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PubMed2003

Persistent organic pollutants in environment of the Pearl River Delta, China: an overview.

In the Pearl River Delta of China, the rapidly developing industrial and agricultural activities, municipal development and use of chemicals caused serious environmental problems. This report summarizes the published scientific data on POPs in the environment of the Pearl River Delta, including the levels of POPs in the air, water, soil, river and estuarine sediments, the marine organisms like fish and shellfish in this region. The data preliminarily reveal the state of contamination in this region and give insight into the fate of POPs in this sub-tropical area. However, most research in this area is limited to a few kinds of POP compounds.

Animals↗
PubMed1985

Irritant dermatitis from tri-N-butyl tin oxide in paint.

Organo-tin compounds are known irritants. Tributyl tin oxide is a common biocide in some marine and other paints. An outbreak of irritant contact dermatitis in painters exposed to paints containing tributyl tin oxide is reported.

Adult↗
PubMed1986

Trimethyltin-induced alterations in brain amino acids, amines and amine metabolites: relationship to hyperammonemia.

An investigation of several neurochemical consequences of exposure of the rat to 3/4 of the estimated single injection LD50 quantity of trimethyltin chloride (TMT) indicated that a significant elevation in the levels of glutamine (Gln) and 5-hydroxyindole acetic acid (5-HIAA) occurred at post-dosing day 7 in each examined region of the brain; elevated Gln persisted in the hippocampus through day 14 and returned to control levels at day 28. At post-dosing day 7, levels of glutamate were decreased in the hippocampus, while levels of GABA were decreased in hippocampus and frontal cortex, but not in corpus striatum; hippocampal glutamate and GABA returned to control levels by post-dosing day 14. Decreased levels of taurine (Tau) occurred on day 7 in both hippocampus and frontal cortex; hippocampal Tau remained below control levels through post-dosing day 28. Levels of other amino acids and of amines and amine metabolites were not altered by TMT in the 7 to 28 day post-dosing interval. At day 7, TMT treatment did not alter brain regional activities of glutamine synthetase; however, plasma ammonia was elevated 100% above the control value. Alterations in several serum enzymes (esp., alkaline phosphatase and aspartate aminotransferase) revealed several other peripheral consequences of TMT exposure which persist through post-dosing day 28. The more prominent and wide-spread neurochemical alterations resulting from TMT exposure appear to reflect consequences of hyperammonemia resulting from a peripheral effect of the organotin compound.

Amino Acids↗
PubMed2000

Chemical specificity of the PDR5 multidrug resistance gene product of Saccharomyces cerevisiae based on studies with tri-n-alkyltin chlorides.

To understand the chemical basis of action for the PDR5-encoded multidrug resistance transporter of Saccharomyces cerevisiae, we compared the relative hypersensitivities of the wild-type (RW2802) and null mutant strains toward a series of tri-n-alkyltin compounds. These compounds differ from each other in a systematic fashion-either by hydrocarbon chain length or by anion composition. Using zone-of-inhibition and fixed-concentration assays, we found that the ethyl, propyl, and butyl compounds are strong PDR5 substrates, whereas the methyl and pentyl compounds are weak. We conclude that hydrophobicity and anion makeup are relatively unimportant factors in determining whether a tri-n-alkyltin compound is a good PDR5 substrate but that the dissociation of the compound and the molecular size are significant.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Cyclosporin A exacerbates skin irritation induced by tributyltin by increasing nuclear factor kappa B activation.

In searching for pharmacologic agents able to reduce xenobiotic-induced skin irritation, we found that cyclosporine A exacerbates the skin irritation induced by tributyltin. We previously demonstrated the involvement of interleukin-1 alpha and tumor necrosis factor alpha in tributyltin-induced skin irritation. Here, we show that cyclosporine A (28 mg per kg), at a dose that results in systemic immunosuppression, potentiates tributyltin-induced skin irritation through increased tumor necrosis factor alpha production, associated with increased tributyltin-induced activation of transcription factor nuclear factor kappa B in cyclosporine-A-treated mice. On the other hand, under the same experimental conditions, cyclosporine A prevented the elicitation phase of oxazolone-induced contact allergy, but was ineffective in preventing benzalkonium-chloride-induced skin irritation. Using a murine keratinocyte cell line (HEL30) we demonstrated, also in vitro, that the cyclosporine A potentiates tributyltin-induced nuclear factor kappa B activation and cytokine production, this being preceded by an increase in cellular oxidative activity, essential for nuclear factor kappa B activation, that is time and dose (0.1-10 microM) dependent. This effect was not exclusive to tributyltin but could be extended to other mitochondrial poisons such as sodium arsenate. It has been reported that cyclosporine A binds to cyclophilins. An 18-mer antisense phosphorothioate oligodeoxynucleotide was used to target mitochondrial cyclophilin D mRNA. After 24 h exposure to the oligonucleotide, the amount of cyclophilin D in the cells was decreased by 54% as judged by Western blot analysis. Cyclophilin D suppression prevented cyclosporine A potentiation of tributyltin-induced cellular oxidative activity, indicating the key role of the binding of cyclosporine A to mitochondrial cyclophilin D in mediating this effect.

Adjuvants, Immunologic↗
PubMed1995

Tributyltin use in interior paints: a continuing health hazard.

We report on five patients who developed mucous membrane irritation after inhalational exposure to an interior use latex paint containing the organotin compound bis(tributyltin) oxide. Stricter regulations regarding the use of bis(tributyltin) oxide with interior paint would most likely have prevented these cases of tributyltin toxicity. Bis(tributyltin) oxide should not be used with paint intended for interior use.

Adult↗
PubMed2004

Management of exogenous threats to Antarctica and the sub-Antarctic Islands: balancing risks from TBT and non-indigenous marine organisms.

The discovery of high levels of tributyltin compounds in Antarctic marine sediments has prompted managers to consider the banning of such substances in this region. We propose that the banning of antifouling coatings may result in an increase in the risk of non-indigenous species invasions. Our studies show that un-treated vessels carry a more diverse community of fouling organisms than treated hulls on which fouling is restricted to specific untreated niches. Up to 40% of the species recruited to the hulls of Southern Ocean vessels are species with invasive histories. Viable fouling assemblages can survive prolonged voyages to high-latitude coastlines, yet passage through sea-ice may remove fouling communities due to mechanical abrasion reducing the hazard of introductions to ice-bound coastlines. The banning of antifouling compounds may be of particular concern for the ice-free sub-Antarctic islands which represent a common anchorage point for vessels on-route to Antarctica.

Antarctic Regions↗
PubMedDate not supplied

Physiological methods for assessment of Trimethyltin exposure.

Trimethyltin has been reported to produce morphological alterations in the brain which are primarily restricted to the limbic system. A variety of physiological measures of limbic system integrity are discussed in terms of their ability to detect TMT-induced dysfunction. In addition, several measures of sensory dysfunction are discussed. It is concluded that limbic system dysfunction induced by this compound is detected more efficiently by intrahippocampal evoked potentials than by more gross measures of dysfunction. It is also concluded that relying upon preliminary descriptions of pathological alterations to direct physiological studies may provide an incomplete description of neurotoxicity.

Animals↗
PubMed1977

The chloride transport induced by triaklyl-tin compound across erythrocyte membrane.

The effect of tripropyl-tin chloride on anion permeability was studied using red cells previously treated with a covalent binding inhibitor 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) to inhibit completely and irreversibly the natural anion transport system. It was demonstrated that the tin compound can mediate chloride-hydroxide and chloride-chloride exchanges across the "impermeabilised" erythrocyte membrane. In the non hemolytic range, the rate of exchange increased with the concentration of the tin compound in a non linear fashion, and no saturation effect was seen. The temperature profile of the chloride self exchange induced by tripropyl-tin was studied and the apparent activation energy found was 29 Kcal/mol. The tripropyl-tin chloride cannot mediate a chloride-bicarbonate exchange. Because of this discriminatory effect between hydroxide and bicarbonate, the tin compound can be useful in certain experimental conditions as seen for the study of the anion "carrier" of the red cell membrane ("cousin, J.L., Motais, R. and Sola, F. (1975) J. Physiol. Lond. 253, 385-399).

Bicarbonates↗
PubMedDate not supplied

Triethyltin-produced decrease and recovery of wheel running and food-reinforced lever pressing in rats.

Behavioral effects of triethyltin were studied in rats living in Wahmann activity cages. Wheel running activity and food-reinforced lever pressing were recorded 23 hr/day from 4 rats. Triethyltin injections (4 mg/kg IP) produced large transient decreases in running, lever pressing, and daily water consumption, without affecting body weight. These measures recovered to pre-treatment levels within 1-2 days. After 4 weekly injections, wheel running was reduced in 2 rats, and increased in 1 rat, while lever pressing remained at baseline levels. Good correlation was noted between the extent of reductions in wheel running and lever pressing, and the extent of characteristic triethyltin-induced morphological lesions in the central and peripheral nervous system. Over the course of repeated treatments, several critical behaviors known to be sensitive to neurotoxicants can be continually monitored using automated testing apparatus. While further validation with more compounds is required, these results suggest that monitoring wheel running, food-reinforced lever pressing, and water consumption may be an inexpensive way to test for behavioral neurotoxicity using small numbers of animals.

Animals↗
PubMed2006

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↗
PubMed2006

Brain cytochrome P450 aromatase gene isoforms and activity levels in atlantic salmon after waterborne exposure to nominal environmental concentrations of the pharmaceutical ethynylestradiol and antifoulant tributyltin.

In this study, the effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen (ethynylestradiol, EE2) and antifoulant (tributyltin, TBT) representing two different modes of action on the endocrine system, were studied on brain steroidogenic pathway of juvenile Atlantic salmon (Salmo salar). Neurosteroidogenesis was studied using brain aromatase gene isoforms and enzyme activity, in parallel with typical xenoestrogen responses, such as brain estrogen receptor (ERalpha) and plasma vitellogenin (Vtg) levels. Fish were exposed to nominal waterborne EE2 (5 and 50 ng/l) and TBT (50 and 250 ng/l) concentrations dissolved in dimethyl sulfoxide (DMSO), singly and in combination. Gene expressions were quantified using real-time PCR with gene-specific primers, aromatase activity was analyzed using the tritiated water-release assay, and plasma Vtg was analyzed using competitive ELISA. Our data show that EE2 induced a concentration-specific modulation of P450aromA, P450aromB, and aromatase activity in addition to ERalpha and plasma Vtg levels in juvenile salmon at day 3 postexposure. TBT exposure caused both the elevation and inhibition of P450aromA, P450aromB, and aromatase activity levels, depending on concentration, at day 7 postexposure. TBT elevated and inhibited ERalpha and plasma Vtg and also antagonized EE2-induced expression of the studied variables at day 7 postexposure. Interestingly, the carrier vehicle DMSO modulated the receptor-mediated and non-receptor-mediated estrogenic responses at day 7 postexposure, compared to day 3. In general, these findings suggest that the exposed animals are experiencing impaired steroidogenesis and modulations of receptor-mediated endocrine responses. Given the integral role of neurosteroids in homeostatic process, growth, metabolism, reproduction, and development of central nervous system and function, these effects may have serious impact on this endocrine pathway and potentially affect organismal reproductive performance and health. In conclusion, the regulation of steroidogenesis is a fundamental mechanism involved in the biosynthesis of important biological compounds, irrespective of organ; therefore, the search for the molecular targets of xenoestrogens, given singly and also in combination, in these pathways will increase our understanding of organismal endocrine disruption and potential consequences.

Animals↗
PubMed1986

Trimethyltin ototoxicity: evidence for a cochlear site of injury.

The environmental contaminant, trimethyltin (TMT), produces a profound elevation in tone intensity necessary to inhibit the acoustic startle reflex in laboratory animals which recovers over a prolonged period except at very high frequencies. The recovery that is observed does not begin until 3 to 5 weeks after a single acute administration depending upon dosage. As opposed to the very temporary threshold shifts by the salicylates and loop diuretics or the permanent and progressive ototoxicity resulting from aminoglycoside antibiotics the time course for recovery of acoustic startle reflex inhibition after TMT appears to be an anomaly for a chemical ototoxicant. In terms of the duration of loss only, this pattern appears similar to that sometimes observed after noise exposure. The current investigation replicates the finding that recovery of acoustic startle reflex inhibition after TMT is frequency related in that only the highest frequency impairment appears to be permanent. While this frequency dependence suggests a cochlear locus of injury, both the known neurotoxic effects of TMT and the time course of the behavioral impairment suggest a more central locus of injury. Compound action potential and cochlear microphonic recordings made from the round window in the current study confirm a preferential high frequency effect of TMT and demonstrate a significant cochlear component to the ototoxic effects of this agent.

Action Potentials↗
PubMed1998

Effects of in vivo exposure to bis(tri-n-butyltin)oxide, hexachlorobenzene, and benzo(a)pyrene on cytokine (receptor) mRNA levels in cultured rat splenocytes and on IL-2 receptor protein levels.

Analysis of cytokine (receptor) mRNA levels has been suggested to be a sensitive technique for predicting the immunomodulatory potential of drugs and chemicals. Furthermore, this type of analysis is thought to be important in unraveling mechanisms of immunotoxicity. To study these issues, male Wistar rats were exposed to the immunotoxic environmental contaminants bis(tri-n-butyltin) oxide (TBTO; 5, 20, or 80 mg/kg diet for 6 weeks), hexachlorobenzene (HCB; 50, 150, or 450 mg/kg diet for 6 weeks), or benzo(a)pyrene (B(a)P; 3, 10, 30, or 90 mg/kg body wt for 5 weeks by a daily (5 times a week) oral intubation). Spleen cells were cultured with Con A and analyzed by dot blot hybridization for IL-2, IFN-gamma, IL-2 receptor alpha-chain (IL-2R alpha; CD25), and IL-4 mRNA levels. In addition, spleen and thymus sections of TBTO-exposed animals were assayed immunohistochemically for CD25 expression. Exposure to TBTO resulted in a dose-dependent decrease in IL-2R alpha mRNA levels from 5 mg/kg, a dose-dependent increase in IFN-gamma mRNA levels from 20 mg/kg, and increased IL-2 mRNA levels at 80 mg/kg diet. Exposure to HCB resulted in a dose-dependent increase in IL-2 and IFN-gamma mRNA levels from 150 mg/kg and increased IL-2R gamma mRNA levels at 450 mg/kg diet. Exposure to B(a)P resulted in a dose-dependent increase in IL-2 and IFN-gamma mRNA levels from 10 mg/kg and increased IL-2R alpha mRNA levels at 90 mg/kg body wt. No effects were seen on IL-4 mRNA levels. Spleen and thymus sections of TBTO-exposed animals showed reduced CD25 expression from 5 mg/kg diet. These results show that (1) the correlation between altered cytokine (receptor) mRNA levels and functional endpoints is variable, depending on the type of functional endpoint tested and the compound studied, (2) these assays are among the most sensitive ones for TBTO and HCB immunotoxicity, and among the more sensitive ones for B(a)P immunotoxicity, and (3) for TBTO, these assays provide a possible clue to a mechanism for thymus atrophy, resulting from exposure to this compound: reduced IL-2R expression may impede thymocyte maturation, resulting in thymus atrophy.

Animals↗
PubMed2003

Uptake of waterborne tributyltin in the brain of fish: axonal transport as a proposed mechanism.

In previous studies, it was shown that waterborne Hg(II), Cd(II), and Mn(II) enter nerves innervating water-exposed sensory organs of fish and are transported to the brain by axonal transport. However, it is not known if organometals, such as tributyltin (TBT), can reach the brain of fish via the same route. In this work, we exposed rainbow trout (Oncorhynchus mykiss) to waterborne [113Sn]-TBT (4.2 kBq/L). Three fish were sampled after a 2-week exposure, and three others were sampled after a 2-week depuration period. Another group of four fish received an intravenous injection of [113Sn]-TBT and were sampled after 2 and 14 d. Distribution of the radiolabel was visualized and quantified by quantitative whole-body autoradiography. The brain accumulated a significant amount of 113Sn, with hot spots being found in parts receiving sensory nerves from water-exposed sensory organs, such as eminentia granulares (lateral lines organs). Labeling of the brain was also seen for i.v.-injected fish, indicating that the blood-brain barrier is not impervious to TBT or its metabolites. Nevertheless, the distribution of radioactivity in the brain was much more uniform, with no evident hot spot. Though the transfer [water --> gills --> blood stream --> blood-brain barrier --> brain] may account for a certain proportion of the radiolabel accumulation in fish brain, exposure to [113Sn]-TBT via water resulted in higher accumulation in some areas of the brain, of which the specific location strongly suggests that it was taken up in different water-exposed sensory nerve terminals and transported directly to the brain by axonal transport, as the parent compound or as a metabolite. The resulting local enhancement of the accumulation of butyltins might jeopardize the integrity of nervous system. Further work is needed to assess the toxicological significance of this process.

Animals↗
PubMed1976

Snail control in urban sites in Brazil with slow-release hexabutyldistannoxane and pentachlorophenol.

Slow release formulations of hexabutyldistannoxane (TBTO) and pentachlorophenol (PCP) were tested for the control of Biomphalaria tenagophila in 52 urban sites in Rio de Janeiro. TBTO acted faster and lasted longer than PCP and at 15 g/m(2) it eliminated snails from 76% of the treated sites for 1 year. Water pollution and rate of flow had no significant influence on the molluscicidal properties of either compound, but alkalinity lowered the activity of TBTO. Failure to control snail populations was due mainly to human interference and to the non-treatment of adjacent breeding sites that were temporarily dry and therefore overlooked.

Animals↗
PubMed1990

Tributyltin stimulates apoptosis in rat thymocytes.

Treatment of rat thymocytes with micromolar concentrations of tributyltin caused a rapid increase in the cytosolic free Ca2+ concentration that was inhibited by Ni2+, which blocks Ca2+ influx through membrane channels. The elevation of cytosolic Ca2+ was associated with extensive DNA fragmentation, which was prevented by pretreatment of the cells with either of the intracellular Ca2+ chelators quin-2 or 1,2-bis(2-amino-phenoxy)ethane-N',N',N',N',-tetraacetic acid. Loss of thymocyte viability, which followed DNA fragmentation, was also prevented by the two Ca2+ chelators or by removing extracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid. The pattern of DNA fragmentation was characteristic of that produced by agents which activate a Ca2(+)- and Mg2(+)-dependent endogenous endonuclease during apoptosis or programmed cell death. Additional studies showed that other organotin compounds, including trimethyltin, triphenyltin, and dibutyltin had minimal effects on cytosolic Ca2+, DNA fragmentation, and cell viability. These results are consistent with a greater susceptibility of thymocytes to tributyltin and provide a basis for understanding its selective immunotoxicity in vivo.

Animals↗
PubMed2006

In vitro tests to evaluate immunotoxicity: a preliminary study.

The implementation of Registration, Evaluation and Authorisation of new and existing Chemicals (REACH) will increase the number of laboratory animals used, if alternative methods will not be available. In the meantime, REACH promotes the use of in vitro tests and, therefore, a set of appropriated alternative testing methods and assessment strategies are needed. The immune system can be a target for many chemicals including environmental contaminants and drugs with potential adverse effects on human health. The aim of this study was to evaluate the predictivity of a set of in vitro assays to detect immunosuppression. The tests have been performed on human, rat and murine cells. Different endpoints have been assessed: cytotoxicity, cytokine release, myelotoxicity and mitogen responsiveness. For each of these endpoints IC50s values have been calculated. Six chemical substances, representative of the full range of in vivo responses and for which good human and/or animal data are available either from databases or literature, have been selected: two chemicals classified as not immunotoxic (Urethane and Furosemide), and four (tributyltin chloride (TBTC), Verapamil, Cyclosporin A, Benzo(a)pyrene) with different effect on immune system. All the tests confirmed the strong immunotoxic effect of TBTC as well as they confirmed the negative controls. For one chemical (Verapamil) the IC50 is similar through the different tests. The IC50s obtained with the other chemicals depend on the endpoints and on the animal species. The clonogenic test (CFU-GM) and the mitogen responsiveness showed similar IC50s between human and rodent cells except for Cyclosporin A and TBTC. All different tests classified the compounds analyzed in the same way.

Animals↗