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Although the Nrf2-ARE pathway plays a critical role in cellular protection against toxicity and oxidative stress from environmental chemical stressors, the association between exposure to per - and polyfluoroalkyl substances (PFAS) mixtures and the changes of Nrf2-ARE pathway remains largely unexplored. This study evaluated the potential of PFAS to induce the Nrf2-ARE pathway as individual compounds and as binary, ternary, and multicomponent mixtures in the ARE reporter-HepG2 cells and compared the mixture toxicity data to the predictions by concentration addition (CA) model. The toxicological interactions between PFAS mixture components were also determined by the model deviation ratio (MDR) between the CA predicted and mixture toxicity values. The induction of the Nrf2-ARE pathway was quantified using the luciferase system, and the endpoint assessed was the concentration that induced an induction ratio (IR) of 1.5 (EC IR1.5). The results showed that exposures to both individual and mixed PFAS induced the Nrf2-ARE pathway in ARE reporter-HepG2 cells. Based on the MDRs, the combinations with PFOS showed synergistic interactive effects, while the combinations with PFOA showed additive effects. These results indicate that the CA model underestimated the mixture toxicity of PFAS with PFOS co-exposures and may have health risk assessment implications. [Display omitted] • Potential inducing effects of mixed PFAS on the Nrf2-ARE pathway were determined. • Inducing effects of individual PFAS increased as the carbon length increases. • The combinations with PFOS showed higher inducing effects than those with PFOA. • CA model may underestimate the mixture toxicity of PFAS with PFOS co-exposures. • Nrf2-ARE modulation may serve as a rapid screening tool for toxicity testing of PFAS. [ABSTRACT FROM AUTHOR]

The uncontrolled release of harmful metal/loids from mega-scale shipbreaking activities in Bangladesh is a significant concern. This study investigated the impact of shipbreaking activities on soil and crop quality and human health in relation to metal/loid contamination. This work covered an area of 1221 km2 surrounding the shipbreaking yards in Chittagong during the wet and dry seasons between 2019 and 2020. Amongst the sixteen elements measured, the concentrations of Pb, Cd, As, V, Cr, Mn, Cu, Zn, Fe, Co, Ni, and Sn in the soil, rice, and vegetables from the four exposure sites were significantly higher compared to the control site in both seasons. Soil pollution indices indicated moderate to higher contamination levels of Pb, Zn, Cd, As, and Se in 30–50% of soil, supporting their accumulation in food crops. Source apportionment analysis identified uncontrolled shipwrecking operations as the primary anthropogenic activity mainly contributing to metal/loid pollution. Health risk analysis showed inorganic arsenic (estimated), Cd, and Pb in food crops could pose potential health threats to the general population. Spinach leaf and gourd were identified as the highest-risk contributing vegetables in the dry and wet seasons. These findings help to inform management strategies to protect agroecosystems and public health. [Display omitted] • A study of 16 metal/loids in soil and food crops related to shipbreaking impact. • Shipbreaking operations were the largest contributor to the elemental contamination. • Cd, Pb, and As were identified as the significant pollutants and risk contributors. • Contamination of metal/loids varied with seasonal effect. • Shipbreaking waste control is prudent to protect agroecosystem and public health. [ABSTRACT FROM AUTHOR]

Humans are exposed to complex mixtures of per- and polyfluoroalkyl substances (PFAS). However, human health risk assessment of PFAS currently relies on animal toxicity data derived from individual substance exposure, which may not adequately predict the risk from combined exposure due to possible interactions that can influence the overall risk. Long-chain perfluoroalkyl acids (PFAAs), particularly perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are recognised as global emerging contaminants of concern due to their ubiquitous distribution in all environmental media, wildlife, and humans, persistency, bioaccumulative-, toxic-, and human health-risk potentials. This article reviews the current understanding of the human health risks associated with PFAS exposure focusing on more recent toxicological and epidemiological studies from 2010 to 2020. The existing information on PFAA mixtures was also reviewed in an attempt to highlight the need for greater focus on their potential interactions as mixtures within the class of these chemicals. A growing number of toxicological studies have indicated several adverse health outcomes of PFAA exposure, including developmental and reproductive toxicity, neurotoxicity, hepatotoxicity, genotoxicity, immunotoxicity, thyroid disruption, and carcinogenicity. Epidemiological findings further support some of these adverse human health outcomes. However, the mechanisms underlying these adverse effects are not well defined. A few in vitro studies focusing on PFAA mixtures revealed that these compounds may act additively or interact synergistically/antagonistically depending on the species, dose level, dose ratio, and mixture components. Hence, the combined effects or potential interactions of PFAS mixtures should be considered and integrated into toxicity assessment to obtain a realistic and more refined human health risk assessment. ga1 • Human health risks associated with PFAS exposure are critically reviewed. • PFAS exposures have been associated with several adverse human health outcomes. • The mechanisms underlying the adverse health effects remain unclear. • Mixed PFAS interactions must be considered for a refined health risk assessment. [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]

BTEX is a group of volatile organic compounds consisting of benzene, toluene, ethylbenzene and xylenes. Environmental contamination of BTEX can occur in the groundwater with their effects on the aquatic organisms and ecosystem being sparsely studied. The aim of this study was to evaluate the toxic effects of individual and mixed BTEX on Euglena gracilis ( E. gracilis ) . We examined the growth rate, morphological changes and chlorophyll contents in E. gracilis Z and its mutant SMZ cells treated with single and mixture of BTEX. BTEX induced morphological change, formation of lipofuscin, and decreased chlorophyll content of E. gracilis Z in a dose response manner. The toxicity of individual BTEX on cell growth and chlorophyll inhibition is in the order of xylenes > ethylbenzene > toluene > benzene. SMZ was found more sensitive to BTEX than Z at much lower concentrations between 0.005 and 5 μM. The combined effect of mixed BTEX on chlorophyll contents was shown to be concentration addition (CA). Results from this study suggested that E. gracilis could be a suitable model for monitoring BTEX in the groundwater and predicting the combined effects on aqueous ecosystem. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examined arsenic and two biomarkers in subjects post the water intervention. [•] Urinary arsenic levels were significantly higher in villagers from the endemic area. [•] Urinary porphyrins and malondialdehyde were elevated when arsenic was high. [•] Skin lesions were observed in 51 out of 178 surveyed people in the As-endemic area. [•] Four out of nine young villagers born after the intervention exhibited As-related skin lesions. [Copyright &y& Elsevier]

Abstract: Using benzene as a candidate air toxicant and A549 cells as an in vitro cell model, we have developed and validated a hanging drop (HD) air exposure system that mimics an air liquid interface exposure to the lung for periods of 1h to over 20 days. Dose response curves were highly reproducible for 2D cultures but more variable for 3D cultures. By comparing the HD exposure method with other classically used air exposure systems, we found that the HD exposure method is more sensitive, more reliable and cheaper to run than medium diffusion methods and the CULTEX® system. The concentration causing 50% of reduction of cell viability (EC50) for benzene, toluene, p-xylene, m-xylene and o-xylene to A549 cells for 1h exposure in the HD system were similar to previous in vitro static air exposure. Not only cell viability could be assessed but also sub lethal biological endpoints such as DNA damage and interleukin expressions. An advantage of the HD exposure system is that bioavailability and cell concentrations can be derived from published physicochemical properties using a four compartment mass balance model. The modelled cellular effect concentrations EC50cell for 1h exposure were very similar for benzene, toluene and three xylenes and ranged from 5 to 15mmol/kgdry weight, which corresponds to the intracellular concentration of narcotic chemicals in many aquatic species, confirming the high sensitivity of this exposure method. [Copyright &y& Elsevier]