Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level urinary biomonitoring data.

Population-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS - Étude nationale nutrition santé) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a urinary excretion fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for urinary tin (26 µg/g creatinine or 20 µg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 µg/g creatinine) and France (0.51 and 2.28 µg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.

Mechanism of action of tin-containing fluoride solutions as anti-erosive agents in dentine - an in vitro tin-uptake, tissue loss, and scanning electron microscopy study.

Solutions containing tin and fluoride exhibit remarkable anti-erosive properties with tin ions as a major agent. To elucidate its mechanism of action in dentine, the tin uptake on and in the tissue was investigated and related to histological findings and substance loss. Samples were treated twice daily, each treatment lasting for 2 min, with fluoride solutions [pH 4.5; 1,500 parts per million (p.p.m.) F] containing 2,100, 1,400, or 400 p.p.m. Sn as SnCl(2). In experiments 1 and 2, samples were eroded with citric acid (pH 2.3) six times each day, each treatment lasting for 5 min; in experiment 2, the demineralized organic matrix was continuously digested by collagenase; in experiment 3, no erosive challenges were performed. Sample surfaces and cross-sections were investigated using energy dispersive X-ray spectroscopy, scanning electron microscopy, and profilometry. Surface retention of tin was found in almost all treatment groups and was highest in experiment 2. On cross-sections, tin was retained within the organic matrix; in mineralized areas, tin was found mainly within a depth of 10 mum. Test solutions inhibited substance loss significantly; in experiment 2, the effect was dose-dependent. Erosion inhibition seemed to depend mainly on the incorporation of tin in the mineralized dentine when the organic portion was preserved, but on surface precipitation when the organic portion was continuously digested.

Development of 68Ga-labeled tin colloids for evaluating phagocytic function of Kupffer cells using preclinical PET imaging.

OBJECTIVE: This study aimed to investigate the optimal conditions for producing 68Ga-labeled tin colloid and the feasibility of 68Ga-tin colloid positron emission tomography (PET) for visualization and evaluation of the phagocytic function of Kupffer cells (KCs) in vivo. METHODS: 68Ga-tin colloid was prepared by adding tin solution (1 mM, 0.2 mL) to 68Ga solution (1.0 mL), followed by pH adjustment with sodium acetate (1 M, 0.2 mL). Various labeling times were tested to find the optimal one. Colloid size was measured by filtering the solution through three-ply membrane filters (with pore sizes of 200, 3000, and 5000 nm), and radioactivity was measured in the whole filtrate and the filters using a gamma counter. The in vitro stability of the colloid was evaluated by the size measurement after incubation under ambient conditions for up to 60 min. PET scanning was performed for 30 min after intravenous administration of 68Ga-tin colloid solution (4 MBq) to healthy rats. Time-activity-curves for the liver, spleen, and blood pool were generated. Finally, liver uptake was compared before and after the establishment of KC-depletion and non-alcoholic steatohepatitis (NASH) rat models. RESULTS: Colloid size increased with increasing labeling time. After pH adjustment, the colloid sizes remained nearly unchanged. The optimal labeling time was determined as 30 min. PET imaging of healthy rats revealed that liver uptake of the 68Ga-tin colloid increased with increasing colloid size. In KC-depleted rats, liver uptake significantly decreased (n = 4, p < 0.01). NASH model rats showed significantly decreased uptake of 68Ga-tin colloid in the livers (n = 5, p < 0.01). CONCLUSIONS: 68Ga-tin colloid, prepared by a simple radiolabeling method, enabled in vivo PET imaging to evaluate the phagocytic function of KCs.

Tin-containing fluoride solutions as anti-erosive agents in enamel: an in vitro tin-uptake, tissue-loss, and scanning electron micrograph study.

Tin-containing fluoride solutions can reduce erosive tissue loss, but the effects of the reaction between tin and enamel are still not clear. During a 10-d period, enamel specimens were cyclically demineralized (0.05 M citric acid, pH 2.3, 6 x 5 min d(-1)) and remineralized (between the demineralization cycles and overnight). In the negative-control group, no further treatment was performed. Three groups were treated (2 x 2 min d(-1)) with tin-containing fluoride solutions (400, 1,400 or 2,100 ppm Sn2+, all 1,500 ppm F-, pH 4.5). Three additional groups were treated with test solutions twice daily, but without demineralization. Tissue loss was determined profilometrically. Energy-dispersive X-ray spectroscopy was used to measure the tin content on and within three layers (10 mum each) beneath the surface. In addition, scanning electron microscopy was conducted. All test preparations significantly reduced tissue loss. Deposition of tin on surfaces was higher without erosion than with erosion, but no incorporation of tin into enamel was found without demineralization. Under erosive conditions, both highly concentrated solutions led to the incorporation of tin up to a depth of 20 mum; the less-concentrated solution led to small amounts of tin in the outer 10 mum. The efficacy of tin-containing solutions seems to depend mainly on the incorporation of tin into enamel.

Kinetics and tissue distribution of bismuth, tin and lead after implantation of miniature shotgun alloy pellets in rats.

INTRODUCTION: Shotgun pellets containing bismuth (Bi) as substitute for lead (Pb) are increasingly being used due to environmental concerns. Information on toxicokinetics of Bi is lacking for the assessment of humans accidentally shot by Bi-containing shotgun alloy pellets. METHODS: Male Wistar rats were exposed to miniature alloy pellets containing Bi, tin (Sn) and minor amounts of Pb by implantation in muscle tissues of the hind legs. RESULTS: The concentrations of Bi in whole blood and urine increased up to 53 weeks after implantation. The highest concentrations of Sn in whole blood were observed three weeks after implantation, then declining to background levels 53 weeks after implantation. Lead in whole blood increased up to 13 weeks of exposure, and declined for the remaining observation period. Bismuth and Sn accumulated mainly in kidney, but also in liver, testicle and brain. Analytical field emission scanning electron microscopy of post-implant pellets showed depletion of Pb towards the pellet surface. Oxygen and chlorine accumulated in Sn rich lamellas in areas next to the pellet surface. The distribution of Bi remained visually unaffected as compared to pre-implant pellets. CONCLUSION: The concentration of Bi increased during the whole observation period in blood, urine, kidney, brain, testicle and liver. The decline in the concentrations of Pb and Sn in blood and urine after reaching the peak concentration may be related to alterations in the chemical composition and element distribution of the implanted alloy pellets.

Comparison of the predicted in vivo behaviour of the Sn(II)-APDDMP complex and the results as studied in a rodent model.

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with ((117m)Sn labelled) Sn(II) complexed to the bone seeking bisphosphonate, N,N-dimethylenephosphonate-1-hydroxy-3-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD, Pamindronate). This work is performed to utilise the idea that the low bone marrow radio toxicity of (117m)Sn could afford a highly effective radiopharmaceutical in pain palliation but also in the curative treatment of bone metastasis. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca(2+), Mg(2+), Zn(2+) as well as the added metal ion, Sn(2+) were measured by glass electrode potentiometry at 25 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from tests on a rodent model. The ((117m)Sn-labelled) Sn(II)-APDDMP complex was found to have only some liver and bone uptake although a high trabecular to normal bone ratio was recorded. From the blood plasma model this was shown to be primarily due to the high affinity of APDDMP for Ca(II) causing some of the Sn(II)-APDDMP complex to dissociate. High kidney uptake and excretion as well as high bladder uptake was recorded which was shown to be due to the dissociation of the Sn(II)-APDDMP complex in blood plasma. Animal model observations could be explained by the blood plasma modelling.

Correlation of splenic function with the splenic uptake rate of Tc-colloids.

The splenic uptake rate of Tc-sulphur colloid or Tc-tin colloid was measured and found to correlate well with splenic function. The normal tracer uptake rate was 0.0002/s-0.0006/s (measured uptake rate divided by measured injected activity). Lower values indicated hyposplenism (sensitivity = 0.97, specificity = 0.95), and values over 0.0006/s indicated hypersplenism (sensitivity = 0.96, specificity = 0.97). Higher values of splenic uptake were associated with proportional reductions in the white blood cell and platelet counts, and to a lesser extent the haemoglobin concentration in peripheral blood. Patients with rheumatoid arthritis had increased tracer uptake, but still below the criteria for hypersplenism, whereas patients with Felty's syndrome had tracer uptake rates in the 'hypersplenic' range.

Effects of tin and lead on organ levels of essential minerals in rabbits.

The effect of tin and lead on levels of essential metals (Zn, Cu, Ca, Fe) in rabbit tissues was compared in relation to the route of administration. Animals received intraperitoneally, or per os, SnCl2 (2 mg Sn/kg) or Pb(CH3COO)2 (3.5 mg Pb/kg) every day for 5 d or for 1 mo. Copper, zinc, iron, and calcium were determined by AAS in the liver, kidneys, spleen, brain, bone marrow, and blood; lead and tin concentration were measured in the blood of animals. Tin and lead administered per os caused either no changes or the decreased concentration of endogenous metals in several tissues. The other route of administration (ip) of both metals generally contributed to the increased storage of essential elements. Blood tin levels of tin treated animals were only about less than or equal to 1/10 of blood lead concentrations of rabbits exposed to lead.

Experimental study on interactions between selenium and tin in mice.

The organ distributions of tin and selenium, and their excretion into urine and feces, were determined in mice. There were four groups; (A) control, (B) Sn (5 mumol/kg/d) ip injection, (C) Se (5 mumol/kg/d) sc injection, and (D) Sn plus Se (5 mumol/kg/d, each). Animals received injections once a day for 12 consecutive days. The results were the following (1) Simultaneous injection of Sn and Se enhanced accumulation of both elements in the body, i.e., in group B, 14.1% of the total injected amount of Sn was excreted into urine and feces; in group C, 46.2% of total injected Se was excreted into urine and feces; in group D, 10.9% of total Sn and 37.5% of total Se were found in excreta. (2) Large amounts of Sn were found in bone, liver, spleen, and kidney in group B. When Se was administered jointly with Sn, the concentrations of Sn in bone and liver were suppressed, whereas those in spleen and pancreas were increased. (3) The effects of Se-injections at this dose on concentrations of Se in organs were small. (4) In plasma, chemical reduction of selenite by stannous chloride was not observed.

Preparation of rhenium-188-tin colloid as a radiation synovectomy agent and comparison with rhenium-188-sulfur colloid.

As a generator-produced beta-emitting radionuclide, the importance of 188Re for radionuclide therapy is increasing rapidly. We prepared 188Re-tin colloid and compared its properties with 188Re-sulfur colloid. Labeling efficiencies reached >98% for tin colloid at 2 h and 89-94% for sulfur colloid at 3 h. All the preparations were stable for 72 h in water, serum, and synovial fluid. If labeled at higher temperature, the particle size of tin colloid increased. The residual radioactivity of 188Re-sulfur colloid in disposable polypropylene syringes after injecting mice was high (62.0+/-7.0%) due to its hydrophobic nature, while that of 188Re-tin colloid was low (2.9+/-1.6%). Although both 188Re-tin colloid and 188Re-sulfur colloid might be useful for radionuclide therapy, we conclude that 188Re tin colloid is more advantageous over 188Re sulfur colloid, due to higher labeling efficiency, control of the particle size, and lower residual activity in the injection syringes.

[Harmful elements versus iron, zinc and copper: their interactions in animals and humans. I. Mercury, tin, nickel, selenium, fluorine and aluminum]. / Pier wiastki szkodliwe a zelazo, czynk i miedz: interakcje w organizmie zwierzat i ludzi. Cz. I. Rtec, cyna, nikiel, selen, fluor, glin.

A literature survey was made of the interactions--in the organism--between some food contaminating elements (mercury, tin, nickel, selenium, fluorine, aluminium) and iron, zinc and copper. The harmful elements may disturb the mineral metabolism already at the stage of intestinal absorption. Moreover, they bring about changes in microelement distribution in the tissues and cells. On account of their approximately similar chemical structure, they compete for the sites of binding to some proteins, including enzymic ones. In this respect a special role is played by ++metallothionein, a protein with the ability of regulating free metal contents in the tissues and thus possibly displaying some detoxifying properties. Many mechanisms and relationships determining the interactions between the surveyed food contaminants and iron, zinc and copper remain, however, not elucidated.

Topical oral cavity pharmacokinetic modeling of a stannous fluoride dentifrice: an unusual two compartment model.

A pharmacokinetic model was developed describing the pharmacokinetics of stannous fluoride in human subjects after oral topical application of a stannous fluoride dentifrice. Twenty subjects participated in an investigation of an experimental dentifrice. Subjects rinsed their mouths with the experimental dentifrice slurry. Saliva and plaque samples were obtained from the subjects at various times up to 6 h after administration. Samples were analyzed for total tin content, used as an analytical marker for the active stannous fluoride ingredient, using a graphite furnace atomic absorption spectrometer. The modeling indicates that there is an obvious kinetic relationship between saliva and plaque compartments and that stannous fluoride is very well retained in and slowly released from plaque (and oral surfaces) into saliva. Additionally, both compartments are simultaneously loaded during administration unlike typical systemic drug behavior, and the elimination rate "constant" from the central compartment (saliva) changes due to changes in salivary flow. Stannous fluoride is cleared from saliva rapidly but very well retained in gingival plaque. The model with simultaneous loading of plaque and saliva describes these observations and may account for the prolonged antiplaque and antigingivitis benefits of stannous fluoride.

99mTc-nitrido radiopharmaceuticals based on nitrogen heterocyclic ligands containing a thiol group.

The chromatographic and in vivo behaviour in mice of the 99mTcN- and 99mTc(Sn)-complexes of 2-mercaptopyridine, 2-mercaptopyrimidine, thiouracil, 6-mercaptopurine and thioguanine is compared. The biological distribution of the 99mTcN-complexes is generally different to that of the 99mTc(Sn)-complexes of the same ligand with the difference being very dependent on the structure of the ligand. The 99mTcN-mercaptopyrimidine complex has potential as a blood-cell labelling agent.

Radiopacities in dentine under amalgam restorations.

Radiopacities, caused by tin or zinc deposits in partly demineralized dental tissue, are frequently seen under amalgam restorations. The aim of this study was to determine to what extent these radiopaque areas could be identified by Caries Detector (1% acid red in propylene glycol) which is claimed to stain the irreversibly demineralized dentine. Twenty-eight extracted teeth showing radiopacities under amalgam fillings were selected. The restorations were removed, and Caries Detector was applied. Caries was excavated until the dentine did no longer stain with the Caries Detector. Standardized radiographs were taken at different stages. In all teeth the radiopaque areas stained with the Caries Detector. Visual inspection of the radiographs, taken after excavation, revealed that the radiopacities had disappeared completely in 6 teeth; in 5 teeth a very small part of the radiopaque area remained; in 17 teeth the cavity floor appeared as a thin white line on X-ray. Overall, line scan analysis confirmed the data obtained by visual observation. The residual radiopacities and radiopaque lines were a very small fraction of the initial radiopacities. Therefore, it is concluded that the radiopaque zone under amalgam fillings represents almost entirely an area of irreversibly demineralized dentine as indicated by the Caries Detector.

Case study: bioavailability of tin and tin compounds.

This article reviews the literature related to the bioavailability of tin, inorganic tin compounds, and organotin compounds. On the one hand, the toxicity of metallic tin and inorganic tin compounds is low. In aqueous systems, the potential bioavailability of tin seems to depend on the concentration of the truly dissolved ion species. Some studies suggest that tin is an essential trace element for humans. However, organotin compounds have been proven to be of toxicological relevance. Triorganotin compounds are particularly toxic explaining their wide use as biocides (e.g., in antifouling paints or pesticides). Persistence of organotin compounds is governed by moderate to fast aerobic biotic degradation processes, slow anaerobic biotic degradation, slow abiotic degradation by photolysis, and fast, but reversible, adsorption/desorption processes. Organotin compounds are ubiquitously distributed in aquatic organisms. Bioconcentration in organisms and ecotoxicity are dependent on the bioavailable fraction. The bioavailability is highest at neutral and slightly alkaline pH and is reduced in the presence of dissolved organic carbon. The biomagnification of organotin compounds via the food chain is of minor importance compared with the bioconcentration from the water phase.

Dentine hypersensitivity. I. Effects produced by the uptake in vitro of metal ions, fluoride and formaldehyde onto dentine.

Dentine has been shown to possess affinity for a large number of varied compounds, many of which have been shown effective in clinical trials, for the treatment of dentine hypersensitivity. The mode of action of these compounds is unclear. The aim of this study was to investigate the uptake of metal ions, fluoride and formaldehyde in solution onto dentine in vitro and determine whether therapeutic effects could be mediated through occlusion of dentinal tubules. Etched dentine sections were exposed for 1 h to 1000 ppm solutions of fluoride and metal salts. Levels of fluoride and respective metals could be extracted and measured from the specimens. Saliva pretreatment had a variable but small effect on uptake of each ion, but post treatment washings reduced all levels of retained fluoride and metals. X-ray microanalysis indicated surface or immediate subsurface deposits of metals. However, surface changes were only consistently produced by zinc and more particularly tin salts. Both zinc and tin salts produced covering or obturation of tubules. The surface effects of zinc could largely be reversed by washing, but not those of tin. Formaldehyde alone or in the presence of saliva produced no effects. A 4-week study involving twice daily exposure of specimens to saliva and fluoride, metals or formaldehyde yielded essentially the same results. It is unlikely that, except for tin, the compounds tested achieve their apparent clinical effects mediated by direct occlusion of dentinal tubules.

The in vitro and in vivo inhibition of intestinal heme oxygenase by tin-protoporphyrin.

The effects of tin-protoporphyrin (SnPP) on the activity of heme oxygenase in the epithelium of the proximal region of the small intestine were examined in male Sprague-Dawley rats. A single dose of SnPP (25 mumol/kg body weight) administered either parenterally or by gavage-produced time-dependent decreases in the activity of microsomal heme oxygenase over 24-48 h. Although heme oxygenase activity reverted to normal levels within 24 h after oral dosing, parenteral treatment resulted in substantial (70%) inhibition of the enzyme through at least 48 h after administration of the metalloporphyrin. In vitro, SnPP was shown to be a competitive inhibitor of microsomal heme oxygenase (Ki = 0.017 microM). Tissue tin levels were determined by graphite furnace atomic absorption spectroscopy 48 h after SnPP treatments. Comparable levels of tin were found in the liver and kidney after parenteral treatment (14.34 +/- 1.50 and 14.39 +/- 0.45 micrograms/g dry weight, respectively) while only 1.5-3% of these amounts were found in these organs after oral treatment with the metalloporphyrin. These studies establish that the rate-limiting enzyme in the catabolism of heme to bilirubin is inhibited in intestinal epithelium to the same extent as the enzyme is inhibited in other organs.

Release of fluoride and metal ions from root surfaces after topical application of TiF4, SnF2, and NaF in vitro.

Aqueous solutions of TiF4 cause a rapid uptake and a long-lasting retention of fluoride when applied to dentin. The aim of this study was therefore to investigate the pattern of fluoride release after TiF4 application in vitro, compared with SnF2 and NaF application. TiF4, SnF2, and NaF were applied for 4 min and 1 min to standardized areas of six groups of root surface specimens immersed in distilled water. Untreated specimens were used as controls. The water was changed daily for 30 days, and F concentrations measured by an ion-selective electrode. All test groups showed a rapid decline in F concentration. In the 4-min group F concentration more than double the detection limit of the F electrode could be registered the first 28 days for TiF4, 11 days for SnF2, and 7 days for NaF. In the 1-min group periods of F registration were shorter. Analysis of Sn by atomic absorption spectrophotometry showed decreasing concentrations in the first 12-day samples in the 1-min and 4-min groups. Traces of Ti were found in the first few samples, but no pattern of release could be observed.

Comparison between the effect of pyrazole, cobalt and tin on hepatic and renal microsomal cytochrome P450 concentration and metabolism of coumarin and 7 ethoxycoumarin

Recently, the metabolism of coumarin and 7-ethoxycoumarin were reported to be enhanced several folds in the mouse liver after pretreatment with either N-containing heteroaromatic compounds [e.g. pyrazole, PL] or heavy metals [e.g. Cobalt, Co and Tin, Sn]. The effect of these compounds on the mouse renal microsomes is not thoroughly investigated. Accordingly the present study was designed to compare the effect of pyrazole. cobalt and tin on hepatic and renal microsomes. The study revealed that in both kidney and liver microsomes, the concentration of Cyt P450 was decreased to about the same extent after pretreatment of male mice [NMRI-type] with these compounds. In contrary the metabolism of 7-ethoxy-coumarin and of Coumarin were increased several folds. In the liver microsomes, the highest increase in the metabolism of the coumarin derivatives, were observed after pretreatment of mice with Sn [Sn > PL > Co]. On the other hand, in the kidney microsomes, the most potent inducer was found to be PL [PL> Co>Sn]. These results indicate that PL, Co or Sn enhance the hepatic and renal metabolism of coumarin derivatives by different rates. Accordingly, these data suggested the different regulation of the coumarin derivatives metabolizing enzymes in the -liver from that in the kidney