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Tissue distribution and bioaccumulation of legacy and emerging per-and polyfluoroalkyl substances (PFASs) in edible fishes from Taihu Lake, China
2021
Chen, Meng | Zhu, Lingyan | Wang, Qiang | Shan, Guoqiang
Tissue distribution of legacy and emerging per-and polyfluoroalkyl substances (PFASs) in several kinds of edible fishes collected from Meiliang bay of Taihu Lake, China were investigated and the related human health risks were assessed. Perfluorooctanesulfonate (PFOS), perfluorooctanesulfonamide (PFOSA) and 6:2 fluorotelomer phosphate diester (6:2 diPAP) were the most abundant legacy perfluoroalkyl acid (PFAA), PFOS related precursor (PreFOS), and the emerging PFASs in all fish tissues, respectively. Similar to the legacy PFAAs, 6:2 diPAP and 6:6 perfluorophosphinate (6:6 PFPiA) had the highest levels in the fish liver, whereas the highest level of PFOSA was in kidney, which might be due to its intensive transformation in fish liver. The concentrations of PFASs were generally positively correlated with the trophic levels. The profiles of PFASs were significantly different among bitterling, crucian and other fish, which might be related to their different metabolic capacities. Bioaccumulation factors (BAFs) of PreFOSs, 6:2 diPAP, and 6:6 PFPiA were lower than those of PFAAs with the same number of perfluorinated carbons. The calculated hazard ratios (HR) of PFOS (Range: 0.0100–0.655) and perfluorooctanoic acid (PFOA) (<0.00200) in all fish muscles were less than 1.0. However, the HR of the ∑PFASs in crucian muscle was 1.04, which implied that frequent consumption of crucian collected from Meiliang Bay might pose potential risks to human health.
Показать больше [+] Меньше [-]Exposure to GenX and its novel analogs disrupts fatty acid metabolism in male mice
2021
Guo, Hua | Sheng, Nan | Guo, Yong | Wu, Chengying | Xie, Weidong | Dai, Jiayin
Perfluoroalkyl ether carboxylic acids (PFECAs), including hexafluoropropylene oxide dimer acid (HFPO-DA, GenX), have been widely used as alternatives to perfluorooctanoic acid (PFOA) and subsequently detected in various environmental matrices. Despite this, public information regarding their hepatotoxicity remains limited. Here, to compare the hepatotoxicity of PFECAs and identify better alternatives for GenX, adult male mice were exposed to different concentrations (0.4, 2, and 10 mg/kg/d) of PFOA, GenX, and its analogs (PFMO2HpA and PFMO3NA) for 28 d. Results demonstrated increased hepatomegaly and disturbed fatty acid metabolism with increasing treatment doses. After dimensionality reduction analysis, significant differences were observed in the relative liver weights and liver and serum biochemical parameters among the four clusters. Furthermore, when chemical concentrations in the liver were similar, no differences in the indicators of liver injury associated with fatty acid metabolism were observed among groups in the same clusters. Our results suggest that dimensionality reduction analysis is a useful strategy for analyzing samples exposed to multiple compounds at different doses. Furthermore, PFECAs exhibit similar hepatotoxicities at the same cumulative hepatic concentration in mice with constant body weight, while PFMO2HpA exhibits lower hepatotoxicity compared to GenX at the same dose.
Показать больше [+] Меньше [-]Toxicokinetics and systematic responses of differently sized indium tin oxide (ITO) particles in mice via oropharyngeal aspiration exposure
2021
Qu, Jing | Wang, Jianli | Zhang, Haopeng | Wu, Jingying | Ma, Xinmo | Wang, Shile | Zang, Yiteng | Huang, Yuhui | Ma, Ying | Cao, Yuna | Wu, Daming | Zhang, Ting
Indium tin oxide (ITO) is an important semiconductor material, because of increasing commercial products consumption and potentially exposed workers worldwide. So, urgently we need to assess and manage potential health risks of ITO. Although the Occupational Exposure Limit (OEL) has been established for ITO exposure, there is still a lack of distinguishing the risks of exposure to particles of different sizes. Therefore, obtaining toxicological data of small-sized particles will help to improve its risk assessment data. Important questions raised in quantitative risk assessments for ITO particles are whether biodistribution of ITO particles is affected by particle size and to what extent systematic adverse responses is subsequently initiated. In order to determine whether this toxicological paradigm for size is relevant in ITO toxic effect, we performed comparative studies on the toxicokinetics and sub-acute toxicity test of ITO in mice. The results indicate both sized-ITO resided in the lung tissue and slowly excreted from the mice, and the smaller size of ITO being cleared more slowly. Only a little ITO was transferred to other organs, especially with higher blood flow. Two type of ITO which deposit in the lung mainly impacts respiratory system and may injure liver or kidney. After sub-acute exposure to ITO, inflammation featured by neutrophils infiltration and fibrosis with both dose and size effects have been observed. Our findings revealed toxicokinetics and dose-dependent pulmonary toxicity in mice via oropharyngeal aspiration exposure, also replenish in vivo risk assessment of ITO. Collectively, these data indicate that under the current OEL, there are potential toxic effects after exposure to the ITO particles. The observed size-dependent biodistribution patterns and toxic effect might be important for approaching the hazard potential of small-sized ITO in an occupational environment.
Показать больше [+] Меньше [-]Carbamazepine induces hepatotoxicity in zebrafish by inhibition of the Wnt/β-catenin signaling pathway
2021
Bai, Zhonghui | Jia, Kun | Chen, Guilan | Liao, Xinjun | Cao, Zigang | Zhao, Yangqi | Zhang, Chunping | Lu, Huiqiang
As drug abuse has become increasingly serious, carbamazepine (CBZ) is discharged into the aquatic environment with municipal sewage, causing potential harm to aquatic organisms. Here, we utilized zebrafish, an aquatic vertebrate model, to comprehensively evaluate the hepatotoxicity of CBZ. The larvae were exposed to 0.07, 0.13, and 0.26 mmol/L CBZ from 72 hpf to 144 hpf, and the adults were exposed to 0.025, 0.05, and 0.1 mmol/L CBZ for 28 days. The substantial changes were observed in the size and histopathology of livers, indicating that CBZ induced severe hepatoxicity in the larvae and adults. Oil red O staining demonstrated CBZ exposure caused severe lipid accumulation in the livers of both larvae and adults. Furthermore, CBZ exposure facilitated hepatocyte apoptosis through TUNEL staining, which was caused by rising ROS content. Subsequently, down-regulation of genes related to the Wnt pathway in exposure groups indicated that CBZ inhibited the development of liver via the Wnt/β-catenin signaling pathway. In conclusion, CBZ induced severe hepatotoxicity by promoting lipid accumulation, generating excessive ROS production, and inhibiting the Wnt/β-catenin signaling pathway in zebrafish. The results reveal the occurrence of CBZ-induced hepatotoxicity in zebrafish and clarify its mechanism of action, which potentially illustrate environmental concerns associated with CBZ exposure.
Показать больше [+] Меньше [-]The association of liver function biomarkers with internal exposure of short- and medium-chain chlorinated paraffins in residents from Jinan, China
2021
Liu, Yi | Han, Xiumei | Zhao, Nan | Fang, Xinxin | Zhang, Shiwen | Li, Shixue | Jiang, Wei | Ding, Lei
Chlorinated paraffins (CPs) are pervasive environmental pollutants which have been reported to be hepatotoxic by laboratory cell and animal studies. However, the related epidemiological reports on their hepatotoxic effects to humans are sparse. In this study, we evaluated the associations between six liver enzymes and serum short-chain CP (SCCP) or medium-chain CP (MCCP) concentrations of 197 residents in Jinan, China. Serum S/MCCPs were detected by quadrupole time-of-flight high-resolution mass spectrometry coupled with atmospheric pressure chemical ionization source (APCI-QTOF-HRMS), and quantified by pattern deconvolution method. The associations between total serum S/MCCP concentrations (ΣS/MCCPs) and continuous liver enzyme levels were assessed by linear regression. Odds ratios (ORs) for the effects of serum ΣS/MCCPs concentrations on liver function biomarkers dichotomized by clinical reference intervals were predicted by logistic regression, either treating ΣS/MCCPs as continuous or categorical dependents. After multivariable adjustment, linear regression results illustrated that 1-ln unit increase in serum ΣSCCPs was negatively associated with male PA levels [-6.08, 95% confidence interval (CI): −11.90, −3.25, p < 0.05], positively associated with male TB levels (1.80, 95% CI: 0.28, 3.31, p < 0.05), and positively associated with female AST levels (1.39, 95% CI: 0.07, 2.70, p < 0.05). One-ln unit increase in serum ΣMCCPs was negatively associated male PA levels (−7.56, 95% CI: −17.15, −4.03, p < 0.05). Logistic regression results suggested that male serum ΣSCCPs were associated with increased prevalence of abnormal PA (OR = 1.47 per 1 ln-unit increase, CI = 1.18, 1.82) and TB (OR = 1.75, 95% CI = 1.12, 2.76) levels, and male serum ΣMCCPs were significantly associated with increased prevalence of abnormal PA (OR = 1.43, 95% CI = 1.03, 1.97) levels. In addition, male participants with concentrations above the median ΣS/MCCPs were associated with increased risk for abnormal PA levels [SCCPs, 2.11-fold (95% CI = 1.15, 3.87); MCCPs, 1.94-fold (95% CI = 1.24, 3.03)]. Male participants with concentrations above the median ΣSCCPs were also associated with increased risk for abnormal TB levels (OR = 1.75, 95% CI = 1.12, 2.76). Conclusively, our results revealed that CP internal exposure was associated with disturbed liver biomarker levels, suggesting the hepatotoxicity of both SCCPs and MCCPs to humans.
Показать больше [+] Меньше [-]Tissue-specific distribution and bioaccumulation of cyclic and linear siloxanes in South Korean crucian carp (carassius carassius)
2021
Wang, Wenting | Cho, Hyeon-Seo | Kim, Kyungtae | Park, Kyunghwa | Oh, Jeong-Eun
The occurrence and distribution of cyclic and linear siloxanes were investigated in South Korean river water and sediment, with a special focus on crucian carp tissues, to evaluate the residual status and potential bioaccumulation of siloxanes. The total siloxanes median concentrations observed in this study were 1495 ng/L in river water, 39.2 ng/g-dry weight [dw] in sediment, and 41.7 ng/g-wet weight [ww] in crucian carp muscle. Cyclic siloxanes (D3–D6) were predominant in all matrices, and D5 (mean: > 81%) was more abundant in biota tissues than in river water (30%) and sediment (26%) samples. Specifically, positive correlations between D5 concentrations and crucian carp sizes (p < 0.01, Spearman) as well as the relatively high estimated biota-sediment accumulation factor value of D5 (D5: 2.31), suggest the high bioaccumulative property of D5 in biota. However, no bioaccumulation potentials were observed for D3, D4, D6, and L3–L17 in this field-scale study. The distributions of major linear siloxanes (L7–L14) in crucian carp gills (17%) and gonads (21%) were higher than in other tissues (brain, 9.6%; liver, 2.6%; muscle, 1.5%). Moreover, relatively high tissue/plasma ratios were observed for linear siloxanes (L7–L10: 1.79–2.12) compared to cyclic siloxanes (D4–D6: 0.829–1.18) (p < 0.01, Mann Whitney U test), which indicated the higher transportability of linear siloxanes to fish tissues than cyclic siloxanes.
Показать больше [+] Меньше [-]Terrestrial dissolved organic matter source affects disinfection by-product formation during water treatment and subsequent toxicity
2021
Franklin, Hannah M. | Doederer, Katrin | Neale, Peta A. | Hayton, Joshua B. | Fisher, Paul | Maxwell, Paul | Carroll, Anthony R. | Burford, Michele A. | Leusch, Frederic D.L.
Restoring woody vegetation to riparian zones helps to protect waterways from excessive sediment and nutrient inputs. However, the associated leaf litter can be a major source of dissolved organic matter (DOM) leached into surface waters. DOM can lead to the formation of disinfection by-products (DBPs) during drinking water treatment. This study investigated the DBPs formed during chlorination of DOM leached from leaf litter and assessed the potential toxicity of DBPs generated. We compared the leachate of two native Australian riparian trees, Casuarina cunninghamiana and Eucalyptus tereticornis, and a reservoir water source from a catchment dominated by Eucalyptus species. Leachates were diluted to dissolved organic carbon concentrations equivalent to the reservoir (~9 mg L⁻¹). E. tereticornis leachates produced more trihalomethanes (THMs), haloacetic acids (HAAs), and haloketones after chlorination, while C. cunninghamiana produced more chloral hydrate and haloacetonitriles. Leachate from both species produced less THMs and more HAAs per mole of carbon than reservoir water. This may be because reservoir water had more aromatic, humic characteristics while leaf leachates had relatively more protein-like components. Using in vitro bioassays to test the mixture effects of all chemicals, chlorinated E. tereticornis leachate induced oxidative stress in HepG2 liver cells and bacterial toxicity more frequently and at lower concentrations than C. cunninghamiana and reservoir water. Overall, this study has shown that the DOM leached from litter of these species has the potential to generate DBPs and each species has a unique DBP profile with differing bioassay responses. E. tereticornis may pose a relatively greater risk to drinking water than C. cunninghamiana as it showed greater toxicity in bioassays. This implies tree species should be considered when planning riparian zones to ensure the benefits of vegetation to waterways are not offset by unintended increased DBP production and associated toxicity following chlorination at downstream drinking water intakes.
Показать больше [+] Меньше [-]A toxicity pathway-oriented approach to develop adverse outcome pathway: AHR activation as a case study
2021
Jin, Yuan | Feng, Meiyao | Ma, Wanli | Wei, Yanhong | Qi, Guangshuai | Luo, Jiao | Xu, Lin | Li, Xinmei | Li, Chuanhai | Wang, Ying | Li, Daochuan | Chen, Jing | Zhao, Yanjie | Hou, Yufei | Zhao, Qianwen | Jiang, Lidan | Xie, Mengyue | Zheng, Yuxin | Yu, Dianke
With numerous new chemicals introduced into the environment everyday, identification of their potential hazards to the environment and human health is a considerable challenge. Developing adverse outcome pathway (AOP) framework is promising in helping to achieve this goal as it can bring In Vitro testing into toxicity measurement and understanding. To explore the toxic mechanism underlying environmental chemicals via the AOP approach, an integration of adequate experimental data with systems biology understanding is preferred. Here, we describe a novel method to develop reliable and sensible AOPs that relies on chemical-gene interactions, toxicity pathways, molecular regulations, phenotypes, and outcomes information obtained from comparative toxicogenomics database (CTD) and Ingenuity Pathway Analysis (IPA). Using Benzo(a)pyrene (BaP), a highly studied chemical as a stressor, we identified the pivotal IPA toxicity pathways, the molecular initiating event (MIE), and candidate key events (KEs) to structure AOPs in the liver and lung, respectively. Further, we used the corresponding CTD information of multiple typical AHR-ligands, including 2,3,7,8-tetrachlorodibenzoparadioxin (TCDD), valproic acid, quercetin, and particulate matter, to validate our AOP networks. Our approach is likely to speed up AOP development as providing a time- and cost-efficient way to collect all fragmented bioinformation in published studies. It also facilitates a better understanding of the toxic mechanism of environmental chemicals, and potentially brings new insights into the screening of critical paths in the AOP network.
Показать больше [+] Меньше [-]Improving pollutants environmental risk assessment using a multi model toxicity determination with in vitro, bacterial, animal and plant model systems: The case of the herbicide alachlor
2021
Pereira, Susana P. | Santos, Sandra M.A. | Fernandes, Maria A.S. | Deus, Cláudia M. | Martins, João D. | Pedroso de Lima, Maria C. | Vicente, Joaquim A.F. | Videira, Romeu A. | Jurado, Amália S.
Several environmental pollutants, including pesticides, herbicides and persistent organic pollutants play an important role in the development of chronic diseases. However, most studies have examined environmental pollutants toxicity in target organisms or using a specific toxicological test, losing the real effect throughout the ecosystem. In this sense an integrative environmental risk of pollutants assessment, using different model organisms is necessary to predict the real impact in the ecosystem and implications for target and non-target organisms.The objective of this study was to use alachlor, a chloroacetanilide herbicide responsible for chronic toxicity, to understand its impact in target and non-target organisms and at different levels of biological organization by using several model organisms, including membranes of dipalmitoylphosphatidylcholine (DPPC), rat liver mitochondria, bacterial (Bacillus stearothermophilus), plant (Lemna gibba) and mammalian cell lines (HeLa and neuro2a).Our results demonstrated that alachlor strongly interacted with membranes of DPPC and interfered with mitochondrial bioenergetics by reducing the respiratory control ratio and the transmembrane potential. Moreover, alachlor also decreased the growth of B. stearothermophilus and its respiratory activity, as well as decreased the viability of both mammalian cell lines. The values of TC₅₀ increased in the following order: Lemna gibba < neuro2a < HeLa cells < Bacillus stearothermophilus. Together, the results suggest that biological membranes constitute a putative target for the toxic action of this lipophilic herbicide and point out the risks of its dissemination on environment, compromising ecosystem equilibrium and human health.
Показать больше [+] Меньше [-]Legacy and emerging per- and polyfluorinated alkyl substances (PFASs) in sediment and edible fish from the Eastern Red Sea
2021
Ali, Aasim M. | Sanden, Monica | Higgins, Christopher P. | Hale, Sarah E. | Alarif, Walied M. | Al-Lihaibi, Sultan S. | Ræder, Erik Magnus | Langberg, Håkon Austad | Kallenborn, Roland
and perfluorinated alkyl substances (PFASs) are ubiquitously detected all around the world. Herein, for the first time, concentrations of 16 selected legacy and emerging PFASs are reported for sediment and edible fish collected from the Saudi Arabian Red Sea. Mean concentrations varied from 0.57 to 2.6 μg kg⁻¹ dry weight (dw) in sediment, 3.89–7.63 μg kg⁻¹ dw in fish muscle, and 17.9–58.5 μg kg⁻¹ dw in fish liver. Wastewater treatment plant effluents represented the main source of these compounds and contributed to the exposure of PFAS to biota. Perfluorooctane sulfonate (PFOS) was the most abundant compound in sediment and fish tissues analysed, comprising between 42 and 99% of the ∑₁₆PFAS. The short chain perfluorobutanoate (PFBA) was the second most dominant compound in sediment and was detected at a maximum concentration of 0.64 μg kg⁻¹ dw. PFAS levels and patterns differed between tissues of investigated fish species. Across all fish species, ∑₁₆PFAS concentrations in liver were significantly higher than in muscle by a factor ranging from 3 to 7 depending on fish species and size. The PFOS replacements fluorotelomer sulfonate (6:2 FTS) and perfluorobutane sulfonate (PFBS) exhibited a bioaccumulation potential in several fish species and 6:2 FTS, was detected at a maximum concentration of 7.1 ± 3.3 μg kg⁻¹ dw in a doublespotted queenfish (Scomberoides lysan) liver. PFBS was detected at a maximum concentration of 2.65 μg kg⁻¹ dw in strong spine silver-biddy (Gerres longirostris) liver. The calculated dietary intake of PFOS, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) exceeded the safety threshold established by the European Food Safety Authority (EFSA) in 2020 in doublespotted queenfish muscle, indicating a potential health risk to humans consuming this fish in Jeddah, Saudi Arabia.
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