Abnormal eyes and spine development in zebrafish (Danio rerio) embryos and larvae induced by triphenyltin.

Triphenyltin (TPT) is widely used in crop pest control and ship antifouling coatings, which leads to its entry into aquatic environment and poses a threat to aquatic organisms. However, the effects of TPT on the early life stages of wild fish in natural water environments remains unclear. The aim of this study was to assess the toxic effects of TPT on the early life stages of fish under two different environments: field investigation and laboratory experiment. The occurrence of deformities in wild fish embryos and larvae in the Three Gorges Reservoir (TGR) and the developmental toxicity of TPT at different concentrations (0, 0.15, 1.5 and 15 µg Sn/L) to zebrafish embryos and larvae were observed. The results showed that TPT content was higher in wild larvae, reaching 27.21 ng Sn/g w, and the malformation of wild fish larvae mainly occurred in the eyes and spine under natural water environment. Controlled experiment exposure of zebrafish larvae to TPT also resulted in eye and spinal deformities. Gene expression analysis showed that compared with the control group, the expression levels of genes related to eye development (sox2, otx2, stra6 and rx1) and spine development (sox9a and bmp2b) were significantly up-regulated in the 15 µg Sn/L exposure group, which may be the main cause of eye and spine deformity in the early development stage of fish. In addition, the molecular docking results further elucidate that the strong hydrophobic and electrostatic interactions between TPT and protein residues are the main mechanism of TPT induced abnormal gene expression. Based on these results, it can be inferred that TPT is one of the teratogenic factors of abnormal eye and spine development in the early life stage of fish in the TGR. These findings have important implications for understanding the toxicity of TPT on fish.

Triphenyltin chloride exposure inhibits meiotic maturation of mouse oocytes by disrupting cytoskeleton assembly and cell cycle progression.

Triphenyltin chloride (TPTCL) is widely used in various industrial and agricultural applications. This study aimed to elucidate the mechanisms underlying the toxicological effects of TPTCL on oocytes. The obtained findings revealed that TPTCL exposure reduced polar body extrusion (PBE) and induced meiotic arrest. Mechanistically, TPTCL disrupted meiotic spindle assembly and chromosome alignment. Further analysis indicated a significant decrease in p-MAPK expression, and disturbances in the localization of Pericentrin and p-Aurora A in TPTCL exposed oocytes, which suggesting impaired microtubule organizing center (MTOC)function. Moreover, TPTCL exposure enhance microtubule acetylation and microtubule instability. Therefore, the spindle assembly checkpoint (SAC) remained activated, and the activity of the anaphase-promoting complex (APC) was inhibited, thereby preventing oocytes from progressing into the entering anaphase I (AI) stage. TPTCL exposure also augmented the actin filaments in the cytoplasm. Notably, mitochondrial function appeared unaffected by TPTCL, as evidenced indicated by stable mitochondrial membrane potential and ATP content. Furthermore, TPTCL treatment altered H3K27me2, H3K27me3 and H3K9me3 levels, suggesting changes in epigenetic modifications in oocytes. Taken together, our results suggest that TPTCL disrupts cytoskeleton assembly, continuously activates SAC, inhibits APC activity, and blocks meiotic progression, ultimately impair oocyte maturation.

Transcriptomics-based analysis reveals the nephrotoxic effects of triphenyltin (TPT) on SD rats by affecting RAS, AQPs and lipid metabolism.

Triphenyltin (TPT) is a class of organotin compounds that are extensively used in industry and agriculture. They have endocrine-disrupting effects and cause severe environmental contamination. Pollutants may accumulate in the kidneys and cause pathological complications. However, the mechanism of TPT's toxicological effects on the kidney remains unclear. This study aimed to investigate the toxic effects and mechanism of action of TPT exposure on renal impairment in rats. Male SD rats were divided into four groups: the Ctrl group (control group), TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 28 days of exposure to TPT, we observed the morphology and structure of kidney tissue using HE, PASM, and Masson staining. We also detected serum biochemical indexes, performed transcriptome sequencing of rat kidney tissue using RNA-seq. Furthermore, protein expression levels were measured through immunohistochemistry and gene expression levels were determined using RT-qPCR. The study results indicated a decrease in kidney weight and relative kidney weight after 28 days of exposure to TPT. Additionally, TPT caused damage to kidney structure and function, as evidenced by HE staining, PASM staining, and serum biochemical tests. Transcriptomics identified 352 DEGs, and enrichment analyses revealed that TPT exposure primarily impacted the renin-angiotensin system (RAS). The expression levels of water channel proteins were reduced, and the expression levels of RAS and lipid metabolism-related genes (Mme, Ace, Fasn, Cyp4a8, Cpt1b and Ppard) were significantly decreased in the TPT-treated group. In summary, exposure to TPT may impair renal structure and function in rats by affecting RAS, AQPs, and lipid metabolism.

Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin.

Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1ß, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.

Exposure to triphenyltin impairs gut integrity, disturbs gut microbiota, and alters fecal metabolites.

Triphenyltin is an environmental contaminant widely used in antifouling paints and can cause toxicity in various organs in living organisms. However, its effects on intestinal function and the microbiome of the gut remain unknown. The objective of this study was to explore the intestinal toxicity of triphenyltin in mice by orally administering 0, 1.875, 3.75, and 7.5 mg/Kg to adult male mice for 8 weeks. Results showed that triphenyltin caused ileum tissue damage, induced oxidative stress, upregulated inflammation-related gene expression and increased serum tumor-necrosis factor α (TNF-α) levels in mice. Triphenyltin impaired ileum barrier function by downregulating Muc2, ZO-1, Occludin and their protein levels at 3.75 and 7.5 mg/Kg. TPT exposure led to partial inflammation and decreased mucin mRNA expression in the colon. Triphenyltin altered intestinal micro-ecological balance and fecal metabolome in mice. In conclusion, triphenyltin alters the mouse gut microbiota and fecal metabolome.

Perinatal exposure to the immune-suppressant di-n-octyltin dichloride affects brain development in rats.

Disruption of the immune system during embryonic brain development by environmental chemicals was proposed as a possible cause of neurodevelopmental disorders. We previously found adverse effects of di-n-octyltin dichloride (DOTC) on maternal and developing immune systems of rats in an extended one-generation reproductive toxicity study according to the OECD 443 test guideline. We hypothesize that the DOTC-induced changes in the immune system can affect neurodevelopment. Therefore, we used in-vivo MRI and PET imaging and genomics, in addition to behavioral testing and neuropathology as proposed in OECD test guideline 443, to investigate the effect of DOTC on structural and functional brain development. Male rats were exposed to DOTC (0, 3, 10, or 30 mg/kg of diet) from 2 weeks prior to mating of the F0-generation until sacrifice of F1-animals. The brains of rats, exposed to DOTC showed a transiently enlarged volume of specific brain regions (MRI), altered specific gravity, and transient hyper-metabolism ([18F]FDG PET). The alterations in brain development concurred with hyper-responsiveness in auditory startle response and slight hyperactivity in young adult animals. Genomics identified altered transcription of key regulators involved in neurodevelopment and neural function (e.g. Nrgrn, Shank3, Igf1r, Cck, Apba2, Foxp2); and regulators involved in cell size, cell proliferation, and organ development, especially immune system development and functioning (e.g. LOC679869, Itga11, Arhgap5, Cd47, Dlg1, Gas6, Cml5, Mef2c). The results suggest the involvement of immunotoxicity in the impairment of the nervous system by DOTC and support the hypothesis of a close connection between the immune and nervous systems in brain development.

Trimethyltin chloride exposure induces apoptosis and necrosis and impairs islet function through autophagic interference.

Trimethyltin chloride (TMT) is a highly toxic organotin compound often used in plastic heat stabilizers, chemical pesticides, and wood preservatives. TMT accumulates mainly through the environment and food chain. Exposure to organotin compounds is associated with disorders of glucolipid metabolism and obesity. The mechanism by which TMT damages pancreatic tissue is unclear. For this purpose, a subacute exposure model of TMT was designed for this experiment to study the mechanism of damage by TMT on islet. The fasting blood glucose and blood lipid content of mice exposed to TMT were significantly increased. Histopathological and ultrastructural observation and analysis showed that the TMT-exposed group had inflammatory cell infiltration and necrosis. Then, mouse pancreatic islet tumour cells (MIN-6) were treated with TMT. Autophagy levels were detected by fluorescence microscopy. Real-time quantitative polymerase chain reaction and Western blotting were used for verification. A large amount of autophagy occurred at a low concentration of TMT but stagnated at a high concentration. Excessive autophagy activates apoptosis when exposed to low levels of TMT. With the increase in TMT concentration, the expression of necrosis-related genes increased. Taken together, different concentrations of TMT induced apoptosis and necrosis through autophagy disturbance. TMT impairs pancreatic (islet ß cell) function.

Reversible leukoencephalopathy associated with organotin poisoning.

INTRODUCTION: Organotin compounds are widely used in the plastic industry. We demonstrate the role of brain magnetic resonance imaging in a patient with leukoencephalopathy. CLINICAL COURSE: A 38-year-old man who worked with trimethyltin and dimethyltin in a polyvinyl chloride factory reported a two-week progression of impaired memory, loss of balance, apathy, tinnitus, scaly darkened skin, and psychomotor slowing that rendered him unable to continue his daily activities. Magnetic resonance imaging revealed diffuse bilateral white matter lesions. Tin concentrations in both blood (344 µ/L) and urine (3,050 µg/L) were elevated. Removal from exposure and treatment with succimer were associated with clinical, laboratory, and imaging improvements. DISCUSSION: The high lipid content of myelin is a likely target for lipid-soluble alkyl tin compounds. CONCLUSIONS: This patient demonstrates the clinical and magnetic resonance imaging findings of organotin toxicity. The contribution of chelation to the patient's recovery is uncertain and warrants further study.

Assessing the ecotoxicity of combined exposure to triphenyltin and norfloxacin at environmental levels: A case study of immunotoxicity and metabolic regulation in carp (Cyprinus carpio).

This paper evaluates the coexistence risks of triphenyltin (TPT) and norfloxacin (NOR) to aquatic organisms in the aquatic environment. Carp (Cyprinus carpio) was used as the test organism, the control and exposure groups (1 µg/L TPT), 1 mg/L (NOR), 1 µg/LTPT+1 mg/LNOR (TPT_NOR)) were set up according to the environmental concentration in the severely polluted area for 42 days. The single/combined toxic effects of TPT and NOR on aquatic organisms were evaluated by analyzing carp brain transcriptome sequencing, gut microbiota structure, and detection of biochemical indicators and RT-qPCR. Our results show that TPT and NOR induce lipid metabolism disorder in carp brain tissue, affecting the metabolism of cytochrome P450 to exogenous substances, and NOR also induces immunosuppression in carp. Long-term exposure to TPT combined with NOR amplifies the monotoxicity of TPT or NOR on lipid metabolism and immunosuppression in carp, induces immune dysfunction in brain tissue and changes in gut microbiota structure. However, TPT_NOR has no obvious neurotoxicity on the brain, but it can inhibit the level of intestinal MDA. This highlights that co-exposure of TPT and NOR amplifies metabolic disorders and immunosuppressive functions in carp.

Organotin and organochlorine toxicants activate key translational regulatory proteins in human immune cells.

Environmental contaminant exposures occur due to the widespread use of synthetic chemicals. Tributyltin (TBT), dibutyltin (DBT), and pentachlorophenol (PCP) are each used in a variety of applications, including antifouling paints and stabilizers in certain plastics. Each of these compounds has been found in human blood, as well as other tissues, and they have been shown to stimulate pro-inflammatory cytokine production in human immune cells, Inflammatory cytokines mediate response to injury or infection. However, if their levels are increased in the absence of an appropriate stimulus, chronic inflammation can occur. Chronic inflammation is associated with a number of pathologies including cancer. Stimulation of pro-inflammatory cytokine production by these toxicants is dependent on activation of ERK 1/2 and/or p38 MAPK pathways. MAPK pathways have the capacity to regulate translation by increasing phosphorylation of key translation regulatory proteins. There have been no previous studies examining the effects of TBT, DBT, or PCP on translation. The current study shows that ribosomal protein S6 (S6), eukaryotic initiation factor 4B (eIF4B), and eIF4E are phosphorylated (activated) and/or their total levels are elevated in response to each of these compounds at concentrations found in human blood. Activation/increased levels of translational proteins occurred at concentrations of the compounds that have been shown to elevate pro-inflammatory cytokine production, but where there is no increase in mRNA for those proteins was seen. Compound-stimulated increases in translation appear to be part of the mechanism by which they elevate protein production in immune cells.

In search of biocatalytic remedy for organotin compounds- the recalcitrant eco-toxicants.

Over the last century, organotin compounds (OTCs) have sprawled over a vast spectrum of applications ranging from industrial to agricultural fields, interlacing with our surrounding environment and the ecosystem in an inseparable manner. The biocidal nature of OTCs, which has been exploited as the servient antifouling property, proved them to be pernicious eco-toxicants and a threat to the entire living system irrespective of the taxonomic hierarchy. Despite the recalcitrant nature of OTCs against chemical decontamination and photodegradation, nature has shown a providential method of their biodegradation by means of organotin-resistant microbes. Although the details of the microbial organotin biodegradation process remain nebulous, the cytochrome P450 (CYP450) family of enzymes has shown to possess the capability of OTC degradation. In this review, we discuss the deep-rooted toxicity problem of the organotin compounds on the biota and explore the plausible mechanistic plots of their enzymatic degradation, keeping the catalytic cycle of the CYP450 enzyme under the limelight. Leveraging the knowledge of CYP450 catalysis and the known organotin metabolites in nature, we attempt to cast transparency on the catalytic mechanism involved in organotin biodegradation, which remains largely elusive. Although several challenges have to be confronted for implementing the process of enzymatic degradation of OTCs in the real world, a sincere attempt will definitely be worth the ultimate greater good for averting the global toxicity problem related to organotin compounds.

Use of GAL4 factor-based yeast assay to quantify the effects of xenobiotics on RXR homodimer and RXR/PPAR heterodimer in scallop Chlamys farreri.

Retinoid X receptor (RXR) and peroxisome proliferators-activated receptors (PPAR) have been shown as important targets of endocrine disrupting effects caused by organotin compounds (OTCs). In vitro methods for non-model species are instrumental in revealing not only mechanism of toxicity but also basic biology. In the present study, we constructed the GAL4 factor-based recombinant yeast systems of RXRα/RXRα (RR), RXRα/PPARα (RPα) and RXRα/PPARγ (RPγ) of the scallop Chlamys farreri to investigate their transcriptional activity under the induction of OTCs (tributyltin chloride, triphenyltin chloride, tripropyltin chloride and bis(tributyltin)oxide), their spiked sediments and five other non­tin compounds (Wy14643, rosiglitazone, benzyl butyl phthalate, dicyclohexyl phthalate and bis(2-ethylhexyl) phthalate). The results showed that the natural ligand of RXR, 9-cis-retinoic acid (9cRA), induces transcriptional activity in all three systems, while four OTCs induced the transcriptional activity of the RR and RPα systems. None of the five potential non­tin endocrine disruptors induced effects on the RPα and RPγ systems. The spiked sediment experiment demonstrated the feasibility of the recombinant yeast systems constructed in this study for environmental sample detection. These results suggest that OTCs pose a threat to affect function of RXRα and PPARα of bivalve mollusks. The newly developed GAL4 factor-based yeast two-hybrid system can be used as a valuable tool for identification and quantification of compounds active in disturbing RXR and PPAR of bivalves.

Physiological responses in Nile tilapia (Oreochromis niloticus) induced by combined stress of environmental salinity and triphenyltin.

Triphenyltin (TPT) has attracted considerable attention owing to its vitality, bioaccumulation, and lurking damage. TPT widely exists in complex salinity areas such as estuaries and coastal regions. However, there are few studies on the toxicological behavior of TPT under different salinity. In the study, juvenile Nile tilapia (Oreochromis niloticus) were utilized as model animals to investigate the effects of environmental relevant TPT exposure on the osmoregulation and energy metabolism in gill under different salinity. The results showed that salinity and TPT single or combined exposure affected the morphology of the gill tissue. After TPT exposure, Na+-K+-ATPase (NKA) activity significantly decreased at 0 ppt, while NKA and Ca2+-Mg2+-ATPase (CMA) activities significantly increased at 15 ppt. In addition, significantly higher succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) activities were found in the control fish compared to the TPT-exposed ones at 15 ppt. Quantitative real-time PCR results showed that TPT exposure affected the expression of osmoregulation and energy metabolism-related genes under different salinity. Overall, TPT exposure interfered with osmoregulation and energy metabolism under different salinity. The study will provide reference data for assessing the toxicity of organotin compounds in complex-salinity areas.

A new perspective on endocrine disrupting effects of triphenyltin on marine medaka: From brain transcriptome, gut content metabolome and behavior.

Triphenyltin (TPT) is an endocrine contaminant that is often detected in the environment. However, the mechanism of the effects of TPT on biological systems is not fully understood. Here we exposed marine medaka (Oryzias melastigma) to TPT for 21 days. Brain transcriptome, intestinal content metabolism group, and behavior analysis were carried out. Through the comprehensive analysis of multiomics for the in-depth understanding of the ways related to health improvement, we determined that the glycine-serine-threonine metabolic axis was most perturbed by TPT. Through behavioral analysis, it was found that there was behavioral hyperactivity in the exposed group; behavioral hyperactivity may be caused by the interference of TPT with the neuroendocrine system. In order to gain a full understanding of the impacts of TPT on human health, transcriptomic screening of differential genes and an impartial attitude based on bioinformatics were used. Gene-disease interaction analysis using the Comparative Toxicogenomics Database (CTD) revealed the possible effects of TPT on human health. Finally, based on these findings, the relevant adverse outcome pathway (AOP), which is the "epigenetic modification of PPARG leading to adipogenesis," was identified from AOP Wiki. Further research is required to validate the potential AOP of TPT.

Prolonged exposure of azocyclotin induced inter- and transgenerational endocrine disruption on Danio rerio linked to transcriptomic and DNA methylomic alterations.

The transgenerational effect assessment linked to epigenetic analysis of environmental pollutants on eco (toxico)logical relevant species is regarded as a potential future risk-assessment tool. As an organotin acaricide widely used in China, azocyclotin can lead to endocrine disrupting effect on directly exposed environmental organisms, but whether it has transgenerational negative impact remains unknown. In order to illustrate this issue, in the present study, zebrafish, an aquatic model animal, was exposed to azocyclotin at less than µg/L level in a time span of embryonic stage to adult stage. Subsequently, the developmental and reproductive endocrine disrupting effects of azocyclotin on exposed F0 and unexposed offspring (F1 and F2) were evaluated. Result indicated that parentally exposed to 0.36 µg/L azocyclotin induced embryonic toxicity to unexposed offspring, and significantly (p < 0.05) reduced body weight (by 8.5%-13.9%), whole body length (by 4.8%-14.3%), hepatosomatic index (by 15.6%-24.3%), gonadosomatic index (by 5.3%-17.1%), egg production (by 19.5%-25.4%), estradiol content (47.0%-65.0%) and proportion of mature germ cells (by 29.3%-41.0% and 39.2%-47.7% for late oocytes and spermatozoa, respectively) in adults of F0 and offspring. Additionally, azocyclotin decreased the contents of 5-methycytosine in gonads of unexposed offspring (by 9.9%-38.6%, p < 0.05), led to genome-wide gene up-regulated expression bias and genomic DNA hypomethylation tendency in unexposed offspring. Moreover, based on the level of differentially methylated cytosine in promoter regions/gene body regions, it was found totally 5331/11,170 (in F1) and 3808/7507 (in F2) differentially expressed genes were closely related with differentially methylated genes (r > 0.6). The present study provided a primary evidence that prolonged exposure to low dose azocyclotin induced inter- and transgenerational endocrine disrupting effects on zebrafish probably linked to transcriptomic and DNA methylomic alterations.

Dibutyltin dichloride exposure affects mouse oocyte quality by inducing spindle defects and mitochondria dysfunction.

Dibutyltin dichloride (DBTCl) is a widespread environmental pollutant that is frequently employed as a light and heat sustainer for polyvinyl chloride (PVC) plastics and is a teratogen in vivo. Nevertheless, its destructiveness in mammalian oocytes remains unclear. This study highlighted the consequences of DBTCl vulnerability on mouse oocyte. Our results revealed that exposure to 5.0 mg/kg/day of DBTCl for ten days reduced the number of mature follicles and oocytes in the ovaries and inhibited the meiotic maturation of oocytes. Single-cell transcriptomic analysis indicated that DBTCl exposure interfered with the expression of more than 400 genes in oocytes, including those involved in multiple biological pathways. Specifically, DBTCl exposure impaired spindle assembly and chromosome alignment. In addition, DBTCl exposure caused mitochondrial dysfunction, which led to the accumulation of reactive oxygen species (ROS) and induced apoptosis. In summary, our study illustrates that mitochondrial dysfunction and redox perturbation are the major causes of the reduced quality of oocytes exposed to DBTCl.

Reproductive toxicity of environmental levels of triphenyltin to the marine rotifer, Brachionus plicatilis.

Triphenyltin (TPT) is a representative organotin often used in marine antifouling coatings, herbicides, and pesticides. However, leaching of TPT into water may be toxic to aquatic life. In this study, environmental concentrations of TPT were used to explore reproductive toxicity of TPT to Brachionus plicatilis, a representative marine rotifer. Toxicity was examined at individual, biochemical, and molecular levels and via phenotypic traits. Rotifers exposed to 10 ng/L TPT group showed increased population size, improved reproductive rate, and a higher weekly growth rate. At 100 ng/L TPT group, the greatest degree of oxidative damage was seen. Exposure to 200 ng/L TPT group shorten generation time, delayed reproduction, and obscured the reproductive peak. Expression of the Vasa gene associated with reproduction was increased after exposure to 10 and 200 ng/L TPT group and decreased at 100 ng/L TPT group. High concentrations of TPT reduced rotifer body length and width and slowed swimming speed. Findings provide a better understanding of the adverse effects of changing TPT concentrations on marine rotifer, by the life cycle parameters, oxidative stress defense mechanisms, expression of a gene related to reproduction, and phenotypic traits. This paper firstly analyzed the reproductive toxicity of environmental levels of organotin compounds to zooplankton, which provided new data support for the comprehensive evaluation of its marine ecological toxicity.

Temporal evolution of imposex and butyltin contamination in Gemophos viverratus from São Vicente (Cabo Verde) - a countercurrent trend on the world scenario.

Organotin (OT) based Antifouling Systems (AFS) were globally banned by the AFS Convention since 2008, but the Republic of Cabo Verde did not ratify this Convention, nor did it develop a national legislation to control OT-AFS. Gemophos viverratus imposex and butyltin tissue contamination were assessed around the São Vicente Island (Cabo Verde) in 2019 and compared with the data available from 2012. The vas deferens sequence index (VDSI), the relative penis length (RPL), the percentage of females with imposex (%I) and the percentage of sterilized females (%S) in 2019 ranged from 0 to 4.0, 0-84.4%, 0-100% and 0-5.1%, respectively, whilst TBT reached maximum values of ≈30 ng TBT-Sn g-1 dw in the whelk tissues. These values are very similar to those registered in 2012, which indicates that TBT pollution has not decreased over the years, in contrast to the declining trend observed worldwide.

Dibutyltin (DBT) inhibits in vitro androgen biosynthesis of rat immature Leydig cells.

Dibutyltin (DBT) is an organotine widely applied in stabilizing plastics and de-worm poultry agents. But the effects of DBT on immature Leydig cells remain elusive. Thus, the present study aims to investigate whether in vitro exposure to DBT affects immature Leydig cell function of androgen production and delineate the underlying mechanisms. 35 days old rat immature Leydig cells were isolated and exposed to DBT at different concentrations (0, 0.1, 0.5, and 1 µM). It was found that 0.5 and 1 µM DBT lowered androgen production from immature Leydig cells under basal conditions. DBT at 1 µM lowered androgen production from immature Leydig cells under the stimulations from luteinizing hormone or 8-Br-cAMP. DBT at 1 µM lowered 22R-hydroxycholesterol and pregnenolone-mediated androgen production from immature Leydig cells. DBT at 0.1, 0.5, and 1 µM down-regulated the mRNA expression levels of Lhcgr, Star, Cyp11a1, Hsd3b1, and Nr5a1. Further investigation found that DBT at 1 µM directly inhibited CYP11A1 and 3ß-HSD1 enzyme activities. In conclusion, this study told us that in vitro exposure to DBT inhibited androgen biosynthesis in immature Leydig cells by selectively interfering with the expressions and enzyme activities of CYP11A1 and 3ß-HSD1.

Toxicity of organotin compounds and the ecological risk of organic tin with co-existing contaminants in aquatic organisms.

Although organotin (OT) use is restricted worldwide, with the development of industry and agriculture, a large amount of OT is still discharged into aquatic environments. These OTs may interact with other pollutants that cause adverse biological effects (through bioaccumulation and/or toxicity), resulting in combined toxicity. Most research on OTs have focused on the exposure of a single analyte. Information on the toxicity of OTs and coexisting pollutants is quite limited, but is developing rapidly. This is the first review paper evaluating the current state of knowledge on the combined effects of OTs with co-pollutants. This paper reviews 1) the degradation of organotin; and 2) the combined toxicity of OTs and emerging pollutants (EP), heavy metals, and organic pollutants. Future research needs are discussed to better understand the risks associated with co-exposure to OT pollutants.