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Toxicity of tin and its compounds.

Inorganic tin salts are poorly absorbed and rapidly excreted in the faeces; as a result they have a low toxicity. Only about 5 per cent is absorbed from the gastrointestinal tract, widely distributed in the body, then excreted by the kidney. Some tin is deposited in lung and bone. Some tin salts can cause renal necrosis after parenteral doses. Mutagenic studies on metallic tin and its compounds have been negative. Long-term animal carcinogenic studies have shown fewer malignant tumours in animals exposed to tin than in controls. Human volunteers developed mild signs of toxicity with tin, given in fruit juices, at a concentration of 1400 mg per litre. The WHO 1973 permissible limit for tin in tinned food is 250 micrograms per kg. The adult daily intake of tin was about 17 mg per day in 1940, but it has now decreased to about 3.5 mg, due to improvements in technique of tinning with enamel overcoat and crimped lids to minimize exposure to tin and lead solder. This level is well below the level of 5-7 mg per kg body weight shown to give rise to toxic symptoms. Tin deficiency has not been described in man. Amounts in excess of 130 mg per day have been shown to accumulate in liver and kidneys. Many of the organotin compounds are toxic; the most toxic being trimethyltin and triethyltin, which are well absorbed from the gastrointestinal tract. Most of the other alkyl and aryltin compounds are poorly absorbed from the gastrointestinal tract, and are therefore less toxic when given orally than when given parenterally. The main results of toxicity are skin and eye irritation; cholangitis of the lower biliary tract, and later hepatotoxicity; and neurotoxicity, which has been shown to be due to intramyelin oedema induced by triethyltin, and neuronal necrosis caused by trimethyltin. Many of the organotin compounds affect mitochondrial oxidative phosphorylation and alter membranes, but the contribution of these biochemical and membrane effects in the cause of intramyelin oedema and neuronal necrosis has not been fully clarified. Widespread degeneration results, especially with trimethyltin. Peripheral neuropathy has not been reported as occurring with either inorganic or organic tin in humans. Certain dialkyltin compounds have been shown to cause adverse effects on cell-mediated immunity, specifically on the T cell lymphocyte. Experimental studies have failed to reveal any evidence of carcinogenicity, mutagenicity, or teratogenicity. Recent studies suggest that tin compounds exhibit some antitumour activity and may have a future role in cancer diagnosis and chemotherapy, and in controlling hyperbilirubinaemia.

Animals↗

Solid-state NMR studies of some tin(II) compounds.

High-resolution NMR spectra of [Formula: see text] nuclei, particularly (119)Sn and (31)P, in solid tin(II) phosphite, SnHPO(3), and tin(II) phosphate, SnHPO(4), are presented. The results are discussed in relation to the crystal structures. Spinning sideband analysis has been carried out for both nuclei, giving information on the shielding tensors. Satellite peaks allow the indirect Sn,Sn coupling constants to be determined. Surprisingly large values of 2600+/-200Hz and 4150+/-200Hz are reported for SnHPO(3) and SnHPO(4) respectively. The satellite peaks were investigated by using a single Hahn echo for each refocusing time, which showed that the observed splittings result from (119)Sn, (117)Sn coupling. For SnHPO(3), the calculated relative intensities of the satellites for six intra-layer coupling interactions are in agreement with the experiment values, but for SnHPO(4) the coupling appears to be inter-layer in nature. Tin-119 (and in one case phosphorus-31) shielding tensor data derived from MAS NMR are also reported for four other crystalline tin(II) compounds, namely tin diphosphate, tin oxalate, tin sulphate and calcium tin ethylenediamine tetraacetate.

Journal Article↗

[Tin-organic compounds and their biocidal properties].

The authors studied the disinfecting action of the vapour of tributyltin oxide in the aerosol chamber and came to the conclusion that the tin-organic compounds possessed a wide buicidal action, still inadequately used in practice. The mentioned vapour served as a disinfectant only in the presence of water vapour. Tribytyltin oxide (0.15% concentration) displayed an ovicidal action on the ova of Ascaris suum. Tributyltin laurate produced a good insecticidal effect on Musca domestica.

Animals↗

Toxicity and health effects of selected organotin compounds: a review.

The toxicity of selected tin compounds is reviewed. Over the years, a variety of uses has been found for organic and inorganic tin compounds, as fungicides, as stablizers in plastics, moluscicides, and miticides; they have also been suggested as insect chemosterilants and for other industrial uses. Many of these products are unpalatable when mixed into diets and have been suggested as rodent repellents. Inhaling tin as dust or fumes may cause a benign pneumoconiosis in exposed workers. The organotin compounds can be divided into alkyltin and aryltin compounds. The trimethyl and triethyltin compounds are well absorbed from the gastrointestinal tract and are the most toxic in this group. Triethyltin particularly produces status spongiosus of the white matter of the central nervous system. Most of the other alkyl and aryl tin compounds are poorly absorbed from the gastrointestinal tract, and are less toxic when given orally than when given parentally. Only one compound, tricyclohexyltin hydroxide, is now registered by the Environmental Protection Agency as a miticide. This product produces skin irritation in rabbits. Studies should be conducted to determine whether it causes contact dermatitis in humans.

Animals↗

Inhibition of Ca2+ transport associated with cAMP-dependent protein phosphorylation in rat cardiac sarcoplasmic reticulum by triorganotins.

Organotin compounds have been shown to interfere with cardiovascular system. We have studied the in vitro and in vivo effects of tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT) on the cardiac SR Ca2+ pump, as well as on protein phosphorylation of SR proteins, in order to understand the relative potency of these tin compounds. All the three tin compounds inhibited cardiac SR 45Ca uptake and Ca(2+)-ATPase in vitro in a concentration-dependent manner. The order of potency for Ca(2+)-ATPase as determined by IC50, is TBT (2 microM) greater than TET (63 microM) greater than TMT (280 microM). For 45Ca uptake, it followed the same order i.e., TBT (0.35 microM) greater than TET (10 microM) greater than TMT (440 microM). In agreement with the in vitro results, both SR Ca(2+)-ATPase and 45Ca uptake were significantly inhibited in rats treated with these tin compounds, indicating that these tin compounds inhibit cardiac SR Ca2+ transport. cAMP significantly elevated (70-80%) the 32P-binding to SR proteins in vitro in the absence of any organotin. In the presence of organotins, cAMP-stimulated 32P-binding to proteins was significantly reduced, but the decrease was concentration dependent only at lower concentrations. The order of potency is TBT greater than TET greater than TMT. In agreement with in vitro studies, cAMP-dependent 32P bound to proteins was significantly reduced in rats treated with TBT, TET and TMT. SDS-polyacrylamide gel electrophoresis of the cardiac SR revealed at least 30 Coomassie blue stainable bands ranging from 9 to 120 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biogeochemistry of organotin compounds and tin in a forested catchment in Germany.

Organotin compounds (OTC) are highly toxic pollutants that have been shown to affect many aquatic ecosystems. Little is known about the input and fate of OTC in terrestrial ecosystems. Here, soil pools, concentrations and fluxes in bulk precipitation, throughfall, fog, litterfall and runoff of OTC and Sntotal were investigated in a forested ecosystem (Picea abies, Karst.) in NE Bavaria, Germany. The concentrations of OTC and Sntotal were generally in the order fog>throughfall>bulk precipitation. Average concentrations of OTCtotal ranged from 57 ng Sn l(-1) in fog to 5.8 ng Sn l(-1) in bulk precipitation. Concentrations of Sntotal were in the same order but between 490 ng Sn l(-1) in fog and 140 ng Sn l(-1) in bulk precipitation, on average. Average OTCtotal concentrations in litterfall were 12.9 ng Sn g(-1) and those of Sntotal in litterfall 38 ng Sn g(-1). All OTC concentrations in runoff were lower than in bulk precipitation, while those of Sntotal were similar to the concentrations in bulk precipitation. Monobutyltin was the dominating OTC in bulk precipitation, throughfall, fog and litterfall, but was seldom detected in the runoff. The annual total deposition of OTCtotal (calculated as throughfall + litterfall) was 172 mg Sn ha(-1) year(-1), with 45 mg Sn ha(-1) year(-1) represented by litterfall. The annual runoff from the catchment of OTCtotal amounted to 25 mg Sn ha(-1) year(-1). The total deposition of Sntotal was 4.9 g Sn ha(-1) year(-1), of which 0.2 g Sn ha(-1) year(-1) was litterfall. The annual runoff of Sntotal was 2.4 g Sn ha(-1) year(-1). The mass balance showed a high retention of OTC and Sntotal in the catchment. The forest soils act as a strong sink for OTC and Sntotal. Only small amounts of deposited OTC are released to runoff. The ratio of soil pools to annual accumulation for total OTC (46 years) indicates that OTC inputs have been occurring already for many decades or have been substantially higher in the past than today.

Air Pollutants↗

Chemical and biological evaluation of sediments from the Wadden Sea, The Netherlands.

We describe the results of an evaluation of marine sediments using chemical measurements and bioassays. Four groups of chemicals, i.e., heavy metals, PAHs, chlorinated aromatic compounds, and tin compounds, were measured at 16 locations in the Wadden Sea, The Netherlands. Extractions of sediments from each location also were assessed using five bioassays. Our objective was to identify chemicals likely to pose biological risks, characterize the relation between bioassay results and particular classes of chemical(s) and determine "clean" reference sites on the basis of the chemical and biological evaluations. A multivariate technique (Principal Component Analysis; PCA) was used to meet these objectives. Results of the PCA indicated that the response of the Microtox Solid Phase bioassay had a positive, significant relationship with the levels of PAHs and organotin compounds. The responses of the other bioassays did not consistently relate to the concentrations of the other measured chemicals. Our findings indicate that the organotin compounds may still be a stressor for aquatic invertebrates in the Dutch Wadden Sea. On the basis of the chemical and biological evaluations, four sites (Dantziggat, Malzwin, Richel and Lauwers) can be considered to be "clean" reference sites.

Biological Assay↗

Determination of butyltin metabolites in the mouse liver by flameless atomic absorption spectrophotometry.

A new analytical method for observation of the metabolic status of butyltin compounds in the mouse liver was devised by a combination of extraction, purification and separation followed by quantitative analysis of each butyltin compound. After the extraction of all tin compounds from liver homogenate with ethyl acetate, these compounds were purified by combination of the fractional extract with organic solvents and column chromatography. The purified fraction was also analyzed by thin-layer chromatography, identifying each tin compound from differences in mobility on a silica gel plate. The tin content in the each separated spot on the plates was measured by flameless atomic absorption spectrophotometry after extraction by acid treatment. About 90% of tin was recovered by this method from the liver of mice which had been administered tri- or dibutyltin compound orally. This method will be useful for quantification of each metabolic product formed from butyltin compounds in vivo.

Animals↗

Formation of a novel trinuclear spirostannoxane tin(IV) compound. Crystal and molecular structure of [Sn(nBu)(Cl)[(OCH2CH2S)2Sn(nBu)]2] and the stannolane [(nBu)Sn(SCH2CH2O)SCH2CH2OH].

The reaction of nBuSnCl3 and the sodium salt of 2-mercaptoethanol (1:1) in ethanol gave the compound Sn(nBu)(Cl)[(OCH2CH2S)2Sn(nBu)]2 (1). [(nBu)Sn(SCH2CH2O)SCH2CH2OH] (2) was initially isolated from the reaction of 1 with nBuMgCl as a rearrangement product but was also synthesized from nBuSn(O)OH and two molar equivalents of 2-mercaptoethanol. Both compounds were characterized by means of IR, 119Sn, 13C, and 1H NMR, FAB mass spectroscopy, and elemental analyses. The structures were determined by single-crystal X-ray diffraction. 1 crystallizes in the monoclinic Cc space group (a = 18.492(3) A, b = 17.329(2) A, c = 10.787(1) A, beta = 111.88(1) degrees, Z = 4), while 2 crystallizes in the orthorhombic Pbca space group (a = 14.458(2) A, b = 10.393(1) A, c = 16.479(2) A, Z = 8). 1 is a trimetallic Tin(IV) compound in which the central atom is in 6-fold coordination, while the two remaining tin atoms show 5-fold coordination. Both pentacoordinated tin atoms are bonded to a butyl group and to the oxygen and the sulfur atoms from two [OCH2CH2S]2- ligands forming two stannolanes, which are fused with the hexacoordinated tin atom forming a distannoxane system. This arrangement is quite different from previous ladder or staircase structures. NMR data point to maintenance of this structure in solution. 2 consists of [(nBu)Sn(SCH2CH2O)(SCH2CH2OH)] units, which are associated via intermolecular Sn-O interactions building up a dimer. The tin atom forms two "stannolane" units by interaction with [OCH2CH2S]2- and [HOCH2CH2S]- ligands.

Journal Article↗

Dietary intake of organotin compounds in Finland: a market-basket study.

The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.

Animals↗

The neurotoxicity of environmental pollutants: the effects of tin (Sn2+) on acetylcholine-induced currents in greater pond snail neurons.

Inorganic and organic tin compounds present in aqueous ecosystems have diverse effects on the behavior of living organisms. With the aim of identifying possible correlates of these actions, we studied the effects of both types of Sn2+. The effects of SnCl2 and Sn(CH3)2 on acetylcholine-activate currents were studied on identified neurons of the mollusk Lymnaea stagnalis L. using a two-microelectrode membrane potential clamping technique and by intracellular dialysis with potential and ion concentration clamping. Experiments were performed on single neurons after isolation and on whole ganglion preparations. SnCl2 decreased acetylcholine-induced influx currents; the effect was dose-dependent. The effective threshold concentration, measured by the two-microelectrode membrane potential clamping method, was 0.1 microM, with saturation occurring at 5 microM SnCl2. After a 10-min preapplication of SnCl2, the effect was stronger (20%) than after treatment for 3 min (7%). Similar results were obtained after application of tin using the intracellular dialysis method with potential and ion concentration clamping. After preapplication of 10 microM SnCl2 for 1 min, acetylcholine-induced influx currents decreased by 41%, we compared differences in the effects induced by inorganic and organic tin compounds. Sn(CH3) induced a decrease in the amplitude of acetylcholine-induced currents in the same way as inorganic tin. The effect of Sn(CH3)2 was irreversible and stronger as the preapplication time increased. These results support the previous conclusion that agonist-activated channels are an important target for the actions of toxic metals. It is concluded that direct actions on neuron membranes represent an important component in the modulation of synaptic transmission and that this should be considered in studies of the mechanisms of toxicity of tin.

Acetylcholine↗

Glutathione modifies the toxicity of triethyltin and trimethyltin in C6 glioma cells.

It has been demonstrated that exposure to mercury or cadmium compounds causes alterations in the glutathione system in a model glial cell line, C6. Here we report that two organic tin compounds, triethyltin (TET) and trimethyltin (TMT), are also toxic to these cells with EC50 values for cell death of c. 0.02 microM and 0.8 microM respectively. Exposure for 24 h to either of these compounds at sub-toxic concentrations caused increases in the amount of reduced glutathione (GSH) per cell. Increases in glutathione-S-transferase enzyme activity were also demonstrated after TET or TMT exposure. This suggests that glutathione increases occur in glial cells after toxic insults below that required to cause cell death, possibly acting as a protective mechanism. To test whether GSH plays a role in organotin-induced cell death we manipulated GSH in the culture media or via intracellular GSH and looked at the effects on sensitivity to TET or TMT toxicity. Adding GSH to the culture media did not protect the cells. Depletion of intracellular GSH with buthionine-[S,R] sulphoximine did not alter cytotoxicity of TET or TMT. However, pre-treatment with (-)-2-oxo-4-thiazolidine carboxylic acid (OTC), which increases intracellular GSH levels, protected the cells against both compounds. The EC50 for TMT was increased from 0.77 to 1.8 microM, a 2.3-fold shift, whereas the EC50 for TET was increased > 20-fold, from 0.022 to 0.47 microM. One interpretation of these results is that GSH protects cells against the toxicity of organic tin compounds without reacting directly with them to any significant extent. Under conditions where GSH is depleted, additional protective mechanisms may be active.

Animals↗

[Biological activity of tin and immunity].

Tin generates a wide variety of biological activities deriving from its chemical character. In this article, the biological activities of tin compounds are reviewed with a focus on the connection with immunity. The table of contents is as follows: Introduction, 1. Inorganic Tin and Immunity, 2. Organic Tin and Immunity, 2.1. Immunotoxicity, 2.1.1. Immunosuppression, 2.1.2. Thymus atrophy, 2.1.3. Changes in the membrane surface antigens of T cells, 2.2. Antitumor activity, 2.3. Anti-inflammatory action, 2.4. Tolerance manifestation of thymus atrophy, 3. Cellular and Biochemical Aspects of the Activity Manifestation, 3.1. Intracellular distribution of organotins 3.2. Effects on structure and function of Golgi apparatus and endoplasmic reticulum, 3.3. Effects on physical properties of phospholipid membrane, 3.4. Suppressive effects on cell proliferation system, 3.5. Consideration, Conclusion. To sum up this article, tin compounds (especially organotin compounds) act mainly on cellular immune systems and the mechanism appears to be due to their hydrophobicity-dependent intracellular distribution and their action on the phospholipid metabolism including the inhibition of intracellular phospholipid transport between organelles through an impairment of the structure and functions of the Golgi apparatus and the endoplasmic reticulum (ER), and the consequent inhibition of the membrane-mediated signal transduction system leading to DNA synthesis via phospholipid turnover and Ca2+ mobilization.

Animals↗

Comparative study of the metabolism of triphenyltin in hamsters and rats after a single oral treatment with triphenyltin chloride.

Our previous work has shown that triphenyltin compound induces the diabetogenic effects, such as hyperglycemia and hypertriglyceridemia, on hamsters, but not on rats. In the present study, it is examined whether the species differences in the metabolic fate of triphenyltin exist for susceptibility between hamsters and rats. Triphenyltin chloride was orally dosed to hamsters and rats, and triphenyltin and its metabolites, mono- and diphenyltin, and inorganic tin, in liver, kidney, pancreas, brain, and blood were determined by gas chromatography periodically for 96 h after the treatment. Triphenyltin levels in the tissues of both species were almost maxima within 24 h after treatment. Although there were relatively high levels of triphenyltin in the tissues of hamsters dosed with triphenyltin chloride, compared with those in the rats, the proportion of metabolites to triphenyltin were lower than those in the rats. In particular, hamsters were more susceptible than rats to the pancreatic accumulations of triphenyltin and good correlation exists between the tin concentrations in the pancreas and the plasma glucose levels in triphenyltin-treated hamsters. These findings suggest that the dearylation of absorbed triphenyltin in hamsters is slower than that in rats and that triphenyltin-induced hyperglycemic action depends upon the amount of tin compounds absorbed into the pancreas. Furthermore, most of the tin compounds in the brains of both species were triphenyltin. This result shows that the metabolism of triphenyltin in the brains of both species was different from that in other tissues.

Administration, Oral↗