Tributyltin (TBT) is a widely used organotin compound around the world and was frequently detected in surface waters, which would pose risk to aquatic organisms. However, the mechanisms of TBT-induced toxicity is not full clear. The present study investigated the effects of the tributyltin (TBT) on the blood parameters, immune responses and thyroid hormone system in zebrafish. Fish were exposed to sublethal concentrations of TBT (10 ng/L, 100 ng/L and 300 ng/L) for 6 weeks. The effects of long-term exposure to TBT on blood parameters (NH3, ammonia; GLU, glucose; TP, total proteins; CK, creatine kinase; ALT, alanine aminotransferase; AST, aspartate aminotransferase), immune responses (Lys, lysozyme; IgM, immunoglobulin M) and some indexes related thyroid hormone system (T3, 3,5,3′-triiodothyronine; T4, thyroxine) were measured in zebrafish, as well as the expression of genes related to immune responses and thyroid hormone system. Based on the results, the physiological-biochemical responses was significantly enhanced with an increase in TBT concentration, reflected by the abnormal blood indices, dysregulation of endocrine system and immunotoxicity in zebrafish under TBT stress. The present study greatly extends our understanding of adverse effects of TBT on aquatic organisms.

Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host’s physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.

The wide ecological relevance of lipid homeostasis modulators in the environment has been increasingly acknowledged. Tributyltin (TBT), for instance, was shown to cause lipid modulation, not only in mammals, but also in fish, molluscs, arthropods and rotifers. In vertebrates, TBT is known to interact with a nuclear receptor heterodimer module, formed by the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR). These modulate the expression of genes involved in lipid homeostasis. In the present work, we isolated for the first time the complete coding region of the Echinodermata (Paracentrotus lividus) gene orthologues of PPAR and RXR and evaluated the ability of a model lipid homeostasis modulator, TBT, to interfere with the lipid metabolism in this species. Our results demonstrate that TBT alters the gonadal fatty acid composition and gene expression patterns: yielding sex-specific responses in fatty acid levels, including the decrease of eicosapentaenoic acid (C20:5 n-3, EPA) in males, and increase of arachidonic acid (20:4n-6, ARA) in females, and upregulation of long-chain acyl-CoA synthetase (acsl), ppar and rxr. Furthermore, an in vitro test using COS-1 cells as host and chimeric receptors with the ligand binding domain (LBD) of P. lividus PPAR and RXR shows that organotins (TBT and TPT (Triphenyltin)) suppressed activity of the heterodimer PPAR/RXR in a concentration-dependent manner. Together, these results suggest that TBT acts as a lipid homeostasis modulator at environmentally relevant concentrations in Echinodermata and highlight a possible conserved mode of action via the PPAR/RXR heterodimer.

DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is the main component of SeaNine-211, a new antifouling agent that replaces tributyltin to prevent the growth of undesirable organisms on ships. There have been some studies on the toxicity of DCOIT, but the mechanism of DCOIT’s toxicity to crustaceans still requires elucidation. This study examined the chronic toxicity (4 weeks) of 0, 3, 15, and 30 μg/L DCOIT to the Pacific white shrimp (Litopenaeus vannamei) from the aspects of growth and physiological and histological changes in the hepatopancreas and gills. A transcriptomic analysis was performed on the hepatopancreas to reveal the underlying mechanism of DCOIT in shrimp. The exposure to 30 μg/L DCOIT significantly reduced the survival and weight gain of L. vannamei. High Na⁺/K⁺-ATPase activity and melanin deposition were found in the gills after 4 weeks of 15 μg/L or 30 μg/L DCOIT exposure. The highest concentration of DCOIT (30 μg/L) induced changes in hepatopancreatic morphology and metabolism, including high anaerobic respiration and the accumulation of triglycerides. Compared with the exposure to 3 μg/L DCOIT, shrimp exposed to 15 μg/L DCOIT showed more differentially expressed genes (DEGs) than those in the control, and these DEGs were involved in biological processes such as starch and sucrose metabolism and choline metabolism in cancer. The findings of this study indicate that L. vannamei is sensitive to the antifouling agent DCOIT and that DCOIT can induce altered gene expression at a concentration of 15 μg/L and can interfere with shrimp metabolism, growth and survival at 30 μg/L.

IMO’s Anti-Fouling Systems convention banned the use of organotin-based antifouling systems in 2008 as the ultimate effort to stop tributyltin (TBT) inputs into the marine environment. One of the hazardous effects of TBT is imposex (the superimposition of male sexual characters onto gastropod females), a phenomenon that may cause female sterility and the gastropod populations decline. Despite previous European Union legislation had already been shown effective in reducing the imposex levels along the Portuguese coast, this study intends to confirm these decreasing trends after 2008 and describe the global evolution in the last 15 years. Imposex levels were assessed in two bioindicators – the dog-whelk Nucella lapillus and the netted-whelk Nassarius reticulatus (Gastropoda, Prosobranchia) – in 2011 and 2014, and the results were compared with previous years. Both species showed progressive decreasing trends in imposex levels over the last 15 years; median values of the vas deferens sequence index (VDSI) fell from 3.96 to 0.78 in N. lapillus and from 3.39 to 0.29 in N. reticulatus. The temporal/spatial evolution of imposex suggests an apparent shift of TBT hotspots, being now restricted to fishing ports and marinas in detriment of large commercial harbours where TBT levels fell rapidly. Butyltins were measured in the whole tissues of N. lapillus females collected in 2014: monobutyltin (MBT) varied from < DL (detection limit: 1 ng Sn/g) to 13 ng Sn/g dw, dibutyltin (DBT) from 2.2 to 27 ng Sn/g dw and TBT from 1.5 to 55 ng Sn/g dw. Although TBT body burden has declined over time, the butyltin degradation index ([MBT]+[DBT])/[TBT] exhibited values < 1 in c. a. 90% of the sites assessed, suggesting that recent TBT inputs are still widespread in the Portuguese coast eventually due to illegal use of TBT antifouling systems and TBT desorption from sediments.

Antifouling biocides in surface sediments and gastropod tissues were assessed for the first time along coastal areas of Panama under the influence of maritime activities, including one of the world's busiest shipping zones: the Panama Canal. Imposex incidence was also evaluated in five muricid species distributed along six coastal areas of Panama. This TBT-related biological alteration was detected in three species, including the first report in Purpura panama. Levels of organotins (TBT, DBT, and MBT) in gastropod tissues and surficial sediments ranged from <5 to 104 ng Sn g⁻¹ and <1–149 ng Sn g⁻¹, respectively. In addition, fresh TBT inputs were observed in areas considered as moderate to highly contaminated mainly by inputs from fishing and leisure boats. Regarding booster biocides, TCMTB and dichlofluanid were not detected in any sample, while irgarol 1051, diuron and DCOIT levels ranged from <0.08 to 2.8 ng g⁻¹, <0.75–14.1 ng g⁻¹, and <0.38–81.6 ng g⁻¹, respectively. The highest level of TBT (149 ng Sn g⁻¹) and irgarol 1051 (2.8 ng g⁻¹), as well as relevant level of DCOIT (5.7 ng g⁻¹), were detected in a marina used by recreational boats. Additionally, relatively high diuron values (14.1 ng g⁻¹) were also detected in the Panama Canal associate to a commercial port. DCOIT concentrations were associated with the presence of antifouling paint particles in sediments obtained nearby shipyard or boat maintenance sites. The highest levels of TBT, irgarol 1051, and diuron exceeded international sediment quality guidelines indicating that toxic effects could be expected in coastal areas of Panama. Thus, the simultaneous impacts produced by new and old generations of antifouling paints highlight a serious environmental issue in Panamanian coastal areas.

Despite their ban on small vessels in 1989 in the EU, organotin compounds (OTCs) are still being released into the environment due to their presence in historic paint layers on leisure boats. 23 paint samples scraped from recreational boats from three countries around the Baltic Sea were analyzed for total tin (Sn) and OTCs. Two antifouling paint products were also subjected to the same analyses. A new method for the detection of Sn in paint flake samples was developed and found to yield more accurate results compared to four different acid digestion methods. A new method was also developed for the extraction of OTCs from ground paint flakes. This endeavor revealed that existing methods for organotin analysis of sediment may not have full recoveries of OTCs if paint flakes are present in the sample. The hull paint samples had Sn concentrations ranging from 25 to 18,000 mg/kg paint and results showed that tributyltin (TBT) was detected in all samples with concentrations as high as 4.7 g (as Sn)/kg paint. TBT was however not always the major OTC. Triphenyltin (TPhT) was abundant in many samples, especially in those originating from Finland. Several other compounds such as monobutyltin (MBT), dibutyltin (DBT), tetrabutyltin (TeBT), monophenyltin (MPhT) and diphenyltin (DPhT) were also detected. These could be the result of degradation occurring on the hull or of impurities in the paint products as they were also identified in the two analyzed paint products. A linear correlation (r2 = 0.934) was found between the total tin content and the sum of all detected OTCs. The detection of tin can therefore be used to indicate the presence of OTCs on leisure boats.

The presence of organic pollutants in the aquatic environment, usually found at trace concentrations (i.e., between ng L−1 and μg L−1 or even lower, known as micropollutants), has been highlighted in recent decades as a worldwide environmental concern due to their difficult elimination by conventional water and wastewater treatment processes. The relevant information on constructed wetlands (CWs) and their application for the removal of a specific group of pollutants, 41 organic priority substances/classes of substances (PSs) and 8 certain other substances with environmental quality standards (EQS) listed in Directive 2013/39/EU as well as 17 contaminants of emerging concern (CECs) of the Watch List of Decision 2015/495/EU, is herein reviewed. Studies were found for 24 PSs and 2 other substances with EQS: octylphenol, nonylphenol, perfluorooctane sulfonic acid, di(2-ethylhexyl)phthalate, trichloromethane, dichloromethane, 1,2-dichloroethane, pentachlorobenzene, benzene, polychlorinated dibenzo-p-dioxins, naphthalene, fluoranthene, trifluralin, alachlor, isoproturon, diuron, tributyltin compounds, simazine, atrazine, chlorpyrifos (chlorpyrifos-ethyl), chlorfenvinphos, hexachlorobenzene, pentachlorophenol, endosulfan, dichlorodiphenyltrichloroethane (or DDT) and dieldrin. A few reports were also published for 8 CECs: imidacloprid, erythromycin, clarithromycin, azithromycin, diclofenac, estrone, 17-beta-estradiol and 17-alpha-ethinylestradiol. No references were found for the other 17 PSs, 6 certain other substances with EQS and 9 CECs listed in EU legislation.

Tributyltin (TBT), a bioaccumulative and persistent environmental pollutant, has been proposed as a metabolism disruptor and obesogen through targeting peroxisome proliferator-activated receptor gamma (PPARγ) receptor pathway. However, it remains unknown whether this biological effect occurs in macrophage, a cell type which cooperates closely with hepatocytes and adipocytes to regulate lipid metabolism. This study for the first time investigated the effect of TBT on PPARγ pathway in macrophages. Our results indicated that nanomolar levels of TBT was able to strongly activate PPARγ in human macrophages. TBT treatment also markedly increased the intracellular lipid accumulation, and enhanced the expression of lipid metabolism-related genes in macrophages, while these effects were all significantly down-regulated in PPARγ-deficient macrophages, confirming the involvement of PPARγ in TBT-induced lipogenesis. Next, a mouse model that C57BL/6 mice were orally exposed to TBT with the doses (250 and 500 μg/kg body weight) lower than NOAEL (no observed adverse effect level) was used to further investigate the in vivo mechanisms. And the in vivo results were consistent with cellular assays, confirming the induction of PPARγ and the increased expression of lipogenesis-regulating and lipid metabolism-related genes by TBT in vivo. In conclusion, this study not only provided the first evidence that TBT stimulated lipogenesis, activated PPARγ and related genes in human macrophages, but also provided insight into the mechanism of TBT-induced metabolism disturbance and obesity through targeting PPARγ via both in vitro cellular assays and in vivo animal models.