[Zinc- and tin-induced apoptotic mechanisms in immune system and cranial nerve system].

This review explains the mechanisms of apoptosis related to the impacts of zinc deficiency and organotin exposure on the immune and central nervous systems. In the immune systems, both zinc deficiency and trialkyltin exposure lead to severe thymic atrophy and affect T-lymphocyte development through apoptosis of double positive stage pre-T-cells(CD4+/CD8+) in the cortex region. Their apoptosis are caused mainly through decrease in Bcl-2 expression, activation of ROS production/release, oxidative stress, mitochondrial cytochrome c release and activation of caspase cascade, with increases in glucocorticoids in zinc deficiency, without the involvement of glucocorticoid in organotin exposure In the central nervous system, both zinc deficiency and trialkyltin exposure reduce learning, memory and sensory functions through neuronal apoptosis caused by activation of ROS production/release, release of pro-apoptotic factors such as cytochrome c or apoptosis-inducing factor(AIF), with Fe excessive accumulation leading to ROS production and with depletion of hippocampus Zn (mossy fiber Zn) causing various Ca2+ channel disorder of synapse in the hippocampus, and with excessive accumulation of Ca through cAMP-dependent Ca(2+)-channel disorder by excessive PTH and cAMP excessive production in the olfactory systems such as olfactory epithelium and olfactory bulb.

[Potential exposure to carcinogens in low-melting alloys processing]. / Potenziale esposizione a cancerogeni nella lavorazione di leghe bassofondenti.

The objective in our study was to evaluate the worker's exposition to lead and cadmium in 32 radiology technicians in an eastern Sicily hospital in workers of low melting point alloy of lead, tin, cadmium and bismuth (league that can be melted at 73 degrees C as CERROBEND). Such alloy is used for the fabrication of objects used for the personal protection of cancer patients subject to high energy treatment. The parameters taken into consideration for this study were sex, age and smoking habits. In the test subject's working cycle reported in our case, there were traces of smoke formation containing lead, tin, bismuth and cadmium. Cadmium is a substance considered by IARC to be cancerous and can be found in both work and living environments, therefore it is often difficult to establish rather its presence in the organism is due to working activities and/or the living environment. In these cases it is necessary to evaluate whether the work represents an added risk to develop neoplasia, compared to the consequences due to normal environmental exposure. The added risk linked to work is evaluated comparing the concentration of toxic substances found in the living environments (Environmental Reference Value) with the toxic and/or metabolite found in the working environment, and comparing the biological reports of the population not directly exposed by work (Biological Reference Value) and those exposed. We performed a biological monitoring for lead and cadmium on the workers examined. The Italian Legislature, aside from lead, has not yet issued guidelines pertaining to professional exposure to cadmium, and therefore it is mandatory to take reference to the American Hygienist's charts both for environmental exposure (TLVs) andfor biological monitoring (BEI). Biological monitoring, which allows to evaluate the absorption by both inhalation and gastrointestinally, was performed through measuring the levels of lend and cadmium in the bloodstream (PbB and CdB) and the Cd in urine (CdU). The results show that in no case the levels of lead in the bloodstream (PbB) were above the reference value and BEI. The levels of cadmium urine (CdU) weren't above the reference level and the BEI, while the haematic levels of cadmium (CdB) were higher than the reference value in 8 subjects, each long time smokers, each of about 20 cigarettes a day. This data shows how, in the evaluation of exposition to cadmium, aside from the exam of data pertaining to work, the study of ways of absorption and the interpretation of the results of environmental and biological monitoring, it is important to consider the possibility of intoxication outside of the workplace. Cigarette smoke, as already indicated by other authors, is also confirmed in our studies as one of the major fonts of non professionally linked inhalation of cadmium.

Early life stage and genetic toxicity of stannous chloride on zebrafish embryos and adults: toxic effects of tin on zebrafish.

Humans are exposed to stannous chloride (SnCl(2)), known as tin chloride, present in packaged food, soft drinks, biocides, dentifrices, etc. Health effects in children exposed to tin and tin compounds have not been investigated yet. Therefore, we evaluated the possible teratogenic effects and genotoxic of SnCl(2) in zebrafish (Danio rerio) adults and their embryos. In the embryo-larval study, SnCl(2) showed embryo toxicity and developmental delay after exposure to the various concentrations of 10-250 µM for 120 h. Teratogenic effects including morphological malformations of the embryos and larvae were observed. The embryos exposed to 100 µM displayed tail deformation at 28 hpf and the larvae exposed to 50 µM showed reduced body growth, smaller head and eyes, bent trunk, mild pericardial edema, and smaller caudal fin at 96 hpf. The results of the teratological study show that SnCl(2) induced a significant decrease in the number of living embryos and larvae. Regarding the chromosome analysis, SnCl(2) induced a dose-dependent increase in the micronucleus (MN) frequency in peripheral erythrocytes of adult zebrafish. In blood cells, the 25 µM dose of SnCl(2) caused a nonsignificant increase in the total chromosomal aberrations, but the high doses significantly increased the total number of chromosomal aberrations compared with the control groups. Overall, the results clearly indicate that SnCl(2) is teratogenic and genotoxic to zebrafish.

[Expression of fragile histidine triad (FHIT) protein and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust].

OBJECTIVE: To study the expression and significance of fragile histidine triad (FHIT) and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust. METHODS: Every second generation of immortalized human bronchial epithelial cells (BEAS-2B) and human embryo lung fibroblasts (WI-38) were exposed to 100 µg/ml Yunnan tin mine dust for 72 h, until the ninth generation. The cells were subsequently co-cultured from the 11th generation. Experimental setup: B group, B (W) group, B (W 100) group, B100 group, B100 (W) group, B100 (W100) group. The expressions of FHIT and Ki-67 in epithelial cells were determined by the method of immunocytochemistry at the 16th, 26th and 36th generation. The percentage of Ki-67 positive cells was calculated as proliferation index. RESULTS: The expression of FHIT was observed in BEAS-2B cells. The expression levels of FHIT among B group, B (W) group and B (W 100) group had not instinctive difference. At the 16th generation, the expression of FHIT in the B100 group was decreased compared with that in the B group and the expression of FHIT between B100 (W) group and B100 (W100) group was lower than that in the B100 group. At the 26th generation, the expression of FHIT was decreased compared with that at the 16th generation in the B100, B100 (W) and B100 (W100) groups. However, At the 36th generation, positive expression were observed again in the B100, B100 (W) and B100 (W100) groups and the expression levels were in incremental order. At the 16th, 26th and 36th generation, the proliferation indexes of B group, B (W) group and B (W 100) group were all < 3%. The proliferation indexes of B100, B100 (W) and B100 (W100) were increased step by step with the generation elongation. CONCLUSIONS: FHIT could be a target at which Yunnan tin mine dust induces transformation of BEAS-2B cells. The proliferation activation of BEAS-2B cells can be improved by Yunnan tin mine dust.

Tin: a potent inducer of heme oxygenase in kidney.

Tin greatly enhances heme breakdown in kidney, thus impairing heme-dependent cellular functions, such as cytochrome P-450 mediated drug biotransformation. This novel action of the metal results from a potent induction effect on heme oxygenase, the enzyme that catalyzes heme oxidation in microsomes. The possible toxicological implications of this tin effect in the kidney merit further investigation.

[Interaction between malignant transformation of human pulmonary epithelial cells and activation of fibroblasts induced by Yunnan tin mine dust].

OBJECTIVE: To study the interaction between transformation of human pulmonary epithelial cells and activation of fibroblasts induced by Yunnan tin mine dust. METHODS: (1) The immortalized human bronchial epithelial cell line BEAS-2B and human embryo lung fibroblast cell line WI-38 were grown in MEM medium containing 5% and 10% FBS, respectively, at 37 degrees C and 5% CO2 with saturated humidity. The cells were subcultured every 6 days. BEAS-2B cells and WI-38 cells were induced with Yunnan tin mine dust on every other generation at the concentration of 100 microg/ml. From the 11th generation, the cells were co-cultured. Epithelial cell transformation was tested using concanavalin A (ConA) agglutination and anchorage-independent growth assays. The cell cycles were analyzed through flow cytometry. The expressions of alpha-SMA in fibroblasts were determined with immunocytochemistry. RESULTS: (1) Cell morphology of mine dust-exposed epithelial cells began to transform at the 28th generation. Similar transformations were observed with mine dust-induced epithelial cells co-cultured with fibroblasts from the 20th generation and mine dust-induce epithelial cells co-cultured with mine dust-induced fibroblasts from the 16th generation. ConA agglutination assay and anchorage-independent growth assays were negative in normal BEAS-2B cells. At the 26 th generation, the agglutination test result of the mine dust-exposed epithelial cells was positive. Co-cultured with fibroblasts and mine dust-exposed fibroblasts, the agglutination time of the mine dust-exposed epithelial cells became short. Epithelial cell anchorage-independent growth assay was positive for mine dust-exposed epithelial cells co-cultured with fibroblasts at the 36th generations and for mine dust-exposed epithelial cells co-cultured with mine dust-exposed fibroblasts at the 26th generations. The clone formation rate of the 26th generation was 6.00 per thousand +/- 1.00 per thousand and 15.33 per thousand +/- 2.52 per thousand respectively, with the significant differences (P < 0.05). With generation adding, the portion of S phase increased for mine dust-exposed epithelial cells. (2) At the 26th generations, fibroblasts expressed alpha-SMA. Co-cultured with epithelial cell, the alpha-SMA expression of fibroblasts increased. Especially, positive cell numbers and intensity of staining dramatically increased with generation adding. CONCLUSIONS: (1) The tin mine dust can induce malignant transformation of human pulmonary epithelial cells BEAS-2B and activation of fibroblasts WI-38. (2) The epithelial cells are major target in carcinogenesis induced by Yunnan tin mine dust. (3) Transformation of epithelia and activation of fibroblasts co-evolve in the developing process of induced lung cancer by Yunnan tin mine dust.

Spatial pattern of the environmental exposure to tin in the vicinity of an alloy industry in Volta Redonda, Rio de Janeiro State, Brazil.

Despite being widely used in industry, the literature on tin and its effects in humans is scarce, especially regarding reference values in biological indicators such as blood and urine. Similarly, environmental limits are also rare. This study sought to assess the spatial distribution of hotspots in the environmental exposure to tin in the vicinity of an alloy industry in the south region of the state of Rio de Janeiro, Brazil. The study population consisted of 74 adults. Graphite furnace atomic absorption spectrometry determined tin in all samples. Households and points around the industry were georeferenced with the use of GPS to identify the most intense tin sites. Results of the first and second campaigns ranged from 0.022 to 0.153 and 0.003 to 0.445µg m-3 for the atmospheric air, whereas such ranges were 0.64 to 1.61 and 1.97 to 8.54µg m-2 for household dust, respectively. The mean tin concentration found in the blood of the population was 3.85 ± 1.57µg L-1. In urine the value was 3.56 ± 1.88µg L-1. The kernel map showed the highest spatial concentrations of tin in household dust in the eastern region of the industry. In the first sampling, atmospheric air samples presented the most elevated concentrations in the southwest and southeast. Although the direction of the wind was northwest, potentially high risks were concentrated in the central area in the second collection. The largest hotspots were in the north, south and southeast regions; however, urine samples showed medium to high levels in the west and east regions. Regarding blood samples, the greatest difference was the absence of hotspot areas in the west. Environmental monitoring becomes necessary to better assess the exposure to tin.

Monoalkyl Tin Nano-Cluster Films Reveal a Low Environmental Impact under Simulated Natural Conditions.

Recently, monoalkyl oxo-hydroxo tin clusters have emerged as a new class of metal-oxide resist to support the semiconductor industry's transition to extreme ultraviolet (EUV) lithography. Under EUV exposure, these tin-based clusters exhibit higher performance and wider process windows than conventional polymer materials. A promising new monoalkyl precursor, [(BuSn)12 O14 (OH)6 ][OH]2 (BuSn), is still in its infancy in terms of film formation. However, understanding potential environmental effects could significantly affect future development as a commercial product. We synthesized and explored the toxicity of nano-BuSn in the alga Chlamydomonas reinhardtii and the crustacean Daphnia magna at exposure concentrations ranging from 0 to 250 mg/L. Nano-BuSn had no effect on C. reinhardtii growth rate irrespective of concentration, whereas high nanoparticle concentrations (≥100 mg/L) increased D. magna immobilization and mortality significantly. To simulate an end-of-life disposal and leachate contamination, BuSn-coated film wafers were incubated in water at various pH values and temperatures for 14 and 90 d to investigate leaching rates and subsequent toxicity of the leachates. Although small quantities of tin (1.1-3.4% of deposited mass) leached from the wafers, it was insufficient to elicit a toxic response regardless of pH, incubation time, or temperature. The low toxicity of the tin-based thin films suggests that they can be an environmentally friendly addition to the material sets useful for semiconductor manufacturing. Environ Toxicol Chem 2019;38:2651-2658. © 2019 SETAC.

Empirical investigation of preparations produced according to the European Pharmacopoeia monograph 1038.

According to the European Pharmacopoeia monograph 1038 (Praeparationes homoeopathicae), homeopathic preparations are produced by successive dilution and succussion steps. Dilution levels beyond Avogadro's limit, however, render specific effects implausible according to standard scientific knowledge. Accordingly, we were interested in a critical empirical investigation of preparations produced according to this monograph. Within a precursor study we developed a bioassay based on a fingerprint metabolomic analysis of Lepidium sativum seeds germinated in vitro in either homeopathic preparations or controls in a blinded and randomized assignment. Results of the precursor study were not consistent with the hypothesis that the effects of a Stannum metallicum 30x preparation are identical to placebo. In the present study we investigated the reproducibility of these effects after scrutinizing and optimizing experimental procedures. Ten independent experiments were performed in a blinded and randomized assignment in two independent laboratories. Additionally, 10 systematic negative water control experiments were performed in both laboratories to critically assess the stability of the experimental set-up. The effects of the Stannum metallicum 30x treatment were reproduced. The systematic negative control experiments did not yield false-positive results, indicating a stable experimental set-up. We thus repeatedly observed biological effects conflicting with the assumption that Stannum metallicum 30x is identical to placebo. We therefore wish to discuss whether these findings are to be considered a scientific anomaly or whether they might stimulate further investigations to clarify whether application of the European Pharmacopoeia monograph 1038 may result in pharmaceutical preparations with specific effects.

Dissolution of copper, tin, and iron from sintered tungsten-bronze spheres in a simulated avian gizzard, and an assessment of their potential toxicity to birds.

The rates of dissolution of copper, tin, and iron from sintered tungsten-bronze spheres (51.1%W, 44.4%Cu, 3.9%Sn, 0.6%Fe, by mass) were measured in an in vitro simulated avian gizzard at pH 2.0, and 42C. Most of the spheres had disintegrated completely to a fine powder by day 14. Dissolution of copper, tin, and iron from the spheres was linear over time; all r>0.974; all P<0.001. The mean rate of release of copper, tin, and iron was 30.4 mg, 2.74 mg, and 0.38 mg per g tungsten-bronze per day, respectively. These rates of metal release were compared to those in published studies to determine whether the simultaneous ingestion of eight spheres of 3.48 mm diameter would pose a toxic risk to birds. The potential absorption rates of iron and tin (0.54 mg Fe/day, and 3.89 mg Sn/day) from eight tungsten-bronze spheres of total mass 1.42 g would not prove toxic, based on empirical studies of tin and iron ingestion in waterfowl. The release of 43.17 mg copper/day from eight tungsten-bronze spheres, while exceeding the daily copper requirements of domesticated birds, is far below the levels of copper known to cause copper toxicosis in birds. We conclude that sintered tungsten-bronze material made into gunshot, fishing weights, or wheel balance weights, would not pose a toxic risk to wild birds when ingested.

Assessing the toxicity of Pb- and Sn-based perovskite solar cells in model organism Danio rerio.

Intensive development of organometal halide perovskite solar cells has lead to a dramatic surge in power conversion efficiency up to 20%. Unfortunately, the most efficient perovskite solar cells all contain lead (Pb), which is an unsettling flaw that leads to severe environmental concerns and is therefore a stumbling block envisioning their large-scale application. Aiming for the retention of favorable electro-optical properties, tin (Sn) has been considered the most likely substitute. Preliminary studies have however shown that Sn-based perovskites are highly unstable and, moreover, Sn is also enlisted as a harmful chemical, with similar concerns regarding environment and health. To bring more clarity into the appropriateness of both metals in perovskite solar cells, we provide a case study with systematic comparison regarding the environmental impact of Pb- and Sn-based perovskites, using zebrafish (Danio Rerio) as model organism. Uncovering an unexpected route of intoxication in the form of acidification, it is shown that Sn based perovskite may not be the ideal Pb surrogate.

[Biological responses of tin mine particles and their association with adverse effects on health in tin mine].

OBJECTIVE: To evaluate the biological and toxicity of tin mine particles mixed with crystalline silica using an in vitro test, and to compare to the pathogenesis of pneumoconiosis and lung cancer. METHODS: Respirable particle samples were sampled from four tin mines, in which elevated mortality of pneumoconiosis and lung cancer were reported in miners exposed to particles. Alveolar macrophages (AM) are considered as the target cells of primary dust effects. The samples were then measured in 15, 30, 60 and 120 microg particle per 106 AM for cytoxicity with the release of glucuronidase, lactate dehydrogenase, for reactive oxygen damage with H2O2 release, and for ability to induce fibrosis using the secretion of tumor necrosis factor-alpha (TNF-(alpha) in guinea pig and/or rat am. pure quartz (dq12) and corundum were used as controls. RESULTS: The results showed the samples from tin mines caused a higher cytoxicity when compared to corundum, yet lower when compared to quartz. However, reactive oxygen species release induced by the samples were significantly higher than that induced by quartz and corundum. Beside particle samples induced higher TNF-alpha secretion than corundum, samples from Limu tin mine also induced greatly higher TNF-alpha levels than that induced by pure quartz, even in the lowest concentration. The results from epidemiological research show that high incidence of silicosis among tin miners. And standardize mortality from all cancer (SMR = 1.58, 95% CI: 1.39-1.76) and lung cancer (SMR = 3.17, 95% CI: 2.59-3.76) are higher than national average level. CONCLUSION: The results from in vitro test may reasonable interpret high risk of pneumoconiosis and lung cancer in tin miners. The in vitro multidimensional reaction patterns of AM can be used to screen workplace particles for adverse effects to health.

In vitro evaluation of biocompatibility of Ti-Mo-Sn-Zr superelastic alloy.

Shape memory alloys (SMAs) including superelastic alloys have unique properties such as shape memory and superelasticity, thus they are recognized as very useful biomaterials. These properties are very advantageous for medical use, and actually the SMA wires have been widely used in medical field. However, biocompatibility of nickel-titanium (Ni-Ti) alloy, which is the only practical SMA at present, has been questioned because of its high nickel content. The aim of this study was to evaluate the biocompatibility of a newly developed Ni-free Ti-based SMA for medical use. The newly developed SMA made of Ti-Mo-Sn-Zr system was processed into a disk of 15.1 mm in diameter. Pure titanium of the same shape was prepared as control. All the disk surfaces were polished using emery papers, #120, #400, and #600. Scanning electron microscopy and a 3D optics profiler were used to evaluate the surface of the materials. In vitro evaluations included colony examination for evaluation of the cell cytotoxicity, DNA quantification for the cell proliferation, Alamar blue assay for metabolic activity, FDA staining for the live cell imaging, and cell cycle analysis, using Chinese hamster fibroblastic V-79 cells and mouse osteoblastic MC3T3-E1 cells. In colony examination and DNA quantification, there was no significant difference between the Ti-Mo-Sn-Zr and the pure titanium. In FDA staining, cultured cells on the Ti-Mo-Sn-Zr alloy showed the same biocompatibility as those on the pure titanium. The present results suggest that the newly developed Ti-Mo-Sn-Zr alloy showed the high biocompatibility comparable to pure titanium and can be used as efficient biomaterial for medical use.

Evaluation of formamidine sulfinic acid and other reducing agents for use in the preparation of Tc-99m labeled radiopharmaceuticals.

Various reducing agents have been evaluated for their potential usefulness in the preparation of 99mTc labeled radiopharmaceuticals for use in nuclear medicine. Adequate labeling of various radiopharmaceuticals was accomplished using formamidine sulfinic acid. Nitrogen-purging of solutions is not required, which is an advantage for in-house preparation. Tagging requires heating, however, so heat-labile material cannot be used. Various compounds that could not be labeled when stannous chloride was used, could be tagged with 99mTc when formanidine sulfinic acid was used as the reducing agent.

Cellular responses to dental amalgam in vitro.

Cytotoxicity of fine cut amalgam was persistent until 24 hours after trituration in vitro, whereas cytotoxicity of spherical amalgam diminished more quickly. Increasing mercury content in spherical amalgam increased cytotoxicity. Possible reactions for the diminution of cytotoxicity of amalgams with time are discussed.

Some toxicological aspects of sttanous fluoride after ingestion as a clear precipitatefree solution compared to sodium fluoride.

Weanling rats were administered 20, 380, and 20,000 ppm F as clear precipitatefree SnF2 solutions. Equivalent ppm F as NaF solution was similarly administered for comparison. The rats were autopsied at the end of the study for histological examination of kidney, liver, and incisors. The pathognomonic manifestations were correlated with the plasma F levels.

[Nutritional and toxicological study of rats fed a diet containing tin (author's transl)]. / Etude nutritionnelle et toxicologique, chez le rat, d'un contaminant alimentaire: l'etain.

A toxicological, nutritional and histological study of rats on a diet containing 0.5 g of tin (Sn Cl2) per 100 g of dry food for one month has been made. By gamma radioactivity measurements (with 113Sn used as a tracer) it is shown that this metal does not practically clear the digestive barrier. Otherwise the classical coefficients of nitrogen nutrition and the urinary parameters (volume, glucose, pH) are not influenced; but the growth of treated animals is obviously slower than control animals because of their reduced ingestion of food. Moreover after one month of treatment a marked anaemia results since the hematocrit and hemoglobin levels are perceptibly reduced. Lastly the histological investigations give evidence of notable irritation of the total gastrointestinal tract. This study, as that of many authors, raises the question of present permissible levels of tin (up to 250 ppm) in foods.

The organ distribution of tin and the effect of tin on concentrations of several essential elements in rabbit.

The organ distribution and the effects of administration of tin, 5 mumol/kg/day, for 6 days on calcium, copper, iron, magnesium, phosphate, and zinc concentrations in plasma, erythrocytes, liver, kidney, and spleen of adult rabbits were studied. Kidney contained the highest concentration of tin, 15.0 +/- 1.64 micrograms/g wet weight (mean +/- S.D., n = 4). The concentrations of copper, phosphate, and magnesium increased significantly in the kidney, while magnesium concentration decreased in erythrocytes 1 day after the administration of tin for 6 consecutive days. A high correlation coefficient between magnesium and phosphate was observed in all organs tested. The correlation coefficients between P vs. Cu, P vs. Ca, and Mg vs. Ca in the liver were lowered during the period of tin administration, whereas those between P vs. Zn, Mg vs. Zn, and Cu vs. Zn in the kidney disappeared after tin administration was completed.