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Arsenic (As) in the aquatic environment is a considerable environmental issue, previous studies have reported the toxic effects of low concentrations (≤ 150 μg/L) of As on fish. However, limited information is available regarding the impact of low levels of As on apoptosis. To evaluate this, zebrafish embryos were exposed to different concentrations (0, 25, 50, 75, and 150 μg/L) of As (arsenite [AsIII] and arsenate [AsV]) for 120 h. Our results indicated that low concentrations of AsIII exposure significantly inhibited the survival of zebrafish larvae, and significantly increased the transcription of Caspase-9 and Caspase-3, the ratio of Bax/Bcl-2 transcription, and protein levels of Caspase-3. In contrast, AsV decreased the ratios of Bax/Bcl-2 transcription and protein levels, as well as protein levels of Caspase-3. Our data demonstrated that AsIII and AsV exert different toxic effects, AsIII induced apoptosis via the mitochondrial pathway and the extrinsic pathway, while AsV induced apoptosis only via the mitochondrial pathway., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Gill, as the organ of fish to contact most directly with xenobiotics, suffered more threat. To evaluate the impact of arsenite (AsIII) on the gill of fish, we measured the antioxidative responses (superoxide dismutase (SOD) and catalase (CAT) activities) and oxidative damage (malondialdehyde (MDA) content), histological changes and mRNA transcriptional responses of zebrafish gill, after exposure to AsIII (0, 10, 50, 100, and 150 μg L -1 ) solutions for 28 days. We found that AsIII increased the activities of CAT by 46%-87%, decreased the activities of SOD and the contents of MDA by 19% and 21%-32%. Furthermore, CuZnSOD and MnSOD mRNA transcription levels were also inhibited, decreasing by 62%-82% and 70%-77%. Besides, ≥ 100 μg L -1 AsIII also caused histological changes (a loss of mucus and desquamation in the surface of the epithelial cells) on zebrafish gill. These results showed that low concentrations of AsIII influenced biochemical and physiological performances of fish gill, which probably aggravates the toxic effect of AsIII on fish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hand-to-mouth activity is an important pathway for children's exposure to contaminated soils, which is often co-contaminated by Pb and As in mining and smelting sites. To reduce soil Pb risk to humans by oral exposure, phosphate amendments have been used to reduce Pb relative bioavailability (RBA), but its efficiency has not been investigated using validated in vitro assays nor its influence on As-RBA. Here, 5 contaminated soils (A-E) were amended with 0.5% phosphoric acid (PA) to study its effect on Pb- and As- RBA using a newly-developed mouse kidney model and bioaccessibility using 4 in vitro assays including UBM, SBRC, IVG, and PBET. Based on the mouse kidney model, Pb-RBA in PA-amended soils decreased from 14.2-62.5% to 10.1-29.8%. In contrast, As-RBA decreased from 26.5% to 15.9% in soil B but increased from 27.5 to 41.2% in soil D, with changes being insignificant in 3 other soils (35.8-58.8 to 28.1-61.1%). When assessing Pb bioaccessibility in PA-amended soils, decreased bioaccessibility were found using PBET and SBRC. For As, its bioaccessibility increased in PA-amended soils, inconsistent with in vivo data. Our results shed light on the importance of method selection to assess risk in Pb- and As-contaminated soils amended with phosphate., (Copyright © 2017 Elsevier B.V. All rights reserved.)

As a replacement for polybrominated diphenyl ethers, bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a novel flame retardant and has been detected in many environmental matrix including human blood. TBPH can be metabolized into mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) by carboxylesterase. However, their adverse effects on human vascular endothelium and their potential impacts on human cardiovascular disease are unknown. In this study, their adverse effects and associated molecular mechanisms on human vascular endothelial cells (HUVECs) were investigated. A concentration-dependent inhibition on HUVECs' viability and growth was observed for TBMEHP but not for TBPH. TBMEHP induced a marked G 0 /G 1 cell cycle arrest and robust cell apoptosis at 1μg/mL by inducing expression of p53, GADD45α and cyclin dependent kinase (CDK) inhibitors (p21and p27) while suppressing the expression of cyclin D1, CDK2, CDK6, and Bcl-2. Unlike TBMEHP, TBPH caused early apoptosis after G 2 /M phase arrest only at 10μg/mL via up-regulation of p21 and down-regulation of CDK2 and CDK4. TBMEHP decreased mitochondrial membrane potential and increased caspase-3 activity at 1μg/mL, suggesting that activation of p53 and mitochondrial pathway were involved in the cell apoptosis. The data showed that TBPH and TBMEHP induced different cell cycle arrest and apoptosis through different molecular mechanisms with much higher toxicity for TBMEHP. Our study implies that the metabolites of TBPH, possibly other novel brominated flame retardants, may be of potential concern for human cardiovascular disease., (Published by Elsevier Inc.)

Mouse is an acceptable animal model to measure lead (Pb) relative bioavailability (RBA) in contaminated soils; however, there is a lack of comparisons among Pb-RBA measurements based on different endpoints and dosing approaches. In this study, 12 soils (47.8-8123mg Pbkg -1 ) were assessed for Pb-RBA using Pb accumulation in mouse liver, kidneys, and/or femur following a 10-d steady state soil dose via diet, with 6 soils being measured using mouse bioassays with area under the mouse blood Pb concentration time curve (AUC) following a single gavaged dose as the endpoint. Based on individual endpoints of the steady state method, Pb-RBA in soils was 2.1-83.4%, being generally consistent among liver, kidneys, and femur with strong linear correlations between them (r 2 =0.74-0.89). To compensate variation in Pb distribution among different tissues, Pb-RBA was further calculated using a combined endpoint (e.g., sum of Pb accumulation in liver, kidneys, and femur). Compared to Pb-RBA based on individual tissue showing relative standard deviation (RSD) of 11.9-15.8%, Pb-RBA using the combined endpoint showed lower RSD (10.8%), thereby being more robust. For the 6 soils with Pb-RBA based on both mouse single gavaged and steady state dosing approach, no significant difference was observed; however, steady state approach was more repeatable among animals with lower RSD (11.4% vs. 34.5%). To ensure robustness of in vivo data, the steady state dosing approach with Pb accumulation in combined tissues is recommended., (Published by Elsevier B.V.)

Arsenic (As) contamination in aquatic environment adversely impacts aquatic organisms. The present study assessed the toxicity of different As species and concentrations on bighead carp (Hypophthalmichthys nobilis) at early life stage, a major fish in Yangtze River, China. We measured the changes in embryo and larvae survival rate, larvae aberration, concentrations of thyroid hormone thyroxine, and transcription levels of thyroid hormone receptors (TRs) in fish larvae after exposing to arsenite (AsIII) or arsenate (AsV) at 0, 10, 30, 50, 100, or 150 μg L(-1) for 78 h. As concentrations ≤ 150 μg L(-1) had limited effect on embryo survival rate (6-8% inhibition), but larvae survival rate decreased to 53-57% and larvae aberration rate increased to 20-24% after As exposure. Moreover, thyroxine levels elevated by 23% and 50% at 100 μg L(-1) AsIII and 150 μg L(-1) AsV. Besides, AsIII and AsV decreased the transcriptional levels of TRα by 72 and 53%, and TRβ by 91 and 81% at 150 μg L(-1) As. Our data showed that AsIII and AsV had limited effect on carp embryo survival, but they were both toxic to carp larvae, with AsIII showing more effect than AsV. As concentrations <150μg L(-1) adversely influenced the development of bighead carp larvae and disturbed their thyroid hormone homeostasis., (Published by Elsevier B.V.)

Antimony (Sb) accumulation in rice is a potential threat to human health, but its uptake mechanisms are unclear. A hydroponic experiment was conducted to investigate uptake, translocation, speciation and subcellular distribution of Sb in rice plants exposed to antimonite (SbIII) and antimonate (SbV) at 0.2, 1.0 or 5.0 mg/L for 4h. More Sb was accumulated in iron plaque than in the plant, with both the roots (~10-12 times) and Fe plaque (~28-54 times) sequestering more SbIII than SbV. The presence of iron plaque decreased uptake of both SbV and SbIII. SbIII uptake kinetics fitted better to the Michaelis-Menten function than SbV. Antimonate (56 to 98%) was the predominant form in rice plant with little methylated species being detected using HPLC-ICP-MS. Cell walls accumulated more Sb than organelles and cytosol, which were considered as the first barrier against Sb entering into cells. Sb transformation and subcellular distribution can help to understand the metabolic mechanisms of Sb in rice., (Published by Elsevier B.V.)