Environmental Relevant Concentrations Research Articles

In vitro evaluation for estrogenic mechanisms of the disinfectant benzalkonium chloride as an emerging contaminant.

This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3β-HSD2, 17β-HSD1, 17β-HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism.

Colloidal stability of hematite nanoparticles in the presence of a common quaternary ammonium compound at environmentally-relevant concentrations

The stability of a model environmental nanomineral, colloidal hematite (α-Fe2O3) nanoparticles, can be strongly affected by environmentally-relevant levels of quaternary ammonium surfactants, a surfactant present in ubiquitous daily-use household products.

Mitochondrial dysfunction and lipometabolic disturbance induced by the co-effect of polystyrene nanoplastics and copper impede early life stage development of zebrafish (Danio rerio)

The co-exposure of NPs and Cu with environmentally-relevant concentration induced mitochondrial dysfunction and lipometabolic disturbance and consequently affected the development and survival of zebrafish at early life stages.

Environmentally relevant UV-light weathering of polystyrene micro- and nanoplastics promotes hepatotoxicity in a human cell line

Environmentally-relevant concentrations of UV-weathered polystyrene micro and nanoplastics induce hepatotoxicity and considerable changes in gene expression of liver disease-relevant pathways.

Charge-dependent negative effects of polystyrene nanoplastics on Oryzias melastigma under ocean acidification conditions

Marine nanoplastics (NPs) have attracted increasing global attentions because of their detrimental effects on marine environments. A co-existing major environmental concern is ocean acidification (OA). However, the effects of differentially charged NPs on marine organisms under OA conditions are poorly understood. We therefore investigated the effects of OA on the embryotoxicity of both positively and negatively charged polystyrene (PS) NPs to marine medaka (Oryzias melastigma). Positively charged PS-NH2 exhibited slighter aggregation under normal conditions and more aggregation under OA conditions than negatively charged PS-COOH. According to the integrated biomarker approach, OA reversed the toxicity of positively and negatively charged NPs towards embryos. Importantly, at environmental relevant concentrations, both types of PS-NPs could enter the embryos through chorionic pores and then transfer to the larvae. OA reversed the internalization of PS-NH2 and PS-COOH in O. melastigma. Overall, the reversed toxicity of PS-NH2 and PS-COOH associated with OA could be caused by the reversed bioavailability of NPs to O. melastigma, which was attributed to altered aggregation of the NPs in acidified seawater. This finding demonstrates the charge-dependent toxicity of NPs to marine fish and provides new insights into the potential hazard of NPs to marine environments under OA conditions that could be encountered in the near future.

Effect of low-density polyethylene, polyvinyl chloride, and high-density polyethylene micro-plastic contamination on the index and engineering properties of clayey soil- an experimental study

Soil health is one of the prominent features of the Sustainable Development Goals (SDGs). The SDGs seek to achieve the target of 75% healthy soils by 2030. On the contrary, the growing accumulation of microplastic contamination in soil environments is an issue of worldwide concern. The effect of a variety of microplastic accumulation on soil index and engineering properties is still unclear. Clayey soil is very important in geotechnical engineering because of its complex behaviour. This study investigates the effects of a variety of microplastics such as Low-Density Polyethylene (LDPE), Polyvinyl Chloride (PVC), and High-Density Polyethylene (HDPE) in environmental relevant concentrations (2%,4%,6% w/w) on index and engineering properties of clayey soil with respect to a number of observation days. In the present study, the non-contaminated soil treated as a control. The detailed experimentation revealed a significant change in the liquid limit, plastic limit, and shear strength values of clayey soil with an increasing percentage of microplastic contamination, whereas minute changes are recorded with respect to the number of observation days, this may be due to inert nature of microplastic. The shear strength is one of the critical engineering properties of soil that determines the strength and stability of the soil. The shear strength value of 0.94 kg/cm2 for control decreased to 0.76 kg/cm2 and 0.73 kg/cm2 and 0.85 kg/cm2 for the addition of 2%, 4%, and 6% respectively of LDPE microplastic contamination, similarly, for PVC microplastic contamination of 2%, 4% the shear strength decreases to 0.77 kg/cm2, 0.85 kg/cm2 respectively, the HDPE microplastic contamination of 2%, 4%, and 6% results in shear strength decrease to 0.52 kg/cm2, 0.53 kg/cm2 and 0.65 kg/cm2.The altered values of shear strength along with other index and engineering properties of soil due to microplastic contamination may lead to instability in structures or may increase the chances of harmful natural threats such as landslides. The present study provides evidence of significant changes in the index and engineering properties and therefore the stability of the soil which is the major contribution of the study.

Characterizing the obesogenic and fatty liver-inducing effects of Acetyl tributyl citrate (ATBC) plasticizer using both in vivo and in vitro models

The global incidence of obesity and non-alcoholic fatty liver disease (NAFLD) is rising rapidly in recent years. Environmental factors including usage of plastics and exposure to chemicals have been proposed as important contributors to the obesity pandemic. Acetyl tributyl citrate (ATBC) is a non-phthalate plasticizer widely used in food packaging, personal care products, medical devices and children’s toys etc. Due to its high leakage rate from plastics, exposure risk of ATBC keeps increasing. Although there are some studies investigating the safety of ATBC on human health, these studies mainly focused on high dosages and information regarding ATBC safety at environmental-relevant low levels is still limited.In this study, we aimed to evaluate the safety of subchronic exposure to environmentally-relevant concentrations of ATBC. C57BL/6J mice were orally exposed to ATBC for 6 or 14 weeks. Results indicated that ATBC exposure increased the body weight gain, the body fat content and the size of adipocytes, induced liver steatosis in mice. Consistent with in vivo effects, ATBC treatment increased the intracellular lipid accumulation in vitro hepatocytes. Transcriptome sequencing, qRT-PCR analysis and western blotting revealed that ATBC exposure affected the expression of genes involved in de novo lipogenesis and lipid uptake.Therefore, based on our subchronic and in vitro results, it suggested that ATBC might be a potential environmental obesogen with metabolism-disturbing and fatty liver-inducing risk, and its application in many consumer products should be carefully re-evaluated.

Assessment by a multi-technique approach of PtNPs' transformations in waters under relevant environmental concentrations and conditions

Once released to the environment, platinum nanoparticles (PtNPs) can undergo different transformations and are affected by several environmental conditions. An only analytical technique cannot provide all the information required to understand those complex processes, so new analytical developments are demanded. In the present work, the potential of asymmetric flow field flow fractionation hyphenated to inductively coupled plasma mass spectrometry (AF4-ICP-MS) for these studies, has been investigated, and classical dynamic and electrophoretic light scattering (DLS & ELS) have been used as complementary techniques. The role of ionic strength, ionic water composition, and natural organic matter (NOM) in the behaviour of PtNPs of different sizes (5 and 50 nm) has been specifically studied. Dynamic and electrophoretic light scattering have been used to track changes in the hydrodynamic diameters (dh) and polydispersity index (PdI) for 50 nm PtNPs (5 nm cannot be studied by DLS) and Z-potential values (for all sizes) to monitor aggregation. AF4-ICP-MS has been also employed to have a solid insight of aggregation at low environmental concentrations for different sizes of PtNPs simultaneously. The information gathered with those techniques was useful to observe changes as the ionic strength increases, which induces aggregation. Also, it was observed that this aggregation process was attenuated in the presence of organic matter. This approach, based on complementary analytical techniques, is needed for a comprehensive study of such complex interactions of NPs in the environment. AF4-ICP-MS is still under-exploited but shows a great potential for this purpose, especially low size NPs and concentrations.

Toxicological effects caused by environmental relevant concentrations of ketoconazole in Chironomus sancticaroli (Diptera, Chironomidae) larvae evaluated by oxidative stress biomarkers

Ketoconazole (KTZ), a broad-spectrum fungicidal drug, has been a significant problem in recent decades due to its toxic action on non-target aquatic organisms. Thus, the present study aimed to evaluate determine the effects that environmental relevant concentration of the commercial formulation of KTZ can exert on benthic macroinvertebrates, more specifically on larvae of the insect Chironomus sancticaroli. Acute toxicity tests with KTZ indicated lethal concentration (LC50) of 9.9 μg/L. Analyses of prolonged exposure to KTZ (chronic toxicity) indicated an increase in the rate of mentum deformity by approximately 3 times at concentrations of 0.6 and 2.4 μg/L. All biomarkers analyzed showed an increase after exposure to KTZ (0.6 and 2.4 μg/L), with average values of 115 % for superoxide dismutase (SOD), 63 % for catalase (CAT), 111 % for glutathione S-transferase (GST) and 59 % for malonaldehyde (MDA) in C. sancticaroli larvae. Thus, the toxic effects on survival, development (length and weight), mentum and redox responses caused by commercial KTZ in low concentrations were observed on C. sancticaroli larvae. In addition, the results suggest that biochemical biomarkers can be used for studies involving environmental disturbances.

NZVI-induced iron poisoning aggravated the toxicity of TCEP to earthworm in soil

Tris (2-chloroethyl) phosphate (TCEP) is a newly developed organophosphorus flame retardant that has been increasingly detected in soil as a contaminant. Nanoremediation is a potential solution for the control of TCEP, while the effectiveness and ecological risks are poorly understood. Here, we investigated the physicochemical interactions and joint toxicity of nano zero-valent iron (nZVI) (50–5000 mg/kg) and TCEP (50–5000 μg/kg) at environmental relevant concentrations to earthworms (Eisenia fetida) in soil. During a 28-d exposure, TCEP in soil was neither self-degraded nor removed by nZVI, and the individual toxicity of TCEP on the physiology of earthworms was significantly higher than that of nZVI. Notably, nZVI was found to synergize the toxicity of TCEP to earthworms without showing the classical “Trojan horse effect”. Mechanically, TCEP mainly induced a typical neurotoxicity, and indirectly inhibited the food ingestion and growth performance of earthworms; nZVI induced iron poisoning aggravated the intestinal damage and directly inhibited the energy metabolism, therefore exacerbated the TCEP-induced malnutrition. Our findings provide new insights into the toxic mechanisms of nZVI-TCEP co-exposure to soil organisms, and emphasize the necessity of risk assessment and cautious usage of nanoremediation in newly emerged contaminations.

Mechanism of bisphenol S exposure on color sensitivity of zebrafish larvae

Color vision, initiated from cone cells, is vitally essential for identifying environmental information in vertebrate. Although the retinotoxicity of bisphenol S (BPS) has been reported, data on the influence of BPS treatment on cone cells are scarce. In the present study, transgenic zebrafish (Danio rerio) labeling red and ultraviolet (UV) cones were exposed to BPS (0, 1, 10, and 100 μg/L) during the early stages of retinal development, to elucidate the mechanism underlying its retinal cone toxicity of BPS. The results showed that 10 and 100 μg/L BPS induced oxidative DNA damage, structural damage (decreased number of ribbon synapses), mosaic patterning disorder, and altered expression of genes involved in the phototransduction pathway in red and UV cones. Furthermore, BPS exposure also caused abnormal development of key neurons (retinal ganglion cells, optic nerve, and hypothalamus), responsible for transmitting the light-electrical signal to brain, and thereby resulted in inhibition of light-electrical signal transduction, finally diminishing the spectral sensitivity of zebrafish larvae to long- and short-type light signal at 5 day post fertilization. This study highlights the cone-toxicity of environmental relevant concentrations of BPS, and clarifies the mechanism of color vision impairment induced by BPS at the cellular level, updating the understanding of visual behavior driven by environmental factors.

Sorption behaviour and toxicity of an herbicide safener “cyprosulfamide”

Cyprosulfamide is a herbicide safener that works against the injurious effects of herbicides such as isoxaflutole, dicamba, nicosulfuron, tembotrione, thiencarbazone-methyl. However, its sorption behaviour in soils and toxicity to aquatic organisms are yet to be thoroughly examined. This study determined the octanol-water partition coefficient, sorption properties, acute and chronic toxic effects, and potency of cyprosulfamide to the cladoceran water flea (Daphnia magna). The influence of soil properties such as organic carbon content, cation exchange capacity, pH, and field capacity on adsorption and desorption properties were also examined. The Log Kow (0.55) of cyprosulfamide was less than that of some other safeners, such as benoxacor or furilazole, found in aquatic environments. The sorption of cyprosulfamide to the soil was driven by pH, so sorption decreased with an increase in pH. Other characteristics, such as cation exchange capacity (CEC), organic carbon content, and field capacity, do not directly correlate with the distribution coefficient. Cyprosulfamide generally has a low affinity for soil and is thus mobile and prone to transport to surrounding surface waters. No lethality was observed at the highest concentration (120 mg/L) tested for acute toxicity to D. magna; hence the LC50 will be >120 mg/L. During chronic exposures, cyprosulfamide caused adverse effects at a concentration of 120 mg/L on the number of neonates and brood size. The death rate for the chronic study was a function of concentration and increased with days of exposure. Cyprosulfamide is unlikely to cause lethality to D. magna at relevant environmental concentrations.

Age matters: Comparing life-stage responses to diluted bitumen exposure in coho salmon (Oncorhynchus kisutch)

Millions of liters of diluted bitumen (dilbit), a crude oil product from Canada's oil sands region, is transported through critical Pacific salmon habitat each day. While the toxicity of the water-soluble fraction of dilbit (WSFd) to early life-stages of salmon is known, quantitative data on life-stage differences in sensitivity to WSFd is missing. To fill this knowledge gap, we exposed two juvenile life-stages of coho salmon (O. kisutch) in parallel to very low (parts per billion), environmentally-relevant concentrations of WSFd for acute (48 h) and sub-chronic (4 wk) durations. The relative sensitivities of the two life-stages (fry and parr) were assessed by comparing the timing and magnitude of biological responses using common organismal and molecular endpoints of crude oil exposure. A significant reduction in body condition occurred in both fry and parr after 4 wk exposure to WSFd. Both life-stages also experienced a concentration-dependent decrease in time-to-loss-of-equilibrium during a hypoxia challenge test at both 48 h and 4 wk of exposure. Although organismal responses were similar, molecular responses were distinct between life-stages. In general, unexposed fry had higher baseline values of hepatic phase I biotransformation indicators than unexposed parr, but induction of EROD activity and cyp1a mRNA expression in response to WSFd exposure was greater in parr than in fry. Neither gst nor hsp70 mRNA expression, markers of phase II biotransformation and cell stress, respectively, were reliably altered by WSFd exposure in either life-stage. Taken together, results of this study do not support differential sensitivities of coho fry and parr to WSFd. All the same, the potential for ontogenic differences in the expression and induction of phase I biotransformation need to be considered because age does matter for these endpoints if they are used as bioindicators of exposure in post-spill impact assessments.

How aminomethylphosphonic acid (AMPA), the main glyphosate metabolite, interferes with chlorophyll biosynthesis?

Aminomethylphosphonic acid (AMPA) has been proposed to interfere with chlorophyll biosynthesis in photoautotrophic organisms – which may explain its greater toxicity to plants in relation to animals. By using the aquatic macrophyte Lemna minor , we investigated the AMPA toxicity and its effects on chlorophyll biosynthesis. Environmentally relevant concentrations (35–50 µg l -1 ) of AMPA reduced L. minor chlorophyll concentration with an EC 10 and EC 50 of 1.3 and 902.9 µg AMPA l -1 after seven days of exposure respectively but did not affect plant fresh weight/growth rate (EC 10 and EC 50 of 178.6/244.4 and 11,922.2/12,513.2 µg AMPA l -1 , respectively). AMPA decreased the activity of glycine decarboxylase (GDC), leading to glycine accumulation and glutamate (Glu) deprivation in plants. The lack of Glu prevents the synthesis of δ-aminolevulinic acid (ALA) in chloroplasts, interfering on chlorophyll synthesis. The negative effect of AMPA on chlorophyll concentration was reversible by supplementing growth media with Glu or ALA. The presence of AMPA in the aquatic ecosystems may contribute to their alteration by its negative effects on photosynthetic organisms through chlorophyll biosynthesis inhibition. Furthermore, we should stress out that AMPA could be toxic for animals and humans due to known toxicity of glycine induced by GDC inhibition. • Environmental relevant concentrations of AMPA reduce chlorophyll concentrations. • AMPA decreased the activity of the enzyme glycine decarboxylase (GDC). • AMPA induces the lack of glutamate and prevents the synthesis of ALA in chloroplasts. • Due to its negative effect on GDC, AMPA could be toxic for animals and humans.

Environmentally-relevant concentrations of the antipsychotic drugs sulpiride and clozapine induce abnormal dopamine and serotonin signaling in zebrafish brain

The presence of drugs in surface and groundwaters adversely affects the physiological function of non-target organisms due special activities that can pose a serious threats to various forms of aquatic life. Psychotropic drugs are one of the most commonly used drugs in the world. Hence, the aim of this study was to investigate the effect of environmentally-relevant concentrations of the antipsychotic drugs, sulpiride and clozapine, on dopaminergic (DAergic) and serotonergic (5-HTergic) neurotransmitter systems in the brain of zebrafish. Adult zebrafish (AB strain) were exposed to the environmentally-relevant concentrations of sulpiride, clozapine, or a mixture of sulpiride and clozapine. The effects of the drugs on the mRNA and protein levels of major functional molecules in DAergic and 5-HTergic systems were then analyzed in the telencephalon and diencephalon. Both drugs induced abnormal mRNA and protein levels of important functional molecules of the DA and 5-HT signaling pathways in both telencephalon and diencephalon, as shown by the abnormal transcriptional levels of TH, DAT, DR D1, DR D2, MAO, TPH, serotonin transporter (SERT), 5-HTR 1AA, 5-HTR 1B, 5-THR 2AA, and 5-HTR 2B, and the abnormal translational levels of DAT, DR D2, SERT, 5-HTR 1A, 5-HTR 1B, and 5-HTR 2B. In addition, we observed a specificity in the adverse effects of these antipsychotic drugs, in terms of doses and brain parts. Compared to their effects alone, the drug mixture had a weaker effect on the DA and 5-HT systems, suggesting an antagonistic interaction between sulpiride and clozapine. Our findings suggest that sulpiride and clozapine interfere with DAergic and 5-HTergic neurotransmitter systems in the telencephalon and diencephalon of zebrafish, resulting in possible effects on brain functions and posing a serious threat to the health of zebrafish.

Limited effects of environmentally-relevant concentrations in seawater of dibutyl phthalate, dimethyl phthalate, bisphenol A, and 4-nonylphenol on the reproductive products of coral-reef organisms

Plastic additives (PAs) are chemical compounds incorporated into the plastic during the manufacturing process. Phthalate acid esters, bisphenols, and nonylphenols are all PAs found in marine environments and associated with endocrine-disrupting processes. However, our knowledge regarding the impact of endocrine-disrupting PAs on coral-reef organisms is limited. As reef population structure is directly linked to reproduction and larval settlement processes, interference with hormonal systems can impact coral-reef community structure, particularly if the effects of PAs differ among species. In the current study we exposed the reproductive products of four tropical coral-reef invertebrates to environmentally-relevant concentrations of four prevalent PAs in seawater: dibutyl phthalate (DBP), dimethyl phthalate, (DMP), 4-nonylphenol (4-NP), and bisphenol A (BPA), as well as to 103 higher laboratory concentrations of these PAs. Our results revealed that apart from the significant negative effect of the 1 μg/L of 4-NP on the settlement of the soft coral Rhytisma fulvum, none of the other tested materials demonstrated a significant effect on the exposed organisms at environmentally-relevant concentrations in seawater. The 4-NP high laboratory concentration (1000 μg/L), however, had significant negative effects on all the examined species. The high laboratory BPA concentration (1000 μg/L) significantly reduced fertilization success in the solitary ascidian Herdmaniamomus, up to its complete failure to reproduce. Moreover, the high laboratory DMP concentration (100 μg/L) had a significant negative effect on planulae settlement of the stony coral Stylophora pistillata. Our findings demonstrate the negative and selective effects of PAs on the development and reproduction of coral-reef organisms; and, specifically, the significant effect found following exposure to 4-NP. Consequently, if we aim to fully understand the impact of these contaminants on this endangered ecosystem, we suggest that the actual concentrations within the living organism tissues should be tested in order to produce relevant risk assessments for brooding-coral species.

Lead and copper led to the dysregulation of bile acid homeostasis by impairing intestinal absorption in Bufo gargarizans larvae: An integrated metabolomics and transcriptomics approach

Bile acids, as metabolic regulators and signaling molecules, play key roles in the regulation of host metabolism and immune responses. Heavy metals such as lead (Pb) and copper (Cu) are widespread environmental pollutants that threaten public health. However, the effects of heavy metals on bile acid metabolism and the underlying molecular mechanisms remain unclear, particularly for ecologically important amphibian species. In the present research, the effects of exposure to environmentally-relevant concentrations of Pb (250 μg/L), Cu (50 μg/L), and a mixture of both (Mix) on bile acid metabolism and the underlying molecular mechanisms in the intestines of Bufo gargarizans larvae were comprehensively investigated using histopathology, metabolomics and transcriptomics analysis. Our results suggested that Pb and/or Cu caused histopathological damage to the intestine and liver, such as decreased intestinal epithelial cell height and dilated hepatic sinusoid. The total bile acid level was decreased in the Pb and Mix exposure groups but elevated in the Cu treatment. A significant decrease in the ratio of conjugated to unconjugated bile acids was present in all treatment groups. Also, the level of GCA was increased while TCA and TCDCA were decreased in all exposure groups. In addition, exposure to Pb and Cu altered the expression levels of genes related to intestinal absorption. For example, mrp2, mrp3 and aqp4 had higher expression in the Pb and Mix treatment groups, and aqp1 and mrp4 were increased in the Cu treatment group. Overall, we speculated that the dysregulation of bile acid homeostasis induced by Pb and Cu exposure may be due to impaired intestinal absorption. These findings raise further concerns about the hazards of Pb and/or Cu in influencing bile acid metabolism that might lead to the development of metabolic diseases and inflammatory disorders.

Trace metal complexation with dissolved organic matter stresses microbial metabolisms and triggers community shifts: The intercorrelations

The response of microorganisms to heavy metal-dissolved organic matter (Me-DOM) complexation is critical for the microbial-mediated coupled biogeochemical cycling of metals and DOM. This study investigated the impact of typical metals [As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn (at an environmentally-relevant concentration of 200 ppb)], model DOM substrates [humic acids (HA) and bovine serum albumin (BSA)], and their complexation on riverine microbial DOM metabolisms. DOM biodegradability decreased after the metal complexation (especially Co, Cr, and Mn for HA and Ni for BSA). While microbial transformation of humics and proteins was observed, components with lower aromaticity and hydrophobicity were accumulated during the cultivation. The substrate difference and metal speciation changed community compositions and resulted in distinctive community member networks, which accounted for the varied metabolic DOM patterns. The correlations indicated that rather than metal uptakes, Me-DOM complexation and community shifts controlled microbial DOM metabolisms. Microbial BSA metabolisms were less correlated to the key genera identified by network analysis or community diversity. Instead, they were sensitive to metal speciation, which may be attributed to the complicated utilization and production of proteins and their essential roles in detoxification. The constructed correlations among metals (Me-DOM complexes), DOM metabolisms, and community shifts provide strong implications for the biogeochemical function of Me-DOM complexes and highlight the effect of metal speciation on microbial protein metabolisms even at trace concentrations.

Identification by Liquid Chromatography-Tandem Mass Spectrometry and Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry of the Contributor to the Thyroid Hormone Receptor Agonist Activity in Effluents from Sewage Treatment Plants.

3,3',5-Triiodothyroacetic acid (TRIAC) was identified as a major contributor to the activity of thyroid hormone receptor (TR) agonists in environmental water. TRIAC contributed 60-148% of the TR-agonist activity in effluents from sewage treatment plants (STPs). Meanwhile, the contributions of 3,5,3'-triiodothyronine (T3), 3,3',5,5'-tetraiodothyronine (T4), and analogues were <1%. TRIAC concentrations in the range of 0.30-4.2 ng/L are likely enough to cause disruption of the thyroid system in living aquatic organisms. The origin of TRIAC in the STP effluents was investigated by analyzing both STP influents and effluents. Relatively high concentrations of T3 and T4 (2.5 and 6.3 ng/L, respectively) were found only in the influents. TRIAC was identified only in the effluents. These findings suggested that T3 and T4 in STP influents were potentially converted into TRIAC during activated sludge treatment or by other means. The evaluation of TRIAC at relevant environmental concentrations by in vivo assays and an appropriate treatment to reduce the TR activity in sewage are needed.

BDE-209 and TCDD enhance metastatic characteristics of melanoma cells after chronic exposure

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and BDE-209 (decabromodiphenyl ether) are persistent organic pollutants (POPs) produced by industrial activities and associated with several diseases. TCDD is a known human carcinogen, but few studies investigated about the effects of exposure to both compounds, i.e., whether BDE-209 and TCDD can render tumor cells more aggressive and metastatic. In the current study we investigated if the exposure of B16–F1 and B16–F10 melanoma murine cells to environmental relevant concentrations of TCDD and BDE-209 at 24 h and 15-day exposure modulates the expression of genes related to metastasis, making the cells more aggressive. Both pollutants did not affect cell viability but lead to increase of cell proliferation, including the upregulation of vimentin, MMP2, MMP9, MMP14 and PGK1 gene expression and downregulation of E-cadherin, TIMP2, TIMP3 and RECK, strongly suggesting changes in cell phenotypes defined as epithelial to mesenchymal transition (EMT) in BDE-209 and TCDD-exposed cells. Foremost, increased expression of metalloproteinases and decreased expression of their inhibitors made B16–F1 cells similar the more aggressive B16–F10 cell line. Also, the higher secretion of extracellular vesicles by cells after acute exposure to BDE-209 could be related with the phenotype changes. These results are a strong indication of the potential of BDE-209 and TCDD to modulate cell phenotype, leading to a more aggressive profile.