STAT3 Pathways Contribute to ß-HCH Interference with Anticancer Tyrosine Kinase Inhibitors.

Organochlorine pesticides (OCPs) are a class of environmentally persistent and bioaccumulative pollutants. Among these, ß-hexachlorocyclohexane (ß-HCH) is a byproduct of lindane synthesis, one of the most worldwide widespread pesticides. ß-HCH cellular mechanisms inducing chemical carcinogenesis correspond to many of those inducing chemoresistance, in particular, by the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathways. For this purpose, four cell lines, representative of breast, lung, prostate, and hepatocellular cancers, were treated with ß-HCH, specific tyrosine kinase inhibitors (TKIs), and a STAT3 inhibitor. All cell samples were analyzed by a viability assay, immunoblotting analysis, a wound-healing assay, and a colony formation assay. The results show that ß-HCH reduces the efficacy of TKIs. The STAT3 protein, in this context, plays a central role. In fact, by inhibiting its activity, the efficacy of the anticancer drug is restored. Furthermore, this manuscript aimed to draw the attention of the scientific and socio-healthcare community to the issue of prolonged exposure to contaminants and their impact on drug efficacy.

Behavioural effects of early-life exposure to parabens in zebrafish larvae.

Parabens are classified as endocrine disrupting chemicals due to their ability to activate several nuclear receptors causing changes in hormones-dependent signalling pathways. Central nervous system of developing organisms is particularly vulnerable to changes in hormonal pathways, which could lead to altered brain function, abnormal behaviour and even diseases later in life. The aim of the present study was to investigate the effects of exposure to butylparaben (BuP), ethylparaben (EtP) and methylparaben (MeP) during early development on nervous system using zebrafish larvae's behavioural models. Zebrafish were exposed until 4 days post fertilization (dpf) to three concentrations of each paraben chosen considering the environmentally realistic concentrations of human exposure and the benchmark-dose lower bound calculated for zebrafish larvae (BuP: 5, 50 and 500 µg/L; EtP: 50, 500 and 5000 µg/L; MeP: 100, 1000 and 10,000 µg/L). Activity in novel and in familiar environment, thigmotaxis, visual startle response and photic synchronization of the behavioural circadian rhythms were analysed at 4, 5 and 6 dpf. Zebrafish larvae exposed to BuP 500 µg/L and EtP 5000 µg/L revealed increased anxiety-like behaviour in novel environment. Larvae treated with 500 µg/L of BuP showed reduced activity in familiar and marginally in unfamiliar environment, and larvae exposed to 5000 µg/L of EtP exhibited hyperactivity in familiar environment. Parabens exposure did not influence the visual startle response and the photic synchronization of circadian rhythms in zebrafish larvae. This research highlighted as the exposure to parabens has the potential to interfere with behavioural development of zebrafish.

Sublethal exposure to propylparaben leads to lipid metabolism impairment in zebrafish early-life stages.

Parabens are widely used in cosmetics, toiletries, food and pharmaceuticals. Toxicological effects of parabens on human lipid metabolism are not well established. The present study used the early-life stages of zebrafish (Danio rerio) to determine the toxicity of propylparaben (PP). The embryos were exposed for 96 hours postfertilization (hpf) at five different concentrations of PP, and lethal and sublethal alterations were recorded daily. The lethal concentration 50 (LC50 ) value was 3.98 mg/L. The most common sublethal alterations recorded at 1 and 2 mg/L were an enlarged and misshaped yolk sac, hyperexcitability, and reduction in head size and swim bladder. At sublethal concentrations of 1 and 2 mg/L, we observed an altered lipid metabolism, in terms of decrease in neutral lipid mobilization from yolk and alteration of phospholipid metabolism, both in the body and in the yolk sac. These observations were combined with strong head cartilage defects, indicating a strong effect of PP on head development. This research demonstrates that PP interferes with lipid utilization in zebrafish during early-life stages that might be involved in neurological and skeletal abnormalities.

Integrated Approach to Evaluate the Association between Exposure to Pesticides and Idiopathic Premature Thelarche in Girls: The PEACH Project.

Several pesticides are recognized as endocrine-disrupting chemicals (EDCs) since they can interfere with the dysregulation of sexual, thyroid and neuro-endocrine hormones. Children are particularly vulnerable to the adverse effects of EDCs due to their developmental stage, peculiar lifestyle and dietary habits. In this context, the exposure to pesticides represents an important risk factor associated with early development. This study deals with the possible association between exposure to pesticides and idiopathic premature thelarche in girls from areas of intensive agriculture practice in the Centre of Italy. An integrated approach was set up, including: (i) a case-control study on girls with idiopathic premature thelarche; (ii) the evaluation of multiple pesticides exposure in girls; (iii) the evaluation of multiple pesticides in food; (iv) the dietary intake of pesticide residues; (v) the assessment of toxicological effects of widely used pesticides by in vitro model. Data integration will provide an estimate of the predictive risk of potential effects on girls' health, linked to dietary intake.

Impact of Endocrine Disruptors on Vitellogenin Concentrations in Wild Brown Trout (Salmo trutta trutta).

The adverse effects of endocrine disruptors (EDs) on aquatic wildlife and human health represent a current issue of high public concern. Substantial knowledge of the level of estrogenic EDs in fish has accumulated from field surveys. For this purpose, a survey of wild brown trout (Salmo trutta trutta) was carried out to assess the incidence of EDs in the feral fish population living in the Liri river (Abruzzi, Italy). The results of this study show that this aquatic environment possesses an estrogenic potency that triggered the increase of vitellogenin levels in both female and male trouts. Fish exposed to different pesticides and urban waste in downstream river showed higher vitellogenin levels in comparison to the headwater site. Furthermore, some trouts coming from the downstream reported the presence of several pesticides and fungicides, some of these banned several years ago.

Toxicological, gene expression and histopathological evaluations of environmentally realistic concentrations of polybrominated diphenyl ethers PBDE- 47, PBDE-99 and PBDE-209 on zebrafish embryos.

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants. Biomonitoring studies have shown widespread presence of PBDEs in humans and their accumulation in food chain cause concern to human health, especially for foetus and infant development. The early-life stages are generally considered more sensitive to exposure to toxic compounds than juvenile or adults. For this reason the aim of this study was to evaluate the effects of the three most environmentally relevant BDE (BDE- 47, 99 and 209) on zebrafish embryos. The fish embryo toxicity (FET) OECD tests on zebrafish were performed followed by histopathogical examination to assess morphological changes. The gene expression of the thyroid stimulating hormone ß (Tshß), the transport proteins transthyretin (Ttr) and thyroxine-binding globulin (Tbg) as well as the enzyme iodothyronine deiodinase 1 (Dio1) was also assessed by Real-time PCR. BDE-47 and BDE-99 showed an increase of the severity of the effects at the lower concentrations while for the BDE-209 the effects were higher to the high concentrations. Although all compounds did not show any acute toxicity for none of the concentrations tested, they reported interesting sub-acute lesions, including yolk and pericardial edema, tail and head malformation, reduced and extremely reduced heart beat rate, blood stasis and spinal curvature, with the highest percentage recorded for BDE-209. Cardiac edema, damage of eye structure and hydrocephaly were confirmed also by histophatological examination. Furthermore, a toxic and dose-dependent liver vacuolization in BDE-209 was observed in all experimental groups. Although no statistically significant difference in gene expression was observed, BDE-209 up-regulated only Dio1 while the other congeners induced Tshß, Ttr, Tbg and Dio1. Overall, this research highlighted that exposure to BDE-47, BDE-99 and BDE-209 at realistic concentrations caused lethal and sub-lethal alterations and impaired genes involved in thyroid hormones homeostasis leading to abnormal development of zebrafish embryos.

Seasonal Trend of PAHs Concentrations in Farmed Mussels from the Coastal Areas of the Naples, Italy.

This paper reports on the results about the chemical pollution pressure in the Gulf of Naples and nearby coastal areas. Farmed mussels were analysed for the presence of polycyclic aromatic hydrocarbons (PAHs). The results documented a decreasing trend in the PAHs levels respect to the past years. The Bay of Pozzuoli remains as the most contaminated site within the Lucrino area with the highest reported number of samples exceeding the benzo(a)pyrene and PAHs sum limits. All the samples with concentrations above the European regulatory limit were collected in the winter period illustrating a seasonal trend of PAHs distribution in mussels during the 4 years investigated.

Heavy metal (As, Cd, Hg, Pb, Cu, Zn, Se) concentrations in muscle and bone of four commercial fish caught in the central Adriatic Sea, Italy.

Heavy metal (As, Cd, Cu, Pb, Zn, Hg and Se) concentrations in the muscle and bone of four fish species (Mullus barbatus, Merluccius merluccius, Micromesistius poutassou, and Scomber scombrus) from the central Adriatic Sea were measured and the relationships between fish size (length and weight) and metal concentrations in the tissues were investigated. Samples were analyzed by inductively coupled plasma-atomic emission spectrophotometry with automatic dual viewing. In the muscle, results of linear regression analysis showed that, except for mercury, significant relationships between metal concentrations and fish size were negative. Only mercury levels were positively correlated with Atlantic mackerel size (p < 0.05). No significant variations of heavy metal concentrations were observed in muscles of the examined species, but a significant difference (p < 0.01) was found for As, Cd, Pb, and Se concentrations in bone. All the investigated metals showed higher values in the muscle than in bone, except for lead and zinc. Regarding cadmium, lead, and mercury maximum levels, set for the edible portion by European legislation, several samples exceeded these values, confirming the heavy metal presence in species caught near the Jabuka Pit.

Nutritional quality and safety related to trace element content in fish from Tyrrhenian Sea.

This study analyzed for the detection of the following trace elements: As, Cd, Cu, Hg, Pb, Se, Zn, in muscle of four widely traded and consumed marine fish species (Mullus surmuletus L., Merluccius merluccius L., Micromesistius poutassou (Risso, 1827), Scomber scombrus L.) selected for their wide trade and consumption. Mean concentrations found in fish muscle, irrespective of species, ranged from 3.61 to 105.49 (As); 0.01-0.08 (Cd); 0.74-4.71 (Cu); 0.09-1.10 (Hg); 0.02-0.58 (Pb); 0.30-2.88 (Se); 11.56-73.37 (Zn) mg/kg wet weight. As, Hg, Cu and Se concentrations showed a significant difference (p < 0.01) among the analyzed species in winter and in summer. Cd exhibited a significant difference (p < 0.01) only in summer. The maximum levels set for Hg, Cd and Pb by European Regulation No 1881/2006 were exceeded by 5 (8.9%), 1 (1.8%) and 4 (7.1%) samples, respectively. In particular the species exceeding the legal limits were red mullet for Cd and Pb, Atlantic mackerel and blue whiting for Hg and Pb.

Sodium valproate effects on the morphological and neurobehavioral phenotype of zebrafish.

The anticonvulsant sodium valproate (SV) is frequently administered as a medicament but bears several negative effects in case of exposure during development. We analyzed extensively these early development effects of using the zebrafish model. Zebrafish embryos were exposed as eggs to two sublethal concentrations of SV, 10 and 25 mg/L. A general embryo toxicity analysis revealed extended anomalies in the cardiovascular system, and in the craniofacial and the spinal skeleton, as well as high mortality, in the embryos exposed to SV. The teratogenic potential of SV was confirmed in hacthed larvae by morphometric and cartilage profile analysis. Last, neurobehavioral impairments due to SV were highlighted in subjects' activity, anxiety, response to stimulations, habituation learning, and daily synchronization of locomotor activity, overall mirroring typical phenotypes associated with autistic spectrum disorders. In conclusion, our results confirmed the presence of extended and multifaced impacts of exposure to SV during development.

Stem-Cell-Driven Chondrogenesis: Perspectives on Amnion-Derived Cells.

Regenerative medicine harnesses stem cells' capacity to restore damaged tissues and organs. In vitro methods employing specific bioactive molecules, such as growth factors, bio-inductive scaffolds, 3D cultures, co-cultures, and mechanical stimuli, steer stem cells toward the desired differentiation pathways, mimicking their natural development. Chondrogenesis presents a challenge for regenerative medicine. This intricate process involves precise modulation of chondro-related transcription factors and pathways, critical for generating cartilage. Cartilage damage disrupts this process, impeding proper tissue healing due to its unique mechanical and anatomical characteristics. Consequently, the resultant tissue often forms fibrocartilage, which lacks adequate mechanical properties, posing a significant hurdle for effective regeneration. This review comprehensively explores studies showcasing the potential of amniotic mesenchymal stem cells (AMSCs) and amniotic epithelial cells (AECs) in chondrogenic differentiation. These cells exhibit innate characteristics that position them as promising candidates for regenerative medicine. Their capacity to differentiate toward chondrocytes offers a pathway for developing effective regenerative protocols. Understanding and leveraging the innate properties of AMSCs and AECs hold promise in addressing the challenges associated with cartilage repair, potentially offering superior outcomes in tissue regeneration.

Embryonic and larval exposure to propylparaben induces developmental and long-term neurotoxicity in zebrafish model.

Parabens are preservatives found in cosmetics, processed foods, and medications. The harmful repercussions on the central nervous system by one of the most common parabens, propylparaben (PrP), are yet unknown, especially during development. In this study, the neurodevelopmental effects of PrP and long-term neurotoxicity were investigated in the zebrafish model, using an integrated approach. Zebrafish embryos were exposed to two different concentrations of PrP (10 and 1000 µg/L), then larvae were examined for their behavioral phenotypes (open-field behavior, startle response, and circadian rhythmicity) and relevant brain markers (cyp19a1b, pax6a, shank3a, and gad1b). Long-term behavioral and cognitive impacts on sociability, cerebral functional asymmetry and thigmotaxis were also examined on juveniles at 30 dpf and 60 dpf. Moreover, proteomics and gene expression analysis were assessed in brains of 60 dpf zebrafish. Interestingly, thigmotaxis was decreased by the high dose in larvae and increased by the low dose in juveniles. The expression of shank3a and gad1b genes was repressed by both PrP concentrations pointing to possible effects of PrP on neurodevelopment and synaptogenesis. Proteomics analysis evidenced alterations related to brain development and lipid metabolism. Overall, the results demonstrated that early-life exposure to PrP promotes developmental and persistent neurobehavioral alterations in the zebrafish model, affecting genes and protein levels possibly associated with brain diseases.

Sodium valproate exposure influences the expression of pparg in the zebrafish model.

Valproic acid (VPA) is an anti-epileptic drug used alone or in combination with other medications to treat seizures, mania, and bipolar disorder. VPA recognized as a teratogenic chemical can cause severe birth defects mainly affecting the brain and spinal cord when administered during pregnancy. However, the potential mechanisms of developmental toxicity are still less studied, and in the present study, the influence of VPA exposure was evaluated on zebrafish early-life stages. Zebrafish were exposed to two sublethal concentrations of sodium valproate (SV) (0.06 mM and 0.15 mM) from 24 hours post-fertilization (hpf) to 96 hpf and the SV teratogenic potential was investigated through morphometric analysis of zebrafish larvae combined with the evaluation of cartilage profile. Moreover, the effect of SV on the transcription level of pparg was also performed. The results of the study showed the teratogenic potential of SV, which disrupts the morphometric signature of the head and body. The marked distortion of cartilage structures was paralleled to a malformation of telencephalon and optic tectum in both concentrations suggesting a high teratogen effect of SV on the brain. These data were further confirmed by the increased expression of pparg in the zebrafish head. Overall, the present study confirms the teratogenic activity of SV in the zebrafish model and, for the first time, points out the potential protective role of pparg in the SV dose-dependent toxicity.

Personal Care Products as a Contributing Factor to Antimicrobial Resistance: Current State and Novel Approach to Investigation.

Antimicrobial resistance (AMR) is one of the world's industrialized nations' biggest issues. It has a significant influence on the ecosystem and negatively affects human health. The overuse of antibiotics in the healthcare and agri-food industries has historically been defined as a leading factor, although the use of antimicrobial-containing personal care products plays a significant role in the spread of AMR. Lotions, creams, shampoos, soaps, shower gels, toothpaste, fragrances, and other items are used for everyday grooming and hygiene. However, in addition to the primary ingredients, additives are included to help preserve the product by lowering its microbial load and provide disinfection properties. These same substances are released into the environment, escaping traditional wastewater treatment methods and remaining in ecosystems where they contact microbial communities and promote the spread of resistance. The study of antimicrobial compounds, which are often solely researched from a toxicological point of view, must be resumed considering the recent discoveries, to highlight their contribution to AMR. Parabens, triclocarban, and triclosan are among the most worrying chemicals. To investigate this issue, more effective models must be chosen. Among them, zebrafish is a crucial study system because it allows for the assessment of both the risks associated with exposure to these substances as well as environmental monitoring. Furthermore, artificial intelligence-based computer systems are useful in simplifying the handling of antibiotic resistance data and speeding up drug discovery processes.

Environmentally relevant concentrations of triclocarban affect behaviour, learning, and brain gene expression in fish.

Many chemicals spilled in aquatic ecosystems can interfere with cognitive abilities and brain functions that control fitness-related behaviour. Hence, their harmful potential may be substantially underestimated. Triclocarban (TCC), one of the most common aquatic contaminants, is known to disrupt hormonal activity, but the consequences of this action on behaviour and its underlying cognitive mechanisms are unclear. We tried to fill this knowledge gap by analysing behaviour, cognitive abilities, and brain gene expression in zebrafish larvae exposed to TCC sublethal concentrations. TCC exposure substantially decreased exploratory behaviour and response to stimulation, while it increased sociability. Additionally, TCC reduced the cognitive performance of zebrafish in a habituation learning task. In the brain of TCC-exposed zebrafish, we found upregulation of c-fos, a gene involved in neural activity, and downregulation of bdnf, a gene that influences behavioural and cognitive traits such as activity, learning, and memory. Overall, our experiments highlight consistent effects of non-lethal TCC concentrations on behaviour, cognitive abilities, and brain functioning in a teleost fish, suggesting critical fitness consequences of these compounds in aquatic ecosystems as well as the potential to affect human health.

Ecotoxicological assessment of water phase exfoliated two-dimensional Group-VI transition metal dichalcogenides using zebrafish embryo model.

Among emerging layered materials, 2D transition metal dichalcogenides (TMDs) nanosheets (n-sheets) have received increasing attention for optoelectronics, energy storage, and, recently, for bioremediation and advanced biomedical applications; however, a lack of ecotoxicological in vivo studies is evident. Herein, for the first time, the potential nanotoxicity of liquid phase exfoliated Group VI TMDs n-sheets (MoS2, WS2, WSe2, and MoSe2) was comparatively investigated using zebrafish embryos (Z-EBs) as an in-vivo model. The 2D n-sheets were produced directly in aqueous-medium, the obtained n-sheets were characterized by scanning electron microscopy, Raman and visible spectroscopy, and their potential nanotoxicity was investigated by fish embryo test OECD TG 236. Chorionated and dechorionated embryos were used to assess the severity of TMD exposure. The survival rate, sublethal alteration during embryogenesis, hatching rate, and mortality were evaluated. TMDs n-sheets tend to adhere to the Z-EBs surface depending on their chemistry. Despite this, TMDs did not show lethal effects; weak sublethal effects were found for MoS2 and WSe2, while slight hatching delays were registered for MoSe2 and WSe2. The observed effects are attributable to the TMDs' tendency to interact with Z-EBs, because of the different chemistry. This work demonstrates how water-dispersed TMDs are potential eco/biocompatible materials.

Early-life exposure to environmentally relevant concentrations of triclocarban impairs ocular development in zebrafish larvae.

Triclocarban (TCC), is an antimicrobial component in personal care products and it is one of the emerging contaminants since it has been detected in various environmental matrices. Its presence in human cord blood, breast milk, and maternal urine raised issues about its possible impact on development and increased concerns about the safety of daily exposure. This study aims to provide additional information about the effects of zebrafish early-life exposure to TCC on eye development and visual function. Zebrafish embryos were exposed to two concentrations of TCC (5 and 50 µg/L) for 4 days. TCC-mediated toxicity was assessed in larvae at the end of exposure and in the long term (20 days post fertilization; dpf), through different biological end-points. The experiments showed that TCC exposure influences the retinal architecture. In 4 dpf treated larvae, we found a less organized ciliary marginal zone, a decrease in the inner nuclear and inner plexiform layers, and a decrease in the retinal ganglion cell layer. Photoreceptor and inner plexiform layers showed an increase in 20 dpf larvae at lower and both concentrations, respectively. The expression levels of two genes involved in eye development (mitfb and pax6a) were both decreased at the concentration of 5 µg/L in 4 dpf larvae, and an increase in mitfb was observed in 5 µg/L-exposed 20 dpf larvae. Interestingly, 20 dpf larvae failed to discriminate between visual stimuli, demonstrating notable visual perception impairments due to compound. The results prompt us to hypothesize that early-life exposure to TCC may have severe and potentially long-term effect on zebrafish visual function.

PCB concentrations in freshwater wild brown trouts (Salmo trutta trutta L) from Marche rivers, Central Italy.

The purpose of this study is to evaluate the degree of PCBs contamination of wild brown trouts (Salmo trutta trutta L) caught in Marche Region rivers and to study the percentage contribution of the sum of the six indicators PCBs with respect to the sum of eighteen congeners in wild brown trouts. The determination of eighteen PCBs was made on the edible portion (fillets) of trouts by GC-ECD analysis. Fish samples were collected from fourteen rivers, selected to represent the fluvial pollution in the Marche Region. The total sum of eighteen congener concentrations was 8.2±0.9 ng/g wet weight. All the analysed samples showed a high variability of their congener profile even though the six PCBs indicators stood for 49.8% of the total PCBs. In the muscle of brown trout the Σ eighteen PCB and the Σ six PCB concentrations were not statistically correlated with the length and the body mass of specimens. Total PCB (Σ eighteen PCBs and Σ six PCBs) concentrations measured in the different sampling sites showed significant statistical differences among districts and, in the same district, among rivers (p<0.01). In particular, the lowest PCB levels (p<0.01) were detected in fish caught in Pesaro-Urbino Province rivers with the mean total PCB concentrations of 102.4±6.3 ng/g fat weight while the highest PCB levels were measured in specimens coming from Macerata Province rivers (1147.8±456.6 ng/g fat weight).

Comparison of the Toxicological Effects of Pesticides in Non-Tumorigenic MCF-12A and Tumorigenic MCF-7 Human Breast Cells.

Humans are exposed to residues of organophosphate and neonicotinoid pesticides, commonly used in agriculture. Children are particularly vulnerable and, among possible adverse outcomes, the increased incidence of premature mammary gland development (thelarche) has raised concern. We evaluated the toxicological effects of chlorpyrifos (CPF), imidacloprid (IMI) and glyphosate (GLY) at exposure concentrations occurring in children on the tumorigenic MCF-7 and non-tumorigenic MCF-12A breast cell lines, as representative of the target organ model, assessing cytotoxicity, apoptosis, necrosis, intracellular reactive oxygen species (ROS) and ATP levels, 17ß-estradiol secretion and gene expression of nuclear receptors involved in mammary gland development. The pesticides decreased cell vitality in MCF-7 and cell proliferation in MCF-12A cells. ATP levels were decreased in MCF-7 cells by pesticides and apoptosis was increased in MCF-12A cells only by GLY (2.3 nM). ROS production was decreased by pesticides in both cell lines, except IMI (1.6 nM) in MCF-7 cells. Endocrine disrupting activity was highlighted by induction of 17ß-estradiol secretion and modulation of the gene expression of estrogen alpha and beta, progesterone, androgen, and aryl hydrocarbon receptors in both cell lines. The use of MCF-7 and MCF-12A cells highlighted dissimilar modes of action of each pesticide at low human relevant concentrations.

Developmental toxicity induced by triclosan exposure in zebrafish embryos.

OBJECTIVES: The present study aimed to investigate the acute toxicity and the developmental alterations induced by triclosan (TCS) exposure in zebrafish early-life stages using fish embryo acute toxicity tests as a methodological approach. MATERIAL AND METHODS: Zebrafish embryos were exposed to five concentrations of TCS and the four lethal alterations were daily recorded to determine the toxicological endpoints of acute toxicity. Furthermore, sublethal alterations were recorded to assess the effect of exposure concentrations on zebrafish embryo's development. RESULTS: The TCS toxicity was determined at 96 h of exposure as lethal concentration 10, lethal concentration 20, lethal concentration 50, lowest observed effects concentration, and no observed effects concentration, reported the following values: 168, 197.2, 267.8, 300, and 200 µg/L. Exposed larvae showed a delay in hatching rate and developed sublethal alterations including reduced blood flow, pericardial oedemata, reduced heartbeat, blood congestion, and craniofacial malformations. The number of zebrafish larvae developing cardiovascular alterations changed according to the tested concentrations and time of evaluation. CONCLUSION: The data confirmed the developmental toxicity of TCS on aquatic organisms and the sublethal alterations developed by zebrafish larvae, indicated its cardiotoxicity and neurotoxicity. Moreover, the developmental toxicity was strongly influenced by the concentration tested and the number of survived zebrafish developing this alteration varying according to the time of exposure.