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With increasing urbanization and rapid industrialization, more and more environmental problems have arisen. Phthalates (PAEs) are the foremost and most widespread plasticizers and are readily emitted from these manufactured products into the environment. PAEs act as endocrine-disrupting chemicals (EDCs) and can have serious impacts on aquatic organisms as well as human health. In this study, the water quality criteria (WQC) of five PAEs (dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP)) for freshwater aquatic organisms were developed using a species sensitivity distribution (SSD) and a toxicity percentage ranking (TPR) approach. The results showed that long-term water quality criteria (LWQC) of PAEs using the SSD method could be 13.7, 11.1, 2.8, 7.8, and 0.53 μg/L, respectively. Criteria continuous concentrations (CCC) of PAEs were derived using the TPR method and determined to be 28.4, 13.1, 1.3, 2.5, and 1.6 μg/L, respectively. The five PAEs are commonly measured in China surface waters at concentrations between ng/L and μg/L. DBP, DEHP, and di-n-octyl phthalate (D n OP) were the most frequently detected PAEs, with occurrence rates ranging from 67% to 100%. The ecological risk assessment results of PAEs showed a decreasing order of risk at the national level, DEHP, DBP, DMP, DEP, D n OP. The results of this study will be of great benefit to China and other countries in revising water quality standards for the conservation of aquatic species. • The LWQC of DMP, DEP, DBP, BBP, DEHP with SSD are 13.7, 11.1, 2.8, 7.8, 0.53 μg/L. • The PAEs are measured in China surface waters at concentration between ng/L and μg/L. • The ERA of PAEs with the order of in Chinese water are DEHP > DBP > DMP > DEP > D n OP. [ABSTRACT FROM AUTHOR]

Abstract Bisphenol F (BPF), one of the alternatives to bisphenol A (BPA), can induce proliferation through the nuclear estrogen receptor ERα (estrogen receptor alpha) pathway in human breast cancer MCF-7 cells. However, the roles of membrane estrogen receptor GPER1 (G-protein-coupled receptor 1)-mediated signaling pathways in MCF-7 cell proliferation caused by BPF are unclear. The influence of BPF on MCF-7 cells was evaluated in terms of cell proliferation, intracellular calcium (Ca2+) fluctuations, and reactive oxygen species (ROS) generation. The molecular mechanisms of the cellular responses to low doses of BPF were studied through detecting the activations of ERα and GPER1-regulated PI3K/PKB or AKT (phosphatidylinotidol 3-kinase/protein kinase B) and ERK1/2 (extracellular-signa1-regulated kinase 1/2) signals. At 0.01–1 μM, BPF significantly promoted cell proliferation and elevated the levels of intracellular ROS and Ca2+. At these concentrations, BPF also significantly upregulated protein expressions of ERα, GPER1, c-myc, and cyclin D and phosphorylations of PKB and ERK1/2. Specific signal inhibitors decreased PKB and ERK1/2 phosphorylations and attenuated the effects of BPF. Silencing of GPER1 also significantly decreased BPF-induced cell proliferation. These results indicate that activating the GPER1-PI3K/PKB and ERK1/2 signals by low doses of BPF can regulate the response of MCF-7 cells and that ERα also influences the effects of exposure to BPF on the cells. The present study suggests a new mechanism by which BPF exerts relevant estrogenic action in cancer cells and also highlights the potential risks in using BPF as an alternative to BPA. Graphical abstract fx1 Highlights • BPF induces cell proliferation, elevates ROS and Ca2+ levels in MCF-7 cells • BPF can activate PI3K/PKB and ERK1/2 pathways via GPER1 • GPER1 signaling pathways mediate BPF-induced biological effects on MCF-7 cells • ERα inhibitor ICI also attenuates the effects of BPF on the cells • BPF exerts estrogenic activity by interactions between ERα and GPER1 pathways [ABSTRACT FROM AUTHOR]

Transition metals in the fourth period of the periodic table of the elements are widely widespread in aquatic environments. They could often occur at certain concentrations to cause adverse effects on aquatic life and human health. Generally, parametric models are mostly used to construct species sensitivity distributions (SSDs), which result in comparison for water quality criteria (WQC) of elements in the same period or group of the periodic table might be inaccurate and the results could be biased. To address this inadequacy, the non-parametric kernel density estimation (NPKDE) with its optimal bandwidths and testing methods were developed for establishing SSDs. The NPKDE was better fit, more robustness and better predicted than conventional normal and logistic parametric density estimations for constructing SSDs and deriving acute HC5 and WQC for transition metals in the fourth period of the periodic table. The decreasing sequence of HC5 values for the transition metals in the fourth period was Ti > Mn > V > Ni > Zn > Cu > Fe > Co > Cr(VI), which were not proportional to atomic number in the periodic table, and for different metals the relatively sensitive species were also different. The results indicated that except for physical and chemical properties there are other factors affecting toxicity mechanisms of transition metals. The proposed method enriched the methodological foundation for WQC. Meanwhile, it also provided a relatively innovative, accurate approach for the WQC derivation and risk assessment of the same group and period metals in aquatic environments to support protection of aquatic organisms. [ABSTRACT FROM AUTHOR]

Mineral elements and antibiotic-resistant bacterial pollutants in livestock and poultry farms' wastewater are often sources of ecological and public health problems. To understand the heavy-metal pollution status and the characteristics of drug-resistant Escherichia coli (E. coli) in swine-farm wastewater in Shandong Province and to provide guidance for the rational use of mineral-element additives, common antibiotics, and quaternary ammonium compound disinfectants on swine farms, 10 mineral elements were measured and E. coli isolated from wastewater and its resistance to 29 commonly used antibiotics and resistance genes was determined. Finally, phylogenetic and multi-locus sequence typing (MLST) analyses was performed on E. coli. The results showed serious pollution from iron and zinc, with a comprehensive pollution index of 708.94 and 3.13, respectively. It is worth noting that average iron levels in 75% (12/16) of the districts exceed allowable limits. Multidrug-resistant E. coli were found in every city of the province. The E. coli isolated from swine-farm wastewater were mainly resistant to tetracyclines (95.3%), chloramphenicol (77.8%), and sulfonamides (62.2%), while antibiotic resistance genes for quinolones, tetracyclines, sulfonamides, aminoglycosides, and β-lactams were all more than 60%. The clonal complex 10 (CC10) was prevalent, and ST10 and ST48 were dominant in E. coli isolates. Multidrug-resistant E. coli were widely distributed, with mainly A genotypes. However, the mechanism of the effect of iron on antibiotic resistance needs more study in this area. Thus, further strengthening the prevention and control of iron and zinc pollution and standardizing the use of antibiotics and mineral element additives in the swine industry are necessary. [Display omitted] • Iron and zinc were the highest detected pollutants in swine-farm wastewater. • Escherichia coli isolates from wastewater mainly resistant to tetracyclines. • Phylotype A of E. coli is the main pathogen in wastewater, among which CC10, like ST10 and ST48, was dominant. [ABSTRACT FROM AUTHOR]

The occurrence and distribution of target estrogenic compounds in a highly urbanized industry-impacted coastal bay were investigated, and contamination profiles were evaluated by estimating total estradiol equivalents (∑ EEQs) and risk quotients (RQs). Phenolic compounds were the most abundant xenoestrogens, but seldom showed contribution to the ∑ EEQs. The diethylstilbestrol (DES) and 17α-ethinylestradiol (EE2) were the major contributors followed by 17β-estradiol (E2) in comparison with a slight contribution from estrone (E1) and estriol (E3). Both ∑ EEQs and RQs indicated likely adverse effects posed on resident organisms. Further, multivariate statistical method comprehensively revealed pollution status by visualized factor scores and identified multiple “hotspots” of estrogenic sources, demonstrating the presence of complex pollution risk gradients inside and particularly outside of bay area. Overall, this study favors the integrative utilization of pollution indices and factor analysis as powerful tool to scientifically diagnose the pollution characterization of human-derived chemicals for better management decisions in aquatic environments. [ABSTRACT FROM AUTHOR]

Over the past 20 years, global production of copper (Cu) and zinc (Zn) rank in the top three compared to other metals such as Pb, Cd, Cr, Ni, As and Hg. However, due to the potential for exposure and toxicity to humans, more attention of environmental pollution was paid to other metals such as Cd and Hg. Aquatic organisms are sensitive to Cu and Zn. Even though internal concentrations of these required elements are homeostatically controlled, toxic effects can occur at the fish gill surface. In this work, concentrations in surface waters and toxic effects of Cu, Zn, Ni, Cr, Pb, Cd, As, Hg were determined and risk of various metals in Tai Lake, China were evaluated using both risk quotients and joint probability distributions. Two transition metals, Cu and Zn posed the greatest risks to aquatic organisms while measured concentrations of other metals were less than thresholds for adverse effects. Approximately 99.9% and 50.7% of the aquatic organisms were predicted to be affected by Cu and Zn in surface water of Tai Lake respectively. Our results highlight ecological risks of Cu and Zn in water of a typical, large, urban lake in Eastern China, which was ignored in the past. [ABSTRACT FROM AUTHOR]

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), an alternative to brominated flame retardants, might pose an exposure risk to humans and wild animals during fetal development. Our recent study suggested that short-term TDCIPP exposure during early development caused sex-dependent behavioral alteration in adults. In the present study, multigenerational neurodevelopmental toxicity upon early-life exposure of parental zebrafish was evaluated, and the possible underlying mechanisms were further explored. Specifically, after embryonic exposure (0–10 days post-fertilization, dpf) to TDCIPP (0, 0.01, 0.10, and 1.00 μM), zebrafish larvae were cultured in clean water until the sexually matured to produce progeny (F1). The results confirmed neurodevelopmental toxicity in F1 larvae characterized by changes of developmental endpoints, reduced thigmotaxis, as well as altered transcription of genes including myelin basic protein a (mbpa), growth associated protein (gap43) and synapsin IIa (syn2a). Sex-specific changes in thyroid hormones (THs) indicated the relationship of abnormal THs levels with previously reported neurotoxicity in adult females after early-life exposure to TDCIPP. Similar changing profiles of TH levels (increased T3 and decreased T4) in adult females and F1 eggs, but not in F1 larvae, suggested that the TH disruptions were primarily inherited from the maternal fish. Further results demonstrated hypermethylation of global DNA and key genes related to TH transport including transthyretin (ttr) and solute carrier family 16 member 2 (slc16a2), which might affect the transport of THs to target tissues, thus at least partially contributing to the neurodevelopmental toxicity in F1 larvae. Overall, our results confirmed that early-life TDCIPP exposure of parental fish could affect the early neurodevelopment of F1 offspring. The underlying mechanism could involve altered TH levels inherited from maternal zebrafish and epigenetic modifications in F1 larvae. [Display omitted] • Multigenerational effects of Tris (1,3-dichloro-2-propyl) phosphate were assessed. • The compound resulted in neurodevelopmental toxicity in unexposed F1 larvae. • Toxicity comprised changes in development, thigmotaxis, and gene transcription. • Altered thyroid hormone levels were inherited from treated female fish. • Thyroid hormone transport was affected by altered DNA methylation patterns. [ABSTRACT FROM AUTHOR]

Transition metals are widespread in aquatic environments and can be harmful when concentrations exceed thresholds. Especially for fish, an important component of the human diet, low concentrations of transition metals will directly affect their well-being. Different taxa are protected by unified water quality criteria (WQC) thresholds, which rarely consider the ecological status and economic value of different species. There is therefore an urgent need to study taxon-specific sensitivity. The present study established the species sensitivity distributions of nine typical transition metals (Cr, Mn, Fe, Ni, Cu, Zn, Ag, Cd and Hg) for protecting freshwater and seawater fish based on non-parametric kernel density estimation methods, and then derived their acute and chronic HC5-values. The results showed that Ag and Hg have the highest acute toxic potency to fish in freshwater as well as seawater. Compared with marine fish, freshwater fish were more tolerant to acute exposure to Cr, Fe, Ni and Zn, whilst being more sensitive to Ag and Cd. Moreover, edible fish are more sensitive than other fish to these metals in both freshwater and seawater, encouraging more protection of economically valuable fish that may potentially affect human health. The study provides a strong reference for future research on taxon-specific WQC for transition metals. [Display omitted] • NPKDE-SSDs of 9 metals for protecting freshwater and seawater fish were developed. • The sensitivity to transition metals between freshwater and marine fish are different. • The sensitive species for 9 metals to freshwater and marine are mainly edible fish. The findings demonstrate edible fish are more sensitive than other fish in both seawater and freshwater and provide a reference for the protection of fish and the establishment of their risk assessment from transition metals pollution. [ABSTRACT FROM AUTHOR]

Cresyl diphenyl phosphate (CDP), as a kind of aryl substituted organophosphate esters (OPEs), is commonly used as emerging flame retardants and plasticizers detected in environmental media. Due to the accumulation of CDP in organisms, it is very important to discover the toxicological mechanism and metabolic process of CDP. Hence, liver microsomes of crucian carps (Carassius carassius) were prepared for in vitro metabolism kinetics assay to estimate metabolism rates of CDP. After 140 min incubation, the depletion of CDP accounted for 58.1%–77.1% (expect 0.5 and 2 μM) of the administrated concentrations. The depletion rates were best fitted to the Michaelis-Menten model (R2 = 0.995), where maximum velocity (V max) and Michaelis-Menten constant (K m) were 12,700 ± 2120 pmol min−1·mg−1 protein and 1030 ± 212 μM, respectively. Moreover, the in vitro hepatic clearance (C Lint) of CDP was 12.3 μL min−1·mg−1 protein. Log K ow and bioconcentration factor (BCF) of aryl-OPEs were both higher than those of alkyl- and chlorinated-OPEs, indicating that CDP may easily accumulate in aquatic organisms. The results made clear that the metabolism rate of CDP was greater than those of other OPEs detected in liver microsomes in previous research. This paper was first of its kind to comprehensively investigate the in vitro metabolic kinetics of CDP in fish liver microsomes. The present study might provide useful information to understand the environmental fate and metabolic processes of these kinds of substances, and also provide a theoretical basis for the ecological risk assessment of emerging contaminants. Image 1 • The in vitro metabolic kinetics of CDP in fish liver microsomes was best fitted with Michaelis-Menten model. • The metabolic rates and Michaelis constants of CDP were much higher than other organophosphate esters. • The relatively higher metabolic rates of CDP were due to its high Log K ow and bioconcentration factor. The in vitro hepatic metabolic rates of cresyl diphenyl phosphate (CDP) were much more than other organophosphate esters, which were best fitted with the Michaelis-Menten model. [ABSTRACT FROM AUTHOR]

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) is a type halogenated organophosphate flame retardants (OPFRs), which has been identified as contaminants of emerging concern (CECs). The use and production of OPFRs began to increase gradually when brominated flame retardants (BFRs) were banned. Halogenated OPFRs, especially TDCPP have been considered to lead to mutagenicity and carcinogenesis and major concerns have been raised regarding their toxicity. In this study, the toxicity effects and mechanisms of TDCPP were summarized and ecological risk assessment was made regarding its potential impact on freshwater organisms. TDCPP has been widely detected in ecosystems throughout the world, with observed toxicity effects on both humans and freshwater organisms. Inhalation of the dust was found to be the main exposure for humans. TDCPP could be metabolized in the human body, and medium stability was achieved in human body with the main metabolite BDCPP. Aside from mutagenicity and carcinogenesis, TDCPP was also found to have the potential for endocrine disruption and impairing the human reproductive system. Furthermore, this study reviewed the results of previous toxicity experiments, including acute toxicity, growth and development toxicity, neurotoxicity, and hepatotoxicity in freshwater organisms. Risk assessment was made using the safety threshold method by comparing the toxicity data with the exposure data in freshwater. HC 5 (hazardous concentration for 5% of organisms) derived based on traditional endpoints of acute toxicity LC 50 (median lethal concentration) or EC 50 (concentration for 50% of maximal effect) was 877 μg/L. This value was much higher than the exposure concentration levels in the surface water with EXD 90 (exposure data with cumulative probability 90%) of 65.22 ng/L. However, based on the growth and development toxicity data, the derived HC 5 was 33.33 ng/L and the calculated MOS (margin of safety) was below 1. Therefore, the results validated the fact that the ecological risk of TDCPP could not be neglected for its growth and development toxicity. Image 1 • Toxicity effects and mechanisms of TDCPP to human beings and freshwater organisms were summarized. • Hazardous concentration for the protection of 95% freshwater organisms of TDCPP were derived. • Risk assessment was conducted with the threshold method of TDCPP. [ABSTRACT FROM AUTHOR]

Tris (2-ethylhexyl) phosphate (TEHP) is one of the most commonly used organophosphorus flame retardant (OPFR) analogues and is commonly detected in surface water and sediments. Limited information is available about the metabolic pathway or metabolite formation related to TEHP in fish. In this study, rare minnows (Gobiocyprisrarus) were exposed to TEHP in static water for 30 d to investigate the bioaccumulation and metabolite distribution in the fish muscle, liver, kidney, gill, GI-tract, ovary and testis. Based on the estimated k up , parent and k d,parent values, the bioconcentration factors (BCF parent) of TEHP in fish tissues were calculated in the order of kidney > ovary ≈ liver ≈ testis > gill ≈ GI-tract > muscle; this finding was consistent with the results of our previous study on other alkyl-substituted OPFRs. In addition, this study identified the metabolic profiles of TEHP in the liver. TEHP was oxidatively metabolized by the fish to a dealkylated metabolite (di 2-ethylhexyl phosphate; DEHP) and hydroxylated TEHP (OH-TEHP). OH-TEHP further underwent extensive phase II metabolism to yield glucuronic acid conjugates. DEHP was mainly distributed in rare minnow in the following order: liver > GI-tract > kidney ≫ other tissues. However, the metabolite showed lower accumulation potential in fish tissues than TEHP, with metabolite parent concentration factors (MPCFs) for DEHP of less than 0.1 in all the investigated tissues. The BCF parent values of TEHP in various fish tissues were only 9.0 × 10−3-7.2 × 10−4 times its estimated tissue-water partition coefficient (K tissue-water) values based on tissue lipid, protein and water contents, which indicated the significance of biotransformation in reducing the bioaccumulation potential of TEHP in fish. The toxicokinetic data in the present study help in understanding the tissue-specific bioaccumulation and metabolism pathways of TEHP in fish and highlight the importance of toxicology research on TEHP metabolites in aquatic organisms. Image 1 • The tissue BCF parent of TEHP followed the order of kidney > ovary ≈ liver ≈ testis > gill ≈ GI-tract > muscle. • TEHP was oxidatively metabolized in fish liver to DEHP and OH-TEHP. • DEHP distributed in tissues following order: liver > GI-tract > kidney ≫ other tissues, with low MPCFs (<1). • Biotransformation significantly reduced TEHP accumulation in fish tissues, as revealed by the low BCF parent. The biotransformation of TEHP to DEHP greatly affected its tissue distribution in rare minnow based on the parameters from two-level compartment toxicokinetic model. [ABSTRACT FROM AUTHOR]