UBE2L3 Promotes Oxidative Stress-regulated Necroptosis to Accelerate Osteosarcoma Progression.

BACKGROUND: Osteosarcoma is a highly invasive bone marrow stromal tumor with limited treatment options. Oxidative stress plays a crucial role in the development and progression of tumors, but the underlying regulatory mechanisms are not fully understood. Recent studies have revealed the significant involvement of UBE2L3 in oxidative stress, but its specific role in osteosarcoma remains poorly investigated. OBJECTIVE: This study aimed to explore the molecular mechanisms by which UBE2L3 promotes oxidative stress-regulated necroptosis to accelerate the progression of osteosarcoma using in vitro cell experiments. METHODS: Human osteoblast hFOB1.19 cells and various human osteosarcoma cell lines (MG-63, U2OS, SJSA-1, HOS, and 143B) were cultured in vitro. Plasmids silencing UBE2L3 and negative control plasmids were transfected into U2OS and HOS cells. The cells were divided into the following groups: U2OS cell group, HOS cell group, si-NC-U2OS cell group, si-UBE2L3-U2OS cell group, si-NC-HOS cell group, and si-UBE2L3-HOS cell group. Cell viability and proliferation capacity were measured using the Tunnel method and clonogenic assay. Cell migration and invasion abilities were assessed by Transwell and scratch assays. Cell apoptosis was analyzed by flow cytometry, and ROS levels were detected using immunofluorescence. The oxidative stress levels in various cell groups and the expression changes of necroptosis-related proteins were assessed by PCR and WB. Through these experiments, we aim to evaluate the impact of oxidative stress on necroptosis and uncover the specific mechanisms by which targeted regulation of oxidative stress promotes tumor cell necroptosis as a potential therapeutic strategy for osteosarcoma. RESULTS: The mRNA expression levels of UBE2L3 in human osteosarcoma cell lines were significantly higher than those in human osteoblast hFOB1.19 cells (p <0.01). UBE2L3 expression was significantly decreased in U2OS and HOS cells transfected with si-UBE2L3, indicating the successful construction of stable cell lines with depleted UBE2L3. Tunnel assay results showed a significant increase in the number of red fluorescent-labeled cells in si-UBE2L3 groups compared to si-NC groups in both cell lines, suggesting a pronounced inhibition of cell viability. Transwell assay demonstrated a significant reduction in invasion and migration capabilities of si-UBE2L3 groups in osteosarcoma cells. The clonogenic assay revealed significant suppression of proliferation and clonogenic ability in both U2OS and HOS cells upon UBE2L3 knockdown. Flow cytometry confirmed that UBE2L3 knockdown significantly enhanced apoptosis in U2OS and HOS cells. Immunofluorescence results showed that UBE2L3 silencing promoted oxidative stress levels in osteosarcoma cells and facilitated tumor cell death. WB analysis indicated a significant increase in phosphorylation levels of necroptosis-related proteins, RIP1, RIP3, and MLKL, in both osteosarcoma cell lines after UBE2L3 knockdown. In addition, the expression of necrosis-associated proteins was inhibited by the addition of the antioxidant N-acetylcysteine (NAC). CONCLUSION: UBE2L3 is upregulated in osteosarcoma cells, and silencing of UBE2L3 promotes oxidative stress in these cells, leading to enhanced necroptosis and delayed progression of osteosarcoma.

Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes.

Exposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In this study, Tri(2-chloroethyl) phosphate (TCEP), an organophosphate ester (OPE), was used as an example to study the PBTK model of mice exposed to different exposure doses by multiple routes. Different routes of exposure (gavage and intradermal injection) can cause differences in the concentration of chemicals in the organs. TCEP that enters the body through the mouth is mainly concentrated in the gastrointestinal tract and liver. However, the concentrations of chemicals that enter the skin into the mice are higher in skin, rest of body, and blood. In addition, TCEP was absorbed and accumulated very rapidly in mice, within half an hour after a single exposure. We have successfully established a mouse PBTK model of the TCEP accounting for multiple exposure Routes and obtained a series of kinetic parameters. The model includes blood, liver, kidney, stomach, intestine, skin, and rest of body compartments. Oral and dermal exposure route was considered for PBTK model. The PBTK model established in this study has a good predictive ability. More than 70% of the predicted values deviated from the measured values by less than 5-fold. In addition, we extrapolated the model to humans. A human PBTK model is built. We performed a health risk assessment for world populations based on human PBTK model. The risk of TCEP in dust is greater through mouth than through skin. The risk of TCEP in food of Chinese population is greater than dust.

Screening Novel Per- and Polyfluoroalkyl Substances in Human Blood Based on Nontarget Analysis and Underestimated Potential Health Risks.

Nontarget analysis has gained prominence in screening novel perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the environment, yet remaining limited in human biological matrices. In this study, 155 whole blood samples were collected from the general population in Shijiazhuang City, China. By nontarget analysis, 31 legacy and novel PFASs were assigned with the confidence level of 3 or above. For the first time, 11 PFASs were identified in human blood, including C1 and C3 perfluoroalkyl sulfonic acids (PFSAs), C4 ether PFSA, C8 ether perfluoroalkyl carboxylic acid (ether PFCA), C4-5 unsaturated perfluoroalkyl alcohols, C9-10 carboxylic acid-perfluoroalkyl sulfonamides (CA-PFSMs), and C1 perfluoroalkyl sulfonamide. It is surprising that the targeted PFASs were the highest in the suburban population which was impacted by industrial emission, while the novel PFASs identified by nontarget analysis, such as C1 PFSA and C9-11 CA-PFSMs, were the highest in the rural population who often drank contaminated groundwater. Combining the toxicity prediction results of the bioaccumulation potential, lethality to rats, and binding affinity to target proteins, C3 PFSA, C4 and C7 ether PFSAs, and C9-11 CA-PFSMs exhibit great health risks. These findings emphasize the necessity of broadening nontarget analysis in assessing the PFAS exposure risks, particularly in rural populations.

Electro-intensified simultaneous decontamination of coexisting pollutants in wastewater.

The treatment of wastewater has become increasingly challenging as a result of its growing complexity. To achieve synergistic removal of coexisting pollutants in wastewater, one promising approach involves the integration of electric fields. We conducted a comprehensive literature review to explore the potential of integrating electric fields and developing efficient electro-intensified simultaneous decontamination systems for wastewater containing coexisting pollutants. The review focused on comprehending the applications and mechanisms of these systems, with a particular emphasis on the deliberate utilization of positive and negative charges. After analyzing the advantages, disadvantages, and application efficacy of these systems, we observed electro-intensified systems exhibit flexible potential through their rational combination, allowing for an expanded range of applications in addressing simultaneous decontamination challenges. Unlike the reviews focusing on single elimination, this work aims to provide guidance in addressing the environmental problems resulting from the coexistence of hazardous contaminants.

A green edge-hosted zinc single-site heterogeneous catalyst for superior Fenton-like activity.

Developing green heterogeneous catalysts with excellent Fenton-like activity is critical for water remediation technologies. However, current catalysts often rely on toxic transitional metals, and their catalytic performance is far from satisfactory as alternatives of homogeneous Fenton-like catalysts. In this study, a green catalyst based on Zn single-atom was prepared in an ammonium atmosphere using ZIF-8 as a precursor. Multiple characterization analyses provided evidence that abundant intrinsic defects due to the edge sites were created, leading to the formation of a thermally stable edge-hosted Zn-N4 single-atom catalyst (ZnN4-Edge). Density functional theory calculations revealed that the edge sites equipped the single-atom Zn with a super catalytic performance, which not only promoted decomposition of peroxide molecule (HSO5-) but also greatly lowered the activation barrier for •OH generation. Consequently, the as-prepared ZnN4-Edge exhibited extremely high Fenton-like performance in oxidation and mineralization of phenol as a representative organic contaminant in a wide range of pH, realizing its quick detoxification. The atom-utilization efficiency of the ZnN4-Edge was ~104 higher than an equivalent amount of the control sample without edge sites (ZnN4), and the turnover frequency was ~103 times of the typical benchmark of homogeneous catalyst (Co2+). This study opens up a revolutionary way to rationally design and optimize heterogeneous catalysts to homogeneous catalytic performance for Fenton-like application.

Occurrence of perfluoroalkyl substances in the environment compartments near a mega fluorochemical industry: Implication of specific behaviors and emission estimation.

With the stringent restrictions on long-chain per- and polyfluoroalkyl substances (PFASs), ether-PFASs are being widely used as alternatives. We estimated that the mega fluorochemical industrial park (FIP) in Shandong, China, had emitted a maximum of 5040 kg and 1026 kg of hexafluoropropylene oxides (HFPOs), and 7560 kg and 1890 kg of perfluorooctanoic acid (PFOA) to water and air during 2021. In the surface water, groundwater, outdoor dust, soil, tree leaf and bark collected in the vicinity of the FIP, PFOA was predominant, followed by HFPOs. The much higher percentage of HFPO dimer acid (HFPO-DA) in groundwater than in surface water verified that this compound was more mobile in porous media. The strong correlations between the main PFASs in outdoor dust and surface soil suggested that the soil PFASs were mainly derived from air deposition, particularly for HFPO trimer acid (HFPO-TA), which has a stronger binding affinity with particles than PFOA. High percentage of the hydroxylated product of 6:2 polyfluorinated ether sulfonic acid was observed in groundwater, implying reductive dechlorination might occur in groundwater. Strong correlations between PFASs in outdoor dust and those in tree leaf and bark magnified that tree could serve as a sampler to effectively monitor airborne PFASs. This study provides the first line of information about the discharge, transport, and fate of novel ether-PFASs in the multiple environmental media near a point source.

Novel insights into the mediating roles of cluster of differentiation 36 in transmembrane transport and tissue partition of per- and polyfluoroalkyl substances in mice.

Transmembrane transport is important for bioaccumulation of per- and polyfluoroalkyl substances (PFASs) in organisms, but has not yet been well understood. Here, the roles of cluster of differentiation 36 (CD36) in accumulation of PFASs were investigated. CD36 was overexpressed in Escherichia coli to get CD36-BL21 strain, and the binding affinities of 20 PFASs with CD36 were determined by microscale thermophoresis, which grew up to 17.5 µM with increasing carbon chain length. Consequently, the accumulation of most PFASs was remarkably promoted in CD36-BL21 in comparison to the wild strain, and the enhancement was proportional to their binding affinities with CD36 (r = -0.96). However, this effect was depressed greatly as CD36 was inhibited by sulfo-N-succinimidyl oleate (SSO). Additionally, as the mice received SSO pretreatment before they were exposed to perfluorododecanoic acid, its accumulation in the tissues rich in CD36, such as liver, was suppressed, but increased by 1.1 times in the serum. These indicated that CD36 played critical roles in the transmembrane transport and tissue partition of PFASs in organisms. The developed relationship between liver-blood partition of PFASs and their binding affinities with intracellular proteins was distinctly improved by incorporating that with CD36 (r = -0.97).

Analysis of Specific Perfluorohexane Sulfonate Isomers by Liquid Chromatography-Tandem Mass Spectrometry: Method Development and Application in Source Apportionment.

Characterization of perfluorohexane sulfonate (PFHxS) isomers, a chemical proposed for listing under the Stockholm Convention, is important to elucidate its environmental behaviors and sources. Optimized chromatographic separation coupled with monitoring of the characteristic fragments enabled the identification of four mono-substituted and two di-substituted branched PFHxS isomers. The transitions of molecular ions m/z 399 to the fragments m/z 80 (n-), m/z 169 (iso-), m/z 319 (1m-), m/z 80 (2m-), and m/z 180 (3m-) were selected for quantifying the mono-substituted isomers. Method accuracy of the established LC-MS/MS was verified by comparing the results of technical products with those determined by 19F-nuclear magnetic resonance (NMR). The developed method was then used to quantify the isomeric compositions of PFHxS in the perfluorooctane sulfonate (PFOS) industrial products which contained PFHxS as an impurity, as well as in several kinds of water samples, with the limits of detection for all isomers in the range of 4 to 30 pg/L. For the first time, a liquid chromatography-tandem mass spectrometry method was established to separate and quantify the PFHxS isomers. The isomeric profiling of water samples suggested that PFHxS in the waters was mainly due to the direct contamination of PFHxS rather than from PFOS contamination.

Predicting bioconcentration factor and estrogen receptor bioactivity of bisphenol a and its analogues in adult zebrafish by directed message passing neural networks.

The bioconcentration factor (BCF) is a key parameter for bioavailability assessment of environmental pollutants in regulatory frameworks. The comparative toxicology and mechanism of action of congeners are also of concern. However, there are limitations to acquire them by conducting field and laboratory experiments while machinelearning is emerging as a promising predictive tool to fill the gap. In this study, the Direct Message Passing Neural Network (DMPNN) was applied to predict logBCFs of bisphenol A (BPA) and its four analogues (bisphenol AF (BPAF), bisphenol B (BPB), bisphenol F (BPF) and bisphenol S (BPS)). For the test set, the Pearson correlation coefficient (PCC) and mean square error (MSE) were 0.85 and 0.52 respectively, suggesting a good predictive performance. The predicted logBCFs values by the DMPNN ranging from 0.35 (BPS) to 2.14 (BPAF) coincided well with those by the classical EPI Suite (BCFBAF model). Besides, estrogen receptor α (ERα) bioactivity of these bisphenols was also predicted well by the DMPNN, with a probability of 97.0 % (BPB) to 99.7 % (BPAF), which was validated by the extent of vitellogenin (VTG) induction in male zebrafish as a biomarker except BPS. Thus, with little need for expert knowledge, DMPNN is confirmed to be a useful tool to accurately predict logBCF and screen for estrogenic activity from molecular structures. Moreover, a gender difference was noted in the changes of three endpoints (logBCF, ER binding affinity and VTG levels), the rank order of which was BPAF > BPB > BPA > BPF > BPS consistently, and abnormal amino acid metabolism is featured as an omics signature of abnormal hormone protein expression.

Precolumn Derivatization High-Performance Liquid Chromatography for Determination of Perfluorocarboxylic Acids in Catalytic Degradation Solutions.

Perfluoroalkyl carboxylic acids (PFCAs), a series of ubiquitous contaminants in the global environment, attracted much attention due to their potential for high bioaccumulation and toxicity to various organisms. There are a lot of measurement requests in currently increasing degradation studies of PFCAs, which usually rely on expensive liquid chromatography-mass spectrometry (LC-MS). The degradation solutions containing high-concentration PFCAs can easily cause the pipeline pollution of the LC/MS instrument, which is usually used for trace analysis of environmental samples. In this study, a simple and reliable precolumn derivatization LC method coupled with an ultraviolet detector (UV) was developed for the determination of the main PFCAs (C4-9) of environmental concern. These PFCAs in degradation solutions were crosslinked to UV-responsive 3, 4-diphenylamine (DCA) by a carbodiimidization method, followed by a simple solid-phase extraction (SPE) cleanup, and quantitatively measured using a conventional LC-UV instrument. Compared to previously reported precolumn derivatization methods, this new derivatization approach has the advantages such as mild reaction conditions, easy operation, enhanced stability of derivatives, and low cost. The instrumental limits of detection (ILDs) for the targeted PFCAs in organic and aqueous mediums were 0.2-0.5 and 0.6-1.5 mg/L, respectively. The method has been successfully applied to the determination of PFCAs in catalytic degradation solutions and recommended for use in other assays involving relatively high-concentration PFCAs.

Insights into the Competitive Mechanisms of Per- and Polyfluoroalkyl Substances Partition in Liver and Blood.

Some per- and polyfluoroalkyl substances (PFASs) tend to be accumulated in liver and cause hepatotoxicity. However, the difficulty to directly measure liver concentrations of PFASs in humans hampers our understanding of their hepatotoxicity and mechanisms of action. We investigated the partitioning of 11 PFASs between liver and blood in male CD-1 mice. Although accumulation of the perfluoroalkanesulfonic acids (PFSAs) in mice serum was higher than their carboxylic acids (PFCAs) counterparts as expected, the liver-blood partition coefficients (RL/S) of PFSAs were lower than the PFCAs RL/S, implying a competition between liver and blood. The in vitro experiments further indicated that the partitioning was dominantly determined by their competitive binding between human liver fatty acid binding protein (hL-FABP) and serum albumin (HSA). The binding affinities (Kd) of PFASs to both proteins were measured. The correlations between the RL/S and log Kd (hL-FABP)/log Kd (HSA) were stronger than those with log Kd (hL-FABP) alone, magnifying that the partitioning was dominantly controlled by competitive binding between hL-FABP and HSA. Therefore, the liver concentrations of the selected PFASs in humans could be predicted from the available serum concentrations, which is important for assessing their hepatotoxicity.

Quantifying Indirect Contribution from Precursors to Human Body Burden of Legacy PFASs Based on Paired Blood and One-Week Duplicate Diet.

The restriction on legacy perfluoroalkyl substances (PFASs) has led to increasing application and contamination of their precursors and novel alternatives. However, the indirect contribution from precursors has not been well characterized. In this study, 24 PFASs were measured in the paired human blood and urine from general volunteers (n = 20), as well as their corresponding exposure matrices (7 day duplicate diet, drinking water and dust). Perfluorooctanoic acid (PFOA) was predominant, followed by 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA), contributing 21.6-47.0 and 6.6-20.0% of the total concentrations, respectively. Total oxidable precursor (TOP) assay and isomeric analysis coupled with a toxicokinetic model suggested that around 19% of perfluorooctane sulfonate (PFOS) in human was contributed by its precursors. The strong correlation between the estimated daily intake (EDI) and human blood concentration for 6:2 Cl-PFESA suggested that it was mainly contributed by direct exposure. The bioavailability of 6:2 Cl-PFESA in the food matrices was estimated as 18.6% by comparing the estimated and measured blood concentrations, implying that human exposure might be overestimated if the bioavailability of PFASs in food was not considered. Assuming that they had a similar bioavailability, it was estimated that ca. 20% of PFOS body burden was from indirect exposure to its precursors, which was supported by TOP assay.

External and internal human exposure to PFOA and HFPOs around a mega fluorochemical industrial park, China: Differences and implications.

Hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA) are used as alternatives to legacy perfluorooctanoic acid (PFOA); however, little is known about their human exposure risks. In this study, the concentrations of PFOA and HFPO were measured in major human exposure matrices and human bio-samples of local residents near a mega fluorochemical industrial park in Shandong, China, to characterize their external and internal exposures. Although HFPO-DA was detected in drinking water and indoor dust, it exhibited a considerably low bioaccumulation potential in animal-origin food and human samples (urine, hair, and serum), implying that it might be a benign alternative to PFOA. Although the estimated daily intake (EDI) of HFPO-TA was comparable to that of PFOA, its concentration in urine was higher than that of PFOA, implying that it might be eliminated faster than PFOA. A simple one-compartment pharmacokinetic model was applied to estimate the serum concentrations of the target compounds and subsequently compare them with the measured concentrations. The predicted concentration of PFOA in serum based on its concentration in urine and half-life was close to the measured value, confirming the distinct internal exposure of PFOA in the local residents. However, the measured concentrations of HFPO in serum were considerably lower than those predicted from the external EDI and urine concentrations, implying that they were eliminated faster than expected in humans. Various perfluoroalkyl substances were detected in human hair, and their compositions were similar to those in human serum, suggesting that hair is a good non-invasive indicator for long-term exposure to legacy long-chain perfluoroalkyl carboxylic acids and HFPOs. This study provided valuable information about the human exposure to legacy PFOA and HFPOs in highly impacted areas near point sources and necessitates studies on the toxicokinetics of HFPOs.

Occurrence and sources of per- and polyfluoroalkyl substances in the ice-melting lakes of Larsemann Hills, East Antarctica.

The contamination and sources of per- and polyfluoroalkyl substances (PFASs) in the Antarctic continent have not been systematically investigated. In this study, 21 PFASs including some new emerging one, were measured in the surface waters collected from 21 ice-melting lakes next to the research stations in Larsemann Hills, East Antarctica (EA). All the PFASs had a median concentration lower than 26.7 pg/L, representing the background levels in EA. The contamination of PFASs in EA was generally lower than in West Antarctica (WA), which might be due to the less on-site human activities in EA than in WA. In the ice-melting lakes, perfluorooctane acid (PFOA) was predominant, and its concentrations in several lakes close to the research stations in EA could be up to 458 pg/L. For the first time, an emerging substitute of perfluorooctane sulfate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA), was detected in several of the samples. Source apportionment methods including isomer profiling were applied, and the results collectively indicated that the PFASs in the melting lakes in EA were mainly derived from airborne input, but local discharge might also contribute to PFOA in some lakes. The results of this study supplied information about the sources of PFASs in Antarctica, and suggested that caution should be taken in future to control the local discharge due to increasing human activities in EA.

Structure-Activity Relationship Investigation on Reaction Mechanism between Chlorinated Quinoid Carcinogens and Clinically-Used Aldoxime Nerve-Agent Antidote under Physiological Condition.

Pyridinium aldoximes are best-known therapeutic antidotes used for clinical treatment of poisonings by organophosphorus nerve-agents and pesticides. Recently, we found that pralidoxime (2-PAM, a currently clinically used nerve-agent antidote) could also detoxify tetrachloro-1,4-benzoquinone (TCBQ), which is a carcinogenic quinoid metabolite of the widely used wood preservative pentachlorophenol under normal physiological conditions, via an unusually mild and facile Beckmann fragmentation mechanism accompanied by radical homolysis. However, it is not clear whether the less-chlorinated benzoquinones (CnBQs, n ≤ 3) act similarly; if so, what is the structure-activity relationship? In this study, we found that (1) The stability of reaction intermediates produced by different CnBQs and 2-PAM was dependent not only on the position but also the degree of Cl-substitution on CnBQs, which can be divided into TCBQ- and DCBQ (dichloro-1,4-benzoquinone)-subgroup; (2) The pKa value of hydroxlated quinones (Cn-1BQ-OHs, the hydrolysis products of CnBQs), determined the stability of corresponding intermediates, that is, the decomposition rate of the intermediates depended on the acidity of Cn-1BQ-OHs; (3) The pKa value of the corresponding Cn-1BQ-OHs could also determine the reaction ratio of Beckmann fragmentation to radical homolysis in CnBQs/2-PAM. These new findings on the structure-activity relationship of the halogenated quinoid carcinogens detoxified by pyridinium aldoxime therapeutic agents via Beckmann fragmentation and radical homolysis reaction may have broad implications on future biomedical and environmental research.

Legacy and emerging per- and poly-fluoroalkyl substances in surface seawater from northwestern Pacific to Southern Ocean: Evidences of current and historical release.

Knowledge on distribution of per- and poly-fluoroalkyl substances (PFASs) in open oceans is limited. By taking part in the 32nd Chinese Antarctic Research Expedition, 41 surface seawater samples were collected in the northwestern Pacific Ocean (NW-PO), eastern Indian Ocean (E-IO) and Southern Ocean (SO), and 23 PFASs comprised of legacy perfluoroalkyl carboxylic acids, perfluoroalkyl sulfonate acids and some new emerging homologs such as 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were measured. The concentrations of the total PFASs decreased in the order of NW-PO>E-IO>SO. Perfluorooctanoic acid (PFOA) was the most dominant, followed by perfluorooctane sulfonate (PFOS). The PFOA concentration declined exponentially with the offshore distance, while such trend was not obvious for PFOS and other legacy PFASs, suggesting that PFOA was mainly derived from the ongoing land-based emissions, while PFOS was mainly from historical residues. 6:2 Cl-PFESA was identified (<11.1-170 pg/L) in the oceanic waters with relatively high level at the sites near Australia. Multiple receptor models indicated that PFASs in the SO were mainly contributed by atmosphere input, while those in the NW-PO and E-IO were originated from land sources. Isomeric profiles of PFOA showed that telomere-based source became more outstanding than electrochemical fluorinated production in recent years.

Concentration, spatial distribution, and health risk assessment of PFASs in serum of teenagers, tap water and soil near a Chinese fluorochemical industrial plant.

Discharges released from fluorochemical industrial plants lead to severe contamination of the environment with per- and polyfluoroalkyl substances (PFASs), which may pose risks to human health. In this study, 187 serum samples from teenagers (age = 14 years), 22 tap water samples and 40 soil samples were collected in areas within 0-11 km of a fluorochemical industrial plant in Huantai County, Shandong Province, and concentrations of 18 PFASs were quantified by UPLC-MS/MS. Perfluorooctanoic acid (PFOA) was found to be predominant, concentrations of which ranged from 40.4 to 845 ng/mL in serum, from 2.88 to 19.3 ng/L in tap water, from 4.40 to 189 ng/g in soil, and accounting for 84.1-98.6%, 15.9-79.8%, and 73.8-96.7% of the total PFASs, respectively. Statistical analysis demonstrated that concentrations of perfluorinated carboxylic acids (PFCAs) in soil (C5-C9) and serum (C8-C10) were associated with the industrial plant. And PFOA concentrations in tap water were not relevant to the industrial plant, which were comparable with the non-contaminated area and lower than the threshold value recommended by U.S. EPA (70 ng/mL), indicating that the contribution to the high concentration of serum PFOA of local teenagers by drinking water was limited. Moreover, PFCAs in soil only made a limited contribution to the serum PFCAs of local residents by direct inhalation and dermal exposure, but the potential health risk by the soil via food chain should be paid attention to. Furthermore, health risk assessment demonstrated that high concentrations of PFOA in serum could pose potential health risk to local teenagers. Therefore, effective measures should be taken to attenuate the health risks caused by the industrial plant to local residents, and further epidemiological studies should be carried out in the future.

Tissue distribution and bioaccumulation of legacy and emerging per-and polyfluoroalkyl substances (PFASs) in edible fishes from Taihu Lake, China.

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.

Estimation of internal human daily intakes of organophosphate esters using one-compartment toxicokinetic model in the whole blood from Hebei Province, China.

To evaluate the human health risks attributed by organophosphate ester (OPE) exposure, it is very important to estimate the daily intakes (DIs) of OPEs in human. In this study, the DIs of OPEs were estimated using a simplified one-compartment toxicokinetic model based on their total clearance rates in human and their whole blood concentrations. Thirty paired human whole blood and plasma samples were collected from participants in Hengshui, Hebei Province, China. The detection frequencies of most OPEs in the whole blood were lower than 50.0%. Thus, the OPE levels in whole blood were converted from the corresponding plasma levels using the fractions of OPEs in plasma (Fp), which were estimated from an in vitro partition assay and the values were in the range of 0.52-0.98. The measured whole blood concentrations of triphenyl phosphate (TPHP) and tris(chloroethyl) phosphate (TCEP) were comparable to those converted from the plasma concentrations, suggesting that the conversion method was reliable. The estimated total DIs of TPHP, TCEP, and tris(2-chloroisopropyl) phosphate were 1-30 times of those derived by the external exposure method, which usually excluded many exposure sources. The estimated human health risks based on the DIs indicated that the carcinogenic and non-carcinogenic effects of OPEs for the participants in Hengshui, Hebei Province, China, were negligible. This study recommended a more reliable and simpler method to estimate the human health risks attributed to the exposure of OPEs.

Probing Mechanisms for the Tissue-Specific Distribution and Biotransformation of Perfluoroalkyl Phosphinic Acids in Common Carp (Cyprinus carpio).

This study investigated the tissue-specific accumulation and biotransformation of 6:6 and 8:8 perfluoroalkyl phosphinic acids (PFPiA) in common carp (Cyprinus carpio) during 90 d exposure and 30 d depuration in water in the laboratory. Both 6:6 and 8:8 PFPiAs could quickly accumulate in the carp, and 6:6 PFPiA displayed higher bioaccumulation potential than 8:8 PFPiA. The highest concentrations of PFPiAs were observed in the blood, while the lowest were found in the muscle. The equilibrium dialysis experiment indicated that both PFPiAs had higher binding affinities with the proteins in the fish serum than in liver, which was supported by the molecular docking analysis. The results also indicated that 6:6 PFPiA had higher binding affinities with the serum and liver proteins than 8:8 PFPiA. These results suggested that the tissue-specific distribution of PFPiAs was highly dependent on the binding affinities with the specific proteins. Both in vivo and in vitro experiments consistently indicated that PFPiAs experienced biotransformation and produced perfluoroalkyl phosphonic acids (PFPAs), and biotransformation of 8:8 PFPiA was more active than 6:6 PFPiA. It was worth noting that perfluorohexanonate and perfluorooctanoic acids were identified in fish as metabolites after long-term exposure to PFPiAs for the first time.