Although the coexistence of heavy metals and environmental hormones always occur in aquatic environment, the information of the combined impacts remains unclear. To explore the multi-generational toxicity of cadmium (Cd) and tributyltin (TBT), adult zebrafish (Danio rerio) (F0) were exposed to different treated groups (100 ng/l Cd, 100 ng/l TBT and their mixture) for 90 d, with their offspring (F1 and F2) subsequently reared in the same exposure solutions corresponding to their parents. Both developmental neurotoxicity and thyroid disturbances were examined in the three (F0, F1, and F2) generations. Our results showed that co-exposure to Cd and TBT induced the developmental neurotoxicity in F1 and F2 generations, reflected by the significant lower levels of neurotransmitters (dopamine and serotonin) and the inhibited acetylcholinesterase (AChE) activities. And the thyroid endocrine disruption were observed in the two-generations larval offspring by parental exposure to Cd and/or TBT, including the significantly decreasing levels of thyroid hormones and the down-regulated the expression of genes involved in the hypothalamus-pituitary-thyroid axis, compared to the control. Additional, the embryonic toxicity and growth inhibition were also determined in the fish larvae. Overall, this study examined the impacts of parental co-exposure to Cd and TBT, with regard to developmental inhibition, nervous system damage and endocrine disruption, which highlighted that co-exposure influences are complicated and need to be considered for accurate environmental risk assessment.

Tributyltin (TBT) is an organotin environmental pollutant widely used as an agricultural and wood biocide and in antifouling paints. Countries began restricting TBT use in the 2000s, but their use continues in some agroindustrial processes. We studied the acute effect of TBT on cardiac function by analyzing myocardial contractility and Ca²⁺ handling. Cardiac contractility was evaluated in isolated papillary muscle and whole heart upon TBT exposure. Isolated ventricular myocytes were used to measure calcium (Ca²⁺) transients, sarcoplasmic reticulum (SR) Ca²⁺ content and SR Ca²⁺ leak (as Ca²⁺ sparks). Reactive oxygen species (ROS), as superoxide anion (O2•⁻) was detected at intracellular and mitochondrial myocardium. TBT depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. TBT increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential. In isolated cardiomyocytes TBT decreased both Ca²⁺ transients and SR Ca²⁺ content and increased diastolic SR Ca²⁺ leak. Decay of twitch and caffeine-induced Ca²⁺ transients were slowed by the presence of TBT. Dantrolene prevented and Tiron limited the reduction in SR Ca²⁺ content and transients. The environmental contaminant TBT causes cardiotoxicity within minutes, and may be considered hazardous to the mammalian heart. TBT acutely induced a negative inotropic effect in isolated papillary muscle and whole heart, increased arrhythmogenic SR Ca²⁺ leak leading to reduced SR Ca²⁺ content and reduced Ca²⁺ transients. TBT-induced myocardial ROS production, may destabilize the SR Ca²⁺ release channel RyR2 and reduce SR Ca²⁺ pump activity as key factors in the TBT-induced negative inotropic and lusitropic effects.

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.

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.

The analysis of lipid disruption in invertebrates is limited by our poor knowledge of their lipidomes and of the associated metabolic pathways. For example, the mechanism by which exposure of the crustacean Daphnia magna to tributyltin, juvenoids, or bisphenol A increase the accumulation of storage lipids into lipid droplets is largely unknown/presently unclear. Here we analyze transcriptome changes subsequent to this lipid accumulation effect induced by either the pesticide pyriproxyfen (a juvenoid agonist), the plasticizer bisphenol A, or the antifouling agent tributyltin. Changes in the whole transcriptome were assessed after 8 and 24 h of exposure, the period showing the greatest variation in storage lipid accumulation. The three compounds affected similarly to a total of 1388 genes (965 overexpressed and 423 underexpressed transcripts), but only after 24 h of exposure. In addition, 225 transcripts became up-regulated in samples exposed to tributyltin for both 8 h and 24 h. Using D. melanogaster functional annotation, we determined that upregulated genes were enriched in members of KEGG modules implicated in fatty acid, glycerophospholipid, and glycerolipid metabolic pathways, as well as in genes related to membrane constituents and to chitin and cuticle metabolic pathways. Conversely, down-regulated genes appeared mainly related to visual perception and to oocyte development signaling pathways. Many tributyltin specifically upregulated genes were related to neuro-active ligand receptor interaction signaling pathways. These changes were consistent with the phetotypic effects reported in this and in previous studies that exposure of D. magna to the tested compounds increased lipid accumulation and reduced egg quantity and quality.

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.

Tributyltin is a biocide used in nautical paints, aiming to reduce fouling of barnacles in ships. Despite the fact that many effects of TBT on marine species are known, studies in mammals have been limited, especially those evaluating its effect on the function of the hypothalamus-pituitary-thyroid (HPT) axis. The aim of this study was to investigate the effects of subchronic exposure to TBT on the HPT axis in female rats. Female Wistar rats received vehicle, TBT 200 ng kg−1 BW d−1 or 1000 ng kg−1 BW d−1 orally by gavage for 40 d. Hypothalamus, pituitary, thyroid, liver and blood samples were collected. TBT200 and TBT1000 thyroids showed vacuolated follicular cells, with follicular hypertrophy and hyperplasia. An increase in epithelial height and a decrease in the thyroid follicle and colloid area were observed in TBT1000 rats. Moreover, an increase in the epithelium/colloid area ratio was observed in both TBT groups. Lower TRH mRNA expression was observed in the hypothalami of TBT200 and TBT1000 rats. An increase in Dio1 mRNA levels was observed in the hypothalamus and thyroid in TBT1000 rats only. TSH serum levels were increased in TBT200 rats. In TBT1000 rats, there was a decrease in total T4 serum levels compared to control rats, whereas T3 serum levels did not show significant alterations. We conclude that TBT exposure can promote critical abnormalities in the HPT axis, including changes in TRH mRNA expression and serum TSH and T4 levels, in addition to affecting thyroid morphology. These findings demonstrate that TBT disrupts the HPT axis. Additionally, the changes found in thyroid hormones suggest that TBT may interfere with the peripheral metabolism of these hormones, an idea corroborated by the observed changes in Dio1 mRNA levels. Therefore, TBT exposition might interfere not only with the thyroid axis but also with thyroid hormone metabolism.

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.

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.