'Environmental standard limit concentration' arsenic exposure is associated with anxiety, depression, and autism-like changes in early-life stage zebrafish.

Arsenic is a worldwide environmental pollutant that can impair human health. Previous studies have identified mental disorders induced by arsenic, but the environmental exposure concentrations in the early life stages associated with these disorders are poorly understood. In the present study, early-life stage zebrafish were used to explore the effects on mental disorders under 'environmental standard limit concentrations' arsenic exposures of 5, 10, 50, 150, and 500 µg/L. The results showed that arsenic exposure at these concentrations changed the locomotor behavior in larval zebrafish and was further associated with anxiety, depression, and autism-like behavior in both larval and juvenile zebrafish. Changes were noted at benchmark dose limit (BMDL) concentrations as low as 0.81 µg/L. Transcriptomics showed that immediate early genes (IEGs) fosab, egr1, egr2a, ier2b, egr3, and jund were decreased after arsenic exposure in larval and juvenile zebrafish. Nervous system impairment and anxiety, depression, and autism-like behaviors in early-life stage zebrafish at 'environmental standard limit concentrations' may be attributed to the downregulation of IEGs. These findings in zebrafish provided new experimental support for an arsenic toxicity threshold for mental disorders, and they suggest that low levels of environmental chemicals may be causative developmental factors for mental disorders.

Neurobehavioral toxic effects and mechanisms of 2-aminobenzothiazole exposure on zebrafish.

2-Aminobenzothiazole (NTH), a benzothiazole derivative, exhibits potent biochemical activities and plays a significant role in modern industry. Widespread and intensive utilization of NTH has led to its detection in aquatic environments, encompassing both groundwater and surface water. Despite its wide usage, the effect of NTH on developmental neurotoxicity in aquatic organisms remains uncharted. Therefore, the aim of this investigation was to create exposure models for short- and long-term studies in order to analyze the neurobehavioral toxic impact of NTH (0, 50, 500, and 5000 µg/L) on zebrafish, which includes motor function, anxiety, and memory performance, as well as to examine the mechanism of neurotoxicity. The results revealed a significant suppression of initial embryonic mobility by NTH. However, during short-term exposure experiments, it did not significantly impact the developmental neurobehavioral functions of zebrafish. In addition, significant effects on zebrafish were observed after long-term exposure to 50 and 500 µg/L NTH, mainly impacting locomotion, social behavior, anxiety, and cognitive functions. Moreover, NTH caused oxidative damage in adult zebrafish brain tissue, which was accompanied by abnormal expression of oxidative damage-related genes. Furthermore, the Real-Time PCR results indicated a significant suppression of genes related to exposure to NTH, specifically those in the GABA synthesis pathway (gabrg2, gad2, gad1b, and abat) and the 5-HT synthesis pathway (tph2, tph1b, pet1, and htr1aa). Taken together, this study demonstrates for the first time that chronic exposure to NTH decreases the expression of genes associated with the zebrafish GABA synthesis pathway and the 5-HT synthesis pathway. This suppression is accompanied by oxidative damage, ultimately resulting in neurobehavioral changes related to motor ability, anxiety, and memory performance.

Insight into the mechanisms of neuroendocrine toxicity induced by 6:2FTCA via thyroid hormone disruption.

6:2 fluorotonic carboxylic acid (6:2 FTCA), a novel substitute for perfluorooctanoic acid (PFOA), is being used gradually in industrial production such as coatings or processing aids, and its detection rate in the aqueous environment is increasing year by year, posing a potential safety risk to aquatic systems and public health. However, limited information is available on the effects and mechanism of 6:2 FTCA. Therefore, this study was conducted to understand better the neuroendocrine effects of early exposure to 6:2 FTCA and the underlying mechanisms on zebrafish. In this study, zebrafish embryos were treated to varied doses of 6:2 FTCA (0, 0.08 µg/mL, 0.8 µg/mL and 8 µg/mL) at 4 h post-fertilization (hpf) for a duration of six days, which exhibited a pronounced inhibition of early growth and induced a disorganized swim pattern characterized by reduced total swim distance and average swim speed. Simultaneously, the thyroid development of zebrafish larvae was partially hindered, accompanied by decreased T3 levels, altered genes associated with the expression of thyroid hormone synthesis, transformation and transportation and neurotransmitters associated with tryptophan and tyrosine metabolic pathways. Molecular docking results showed that 6:2 FTCA has a robust binding energy with the thyroid hormone receptor (TRß). Moreover, exogenous T3 supplementation can partially restore the adverse outcomes. Our findings indicated that 6:2 FTCA acts as a thyroid endocrine disruptor and can induce neuroendocrine toxic effects. Furthermore, our results show that targeting TRß may be a potentially therapeutic strategy for 6:2 FTCA-induced neuroendocrine disrupting effects.

Potential adverse outcome pathway (AOP) of emamectin benzoate mediated cardiovascular toxicity in zebrafish larvae (Danio rerio).

Emamectin benzoate (EMB) is an efficient insecticide which widely used as an anthelmintic drug additive in aquaculture fish. However, its extensive use has resulted in widespread pollution in the aquatic environment. Previous studies have identified the potential developmental and neurotoxic effects of EMB, however, systematic studies pertaining to the cardiovascular toxic effects of EMB on fish are scarce. In this study, zebrafish embryos were exposed to EMB at concentrations of 0, 0.1, 0.25, 0.5, 1, 2, 4, and 8 mg/L for 3 days, aiming to investigate the cardiovascular toxic effects of EMB via examining morphology, cardiac function, and vascular development phenotypes. It revealed that EMB exposure led to marked deteriorated effects, including adverse effects on mortality, hatching rate, and general morphological traits, such as malformation, heart rate, body length, and eye area, in zebrafish embryos/larvae. Furthermore, EMB exposure resulted in abnormal cardiac function and vascular development, triggering neutrophil migration and aggregation toward the pericardial and dorsal vascular regions, and finalized apoptosis in the zebrafish heart region, these phenomena were further deciperred by the transcriptome analysis that the Toll-like receptor pathway, P53 pathway, and apoptotic pathway were significantly affected by EMB exposure. Moreover, the molecular docking and aspirin anti-inflammatory rescue assays indicated that TLR2 and TLR4 might be the potential targets of EMB. Taken together, our study provides preliminary evidence that EMB may induce apoptosis by affecting inflammatory signaling pathways and eventually lead to abnormal cardiovascular development in zebrafish. This study provides a simple toxicological AOP framework for safe pesticide use and management strategies.

Paroxetine induced larva zebrafish cardiotoxicity through inflammation response.

Paroxetine (PRX) is a common antidepressant drug which widely existence in natural environment. Numerous studies in the past few decades have focused on the beneficial effects of PRX on depression, however, the toxic properties and the potential mechanisms remain unclear. In this study, zebrafish embryos were exposed to 1.0, 5.0, 10 and 20 mg/L of PRX from 4 to 120-hour-post-fertilization (hpf), and it showed that PRX exposure caused adverse effects in zebrafish embryos, including decreased body length, blood flow velocity, cardiac frequency, cardiac output and increased burst activity and atria area. Meanwhile, the Tg (myl7: EGFP) and Tg (lyz: DsRed) transgenic zebrafish were used to detect the cardiotoxicity and inflammation response of PRX. Moreover, the heart development associated genes (vmhc, amhc, hand2, nkx2.5, ta, tbx6, tbx16 and tbx20) and inflammatory genes (IL-10, IL-1ß, IL-8 and TNF-α) were up-regulated after PRX challenge. In addition, Aspirin was used to alleviate the PRX-induced heart development disorder. In conclusion, our study verified the PRX induced inflammatory related cardiotoxicity in larva zebrafish. Meanwhile, the current study shown the toxic effects of PRX in aquatic organism, and provide for the environmental safety of PRX.

PCDD/F and DL-PCB exposure among residents upwind and downwind of municipal solid waste incinerators and source identification.

Understanding the environmental and human impacts associated with polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) exposure from municipal solid waste incinerators (MSWIs) is challenging because information on ambient and dietary exposure levels, spatial characteristics, and potential exposure routes is limited. In this study, 20 households from two villages located on the upwind and downwind sides of a MSWI were selected to characterize the concentration and spatial distribution of PCDD/F and DL-PCB compounds in ambient and food samples, such as dust, air, soil, chicken, egg, and rice samples. The source of exposure was identified using congener profiles and principal component analysis. Overall, the dust and rice samples had the highest and lowest mean dioxin concentrations, respectively. Significant differences were observed (p < 0.01) in PCDD/F concentrations in chicken samples and DL-PCB concentrations in rice and air samples between the upwind and downwind villages. The exposure assessment indicated that the primary risk source was dietary exposure, especially from eggs, which had a PCDD/F toxic equivalency (TEQ) range of 0.31-14.38 pg TEQ/kg body weight (bw)/day, leading to adults in one household and children in two households exceeding the World Health Organization-defined threshold of 4 pg TEQ/kg bw/day. Chicken was the main contributor to the differences between upwind and downwind exposure. Based on the established congener profiles, the exposure routes of PCDD/Fs and DL-PCBs from the environment to food to humans were clarified.

Neurodevelopmental Toxicity of Emamectin Benzoate to the Early Life Stage of Zebrafish Larvae (Danio rerio).

Emamectin benzoate (EMB) is a widely used pesticide and feed additive in agriculture and aquaculture. It easily enters the aquatic environment through various pathways, thus causing adverse effects on aquatic organisms. However, there are no systematic studies regarding the effects of EMB on the developmental neurotoxicity of aquatic organisms. Therefore, the aim of this study was to evaluate the neurotoxic effects and mechanisms of EMB at different concentrations (0.1, 0.25, 0.5, 1, 2, 4 and 8 µg/mL) using zebrafish as a model. The results showed that EMB significantly inhibited the hatching rate, spontaneous movement, body length, and swim bladder development of zebrafish embryos, as well as significantly increased the malformation rate of zebrafish larvae. In addition, EMB adversely affected the axon length of motor neurons in Tg (hb9: eGFP) zebrafish and central nervous system (CNS) neurons in Tg (HuC: eGFP) zebrafish and significantly inhibited the locomotor behavior of zebrafish larvae. Meanwhile, EMB induced oxidative damage and was accompanied by increasing reactive oxygen species in the brains of zebrafish larvae. In addition, gene expression involvement in oxidative stress-related (cat, sod and Cu/Zn-sod), GABA neural pathway-related (gat1, gabra1, gad1b, abat and glsa), neurodevelopmental-related (syn2a, gfap, elavl3, shha, gap43 and Nrd) and swim bladder development-related (foxa3, pbxla, mnx1, has2 and elovlla) genes was significantly affected by EMB exposure. In conclusion, our study shows that exposure to EMB during the early life stages of zebrafish significantly increases oxidative damage and inhibits early central neuronal development, motor neuron axon growth and swim bladder development, ultimately leading to neurobehavioral changes in juvenile zebrafish.

Improving the protective ability of lignin against vascular and neurological development in BPAF-induced zebrafish by high-pressure homogenization technology.

The lack of a sufficient amount of functional groups in the lignin structure limits its bioapplication. In this work, high-pressure homogenization was performed on original kraft lignin (L-ORI) to prepare lignin nanoparticles (L-NANO), which aimed to improve its functional group contents for further vascular and neurological applications. The results showed that the prepared L-NANO possessed spherical structures with diameters of 40.3-160.4 nm and increased amount of hydroxyl groups. Compared to L-ORI, L-NANO possessed better in vivo and in vitro antioxidant capacity, which could endow it with enhanced protective effects for the vascular and neural development of bisphenol AF (BPAF)-induced zebrafish. In addition, L-NANO reduced the neurotoxicity and cardiovascular toxicity of BPAF in zebrafish by upregulating the expression levels of oxidative stress-related genes (Cu/Zn-Sod and cat), which could further significantly upregulate the expression levels of neurogenesis genes (elavl3, gap43, mbp, and syn2a) and protect the contraction of the cardinal vein (CCV) and early central nervous system development by upregulating the expression levels of vascular genes (flk1 and flt4). The excellent cardiovascular and neurodevelopmental protective ability of L-NANO indicated that high-pressure homogenization is a promising technology for improving the bioactivity of lignin.

The toxic effect of bisphenol AF and nanoplastic coexposure in parental and offspring generation zebrafish.

Microplastics (MPs) and bisphenol AF (BPAF) are two environmental pollutants that usually coexist in the natural environment. Studies of MPs or BPAF have gradually increased in recent years, but few studies have focused on the combination toxic effects. In this study, the subchronic model of adult zebrafish was exposed to 1 mg/L nanolevel microplastics and 200 µg/L BPAF for 45 days; the parental zebrafish were spawning every 3 days during exposure, and the effects of continuous poisoning were examined on the offspring after 1-9 spawns. The results showed that single BPAF exposure or BPAF and nanoplastic coexposure can both decrease the number of eggs laid and the locomotor behavior of parental zebrafish and impact the hatching rate, mortality, body length and locomotor behavior of offspring zebrafish, especially in 7-9 spawn. BPAF were accumulated in parental zebrafish intestinal in 334.62 ng/g in BPAF group and 594.52 ng/g in nm+BPAF group, and accumulated in whole offspring zebrafish for 281.6 ng/g in BPAF group and 321.46 ng/g in nm+BPAF group. Neurodevelopmental, inflammation, apoptosis and oxidative stress-related genes were also significantly increased after 7-9 spawn. In addition, the exacerbated accumulation in the BPAF+nm group in parental and offspring zebrafish may be the reason for the accelerated toxic effect in the present research. In this study, we investigated the combined effects of nanoplastics and BPAF on parental and offspring zebrafish in the aquatic environment to identify the accumulative toxic effects and provide new experimental support for assessing the effects of coexposure on aquatic organisms.

Long-term exposure of zebrafish to bisphenol F: Adverse effects on parental reproduction and offspring neurodevelopment.

Bisphenol F (BPF), an alternative to bisphenol A (BPA) has potential endocrine and reproductive toxicity; however, the effects of environmental concentrations of BPF on the reproductive and developmental toxicity of offspring following parental exposure to BPF remain unclear. In the present study, the effects of life-cycle BPF exposure at environmental concentrations on zebrafish reproduction, offspring growth, and development were investigated. The results showed that the life-cycle of BPF exposure significantly elevated oxidative stress levels, increased gonadal apoptosis, and reduced zebrafish (F0) spawning. Notably, through maternal transfer, BPF exposure significantly affected offspring development. Developmental parameters such as hatching rate, spontaneous movements, heart rate, body length, and locomotor behavior decreased in zebrafish larvae (F1). In addition, the expression levels of genes related to oxidative stress, apoptosis, and neurodevelopment were altered in F1 larvae. Therefore, the present study provides evidence that BPF, even at environmental concentrations, can be potentially adverse in terms of reproductive defects and offspring neurodevelopmental disorders. Therefore, BPF, as a substitute for BPA, is worthy of in-depth evaluation.

The potential mechanism of BPF-induced neurotoxicity in adult zebrafish: Correlation between untargeted metabolomics and gut microbiota.

Bisphenol F (BPF) is becoming the main substitute for bisphenol A (BPA) in plastics for food and beverage applications. Previous studies have demonstrated the neurotoxicity of BPF; however, its lifecycle toxicity and the underlying mechanisms remain poorly understood. In the current study, zebrafish were continuously exposed to BPF for four months from the embryo to adult stages in order to assess its neurotoxicity. Locomotor behaviors significantly decreased after BPF exposure, which was accompanied by a decrease in body weight, length, and hatching rate. Additionally, BPF increased the expression of inflammatory genes in the brain and destroyed the zebrafishes' intestinal integrity. Meanwhile, the 16S rRNA gene sequence results showed a significantly decreased microbiota abundance and diversity following BPF treatment. Neurotransmitter metabolites were also altered by BPF. Notably, the correlation analysis between microbiota and neurotransmitter metabolism verified that gut microbiota dysbiosis was closely related to the disturbance of neurotransmitter metabolites. Therefore, the present study evaluated the neurotoxicity of lifecycle exposure to BPF and unraveled a novel mechanism involving disturbance of neurotransmitter metabolism and gut dysbiosis, which may provide potential targets for BPF-mediated neurotoxicity.

Exposure of preschool-aged children to highly-concerned bisphenol analogues in Nanjing, East China.

Bisphenol analogues (BPs) have already attracted wide concern owing to the environmental and health risks they pose. The exposure pathways and health risk of preschool-aged children to BPs, however, are still poorly understood. In this study, we choose population survey with 184 preschool-age children from a suburb of Nanjing, eastern China, further reveal the internal and external exposures concentrations, distribution profiles, potential sources and eventually assess health risk of preschool-age children to eight kinds of BPs. The results verify that the 95th percentile (P95) concentrations of Æ©8BPs ranged from 0.27 to 41.6 ng/mL, with a median concentration of 7.83 ng/mL in the urine samples. BPA, and BPF were the predominant BPs in urine, accounting for 67.3%, and 18.0% of Æ©8BPs. The urine-based estimated daily intake (EDI) of Æ©8BPs was 187 ng/kg body weight/day. Similarly, BPA, and BPF were the main BPs in the environmental exposure sources, accounting for 80.8%, and 11.7% of the total BPs. Moreover, the total external exposure dose of Æ©8BPs via the environmental sources was 68.1 ng/kg body weight/day, including BPA (56 ng/kg body weight/day), BPF (7.68 ng/kg body weight/day) and BPB (2.62 ng/kg body weight/day). The oral intake of drinking water and food (vegetables and rice) was the main exposure pathways of BPs in preschool-age children. Furthermore, the hazard quotient (HQ) of BPs have been evaluated and the results show no occurrence of high risk. Additionally, the urine-based EDI was significantly higher than the total external exposure dose, suggesting the existence of other pathways of BP exposure to be further explored. To the best of our knowledge, this is the first study to conduct both an internal and external exposure assessment of BPs.

A systematic comparison of neurotoxicity of bisphenol A and its derivatives in zebrafish.

As more and more countries have prohibited the manufacture and sale of plastic products with bisphenol A (BPA), a number of bisphenol analogues (BPs), including BPS, BPF and BPAF, have gradually been used as its primary substitutes. Ideally, substitutes used to replace chemicals with environmental risks should be inert, so it makes sense that the risk of the similar chemical substitutes (BPS, BPF, and BPAF) should be assessed before they used. Therefore, in the present study, the neurotoxicity of four BPs at environmentally relevant concentration (200 µg/L) were systematically compared using zebrafish as a model. Our results showed that the four BPs (BPA, BPS, BPF and BPAF) exhibited no obvious effect on the hatchability, survival rate and body length of zebrafish larvae, noteworthily a significant inhibitory effect on spontaneous movement at 24 hpf was observed in the BPA, BPF and BPAF treatment groups. Behavioral tests showed that BPAF, BPF and BPA exposure significantly reduced the locomotor activity of the larvae. Additionally, BPAF treatment adversely affected motor neuron axon length in transgenic lines hb9-GFP zebrafish and decreased central nervous system (CNS) neurogenesis in transgenic lines HuC-GFP zebrafish. Intriguingly, BPAF displayed the strongest effects on the levels and metabolism of neurotransmitters, followed by BPF and BPA, while BPS showed the weakest effects on neurotransmitters. In conclusion, our study deciphered that environmentally relevant concentrations of BPs exposure exhibited differential degrees of neurotoxicity, which ranked as below: BPAF > BPF ≈ BPA > BPS. The possible mechanisms can be partially ascribed to the dramatical changes of multiple neurotransmitters and the inhibitory effects on neuronal development. These results suggest that BPAF and BPF should be carefully considered as alternatives to BPA.

High mortality and high PCDD/Fs exposure among residents downwind of municipal solid waste incinerators: A case study in China.

Studies on the human body burden of dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in populations around municipal solid waste incinerators (MSWIs) in China are limited. The objective of this study was to assess the potential adverse health effects of an 8-year MSWI on the surrounding population and identify possible exposure pathways. We hypothesized that the MSWI would result in different environmental impacts and population health outcomes between upwind and downwind of its 3 km vicinity. We conducted a 10-year retrospective mortality survey on the population surrounding the MSWI. Then, we selected 50 residents aged 50 years or older on each of the upwind and downwind sides of MSWI to test serum PCDD/Fs. Meanwhile, environmental and food exposures to PCDD/Fs were tested for selected residents. The age-adjusted mortality rates were significantly higher for residents downwind than upwind, but no significant difference was found in the standardized mortality ratio before and after the MSWI operation. The toxic equivalents (TEQ) and major congeners of PCDD/Fs were significantly higher in the sera of the downwind residents than in the upwind. The PCDD/Fs in air, soil, dust, and vegetables on the downwind side were not significantly different from those on the upwind side, but the mean concentrations of PCDD/Fs in downwind hen eggs was significantly higher than those from upwind. In conclusion, downwind residents living within 3 km of the MSWI had higher age-adjusted mortality and serum level of PCDD/Fs than upwind residents. This higher mortality rate among downwind residents was not associated with MSWI. However, the higher levels of PCDD/Fs in downwind hen eggs suggest that the downwind population dioxin exposure was related to their location.

A systematic comparison of the developmental vascular toxicity of bisphenol A and its alternatives in vivo and in vitro.

Due to the potential toxicity of bisphenol A (BPA), several bisphenols (BPs), including bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF), have been gradually used as its main substitutes, and the levels of these alternatives in different environmental media have been constantly increasing. Although some previous studies have shown that bisphenol substitutes have similar or greater acute toxicity and estrogenic effects than BPA, comparative studies on the cardiovascular toxicity of BPs have not been evaluated. In this study, the developmental vascular toxicity of BPA and three predominant substitutes (BPF, BPS and BPAF) were evaluated using zebrafish embryos and human vascular endothelial cells (HUVECs). BP exposure at a sublethal concentration of 1/10 96 h median lethal concentration (96 h-LC50) significantly hindered intersegmental vessel (ISV) growth, delayed common cardinal vein (CCV) remodeling and decreased subintestinal vessels (SIVs) in Tg (fli1:EGFP) zebrafish embryos. Meanwhile, the results of the endothelial tube formation assay showed that in vitro angiogenesis was inhibited by BP exposure. Mechanistically, BP exposure increased oxidative stress characterized by a significant decrease in superoxide dismutase (SOD) and catalase (CAT) activity, accompanied by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in both zebrafish and HUVECs. Therefore, the vascular toxicity and oxidative stress potency of the BPs were compared and evaluated, ranking as follows: BPAF > BPF > BPA > BPS. To the best of our knowledge, the present work, for the first time, systematically provides direct evidence for BPA and its alternatives on developmental vascular toxicity in vitro and in vivo. Therefore, these findings will provide insight into the rational and safe application of BPA substitutes.

Protective Effects of Lignin-Carbohydrate Complexes from Wheat Stalk against Bisphenol a Neurotoxicity in Zebrafish via Oxidative Stress.

Lignin-carbohydrate complexes (LCCs) from different lignocellulosic biomass have shown biological qualities as antioxidant and immunostimulant. By contrast, the application of LCCs as protectant against neurotoxicity caused by different compounds is scarce. In this work, two kinds of LCCs with carbohydrate-rich and lignin-rich fractions were obtained from wheat stalk and used to protect against BPA-neurotoxicity in zebrafish. The results showed that BPA at a concentration of 500 µg/L results in neurotoxicity, including significant behavioral inhibition, and prevents the expression of central nervous system proteins in transgenic zebrafish models (Tg (HuC-GFP)). When the zebrafish was treated by LCCs, the reactive oxygen species of zebrafish decreased significantly with the change of antioxidant enzymes and lipid peroxidation, which was due to the LCCs' ability to suppress the mRNA expression level of key genes related to nerves. This is essential in view of the neurotoxicity of BPA through oxidative stress. In addition, BPA exposure had negative effects on the exercise behavior, the catalase (CAT) and superoxide dismutase (SOD) activity, and the larval development and gene expression of zebrafish larvae, and LCC preparations could recover these negative effects by reducing oxidative stress. In zebrafish treated with BPA, carbohydrate-rich LCCs showed stronger antioxidant activity than lignin-rich LCCs, showing their potential as a neuroprotective agents.

Comparison of seven in silico tools for evaluating of daphnia and fish acute toxicity: case study on Chinese Priority Controlled Chemicals and new chemicals.

BACKGROUND: A number of predictive models for aquatic toxicity are available, however, the accuracy and extent of easy to use of these in silico tools in risk assessment still need further studied. This study evaluated the performance of seven in silico tools to daphnia and fish: ECOSAR, T.E.S.T., Danish QSAR Database, VEGA, KATE, Read Across and Trent Analysis. 37 Priority Controlled Chemicals in China (PCCs) and 92 New Chemicals (NCs) were used as validation dataset. RESULTS: In the quantitative evaluation to PCCs with the criteria of 10-fold difference between experimental value and estimated value, the accuracies of VEGA is the highest among all of the models, both in prediction of daphnia and fish acute toxicity, with accuracies of 100% and 90% after considering AD, respectively. The performance of KATE, ECOSAR and T.E.S.T. is similar, with accuracies are slightly lower than VEGA. The accuracy of Danish Q.D. is the lowest among the above tools with which QSAR is the main mechanism. The performance of Read Across and Trent Analysis is lowest among all of the tested in silico tools. The predictive ability of models to NCs was lower than that of PCCs possibly because never appeared in training set of the models, and ECOSAR perform best than other in silico tools. CONCLUSION: QSAR based in silico tools had the greater prediction accuracy than category approach (Read Across and Trent Analysis) in predicting the acute toxicity of daphnia and fish. Category approach (Read Across and Trent Analysis) requires expert knowledge to be utilized effectively. ECOSAR performs well in both PCCs and NCs, and the application shoud be promoted in both risk assessment and priority activities. We suggest that distribution of multiple data and water solubility should be considered when developing in silico models. Both more intelligent in silico tools and testing are necessary to identify hazards of Chemicals.

Aerobic and Anaerobic Biodegradability of Organophosphates in Activated Sludge Derived From Kitchen Garbage Biomass and Agricultural Residues.

Organophosphates (also known as organophosphate esters, OPEs) have in recent years been found to be significant pollutants in both aerobic and anaerobic activated sludge. Food waste, such as kitchen garbage and agricultural residues, can be used as co-substrates to treat the active sludge in sewage treatment plants (STPs). We investigated the biodegradability of nine OPEs derived from kitchen garbage biomass and agricultural residues under different conditions. Under anaerobic conditions, the rate of removal of triphenyl ester OPEs was significantly higher than that of chloride and alkyl OPEs. The addition of FeCl3 and Fe powder increased the rate of degradation of triphenyl ester OPEs, with a DT50 for triphenyl ester OPEs of 1.7-3.8 d for FeCl3 and 1.3-4.7 d for Fe powder, compared to a DT50 of 4.3-6.9 d for the blank control. Addition of an electron donor and a rhamnolipid increased the rate of removal of chlorinated OPEs, with DT50 values for tris(2-carboxyethyl)phosphine) (TCEP) and tris(1,3-dichloroisopropyl)phosphate (TDCPP) of 18.4 and 10.0 d, respectively, following addition of the electron donor, and 13.7 and 3.0 d, respectively, following addition of the rhamnolipid. However, addition of an electron donor, electron acceptor, surfactant, and Fe powder did not always increase the degradation of different kinds of OPEs, which was closely related to the structure of the OPEs. No treatment increased the removal of alkyl OPEs due to their low anaerobic degradability. Tween 80, a non-ionic surfactant, inhibited anaerobic degradation to some degree for all OPEs. Under aerobic conditions, alkyl OPEs were more easily degraded, chlorinated OPEs needed a long adaptation period to degrade and finally attain a 90% removal rate, while the rates of degradation of triphenyl ester OPEs were significantly affected by the concentration of sludge. Higher sludge concentrations help microorganisms to adapt and remove OPEs. This study provides new insights into methods for eliminating emerging pollutants using activated sludge cultured with kitchen garbage biomass and agricultural residues.

Titanium dioxide nanoparticle affects motor behavior, neurodevelopment and axonal growth in zebrafish (Danio rerio) larvae.

More attention has been recently paid to the ecotoxicity of titanium dioxide nanoparticles (nano-TiO2) owing to its common use in many fields. Although previous studies have shown that nano-TiO2 is neurotoxic, the mechanism is still largely unknown. In the present study, zebrafish embryos were exposed to 0.01, 0.1, and 1.0 mg/L nano-TiO2 and 1.0 mg/L micro-TiO2 for up to 6 days post-fertilization (dpf). Exposure to 1.0 mg/L nano-TiO2 significantly decreased the body length and weight of zebrafish larvae; however, the hatching and mortality rate of zebrafish embryos did not change. Behavioral tests showed that nano-TiO2 exposure significantly reduced the swimming speed and clockwise rotation times of the larvae. The results revealed that nano-TiO2 treatment adversely affected motor neuron axon length in Tg (hb9-GFP) zebrafish and decreased central nervous system (CNS) neurogenesis in Tg (HuC-GFP) zebrafish. Additionally, real-time polymerase chain reaction analysis demonstrated that genes associated with neurogenesis (nrd and elavl3) and axonal growth (α1-tubulin, mbp, and gap43) were significantly affected by nano-TiO2 exposure. In conclusion, our study demonstrated that early-life stage exposure of zebrafish to nano-TiO2 causes adverse neural outcomes through the inhibition of neurodevelopment and motor neuron axonal growth.

Oxidative stress in bisphenol AF-induced cardiotoxicity in zebrafish and the protective role of N-acetyl N-cysteine.

Research has shown that there is a relationship between bisphenol A (BPA) exposure and the incidence of cardiovascular diseases. However, the effect of bisphenol AF (BPAF), a main substitute for BPA, on heart development remains unclear. In this study, the cardiotoxicity of BPAF was evaluated in zebrafish in vivo and in human cardiac myocytes (HCMs) in vitro. Our results showed that BPAF at a concentration of 200 µg/L results in cardiotoxicity, including a reduced number of cardiomyocytes and endocardial cells in the heart, and reduced heart size in two transgenic zebrafish models (myl7:: dsred2-nuc and fli1a::nGFP). An increase in apoptosis was observed along with antioxidant enzyme inhibition and lipid peroxidation. In addition, the mRNA expression levels of several key genes involved in cardiac development were suppressed by BPAF treatment. In the HCM cell model, BPAF at 2 mg/L induced reactive oxygen species generation, antioxidant enzyme inhibition, mitochondrial dysfunction and oxidative DNA damage. These adverse outcomes can be attenuated by the antioxidant N-acetyl-L-cysteine (NAC), suggesting that oxidative stress is involved in BPAF-induced cardiotoxicity. These data indicated that BPAF exposure increased oxidative stress and apoptosis and that it suppressed the expression of genes involved in cardiac development, which may play crucial roles in the mechanisms of BPAF-induced cardiotoxicity.