: The ingestion of F in soil by sheep markedly increased their concentrations of F in serum and bone, but when the soil was removed and they were fed a low-F diet, concentrations of F in serum decreased to baseline levels within 14 days while concentrations in the bone only decreased to 60-70% of the peak concentration, indicating that some of the F in bone was remobilised.

[Comparison of various methods of early management of hydrofluoric acid burn in rabbits].

OBJECTIVE: To compare the effects of different kind of methods in the management of hydrofluoric acid burn in early postburn stage in rabbits. METHODS: Thirty-three rabbits were inflicted with burn by 55% of hydrofluoric acid covering 5% TBSA, and were randomly divided into 3 groups, i.e. A (n = 13, with 5 ml.kg(-1).h(-1)of isotonic saline intravenous infusion), B (n = 10, with isotonic saline and 50 g/L of calcium gluconate infusion in dose of 20 mg/kg at different time points), and C (n = 10, with the same treatment as B group, and with excision of burn wound at 0.5 post burn hour) groups. The serum levels of fluorine and calcium were determined before and after various postburn hours, and the mortality rate was statistically analyzed. RESULTS: (1) The serum level of fluorine in A (8.37 +/- 2.62 mg/L) and B (8.59 +/- 2.25 mg/L) groups reached the peak value at 1 postburn hour (PBH), which was 107 times higher than that before the burn injury. The serum level of fluorine in B group was significantly lower than that in A group at 24 PBH (P < 0.05), while that in C group declined to (6.20 +/- 0.23) mg/L, which was obviously lower than that in A and B groups (P < 0.01). (2) The serum calcium level declined after burns, reaching the lowest level at 8 to 12 PBH. and began to increase at 24 PBH. Compared with normal calcium value, the serum level of calcium in A, B and C groups declined to as much as 46%, 32% and 26%, respectively. Statistically significant difference was found between C and B groups (P < 0.01). (3) The mortality rate in the three groups within 72 PBH were 30.8%, 12.5% and 0.0%, respectively. CONCLUSION: Early removal of burn area and calcium supplementation could help quickly decrease blood fluorine, reverse the fatal hypocalcemia and the multiple systemic toxic injury in rabbits inflicted with hydrofluoric acid injury.

Effect of volcanic gas exposure on urine, blood, and serum chemistry.

AIMS: This pilot study tested the hypothesis that aluminium (Al), rubidium (Rb), arsenic (As), lead (Pb), mercury (Hg), fluorine (F), and chlorine (Cl), which are all known to be present in volcanic emissions, may be useful biological markers for occupational gas exposure in volcanologists. METHODS: Ten human subjects were exposed to fumarole gases on White Island, New Zealand, for approximately 20 minutes. Sulphur dioxide (SO2) exposure was recorded by personal monitoring tubes. Pre- and post-exposure urine, blood and serum samples (collected using standard protocols) were analysed in the pathology laboratory for trace element and halogen content. RESULTS: Average personal exposure was measured at <75 ppm SO2 and calculated at approximately 25 ppm HCl, approximately 8 ppm hydrogen fluoride (HF), approximately 1 ppm Al, approximately 0.1 ppb Rb and approximately 4 ppb Pb. These concentrations almost certainly exceed those usually found in occupational exposure settings. Advanced levels of urinary Al and Rb were found following gas exposure and were statistically significant in the population at p<0.005 and p<0.001, respectively. The other chemical elements that were analysed (urinary Cl, F, and Hg; blood Pb, and serum Al) did not show such patterns. CONCLUSIONS: It is possible that urinary Al and Rb may be useful markers for exposure, a hypothesis which should be followed up in future work.