Evaluation of malnutrition as a cause of tributyltin-induced pregnancy failure in rats.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Trialkyltin Compounds”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Dietary TBTO exposure to the Japanese quail: relation between exposure period and appearance of reproductive effects.
Explore the source record for details and available documents.
Animals↗
Toxicity of cadmium and mercury to horseshoe crab (Limulus polyphemus) embryos and larvae.
Explore the source record for details and available documents.
Animals↗
Effect of tributyltin on the N-methyl-D-aspartate (NMDA) receptors in the mouse brain.
The purpose of this study was to determine the effect of tributyltin chloride (TBTCI) on the NMDA receptor by in vitro and in vivo experiments. In the first in vitro experiment, the binding of [3H]MK-801 and of [3H]-CGP39653 were studied in membrane preparations from the cerebral cortex of intact mice to obtain control values. Saturation experiments for [3H]MK-801 and [3H]CGP39653 revealed single binding sites with Kd values of 10.27 and 37.8 nM, and receptor densities of 1.75 and 2.20 pmol/mg of protein, respectively. In the second in vitro experiment, displacement studies were carried out with TBTCI over a concentration range of 0.1 microM to 2 mM. TBTCI inhibited [3H]MK-801 binding but did not affect [3H]CGP39653 binding. In the in vivo experiments, the mice received 1-125 ppm TBTCI in the diet ad libitum for 30 days. Ligand binding to cortical membrane preparations from each mouse was measured by a one-concentration point (2 nM) binding assay. [3H]MK-801 binding was significantly lowered (P < 0.05) in the 5 and 125 ppm TBTCl-exposed animals compared with the controls. [3H]CGP39653 binding was also significantly lowered (P<0.05) in the 1 and 125 ppm TBTCI-exposed animals compared with the controls. These results suggest that the NMDA receptors in the mouse brain are sensitive to relatively low level exposure to TBTCl.
2-Amino-5-phosphonovalerate↗
Effects of interleukins 2 and 12 on the levels of granzyme B and perforin and their mRNAs in tributyltin-exposed human natural killer cells.
Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells and antibody coated cells. Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as: slime control in paper mills, disinfection of circulating industrial cooling waters, anti-fouling agents, and the preservation of wood. TBT can be found in edible items such as fish. A previous study showed that a 1 h exposure of NK cells to TBT caused persistent inhibition of NK-cell ability to destroy tumor cells in the 24 and 48 h periods following exposure and that this loss of function could be significantly prevented and/or reversed if the NK-stimulatory interleukins (IL) 2 or 12 were present during the 24 and 48 h periods. We had also shown that TBT exposure was able to significantly decrease the protein and mRNA levels of the cytotoxic proteins, granzyme B and perforin, and the phosphorylation of cAMP-response-element-binding protein (CREB) under these conditions. In this study we address the effects of IL-2 and IL-12 on the TBT-induced decreases in NK-cell levels of the cytotoxic proteins, their mRNAs, and CREB phosphorylation. IL-2 appeared to prevent/reverse TBT-induced declines in perforin protein levels and the mRNA for perforin seen in the 24 h period following a 1 h exposure to 300 nM TBT. However, the TBT-induced decreases in the levels of perforin and perforin mRNA seen in the 48 h period following a 1 h exposure to TBT were not statistically significantly prevented/reversed by IL-2. Additionally, the TBT-induced decreases in granzyme B, granzyme B mRNA, and CREB phosphorylation were not statistically significantly reversed by either IL-2 or IL-12 after 24 or 48 h.
Adult↗
Pattern of MAP kinases p44/42 and JNK activation by non-lethal doses of tributyltin in human natural killer cells.
Tributyltin (TBT) has been shown to disrupt the ability of natural killer (NK) cells to destroy tumor targets in vitro even at exposures of 25 nM for 24 h, but cell viability was not significantly impacted. Thus, evaluation of intracellular molecular events that regulate cell viability in TBT exposed NK cells are of interest. It has been suggested that activation of the mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), may promote apoptosis while activation of the MAPK p44/42 may be crucial in mediating anti-apoptotic stimuli. However, it is well established that increases in pro-apoptotic BCL-2 family members, such as Bax, results in cell death. We have set out to study the effects of a range of TBT concentrations on the MAPKs, JNK and p44/42. Additionally, we examined the effects of TBT on the levels of pro-apoptotic proteins Bax and p53 as well as anti-apoptotic protein Bcl-2. The results show that 300-25 nM TBT activated JNK within 10 min. MAPK p44/42 was also activated by 300-50 nM TBT within 10 min. These data show that while 300-200 nM TBT activates p44/42 significantly more than JNK, the pattern of 100-25 nM TBT activation of these MAPKs may be similar. TBT exposure alters neither pro-apoptotic proteins Bax and p53 nor anti-apoptotic protein Bcl-2 levels at any exposure studied. The results suggest that exposure to TBT activated the anti-apoptotic regulatory p44/42 pathway to a greater extent than the pro-apoptotic JNK pathway, which may explain to some extent how NK cell viability is maintained.
Adult↗
Suppression of decidual cell response induced by tributyltin chloride in pseudopregnant rats: a cause of early embryonic loss.
In our previous studies, tributyltin chloride (TBTCl) at doses of 16.3 mg/kg and above caused implantation failure (preimplantation embryonic loss) and postimplantation embryonic loss in rats following administration on gestational day (GD) 0 through GD 3 and GD 4 through GD 7, respectively. This study was designed to assess the effects of TBTCl on uterine function as a cause of early embryonic loss in pseudopregnant rats. TBTCl was given orally to pseudopregnant rats at doses of 4.1, 8.1, 16.3 and 32.5 mg/kg on pseudopregnant day (PPD) 0 to PPD 3 or 8.1, 16.3, 32.5 and 65.1 mg/kg on PPD 4 to PPD 7. The decidual cell response was induced by bilateral scratch trauma on PPD 4. The uterine weight on PPD 9 served as an index of uterine decidualization. Uterine weight and serum progesterone levels on PPD 9 were significantly decreased after administration of TBTCl at doses of 16.3 mg/kg and above on PPD 0 to PPD 3 or PPD 4 to PPD 7. Administration of TBTCl at doses of 8.1 mg/kg and above on PPD 0 to 3 also significantly decreased serum progesterone levels on PPD 4. TBTCl had no effect on ovarian weight and number of corpora lutea. It can be concluded that TBTCl suppresses the uterine decidual cell response and decreases progesterone levels, and these effects are responsible for early embryonic loss due to TBTCl exposure.
Animals↗
Sweat gland toxicity induced by bis (tributyltin) oxide: an ultrastructural and X-ray microanalysis study.
Acute toxicity of bis (tributyltin) oxide in the sweat glands in the rat footpad was investigated by electron microscopy and an energy-dispersive X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg bis (tributyltin) oxide. After 6-8 h, swelling of mitochondria appeared in the secretory cells of the sweat glands. After 12 h, the secretory cells began to show intracytoplasmic edema. After 16-20 h, secretory cells in some sweat glands showed marked hydropic degeneration with swollen cytoplasm. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria of the affected secretory cells. Mitochondria dysfunction due to the toxic effects of bis (tributyltin) oxide induced changes in the secretory cells of rat sweat glands. After 24-48 h, the secretory portion of the sweat glands contained three types of cells: degenerating dark cells, regenerating cells carrying injured mitochondria, and light cells which were morphologically very similar to the cells in the transitional portion of the sweat gland. These light cells appeared to differentiate into active secretory cells after settling down in the secretory portion. Based on these observations, we concluded that the cells in the transitional portion could play an important role at least as reserve cells against secretory cell toxicity. In association with the regenerating process of the damaged secretory portions, increased mitotic activities were seen in different areas of all the dermal sweat ducts. The above-mentioned morphological observations for cell damage and subsequent regeneration and renewal ofsecretory cells in sweat gland intoxication have not been reported so far.
Animals↗
Selective preconcentration and determination of tributyltin in fresh water by electrothermal atomic absorption spectrometry.
A rapid and simple method for separation and determination of tributyltin (TBT) in mineral and tap water is described. The procedure is based on the selective retention of TBT by a chelating resin, Amberlite XAD-2 impregnated with tropolone. The addition of 0.8% sulfuric acid to the water sample leads to the retention of TBT by the resin while monobutyltin (MBT), dibutyltin (DBT) and inorganic tin remain in solution. TBT is eluted with methyl isobutyl ketone (MIBK) obtaining a preconcentration factor of 80. Tin concentration is determined by ETAAS using zirconium coated tubes. Multi-injection and hot injection techniques are used in order to enhance the sensitivity of the method. A detection limit of 14.4 ng L(-1) is achieved with recoveries near to 100%. The procedure has been successfully applied to TBT determination in various fresh water samples.
Acids↗
Effects of hyperthermia on intracellular chloride.
Hyperthermia induces transient changes in [Na+]i and [K+]i in mammalian cells. Since Cl- flux is coupled with Na+ and K+ in several processes, including cell volume control, we have measured the effects of heat on [Cl-]i using the chloride indicator, MQAE, with flow cytometry. The mean basal level of [Cl-]i in Chinese hamster ovary cells was 12 mM. Cells heated at 42.0 degrees or 45.0 degrees C for 30 min had about a 2.5-fold increase in [Cl-]i above unheated control values when measured immediately after heating. There was about a 3-fold decrease in [Na+]i under the same conditions, as measured by Sodium Green. The magnitude of the increase in [Cl-]i depended upon time and temperature. The [Cl-]i recovered in a time-dependent fashion to control values by 30 min after heating. When cells were heated at 45.0 degrees C for 30 min in the presence of 1.5 mM furosemide, the heat-induced [Cl-]i increase was completely blocked. Since furosemide inhibits the Na+/K+/2Cl- cotransporter, Cl- channels, and even Cl-HCO3 exchange, these ion transporters may be involved in the heat-induced increase in [Cl-]i.
Animals↗
Effects of sublethal levels of tributyltin chloride in a new toxicity test organism: the Chinese rare minnow ( Gobiocypris rarus).
A newly developed toxicity test organism, the Chinese rare minnow ( Gobiocypris rarus), which has similar merits to some common experimental fishes and could become a standardized test species for China, was used in a short-term study with emphasis on accumulation in fish muscles and cytological effects of sublethal concentrations of tri-n-butyltin chloride (TBT). The 1-year-old fish were exposed for 1 or 2 weeks to a concentration range of 50 to 5,000 ng TBT/L in static systems. Hepatosomatic Index (HSI) and Gonad Somatic Index (GSI) sensitively showed the adverse effects of TBT to the fish. Compared with the nominal TBT concentrations in water phase, 459-(5,000 ng TBT/L, 1 week) to 4,065- (50 ng TBT/L, 2 weeks)-fold higher concentrations of butyltin species were detected in the corresponding exposure fish muscle. Contaminations of TBT in muscle tissue increased with both the exposure levels and exposure time. The cellular pathological effects in the liver were studied. These included vacuoles with increasing number and size, swelling of mitochondria, abnormal nuclei, and decreases of rough endoplasmic reticulum cisternaes. The results confirmed that the Chinese rare minnow ( G. rarus) could be utilized as a useful species to evaluate water toxicity in the laboratory.
Animals↗
Accumulation of tributyltin in olive flounder, Paralichthys olivaceus: its effect on hepatic cytochrome P450.
Accumulation of tributyltin (TBT) was determined in liver of olive flounder exposed to TBT (3.65, 36.5, 365, 3,650, and 7,300 ng Sn/L) for 10 or 30 days, followed by 60 days depuration. Effect of TBT on hepatic cytochrome P450 content was also measured in liver of olive flounder. TBT was highly accumulated in liver of fish during the 10- to 30-day exposures, and hepatic cytochrome P450 content decreased with increasing TBT concentration. Hepatic cytochrome P450 contents were affected in olive flounder exposed to even environmentally relevant TBT concentrations, such as 3.65 ng Sn/L. In addition, the liver TBT levels demonstrated strong negative correlation to the hepatic cytochrome P450 content. The effects started to appear from 20 ng Sn/g dry weight of TBT in liver. Tributyltin concentrations and hepatic cytochrome P450 were also determined in feral fine-spotted flounder. The relationship between other organic pollutants known as cytochrome P450 inducers (e.g., polychlorinated biphenyls) as well as TBT and hepatic cytochrome P450 in the feral fish implied that TBT even at ppt level could impose antagonistic effects on hepatic cytochrome P450 induction.
Animals↗
Contaminants of concern in Dutch marine harbor sediments.
The status of the contamination of Dutch marine harbor sediments was reevaluated after a period in which emissions from point sources had been greatly reduced. Data on sediment chemistry from 1999 and 2000 were assessed against screening levels (SLs) selected from available sediment quality guidelines and representing a low probability of adverse biological effects. This yielded a ranking of the environmental hazard of 22 contaminants. Most of the sediments were silty material; every year 15 to 25 million m3 of such material is dredged from Dutch harbors. Some 34% of the volume exceeded one or more SLs. The contaminants of concern were tributyltin (TBT), mineral oil (petroleum hydrocarbons), polychlorinated biphenyls (PCBs), and mercury. The PCB and mercury contamination is the legacy of historic inputs; the TBT and mineral oil contamination is related to present-day shipping activity. Concentrations of trace metals, rare earth elements, organochlorine pesticides, and polycyclic aromatic hydrocarbons (PAHs) were low and apparently of minor environmental concern. It is concluded that the risk assessment would be improved by laboratory testing of adverse biological effects.
Environmental Monitoring↗
Effects of three antifouling agents on algal communities and algal reproduction: mixture toxicity studies with TBT, Irgarol, and Sea-Nine.
The toxicity of three antifoulants (Sea-Nine, Irgarol, and TBT) was determined individually and in mixtures in two tests with microalgae. Effects on periphyton community photosynthesis and reproduction of the unicellular green algae Scenedesmus vacuolatus were investigated. The tested antifoulants were highly toxic in both tests. Observed mixture toxicities were compared with predictions derived from two concepts: Independent Action (IA), assumed to be more relevant for the tested mixtures that were composed of dissimilarly acting substances, and Concentration Addition (CA), regarded as a reasonable worst-case approach in predictive mixture hazard assessment. Despite the corresponding mechanistic basis, IA failed to provide accurate predictions of the observed mixture toxicities. Results show the same pattern in both assays. Mixture effects at high concentrations were slightly overestimated and effects at low concentrations were slightly underestimated. Maximum observed deviations between observed and IA-predicted concentrations amount to a factor of 4. The suggested worst-case approach using CA was protective only in effect regions above 20%. Nevertheless, the application of any concept that accounts for possible mixture effects is more realistic than the present chemical-by-chemical assessment.
Dose-Response Relationship, Drug↗
The effects of tributyltin (TBT) and 3,3',4,4',5-pentachlorobiphenyl (PCB-126) mixtures on antibody responses and phagocyte oxidative burst activity in channel catfish, Ictalurus punctatus.
The organotin tributyltin (TBT) is an antifouling biocide used in marine paints and is a common pollutant in harbor estuaries. We previously demonstrated that the immune system of channel catfish, Ictalurus punctatus, is a sensitive target organ of TBT. Exposure strongly suppresses humoral immune responses. Harbor estuaries often contain polychlorinated biphenyls (PCBs) due to their ubuquitous distribution. The coplanar congener 3,3',4,4'5'-polychlorinated biphenyl (PCB-126) is also immunotoxic to channel catfish, but it suppresses only the innate immune responses and only at high doses. In this study we exposed channel catfish to TBT, PCB-126, or both in mixtures, with canola oil (CO) serving as the carrier control. Antibody responses to Vibrio anguillarum and phagocyte oxidative burst activity were measured after (1) a single dose of 0.01 or 1 mg/kg of each or both in combination, and (2) six injections of 1.7 or 170 microg/kg of each (or in combination) given every 3 days over a 16-day period to yield a cumulative dose of 0.01 or 1 mg/kg, respectively. We measured antibody responses to V. anguillarum 21 days after immunization and oxidative burst activities 14 and 21 days after the final treatment. The highest dose of TBT suppressed antibody responses after a single exposure. The high dose of PCB-126 also suppressed antibody responses. The addition of PCB-126 to TBT doses did not alter the antibody responses beyond the effects of TBT alone. In the repeated exposure group, only the high dose of TBT suppressed antibody responses. In animals exposed to mixtures, high levels of PCB-126 enhanced suppression associated with low levels of TBT, whereas PCB-126 protected against suppression associated with high levels of TBT. Single exposures to TBT or PCB-126 suppressed phagocyte oxidative burst activity. In animals exposed to mixtures, as a single exposure, the addition of a low dose PCB-126 protected against low dose TBT-related oxidative burst activity suppression. In the repeated exposure groups TBT suppressed oxidative burst activity, but only at the highest dose on day 21, while high doses of PCB-126 suppressed activity on day 14. Furthermore, low levels of PCB-126 reversed the suppressed oxidative burst activity associated with high levels of TBT on day 21. Overall, this study demonstrates moderate additivity in terms of the immunotoxicity of TBT and PCB-126 mixtures using these two endpoints of immune function in the channel catfish model.
Animals↗
Effect of the day of administration on the developmental toxicity of tributyltin chloride in rats.
The objective of this study was to determine the susceptible day for the teratogenicity of tributyltin chloride (TBTCI) by a single administration on one of the days during organogenesis. Pregnant rats were given a single dose of TBTCI by gastric intubation at 100 mg/kg on either day 7, day 8, or day 9 and at 200 mg/kg on either day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, or day 15 of pregnancy. The maternal body weight gain in the period immediately following administration in all TBTCI-treated groups was significantly decreased. A significant increase in the incidence of postimplantation loss was found after administration of TBTCI on day 7, day 8, and day 9 at 100 and 200 mg/kg and on day 10 and day 11 at 200 mg/kg. A significantly increased incidence of fetuses with external malformations was detected when TBTCI was given on day 8 at 100 and 200 mg/kg and on day 11, day 12, day 13, and day 14 at 200 mg/kg, and the most pronounced effect occurred after administration on day 13 of pregnancy. Cleft palate was observed exclusively after administration during late organogenesis. It could be concluded that the manifestation and susceptibility of the developmental toxicity of TBTCI vary with the developmental stages at the time of administration and that TBTCI has the biphasic sensitivity to teratogenicity on day 8 and days 11-14 of pregnancy.
Abnormalities, Drug-Induced↗
Alteration of [14C]-testosterone metabolism after chronic exposure of Daphnia magna to tributyltin.
Tributyltin (TBT) is a marine biocide that has been shown to alter the activity of cytochrome P450 monooxygenases and elicit toxicity indicative of androgenization in some species. The present study was conducted to determine whether TBT altered P450-, reductase-, and transferase-mediated testosterone metabolic processes in Daphnia magna at sublethal exposure concentrations. Two generations of daphnids were continuously exposed for 21 days to nominal TBT concentrations ranging from 0.31 to 2.5 microg/L TBT. The highest TBT concentration (2.5 microg/L) was lethal to 60% of the exposed organisms. Lower TBT concentrations elicited no adverse effects on molting or reproduction of the daphnids. No differences were observed in the response of the first- and second-generation daphnids to the toxicity of TBT. The ability of daphnids to metabolize [14C]-testosterone in vivo was assessed following exposure of each generation to TBT. Production of hydroxylated, reduced/dehydrogenated, and glucose-conjugated metabolites of testosterone were all elevated following exposure of both generations to 1.25 microg/L TBT. These findings indicate that, under these conditions, TBT elicits no discernible effects on molting and reproduction of daphnids at sublethal concentrations, and testosterone metabolism is enhanced at concentrations approaching those that are lethal to organisms. Alterations of steroid metabolism by xenobiotics can be used as a more sensitive indicator of sublethal exposure in daphnids than reproductive endpoints.
Animals↗
Evaluation of early embryonic loss induced by tributyltin chloride in rats: phase- and dose-dependent antifertility effects.
In our previous study, tributyltin chloride (TBTCl) on days 0-7 of pregnancy was found to produce implantation failure in rats. The objective of the present study was to determine the susceptible period for the antifertility effect of TBTCl in rats. Inseminated females were orally administered TBTCl at 8.1, 16.3, or 32.5 mg/kg on days 0-3 of pregnancy, or at 8.1, 16.3, 32.5, or 65.1 mg/kg on days 4-7 of pregnancy. Pregnancy outcome was determined on day 20 of pregnancy. Dosing with TBTCl on days 0-3 of pregnancy at 16.3 mg/kg and higher produced a significant increase in the rate of implantation failure. Dosing with TBTCl on days 4-7 of pregnancy caused a significant increase in the incidence of postimplantation loss at 16.3 mg/kg and higher in females with implantations. No increase in the incidence of fetal malformations was found in any TBTCl-treated groups. It could be concluded that the susceptibility to and manifestation of the antifertility effects of TBTCl vary with the gestational stage at the time of administration.
Administration, Oral↗