Tri-n-butyltin)oxide Research Articles

Sublethal effects of bis(tri-n-butyltin)oxide on Crassostrea gigas spat

Hatchery produced spat of the Pacific Oyster Crassostrea gigas were exposed to low levels of bis(tri-n-butyltin)oxide (TBTO) 0.2, 0.1, 0.05, 0.02, and 0.01 μg I −1. Their oxygen consumption, feeding rate, compensation for hypoxia, and growth rate was examined after exposure to TBTO and compared to their performance prior to this. In all cases highly significant relationships between TBTO concentration and the physiological variable in question were observed. Significant effects were found down to levels of 0.05 μg I −1 for oxygen consumption and feeding rate, to 0.02 μg I −1 for growth and to 0.01 μg I −1 for compensation for hypoxia. These levels are far lower than those reported for many UK sites and the results are discussed in relation to the possible environmental impact of the observed effects.

Toxicity of tri- n-butyl-tin to chinook salmon, Oncorhynchus tshawytscha, adapted to seawater

The median lethal concentrations (LC 50s) of tri- n-butyl-tin oxide (TBTO) to juvenile chinook salmon, Oncorhynchus tshawytscha, adapted to seawater were determined in a static renewal bioassay. LC 50s were 54, 20, and 1.5 μg TBTO/l after exposures for 6, 12, and 96 h, respectively. LC 50s decreased logarithmically with time for exposures between 12 and 96 h. Also determined were the average tri- n-butyl-tin (TBT) concentrations in liver, brain, and muscle tissues of salmon that died during the bioassay: 7.0, 3.5, and 0.52 μg TBT/g wet weight tissue, respectively. TBT concentrations in liver, brain, and muscle tissues of salmon that survived until day 4 of the bioassay were 4300, 1300, and 200 times exposure concentrations, respectively. Our results implicate TBT exposure as the cause of death of chinook salmon exposed to TBT-treated marine net pens at one aquaculture facility.

Synthesis of tri‐n‐butyltin taurocholate, taurodeoxycholate and glycocholate

AbstractThe bile acids, taurocholic, taurodeoxycholic and glycocholic acid, were reacted with bis(tri‐n‐butyltin) oxide (TBTO) to form 1:1 derivatives. The water of reaction was removed with 2, 2‐dimethoxypropane or by azeotropic distillation with benzene. The compounds were characterized by 13C and 119Sn NMR, IR, elemental analysis, molecular weight determination, DTA, TGA, and conductance measurements. The data indicated that tri‐n‐butyltin glycocholate forms a covalent ester, tin being tetracoordinated. The taurocholic and taurodeoxycholic acid derivatives contain one molecule of coordinated water. They partially dissociate in polar solvents. The taurocholic and glycocholic acid derivatives were tested in vitro as anticancer agents and exhibited ED50 in the 0.2–0.4 ppm (mg kg−1) range against KB epidermoid tumor and P‐388 leukemia using NCI protocols.

Eco-biotoxicology of chemical pollutants.

The major toxicological problem today is to establish a useful method to cope with a low level and prolonged pollution. The toxicological method under such circumstances should include ecotoxicology and biotoxicology as well as classical toxicology, and is named as eco-biotoxicology. This method includes not only investigations on kinetics and levels of chemicals in the environment, human reaction and adaptation to chemicals or biophysiological and pathophysiological clarification of the effects, but also the establishment of countermeasures to prevent health hazards from chemicals, including biological monitoring and development of exposure parameters. The followings were the results recently obtained in our laboratory in support of the object of eco-biotoxicology. 1. Two low-molecular-weight chromium binding substances were purified from the liver of dogs. Chromium bound to them showed a lower toxicity and higher rates of urinary excretion than inorganic chromium compounds. A low-molecular-weight nickel binding substance was also purified from the liver of rats. Nickel bound to it showed a lower cytotoxity, but a higher malignant transformation induction of cultured cells than inorganic nickel compounds. These results indicate that chemical form of metals and binding protein in the body are important factors in their toxicity. 2. Triphenyl and tributyltins showed to inhibit insulin release from pancreas, collagen-induced aggregation of platelets, O2-production and chemotaxis of leukocytes, histamine release from mast cells, etc. A common mechanism seemed to be an inhibition of the stimulus-response coupling in the cell membrane. 3. Carcinogenic heterocyclic amines were measured in food and biological materials by a newly developed method. Their levels in plasma of uremic patients were higher than normal subjects and decreased by the treatment with hemodialysis. 4. Safety evaluation of bis (tri-n-butyltin) oxide (TBTO) in fishes was carried out according to a toxicological approach. Acceptable daily intake of TBTO in food was estimated to be 1.6 μg/kg/d.

Results of in Vivo and in Vitro Studies for Assessing Prenatal Toxicity

Examples of a combined approach using in vivo as well as in vitro methods for the assessment of prenatal toxicity are presented. The topics discussed include the analysis of the possible embryotoxic potential of valproic acid (VPA), female sex hormones, bis(tri-n-butyltin) oxide (TBTO), and acyclovir and the problem of supplementing in vitro systems with drug-metabolizing activity.

Results of in vivo and in vitro studies for assessing prenatal toxicity.

Examples of a combined approach using in vivo as well as in vitro methods for the assessment of prenatal toxicity are presented. The topics discussed include the analysis of the possible embryotoxic potential of valproic acid (VPA), female sex hormones, bis(tri-n-butyltin) oxide (TBTO), and acyclovir and the problem of supplementing in vitro systems with drug-metabolizing activity.

Lugworm (Arenicola cristata) larvae in toxicity tests: Survival and development when exposed to organotins

AbstractA test is described for the exposure of the lugworm Arenicola cristata to toxicants. Embryos of A. cristata were exposed for 96 and 168 h to bis(triphenyltin) oxide (TPTO), triphenyltin chloride (TPTC), bis(tri‐n‐butyltin) oxide (TBTO) and tributyltin acetate (TBTA). The toxic effects were death and abnormal development of larvae. Concentrations that killed all animals were 4 μg L−1 (96 h) and 2 μg L−1 (168 h) TPTO; 10 μg L−1 (96 h) and 5 μg L−1 (168 h) TPTC; 4μg L−1 (96 h) TBTO; and 10 μg L−1 (96 h) and 5 μg L−1 (168 h) TBTA. Abnormal morphology was caused by 0.75 μg L−1 TPTO, 1 μg L−1 TPTC and 5 μg L−1 TBTA. Several developmental stages, from embryo to swimming larva, were exposed to TPTO. The most sensitive stages were early trochophore and early settled stage. The range of concentrations between 100% survival and 100% mortality was narrow in all tests. The exposure system is simple and detects teratogenicity.

In vitro studies on the embryotoxic potential of (bis[tri-n-butyltin])oxide in a limb bud organ culture system.

(Bis[tri-n-butyltin])oxide (TBTO) was studied for its toxic potential on prenatal development. The effect of this substance on limb differentiation (mouse embryos) in organ culture was evaluated. In the organ culture system using mouse limb buds, TBTO interfered with morphogenetic differentiation at doses as low as 0.03 microgram/ml (5 X 10(-8)M). This is one of the lowest concentrations of a substance ever found to be active in this in vitro system. The in vitro studies suggest a high embryotoxic potential of TBTO. The low embryotoxicity found in the in vivo studies may be due to limited exposure of the embryos by the original unmetabolized substance.

Comparison of avoidance responses of an estuarine fish, Fundulus heteroclitus, and crustacean, Palaemonetes pugio, to bis (tri-n-butyltin) oxide

Avoidance responses of an estuarine fish, mummichog (Fundulus heteroclitus), and crustacean, grass shrimp (Palaemonetes pugio) to the antifoulant his (tri-n-butyltin) oxide (TBTO) were evaluated. Four out of six groups of mummichogs tested at 1.0 μg total organic Sn L−1 showed avoidance. Total organic Sn concentrations of ≥ 3.7 μg L−1 were avoided by this fish species in all cases. Higher concentrations of total organic Sn did not result in greater avoidance responses. Grass shrimp did not avoid total organic Sn concentrations between 2.3 and 30.0 μg L−1. Response data at 2.3 and 30 μg L−1 were similar. Mummichogs and grass shrimp differed greatly in their abilities to avoid potentially adverse concentrations of total organic Sn. Since mummichogs are major predators of grass shrimp, these behavioral responses may have important implications for tidal marsh ecosystems.

Toxicity of bis(tri- n-butyltin)oxide in the rat : II. Suppression of thymus-dependent immune responses and of parameters of nonspecific resistance after short-term exposure

To evaluate the functional significance of bis(tri- n-butyltin)oxide (TBTO)-induced thymus atrophy, lymphocyte depletion in spleen and lymph nodes, lymphopenia, and increased serum IgM and decreased IgG concentrations, in vivo and in vitro function studies were performed for specific and nonspecific resistance. Weaned male rats were fed diets containing 0, 20, or 80 mg TBTO/kg for a least 6 weeks. Regarding the thymus-dependent immunity, delayed-type hypersensitivity reactions to ovalbumin as well as tuberculin were significantly depressed at both dietary concentrations. Resistance to the nematode Trichinella spiralis was significantly suppressed as shown by a retarded expulsion of adult worms from the small intestine, increased counts of muscle larvae, reduced inflammatory reaction in parasitized musculature, and suppressed serum IgE titers. Also the secondary mercaptoethanol-resistant (presumably IgG) hemagglutinating antibody titer to sheep red blood cells was significantly reduced, while no significant alterations were found in IgM and IgG titers to T. spiralis, ovalbumin, and tetanus toxoid. TBTO exposure reduced the response of thymocytes in both treatment groups and of spleen cells in the 80-mg/kg group upon stimulation with T-cell mitogens and increased the response of spleen cells to B-cell mitogens. When calculated per whole spleen, the response to T-cell mitogens was strongly impaired but unaltered by B-cell mitogens. This difference can be explained by a relative increase of splenic B cells as a result of reduced numbers of T cells, as shown by cell surface marker analysis using monoclonal antibodies. Reduced splenic T-cell numbers appeared equally due to a decreased number of T helper and to T suppressor cells. From these data and from results of a time-sequence study in which effects of TBTO on cell count and cell viability of thymus, spleen, and bone marrow were investigated, it is concluded that TBTO-induced immunodeficiency was primarily due to its direct toxic action on thymocytes. When cultured in vitro in the presence of TBTO, viability of thymus and bone marrow cells was equally reduced, while after in vivo treatment viability of bone marrow cells was unaffected. Thus, the in vitro situation does not mimic the in vivo one. Concerning the nonspecific resistance. TBTO reduced macrophage function as shown by impaired splenic clearance of Listeria monocytogenes bacteria. From in vitro studies it is concluded that impaired in vivo splenic clearance was due to a reduction in both the number of adherent cells in the spleen and bacterial digestion on a cell for cell basis. The effect of TBTO on natural cell-mediated cytotoxicity was investigated in a 51Cr-release assay with YAC lymphoma target cells. In this test, the activity of natural killer (NK) cells in the spleen was significantly suppressed in the 80 mg/kg group while NK cell activity of peritoneal cells was unaltered. However, the activity of adherent peritoneal cells (cytotoxic macrophages) was significantly reduced in the 20 and 80 mg/kg groups. Finally, TBTO did not render rats more susceptible to the lethal effects of endotoxin. From the results it is concluded that low-dose feeding of TBTO suppresses thymus-dependent immune responses as well as parameters of the nonspecific resistance.

Toxicity of bis(tri- n-butyltin)oxide in the rat : I. Short-term effects on general parameters and on the endocrine and lymphoid systems

Male and female Wistar rats were fed bis(tri- n-butyltin)oxide (TBTO) at 0, 5, 20, 80, or 320 mg/kg diet for 4 weeks. Clinical signs and decreases in feed and water consumption were observed in the 80 and 320 mg/kg groups. The serum transferase activities (alanine amino transferase and aspartate amino transferase were increased at 20 (males only), 80, and 320 mg/kg. The serum glucose and liver glycogen concentrations were lowered in the 320 mg/kg group. At 80 and 320 mg/kg the serum IgG level was reduced and IgM level was increased. Compared to controls the mean relative weight of the thymus was decreased at 20 (males), 80, and 320 mg/kg. In the groups receiving 80 or 320 mg/kg microcytic anemia was found. The white blood cell counts were decreased, due to the reduction in the number of lymphocytes in the 80 (males) and 320 mg/kg groups. The concentration of neutrophilic granulocytes was increased in the highest dose group. Histopathologic effects included a dose-related lymphocyte depletion of thymic cortex and of T lymphocytes in spleen and mesenteric lymph nodes. In the spleen also depletion of iron stores was found, and in the medullary sinuses of mesenteric lymph nodes, rosettes of erythrocytes were found around mononuclear cells; the occurrence of rosettes increased with dose from 5 to 80 mg/kg, and appeared to be the most sensitive parameter. A low incidence of areas of liver necrosis with inflammatory reaction and bile duct hyperplasia was found in the 320 mg/kg group. A viral or bacterial etiology could not be demonstrated for these liver lesions, but they appeared associated with TBTO-induced ulcerative inflammation of the common bile duct as shown in an additional study. In 6-week studies exposure of male weanlings to the 0, 20, and 80 mg/kg diets, the serum insulin concentration in the treated groups was decreased, although the response to glucose challenge was unaffected. The serum thyroxin and thyrotropin (TSH) concentrations were reduced, whereas the luteinizing hormone (LH) concentration was increased in the 80 mg/kg group. The concentrations of follicle-stimulating hormone (FSH) and corticosterone were not changed. The release of LH and FSH was enhanced in the 80 mg/kg group and a tendency toward reduced release was found for TSH. Using immunocytochemistry a dose-related reduction was found in the number and staining intensity of TSH-producing cells in the pituitary, correlating with histopathologically decreased activity of the thyroid. On the other hand, a dose-related increase was seen in the number of cells staining strongly for luteinizing hormone. No effect was observed on FSH, growth hormone and adrenocorticotropin-producing cells, nor on the pancreatic insulin and glucagon-producing cells. In tissues, a dose-dependent increase of the total tin concentration was found, with the highest residues in liver and kidney. Residues in adipose tissue and brain were 5–10 times lower. From these studies it is concluded that low-dose dietary TBTO exposure induces atrophy of the thymus and peripheral lymphoid organs, depletion of splenic iron stores, erythrocyte rosettes in mesenteric lymph nodes, decreased activity of the pituitary-thyroid axis, and increased LH immunoreactivity and secretion.

Quantitative measurement of tributyltin oxide in sea water by differential pulse anodic stripping voltammetry

Bis(tri-n-butyltin) oxide (TBTO) was measured directly in sea water at μg l −1 levels at a hanging drop mercury electrode (HDME) and at a mercury-film rotating-disc glassy carbon electrode (MFE) by differential pulse anodic stripping voltammetry. The HDME responded to TBTO additions in sea water purged either with nitrogen (pH 8.2) or carbon dioxide (pH 4.8) with two distinct stripping peaks. The MFE produced stripping peaks for TBTO at pH 8.2 and no response at pH 4.8. Peak potentials and peak heights varied depending upon the history of the water sample, suggesting an influence by dissolved organic materials. The limit of detection for TBTO in sea water on the HMDE was approximately 5 μg l −1. The HMDE responded to additions of inorganic tin in sea water at both pH 4.8 and 8.2, whereas the MFE did not respond at either pH.

Predator—prey (Vole—Cricket) interactions: The effects of wood preservatives

AbstractThe rate of loss of crickets (Acheta domestica L.), with and without the presence of an adventitious predator, the gray‐tailed vole (Microtus canicaudus), has been studied in Terrestrial Microcosm Chambers (TMC‐II) treated with pine stakes impregnated with creosote, bis(tri‐n‐butyltin)oxide (TBTO), dieldrin (HEOD), pentachlorophenol (PCP) or a toluene solvent control. The first‐order rate of cricket loss (‐k) increased only for HEOD, to a maximum at 33 d post‐treatment, with oscillations of about a 16‐d period. This result infers a “cricket‐available” compartment of HEOD and/or metabolites with concentrations that must be greater than those measured in air, soil, water or plants and other biota. When a gravid vole was subsequently added to each TMC, the predation index (Δkv) increased for control and PCP, but declined markedly for creosote and HEOD, and to a lesser extent for TBTO.

Effects of bis (tri-n-butyltin) oxide on endocrine and lymphoid organs of male rats.

A total of 160 Sprague-Dawley rats averaging in body weight, were used for histopathological and biochemical studies of toxicity of bis (tri-n-butyltin) oxide (TBTO). Short-term effects and long-term effects were examined. LD50 of TBTO by gastric tubing was 197 mg/kg. The effects of a single dose of TBTO were transient, and rapid recovery followed. TBTO at a a single dose of 100 mg/kg, or a total dose of 390 to 780 mg/kg in 13 weeks, or 780 to 1,560 mg/kg in 26 weeks, caused adrenal hypertrophy, flattening of the thyroid epithelium and atrophy of the thymus and lymph nodes. A single or repeated administration induced swelling and vacuolation of aldehyde-fuchsin-positive cells in the adenohypophysis. The immunohistochemical stainability of the cytoplasm of ACTH-cells was markedly depressed 24 hours after TBTO treatment, and that of the cytoplasm of TSH-cells was enhanced. Analogous an inverse relationship was also manifested in the hormonal levels of serum: levels of cortisol were elevated, while those of T-4 and TSH were depressed.

A modified phenylfluorone method for determining organotin compounds in the ppb and sub-ppb range.

The phenylfluorone method for tin analysis has been modified to be specific for organotin samples in the ppb and sub-ppb range (4-.1 micrograms of tin). Two extractions of an aqueous solution containing bis (tri-n-butyltin) oxide (TBTO) and tin sulfate yield results which are quantitative for TBTO without interference from the tin sulfate. The extracts are wet oxidized with hydrogen peroxide and sulfuric acid. The tin is determined from its lambda max near 530 nm through its complex with 2,6,7-trihydroxy-9-phenylisoxanthane-3-one (phenylfluorone) in the presence of cetyltrimethylammonium bromide. A Beer Lambert plot is obtained in the range of 0.1 to 7.0 micrograms of tin/sample with slope of 0.0344 with a correlation coefficient of greater than 0.990. The method has been successfully used to analyze over 400 environmental samples.

Electrochemical behaviour of organotin compounds Part I. Application to the determination of trialkyl- and triaryltin derivatives

The electrochemical behaviour of triphenyltin and bis(tri-n-butyltin) oxide (TBTO) in 50% (v/v) ethanol solution has been investigated by various electrochemical techniques including d.c. polarography, cyclic voltammetry and controlled potential coulometry. TBTO undergoes slow hydrolysis producing tributyltin hydroxide. The first electrochemical step involves reduction of tributyltin hydroxide forming a radical which is strongly adsorbed onto the DME giving rise to an adsorption prewave. The radical undergoes further reduction in the second step along with the unhydrolysed TBTO molecules. The products have been found to be adsorbed at the electrode surface. A mechanism of reduction is proposed and a polarographic method has been developed for determining triphenyltin and TBTO down to submicrogram level. The method has been used for determining Fentin residue in formulation samples.

Electrochemical behaviour of organotin compounds: Part I. Application to the determination of trialkyl- and triaryltin derivatives

The electrochemical behaviour of triphenyltin and bis(tri-n-butyltin) oxide (TBTO) in 50% (v/v) ethanol solution has been investigated by various electrochemical techniques including d.c. polarography, cyclic voltammetry and controlled potential coulometry. TBTO undergoes slow hydrolysis producing tributyltin hydroxide. The first electrochemical step involves reduction of tributyltin hydroxide forming a radical which is strongly adsorbed onto the DME giving rise to an adsorption prewave. The radical undergoes further reduction in the second step along with the unhydrolysed TBTO molecules. The products have been found to be adsorbed at the electrode surface. A mechanism of reduction is proposed and a polarographic method has been developed for determining triphenyltin and TBTO down to submicrogram level. The method has been used for determining Fentin residue in formulation samples.

2031. From head to foot—in reverse: Acheson, E. D., Cowdell, R. H. & Jolles, B. (1970). Nasal cancer in the Northamptonshire boot and shoe industry. Br. med. J.1, 385

The electrochemical behaviour of triphenyltin and bis(tri-n-butyltin) oxide (TBTO) in 50% (v/v) ethanol solution has been investigated by various electrochemical techniques including d.c. polarography, cyclic voltammetry and controlled potential coulometry. TBTO undergoes slow hydrolysis producing tributyltin hydroxide. The first electrochemical step involves reduction of tributyltin hydroxide forming a radical which is strongly adsorbed onto the DME giving rise to an adsorption prewave. The radical undergoes further reduction in the second step along with the unhydrolysed TBTO molecules. The products have been found to be adsorbed at the electrode surface. A mechanism of reduction is proposed and a polarographic method has been developed for determining triphenyltin and TBTO down to submicrogram level. The method has been used for determining Fentin residue in formulation samples.