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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., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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 15 mg As kg(-1) b.w.) or intravenous (0.5 mg 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 2.5 mg As kg(-1) b.w. solo and in combination with Cd as cadmium chloride at 3 or 6 mg 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 13-22 days in the presence of 3 and 6 mg 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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)