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Frailty and body composition contribute to adverse pre-transplant outcomes including hospitalization and waitlist mortality, but the interaction between frailty and body composition remains uncertain. Frailty was diagnosed by Clinical Frailty Scale (CFS) and a standard Frailty Questionnaire (FQ). Nutrition was evaluated by serum albumin level, subjective global assessment (SGA) and comprehensive malnutrition-inflammation score (MIS). Body composition was assessed by bioimpedance spectroscopy. All patients were followed up for three years. Primary outcome measure was a composite of death and permanent removal from waitlist. Secondary outcomes were emergency room attendance and hospitalization. 432 prevalent peritoneal dialysis (PD) patients were recruited. 148 (34.3%) were listed on transplant waitlist. Frailty, age and comorbidity load predicted waitlisting. With time, 47 patients were delisted. Frailty by FQ (p = 0.028), serum albumin level (p = 0.005) and waist circumference (p = 0.010) predicted delisting after adjustment for confounders. Frailty significantly interacted with lean tissue wasting (FQ: p = 0.002, CFS: p = 0.048), and MIS (FQ: p = 0.004; CFS: p = 0.014) on delisting. Lean tissue wasting caused 2.56 times risk of delisting among frail individuals identified by FQ (p = 0.016), while serum albumin and the presence of diabetes mellitus predicted the risk of delisting among non-frail individuals. Lean tissue wasted and frail subjects had a higher all-cause and infection-related hospitalization. Frailty predicted both kidney transplant waitlisting and subsequent delisting. Frailty interacted with body composition on transplant waitlist delisting. Lean tissue wasting and malnutrition independently predicted delisting in frail and non-frail listed subjects respectively. [ABSTRACT FROM AUTHOR]

Inflammation is one of the well-recognized nontraditional risk factors that contributes to the excessive cardiovascular mortality in peritoneal dialysis (PD) patients. Serum C-reactive protein and interleukin-6 levels are common surrogate markers used to measure inflammatory burden and predict adverse clinical outcomes in PD patients. Causes of inflammation are complex and can be categorized into factors related to a decrease in renal function and factors related to dialysis. They interact with each other and finally result in systemic and intraperitoneal inflammation. This review discusses the various causes and clinical implications of inflammation in PD patients. More importantly, potential therapeutic options that target the underlying pathogenic mechanisms are explored. [ABSTRACT FROM AUTHOR]

Metal/loid pollution from shipwrecking activities has drawn significant concern due to their persistent threat to the marine ecosystem and human health. We investigated the spatiotemporal distribution, pollution characteristics, risks, sources, and potential impact of metal/loids in the sediments and seafood in the Bay of Bengal at nearby open beaching shipwrecking yards in Bangladesh. We collected 78 sediments and 208 seafood samples from the exposed and control sites from 2018 to 2020 during the dry and wet seasons. The concentrations of 16 elements, including cadmium, arsenic, lead, chromium, manganese, copper, zinc, iron, tin, antimony, nickel, cobalt, molybdenum, vanadium, selenium, and thallium were measured using validated inductively coupled plasma-mass spectrometry (ICP-MS) methods. Based on the pollution indices (enrichment factor, geoaccumulation index, pollution index, and pollution load index), lead, arsenic, cadmium, selenium, copper, zinc, and tin from the dry season showed higher contaminations compared to the wet and their concentrations were increased from 2018 to 2020 with seasonal fluctuations. Sediment cadmium and arsenic posed relatively higher and moderate ecological risks. Health risk analysis indicated that lead, cadmium, and inorganic arsenic (estimated) in seafood species pose a possible health threat to the general population. Further, there were possible ecological and health risks for the metal/loids in combination based on the ecological risk index in sediment and the hazard index in seafood, respectively. Source apportionment suggested that anthropogenic activities through uncontrolled shipwrecking operations over the last four decades were the largest polluting dominator, contributing 55–77% of the metal/loid concentrations. Therefore, the data may inform mitigation strategies for emission control at the shipwrecking yards to protect marine ecosystems and their local population. [Display omitted] • A study of metal/loids in sediments and seafood related to shipwrecking impact. • Shipwrecking activities contributed 55–77% of the elemental concentrations. • Cd, Pb, and As were identified as the significant pollutants and risk contributors. • Contamination of metal/loids was increased with seasonal fluctuations. • Emission control is prudent to protect the marine ecosystem and human health. [ABSTRACT FROM AUTHOR]

Aqueous film-forming foam (AFFF) has historically contained high concentrations of long-chain per-and polyfluoroalkyl substances (PFAS), which have been linked with adverse health outcomes. However, the toxicity of historical AFFFs remains largely unknown, presenting uncertainties in their risk assessment. This study assessed the toxicity of historical AFFFs by exposing human liver cells (HepG2) to various dilutions of 3M Light Water AFFF or Ansulite AFFF (0.001%, 0.002%, 0.005%, 0.009%, 0.019%, 0.038%, 0.075%, 0.15%, and 0.3%) for 24 h. The effects of the two AFFF formulations on the cell viability, intracellular reactive oxygen species (ROS) production, Nrf2-ARE activity, and DNA damage were assessed by CellTiter 96® Aq ueous One Solution Cell Proliferation Assay (MTS kit), dichlorofluorescein diacetate assay, luciferase assay, and alkaline Comet assay, respectively. The results revealed that the two brands of AFFFs tested were toxic to HepG2 cells at dilutions lower than the recommended 3% application formulation. Specifically, exposure to 3M Light Water AFFF or Ansulite AFFF induced a dilution-dependent decrease in cell viability, increased intracellular ROS production, and increased Nrf2-ARE activity. However, except for the highest concentration (lowest dilution) of 3M Light Water AFFF tested (0.038%.), both 3M Light Water AFFF and Ansulite AFFF did not significantly induce cellular DNA damage. Overall, 3M Light Water AFFF was more toxic than Ansulite AFFF. The findings from this study provided valuable in vitro toxicity data that may better inform the health risk assessment of these historical AFFFs. [Display omitted] • The toxicity of 3M Light Water AFFF and Ansulite AFFF was assessed in HepG2 cells. • Both formulations induced a dilution-dependent decrease in cell viability. • Both formulations induced a dilution-dependent increase in oxidative stress response. • Both formulations did not significantly induce cellular DNA damage. • 3M Light Water AFFF was comparatively more toxic than Ansulite AFFF. [ABSTRACT FROM AUTHOR]

A drastic decrease in the suspended sediment of Dongting Lake (DTL) has been observed due to Three Gorges Dam (TGD) impoundment operation since 2003. However, the relationship between sediment loads and metal fluxes has not been studied. This study comprehensively analyzed the content characteristics of seven metal(loid)s (As, Cd, Cr, Cu, Hg, Pb, and Zn) in the surface sediment of DTL from 2000 to 2019. The period of 2005–2009 corresponded to a metal(loid) enrichment stage in the sediment of DTL. The metal(loid) cumulative input of DTL from 2000 to 2019 reached 153 × 103 t, and the increasing rate was gradually diminished because of TGD operation, while the metal(loid) cumulative output reached 132 × 103 t. Undergoing an input-output state transition, the metal(loid) cumulative deposition of DTL in 2019 was only 42% of its peak in 2007. Especially, the metal(loid) fluxes of DTL all became negative for the first time in 2006. It is worth noting that Cd in DTL has shifted to a net export during the study period. Finally, the assessment results of pollution, risk, and toxicity indicated that metal(loid) effects on sediment quality were weakening in recent years. This study confirmed that DTL has shifted from metal(loid) deposition to export, providing new information for future DTL management options. [Display omitted] • Metal(loid) fluxes of Dongting Lake (DTL) were studied from 2000 to 2019. • Operation of Three Gorges Dam has changed DTL metal(loid) fluxes. • Metal(loid) annual output of DTL has exceeded their input in recent years. • The extent of metal(loid) pollution in the sediment of DTL was decreasing. • The pollution of Cd and Hg in the sediment of DTL remains to be a problem. [ABSTRACT FROM AUTHOR]

Summary: Transplant professionals strive to improve domestic kidney transplantation rates safely, cost efficiently, and ethically, but to increase rates further may wish to allow their recipients and donors to traverse international boundaries. Travel for transplantation presents significant challenges to the practice of transplantation medicine and donor medicine, but can be enhanced if sustainable international registries develop to include low- and low-middle income countries. Robust data collection and sharing across registries, linking pretransplant information to post-transplant information, linking donor to recipient information, increasing living donor transplant activity through paired exchange, and ongoing reporting of results to permit flexibility and adaptability to changing clinical environments, will all serve to enhance kidney transplantation across international boundaries. [ABSTRACT FROM AUTHOR]

The fraction transformation from stable to mobile forms in sediments is continuous, slow, and spontaneous chain reactions causing static risks to the aquatic system. However, this process may change into abrupt, rapid, and dynamic paths when certain physicochemical conditions changed. Using the Delayed Geochemical Hazard (DGH) model, comprehensive methods combing both static and dynamic risk assessment were therefore conducted to evaluate the aforementioned processes. By applying these methods, arsenic (As) pollution in surface sediments of the Baiyangdian Lake (BYD Lake) was investigated thoroughly as a case study area. The results showed that the total As concentrations in those sediment samples ranged from 4.87 to 17.94 mg/kg, with an average of 8.75 mg/kg. In a fraction, Fe and Mn were observed to pose effects on the surface-adsorbed (As S) and residual fractions (As R) with the coefficient analysis. The static risk assessment showed that both the contamination and ecological risk are at a low level in the total content but a low to moderate risk in the fraction. The dynamic risk assessment posted the potential transformation paths of As in the sediments, indicating a trend of potential DGH burst in 45.24%–78.57% of the BYD Lake. In summary, this study provides a methodology for the risk assessment of arsenic that may extend to other heavy metal(loid)s combining static and dynamic processes in sediments. • As content and fraction in surface sediments were investigated in Baiyangdian Lake. • Comprehensive risks including static and dynamic risk were assessed synchronously. • Static risk of As was analyzed by employing four indices (I geo , ICF, E r i , and RAC). • DGH model provided potential transformation paths of As for revealing the dynamic risk. [ABSTRACT FROM AUTHOR]

Beijing parks always have a large flow of local residents and tourists, and the soil Pb could threaten human health by incidental ingestion. Soil samples from eleven parks in Beijing were collected to assess the human health risk associated with Pb. Lead bioaccessibility in these parks ranged from 3.2 ± 0.4% to 12.1 ± 0.5% in the physiologically based extraction test (PBET) gastric phase and increased when approaching the city center. The chemical forms and soil properties (Fe, organic matter, and grain size) were important factors affecting the soil Pb bioaccessibility. The geo-accumulation index of Beihai Park (BH, near the city center) reached 1.3 ± 0.1 indicating moderate contamination. Lead health risk to children in BH should be of concern though its hazard quotient was below one. Results obtained from the Diffusive Gradients in Thin-films (DGT)-induced fluxes in the soils (DIFS) model showed that Pb-release in some parks farther from the city center was a "partially sustained case" (R diff < R < 0.95) indicating that soil particles could partially replenish effective Pb to the soil solution. A relatively higher desorption rate constant (k 1) and shorter characteristic response time (T c) were also found in these parks, indicating non-negligible release risk. Soil Pb based on the PBET method and DIFS model could provide a reliable reference to park managers for the health risk management of Pb pollution. Image 1 • Lead pollution and risk in urban park soils were systematically investigated. • In vitro methods were used to assess Pb accumulation and health risk. • DIFS model was used to study Pb resupply capacity in urban park soils. [ABSTRACT FROM AUTHOR]

The combined effects and toxicological interactions of perfluoroalkyl and polyfluoroalkyl substances (PFAS) mixtures remain largely unknown even though they occur as complex mixtures in the environment. This study investigated the toxicity of individual and combined PFAS to human liver cell line (HepG2). The Combination Index (CI)-isobologram equation method was used to determine the toxicological interactions of PFAS in binary, ternary and multi-component mixtures. The results indicated that the cytotoxicity of individual PFAS to HepG2 cells increased with increasing carbon chain lengths when separated into non-sulfonated and sulfonated groups. The respective cytotoxicity of PFAS is in the order of PFDA > PFNA > PFOA > PFHpA for perfluoroalkyl carboxylic acids and in the order of PFOS > PFHxS for perfluoroalkane sulfonic acids. The toxicological interaction of PFOS and PFOA with other PFAS clearly showed a different pattern of combined toxicity in HepG2 Cells. The binary, ternary, and multi-component combinations of PFOS with PFOA, PFNA, PFDA, PFHxS, and PFHpA displayed synergistic interactions for almost all inhibitory effect levels tested, whereas, either synergistic or antagonistic effect was observed in mixtures with PFOA. Overall, the pattern of interactions of PFAS mixtures is predominated by synergism, especially at low to medium effect levels; the exceptions to this were the antagonistic interactions found in mixture with PFOA, PFHxS, and PFHpA. These cytotoxicity results may have an implication on the health risk assessment of PFAS mixtures. Image 1 • Combined toxicity of up to 6 PFAS was evaluated in HepG2 cells for the first time. • Cytotoxicity of individual PFAS increased with increasing carbon chain lengths. • PFOS and PFOA interact differently with PFHxS and PFHpA in HepG2 cells. • Toxicity interaction of PFAS mixtures is mostly predominated by synergism. • Understanding PFAS mixture toxicity can better inform their risk assessment. Cytotoxic effects of individual PFAS to HepG2 cells increased with increasing carbon chain lengths, and the pattern of interaction of PFAS mixtures is mainly predominated by synergism. [ABSTRACT FROM AUTHOR]

Indospicine is a hepatotoxic non-proteinogenic amino acid that has only been found in Indigofera plants including a number of species abundant in central Australia. These legumes are palatable to feral camels and indospicine residues derived from these plants accumulates in camel meat tissue. Indospicine-contaminated camel meat has caused liver disease and mortalities in dogs after a short period of dietary exposure. Since camel meat is also exported for human consumption, this raises concern about the human health risks of consuming indospicine-contaminated camel meat harvested from central Australia. The objective of this study was to assess the indospicine levels in camel meat and its associated potential health risk to the Australian population and the vulnerable sub-population of indigenous Australians from the consumption of such feral camel meat. Two main quantitative probabilistic exposure assessments were conducted through the use of Monte Carlo simulations. The first exposure assessment considered the indospicine concentrations in real-field camel meat samples. The second assessment was based on a simulated probabilistic distribution of indospicine residues in camel meat, involving eight (8) predictive factors that were derived from our published research data and other secondary sources. The first assessment predicted that the estimated risk of developing indospicine₋induced hepatotoxicosis from contaminated camel meat consumption was 800 per 10 000 of the average Australian population (8.0%), and higher for the indigenous Australians (10.0%). The second exposure assessment demonstrated there was a higher risk (>31%) for the whole Australian population and for the indigenous Australian population. In conclusion, this risk assessment study shows that, while there is a low risk amongst Australians of hepatotoxicosis being associated with the consumption of indospicine-contaminated camel meat, such consumption is still a cause for concern, since the assessment based on the simulated probabilistic distribution of indospicine concentrations in camel meat demonstrated a substantially higher risk. It is therefore advisable that an indospicine residue monitoring program should be implemented to ensure food safety of Australian camel meat. Additionally, the risk of dietary indospicine exposure from other livestock grazing Indigofera in all global regions should also be considered. Image 1 • Heptatotoxic indospicine forms residues in meat tissue of camels grazing Indigofera. • Dogs have died from eating contaminated meat and human health risk is of concern. • Quantitative probabilistic exposure assessments characterised potential health risk. • Assessments based on real-field camel meat samples suggest low health risk. • Residue monitoring program warranted to ensure food safety of Australian camel meat. [ABSTRACT FROM AUTHOR]

Some polyaromatic hydrocarbons (PAHs) and metals are known human carcinogens and the combined toxicity data of these co-contaminants are important for assessing their health risk. In this study, we have evaluated the combined genotoxicity, AhR activity and cell cycle parameters of four PAHs (benzo[a]pyrene (Ba]P), naphthalene (Nap), phenanthrene (Phe) and pyrene (Pyr)) and three metals (arsenic (As), cadmium (Cd), and lead (Pb)) in HepG2 cells using a flow cytometry based micronucleus (MN) test CAFLUX assay and nuclear fluorescence assay, respectively. The mixtures of B[a]P and metals induced a maximum of four fold increase in the MN formation compared to B[a]P alone. The higher combination of PAHs and metals did not significantly increase the MN formation. The mixtures of metals or non-carcinogenic PAHs were found to increase or decrease the aryl hydrocarbon receptor (AhR) activation of B[a]P in HepG2 cell based CAFLUX assay. Overall, the results showed that combined genotoxicity of PAHs and metals in HepG2 cells vary depending on the concentrations and number of the chemicals that are present in the mixtures and the effects of higher order combinations appear to be largely unpredictable from binary combinations. In this study, we have demonstrated the use of flow cytometry based MN test to screen the genotoxicity of environmental chemicals and its mixtures. [ABSTRACT FROM AUTHOR]

The human health risk associated with arsenic in food in Southeast Brazil was quantified. Based on the most commonly consumed food types in the Brazilian diet, the maximum inorganic As (iAs) daily intake from food (0.255 μg kg −1 body weight per day) is approximately 9% of the Benchmark Dose Lower Limit (BMDL 0.5 ) of 3 μg kg −1 body weight per day set by the World Health Organization (WHO) and Food and Agriculture Organization (FAO) Joint Expert Committee in Food Additives (JECFA). When water is included, the contribution of food to the total intake varies from 96.9% to 39.7%. Rice and beans, the main Brazilian staple food, contribute between 67 and 90% of the total As intake from food (46–79% from rice and 11–23% from beans). The substantial contribution of beans to total As food intake is reported for the first time. The broad range of As concentrations in rice and beans highlights the variable and potentially large contribution of both to As food intake in places where diet consists largely of these two food categories. [ABSTRACT FROM AUTHOR]

Mixed contamination of benzo[ a ]pyrene (B[ a ]P), arsenic (As), cadmium (Cd), and lead (Pb) is a major environmental and human health concern. The mixture toxicity data on these co-contaminants are important for their risk assessment. In this study, we have determined the mixture toxicity of As, Cd and Pb, and B[ a ]P with As, Cd or Pb in HepG2 cells. The binary mixtures of Cd + As, Cd + Pb and As + Pb and B[ a ]P + metals (B[ a ]P + As, B[ a ]P + Cd and B[ a ]P + Pb) were evaluated for their interaction on the cytotoxicity using the MTS assay. A full factorial design (4 × 5) was used to determine the interaction toxicity and all the six mixtures showed significant interaction on the cytotoxicity. We further investigated the role of oxidative stress (reactive oxygen species (ROS) generation) and antioxidant defense mechanism (total glutathione (GSH) level) with the observed cytotoxicity. The mixtures of metals reduced the total GSH level and increased the ROS generation, respectively. In the case of mixtures of B[ a ]P and metals, both total GSH level and ROS generation were increased. Overall, the binary mixtures of metals and B[ a ]P with metals caused a dose dependent toxicity to HepG2 cells. The results also showed a significant contribution of oxidative stress to the observed toxicity and the potential protective role of the total GSH level against this mixture toxicity. The findings of interaction between B[ a ]P and metals might have an impact on the potential human health risk of this mixtures at contaminated sites. [ABSTRACT FROM AUTHOR]

Cytotoxicity of benzene, toluene, ethylbenzene and xylenes (BTEX) to human lung cells was explored using three different exposure methods: Method 1 – in normal 96-well plates using DMSO as a carrier vehicle, we exposed (a) human lung carcinoma A549 cells, (b) A549 cells over-expressed with cytochrome P450 2E1 cells, and (c) normal lung fibroblast LL-24 cells to benzene, toluene, ethylbenzene and xylene individually and in a mixture which models car exhaust gases for between 1–88 h. We found that the order of the BTEX potency is benzene < toluene < ethylbenzene = m- xylene with acute BTEX toxicity to A549 ≈ LL-24 > CYP2E1 over-expressed A549 cells. A significant difference was found between inter-assay responses for all 24 h exposures ( P < 0.005) suggesting a poor assay repeatability. No sign of potency increase was found from 6 to 72 h exposures. Method 2 – Using sealed vials to expose A549 cells to benzene, toluene and ethylbenzene, we observed a twenty-fold increase in their cytotoxicity, but also with no time-course effect. Method 3 – Using air exposed hanging-drop cell culture, we were able to see both an increase of demonstration of toxicity and a time-course effect from 1 to 12 h exposure. We conclude that exposing cells in sealed and unsealed media using DMSO as a carrier vehicle was not suitable for BTEX exposure studies. Hanging-drop air exposure has more potential. It should be noted that if there are any changes in their exposure matrixes, its exposure mass distribution in cells could differ. [ABSTRACT FROM AUTHOR]

Mine wastes contain a mixture of metals and metalloids including arsenic (As) and cadmium (Cd). This study investigated the potential interaction between As and Cd in a rat model. Sprague Dawley rats were dosed with sodium arsenate via the oral (0, 0.5, 5 and 15mg As kg−1 b.w.) or intravenous (0.5mg As kg−1 b.w.) route to establish its dose-response relationship in terms of bioavailability and pharmacokinetic parameters. Bioavailability of As reduced when the dose of As increased. For the interaction study a fixed oral dose of As at 2.5mg As kg−1 b.w. solo and in combination with Cd as cadmium chloride at 3 or 6mg Cd kg−1 b.w. were administered to rats. Bioavailability of As was decreased by 34-35% in the presence of Cd. Elimination half-life of As was also decreased from 69 days in the As solo group to 13-22days in the presence of 3 and 6mg Cd kg−1 b.w. respectively. Decreased urinary excretion of As and tissue accumulation were also observed. A probable explanation for these findings is that As co-administration with Cd could have resulted in the formation of less soluble cadmium-arsenic complexes in the guts of the rats. Nevertheless, such an interaction between As and Cd could only explained about 44-48% of the variation when mine waste materials containing both of these elements were administered to rats. This suggests other physical properties and chemical compound formation could contribute to the observed bioavailability of arsenic in complex environmental samples. [ABSTRACT FROM AUTHOR]

Bioaccessibility (BAC) of fine surface dust (FSD, particle size ≤10 μm) and surface dust samples (particle size ≤250 μm) collected from a gold mining district was used as a tool to determine the portion of arsenic that would be available via simulated lung and gastrointestinal (G.I) fluids. BAC was considered low for both tests (lung 2.7 ± 1%, n = 5 and G.I 3.4 ± 2%, n = 14 for residential surface dust samples). An analytical procedure was developed to further identify arsenic-bearing phases found in FSD samples and analyze the main components that regulate arsenic solubility. Up to five different arsenic-bearing phases were identified among a total of 35 minerals surveyed by scanning electron microscopy-based automated image analysis (Mineral Liberation Analyzer - MLA). Arsenic-bearing Fe oxy-hydroxides and mixed phases comprised the main arsenic phases encountered in FSD samples, thus likely being responsible for regulating arsenic bioaccessibility. Transmission electron microscopy showed that the mixed phases comprised a mix of oriented nanostructure aggregates formed by hematite and goethite entangled with phyllosilicates. The main As-bearing phases identified in FSD samples are similar to those reported in soil samples in the same region. The predominant arsenic-bearing phase encountered in the ore was arsenopyrite, mostly in large particles (>10 μm in size), and therefore unlikely to be found in residential dust. Arsenic intake from both inhalation and ingestion were minimal when compared to total arsenic intake (considering food and water ingestion), which itself was <7% of the value established by the Food and Agriculture Organization of the United Nations Benchmark Dose Lower Confidence Limit (BMDL 0.5) of 3.0 μg per kg−1 body weight per day. These results indicated that the relative risks associated with arsenic exposure by inhalation and oral ingestion in this region are low. Unlabelled Image • Single particle As-bearing phase identification in <10 μm particles ca. gold mine. • Arsenic was mainly associated with nanostructured iron oxy-hydroxides in dust. • Arsenic was mainly found as arsenopyrite in the ore. • PBET (3.4%) and lung (2.7%) As bioaccessibility were low in residential areas. • Risk to human health by ingestion/inhalation was low despite high As concentrations. [ABSTRACT FROM AUTHOR]

Environmental exposure to multiple metals and metalloids is widespread, leading to a global concern relating to the adverse health effects of mixed-metals exposure, especially in young children living around industrial areas. This study aimed to quantify the concentrations of essential and potentially toxic elements in blood and to examine the potential associations between multiple elements exposures, growth determinants, and liver and kidney function biomarkers in children living in several industrial areas in Dhaka, Bangladesh. The blood distribution of 20 trace elements As, Ag, Bi, Br, Cd, Co, Cr, Cu, I, Mn, Hg, Mo, Ni, Pb, Se, Sb, Tl, V, U, and Zn, growth determinants such as body mass index and body fats, blood pressure, liver and kidney injury biomarkers including serum alanine aminotransferase and alkaline phosphatase activities, serum calcium, and creatinine levels, blood urea nitrogen, and hemoglobin concentrations, and glomerular filtration rate were measured in 141 children, aged six to 16 years. Among these elements, blood concentrations of Ag, U, V, Cr, Cd, Sb, and Bi were measured below LOQs and excluded from subsequent statistical analysis. This comprehensive study revealed that blood concentrations of these elements in children, living in industrial areas, exceeded critical reference values to varying extents; elevated exposure to As, Pb, Br, Cu, and Se was found in children living in multiple industrial areas. A significant positive association between elevated blood Tl concentration and obesity (β = 0.300, p = 0.007) and an inverse relationship between lower As concentration and underweight (β = −0.351, p < 0.001) compared to healthy weight children indicate that chronic exposure to Tl and As may influence the metabolic burden and physical growth in children. Concentration-dependent positive associations were observed between the blood concentrations of Cu, Se, and Br and hepatic- and renal dysfunction biomarkers, an inverse association with blood Mo and I level, however, indicates an increased risk of Cu, Se, and Br-induced liver and kidney toxicity. Further in-depth studies are warranted to elucidate the underlying mechanisms of the observed associations. Regular biomonitoring of elemental exposures is also indispensable to regulate pollution in consideration of the long-term health effects of mixed-elements exposure in children. [ABSTRACT FROM AUTHOR]

The bioavailability and bioaccessibility of heavy metals mainly depend on their speciation in soils; however, the relationship between bioaccessibility and its speciation as determined as fractionation remains to be better characterized. Therefore, Cd fractionations in three types of long-term Cd-spiked soils were determined using a modified BCR method, and compared with Cd bioaccessibility data obtained from four in vitro gastrointestinal simulation assays including the IVG, PBET, SBRC, and UBM. The results shows that the majority of Cd were found in the exchangeable/acid soluble (B1) and reducible (B2) fractions (total percentage > 97%) after being spiked and aged for three years, indicating high Cd bioavailability; the bioaccessibility of Cd ranged from 57.7 ± 1.8% to 99.3 ± 2.8% in the gastric phase, and from 5.8 ± 2.0% to 35.9 ± 1.8% in the intestinal phase, respectively. Among the four assays, the strongest positive correlation was observed between Cd bioaccessibility based on the PBET assay and its B1 fraction in the spiked soils (r 2 gastric: 0.62 and intestinal: 0.52), suggesting that the PBET assay maybe more suitable for determining Cd bioaccessibility in aged contaminated soils. [ABSTRACT FROM AUTHOR]

A new analytical protocol was developed to provide quantitative, single-particle identification of arsenic in heterogeneous nanoscale mineral phases in soil samples, with a view to establishing its potential risk to human health. Microscopic techniques enabled quantitative, single-particle identification of As-bearing phases in twenty soil samples collected in a gold mining district with arsenic concentrations in range of 8 to 6354 mg kg −1 . Arsenic is primarily observed in association with iron (hydr) oxides in fine intergrowth with phyllosilicates. Only small quantities of arsenopyrite and ferric arsenate (likely scorodite) particles, common in the local gold mineralization, were identified (e.g., 7 and 9 out, respectively, of app. 74,000 particles analyzed). Within the high-arsenic subgroup, the arsenic concentrations in the particle size fraction below 250μm ranges from 211 to 4304 mg kg −1 . The bioaccessible arsenic in the same size fraction is within 0.86–22 mg kg −1 (0.3–5.0%). Arsenic is trapped in oriented aggregates of crystalline iron (hydr)oxides nanoparticles, and this mechanism accounts for the low As bioaccessibility. The calculated As exposure from soil ingestion is less than 10% of the arsenic Benchmark Dose Lower Limit - BMDL 0.5 . Therefore, the health risk associated with the ingestion of this geogenic material is considered to be low. [ABSTRACT FROM AUTHOR]

Atrazine (AZ) is an environmental endocrine disrupting chemical which can affect the development of amphibians. In our past studies, we demonstrated that chronical exposure to 100 μg/L AZ can cause abnormalities in development and related genes expression of gonads in developing male Xenopus laevis ( X. laevis ) tadpoles. Recent studies by others have demonstrated that circular RNAs (circRNAs) are implicated in multiple developmental anomalies. However, whether circRNAs involve in the effects in AZ-exposed X. laevis remains unknown. In this study, over 68575 circRNAs were detected by circRNA sequencing of testis tissues from control groups ( n  = 3) and AZ-treated X. laevis ( n  = 3). Treatment of AZ led to 405 circRNAs differentially expressed including 44 upregulated and 361 downregulated compared with froglets in the control groups. Two upregulated and 6 downregulated circRNAs were further validated by real-time PCR assay which displayed consistent regulation patterns as shown by the transcriptome sequencing results. Two hundreds and eighty two differentially expressed circRNAs played miRNA sponges roles. Kyoto Encyclopedia of Genes and Genomes pathway analysis of miRNA targets showed that AZ-affected circRNAs are mainly involved in 19 pathways. The Wnt signaling pathway and progesterone-mediated oocyte maturation pathway may be two involved signal pathways. This study for the first time provides evidence that AZ can alter circRNAs which play a role in AZ-induced testicular degeneration of developing male X. laevis through regulation of expressions of functional genes in the testes of X. laevis. [ABSTRACT FROM AUTHOR]

On 25th May 2016, the U.S. EPA released reference doses (RfDs) for Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) of 20 ng/kg/day, which were much more conservative than previous values. These RfDs rely on the choices of animal point of departure (PoD) and the toxicokinetics (TK) model. At this stage, considering that the human evidence is not strong enough for RfD determination, using animal data may be appropriate but with more uncertainties. In this article, the uncertainties concerning RfDs from the choices of PoD and TK models are addressed. Firstly, the candidate PoDs should include more critical endpoints (such as immunotoxicity), which may lead to lower RfDs. Secondly, the reliability of the adopted three-compartment TK model is compromised: the parameters are not non-biologically plausible; and this TK model was applied to simulate gestation and lactation exposures, while the two exposure scenarios were not actually included in the model structure. [ABSTRACT FROM AUTHOR]

Background The role of microRNA (miRNA) in peritoneal fibrosis and longitudinal change in transport is uncertain. Methods We studied 80 new peritoneal dialysis (PD) patients. Peritoneal transport was determined by standard peritoneal equilibration test (PET) of creatinine at baseline. Based on published literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA quantification were repeated one year later in 46 patients. Results Baseline PD effluent levels of all targets tested had modest but significant correlation with peritoneal transport parameters. PD effluent miR-21 and miR-589 levels correlated with dialysate-to-plasma creatinine concentration at 4 h (D/P4) at baseline (r = 0.377, p = 0.001 and r = 0.237, p = 0.037, respectively) and after one year of PD (r = 0.362, p = 0.014 and r = 0.402, p = 0.007). The change in PD effluent − 21 and miR-589 levels over one year correlated with the corresponding change in D/P4 (r = 0.470, p = 0.001 and r = 0.479, p = 0.002). The number of peritonitis episodes during follow up significantly correlated with the change in PD effluent miR-21 (r = 0.387, p = 0.009) and miR-589 (r = 0.336, p = 0.027) levels. There was no significant correlation between PD effluent miRNA level and ultrafiltration volume. Conclusion Amongst the 10 miRNA targets tested, miR-21 and miR-589 showed consistently significant relation with peritoneal transport. Further studies are needed to delineate their mechanisms of regulating peritoneal transport. [ABSTRACT FROM AUTHOR]

As a widely used herbicide, atrazine (AZ) has been extensively studied for its adverse effects on the reproductive system, especially feminization in male animals. However, the relationship of gene expression changes and associated toxicological endpoints remains unclear. In this study, developing Xenopus laevis tadpoles were exposed to concentration of AZ at 0.1, 1, 10 or 100 μg/L continuously. Compared with froglets in the control group, there were no significant differences in body length, body weight, liver weight and hepatosomatic index (HSI) of males in groups treated with AZ for 90 d. At 100 μg/L AZ treatment caused a significant reduction of gonad weight and gonadosomatic index (GSI) of males ( p < 0.01). In addition, AZ at all dose levels caused testicular degeneration, especially in froglets from the groups with 0.1 and 100 μg/L which exhibited U-shaped dose-response trend. We further investigated the gene expression changes associated with the testicular degeneration induced by AZ. We found that the expression of 1165 genes was significantly altered with 616 upregulated and 549 downregulated compared to the expression profile of the control animals. KEGG analysis showed that genes which were significantly affected by AZ are mainly involved in arginine and proline metabolism, cell cycle, riboflavin metabolism, spliceosome, base excision repair and progesterone-mediated oocyte maturation pathway. Our results show that AZ may affect reproductive and immune systems by interference with the related gene expression changes during the male X. laevis development. The findings may help to clarify the feminization mechanisms of AZ in male X. laevis . [ABSTRACT FROM AUTHOR]

The bioaccessibility of lead (Pb) in contaminated soils has been extensively studied, including the influence of soil properties on Pb bioaccessibility. However, little is known about the effects of other metals/metalloid, such as arsenic (As), cadmium (Cd) on the bioaccessibility of Pb, i.e. whether As or Cd could increase or decrease the solubility of Pb in human gastrointestinal tract when Pb-contaminated soil and As-contaminated (or Cd-contaminated) soil are ingested simultaneously. Furthermore, it is far from clear that if soil property could make a difference to these effects. In this study, seven types of soils were collected in Australia and spiked with As, Cd or Pb. Gastric bioaccessibility of Pb ranged from 44 ± 0.9% to 100 ± 6.7% whilst intestinal bioaccessibility dropped to 1 ± 0.2% to 36 ± 1.7%. Statistical analysis shows total Pb in soil was the most significant controller for bioaccessible Pb. Effects of As and Cd on the bioaccessibility of Pb in simulated human digestive system were studied by mixing As-spiked soil (or Cd-spiked soil) with Pb-spiked soil of the same type during bioaccessibility test. Results reveal that neither As nor Cd had impact on Pb bioaccessibility, which indicates when As, Cd and Pb aged in soils separately, they may behave independently in the bioaccessibility measuring system. This finding can be part of evidence to assume additive effect when it comes to estimate the bioaccessibility of mixtures of independently-aged As and Pb (or Cd and Pb) in soils. [ABSTRACT FROM AUTHOR]

Recent decades have seen a growing popularity of in vitro bioaccessibility being utilised as a screening tool in human health risk assessment. However the existing bioaccessibility studies only focus on single contaminant. Considering human are likely to ingest multi-contaminants, these contaminants could interact within human gastrointestinal tract which may lead to an increase or decrease in bioaccessibility. In this study, seven different types of soil were spiked with arsenic (As) or cadmium (Cd) and aged for one year. The effects of soil properties on the bioaccessibility were examined. Moreover, the interaction between As and Cd in simulated human digestive system was studied by mixing As-spiked soil with Cd-spiked soil of the same type during bioaccessibility test. Results shows the bioaccessibility of As ranged from 40 ± 2.8 to 95 ± 1.3% in the gastric phase and 16 ± 2.0 to 96 ± 0.8% in the intestinal phase whilst a significant difference was observed between Cd gastric bioaccessibility (72 ± 4.3 to 99 ± 0.8%) and intestinal bioaccessibility (6.2 ± 0.3 to 45 ± 2.7%). Organic carbon, iron oxide and aluminium oxide were key parameters influencing the bioaccessibility of As (gastric and intestinal phases) and Cd (intestinal phase). No interactions between As and Cd during bioaccessibility test were observed in any soils, which indicates As and Cd may age independently and did not interact while being solubilised during bioaccessibility test. Thus additive effect may be proposed when estimating the bioaccessibility of mixtures of independently-aged As and Cd in soils. [ABSTRACT FROM AUTHOR]

Malathion has a broad range of toxicities while its reproductive effects have not been fully elucidated. In this study, we treated animals with malathion by gavage at doses of 0, 33.75, 54, and 108 mg/kg for 60 days and evaluated the alterations in histology, biochemistry and serology. Malathion caused the reduction in the sperm counts and motility. The reduced body and testis weights were coupled with mild to severe degenerative changes in seminiferous tubules. We found malathion at 54 mg/kg increased spermatogenic apoptosis rate which was confirmed by changes in protein expression of Bax and Bcl-2. The activities of testicular enzymes including ACP, LDH and γ-GT were significantly altered with the reduced level of reproductive hormones such as LH, FSH and T. These results indicate that malathion can elicit deleterious effects on reproductive system of rats. The abnormal levels of hormones and apoptotic proteins induced by malathion may play important roles. [ABSTRACT FROM AUTHOR]

[Display omitted] • Many brown rice samples contained hazardous concentrations of arsenic and cadmium. • Concentration of toxic elements in brown rice is grain-size dependent. • Sum of non-carcinogenic risk associated with As and other elements exceeds unity. • Carcinogenic risk from As or Cr in brown rice may be as high as one in every 10,000. • Results can inform the national monitoring program for rice quality and type. Twenty-two brown rice varieties available in the Qatari market were analyzed for essential and toxic elements by ICP-MS. Found concentrations (µg/kg) were: As: 171 ± 78 (62–343), Cd: 42 ± 60 (4–253), Cr: 515 ± 69 (401–639), Pb: 6 ± 7 ( 1 in million, may possibly be > 1 in 10,000 based on conservatively high brown rice consumption rates of 200 g/d or 400 g/d in Qatar. These elevated risks may be applicable to specific population subgroups with diabetic conditions who consume only brown rice. Non-cancer risks are mainly derived from Mn, V, Se, and Cd with a hazard index > 1 from some brown rice samples. [ABSTRACT FROM AUTHOR]

Although human exposure is to mixtures of per- and polyfluoroalkyl substances (PFAS), their combined effects and underlying mechanisms remain largely unknown. In this study, the combined effects of PFAS was investigated by treating human liver cells (HepG2) with various concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluorohexanoic acid (PFHxS) individually or in binary combinations (PFOS + PFOA, PFOS + PFDA, PFOS + PFNA, PFOS + PFHxS, PFOA + PFDA, PFOA + PFNA, and PFOA + PFHxS) for 24 h using an orthogonal design. The individual and binary combination effects of PFAS on the cytotoxicity, intracellular reactive oxygen species (ROS) production, and glutathione (GSH) levels were determined by MTS assay, dichlorofluorescein diacetate assay, and GSH-Glo™ Glutathione assay, respectively. The results showed that exposure to PFOA, PFOS, PFDA, PFNA, and PFHxS individually and in binary combinations caused concentration-dependent cytotoxicity to HepG2 cells. Also, intracellular ROS production was not significantly induced in both the individual and co-treatment groups, indicating that ROS production may not be likely influencing the combined cytotoxicity of PFAS to HepG2 cells. However, the depletion of the intracellular glutathione levels was correlated with cytotoxicity. Moreover, the factorial analysis results showed no significant interactive effects between PFOS + PFOA, PFOS + PFDA, PFOS + PFNA, PFOS + PFHxS, PFOA + PFDA, PFOA + PFNA, and PFOA + PFHxS. Taken together, the results showed that both individual and combined PFAS could induce concentration-dependent cytotoxicity and depletion of GSH levels, but could not induce significant increases in ROS production at the concentration range tested. Overall, these results provided valuable toxicological data on the combined effects of mixed PFAS that may help to better assess their human health risk. [Display omitted] • Combined effects of five PFAS on oxidative stress biomarkers were determined. • Individual and co-exposure to PFAS showed dose-dependent cytotoxicity. • Individual and co-exposure to PFAS did not significantly increase ROS production. • Individual and co-exposure to PFAS showed a dose-dependent decrease in GSH levels. • PFAS combinations showed no significant interactive effects on oxidative stress. [ABSTRACT FROM AUTHOR]

This paper presents a summary of some relevant documents published during the last decades regarding arsenic contamination in Brazil until December 2018, including scientific papers, reports and regulatory documents. Natural and anthropogenic arsenic sources were covered, excluding those related to agriculture. International "key" documents related to arsenic contamination were used to support the discussion and comparative analysis. This paper aims: (a) to summarize and discuss some available data (including Portuguese written documents) concerning arsenic contamination in Brazil, mainly geographical, geological, geochemical, environmental and health studies; (b) to critically review the published studies comparing their main findings; (c) to describe and compare ancient and recent contamination events; and (d) to highlight key knowledge gaps, and identify promising areas for future researches. The arsenic contamination scenario in Brazil results not only from mining. Natural or anthropogenic emissions caused by great magnitude phenomena as flooding, erosion, landslide and, water scarcity equally impact arsenic mobilization/immobilization equilibria. Our literature review demonstrates that arsenic contamination of soils, sediments and water sources is observed at least at three of the five geographically defined Brazilian regions (Northern, Southern and, Southeastern regions). Arsenic enriched soils, and waters naturally occur all around the country and anthropogenic activities have been the main contributory factor to the environmental contamination since the 18th Century. Geogenic materials (topsoil and mining tailings), and water samples could contain extremely high arsenic concentrations, i.e. 21,000 mg kg−1 or 1,700,000 μg L−1, respectively, have been found mainly at the "Iron Quadrangle". Moreover, if we consider both the Brazilian and international parameters, the health risks associated with the human exposition to arsenic are of significant concern. For those reasons, constant monitoring of As contaminated areas in Brazil is mandatory. Furthermore, it is necessary to learn from the mistakes made in the past in order to prevent or minimize future problems. Unlabelled Image • A scenario of arsenic contamination in Brazil was depicted. • Arsenic contamination from mining activities in Brazil is an ongoing concern. • Collapse of Fundão Dam led to extensive As contamination in the Rio Doce Basin. • Mobility of As in and out of different environmental compartments is complex. • Arsenic equilibrium is influenced by anthropogenic factors. [ABSTRACT FROM AUTHOR]