From molecules to organisms: A multi-level approach shows negative effects of trace elements from sewage sludge used as soil improver on honeybees.

The use of sewage sludge as a soil improver has been promoted in agroecosystems. However, sludges can contain toxic trace elements because of suboptimal wastewater treatment. Nonetheless, field studies investigating the negative effects of these practices on pollinators are lacking. We collected honeybees from an area where sewage sludge use is widespread, and one where it is precluded. Trace elements in soils and bees were quantified. Cadmium, chromium, lead, mercury, and nickel were investigated because they were the least correlated elements to each other and are known to be toxic. Their levels were related to oxidative stress and energy biomarkers, midgut epithelial health, body size and wing asymmetry of honeybees. We found increased carbohydrate content in sites with higher cadmium levels, increased histological damage to the midgut epithelium in the sewage sludge area, and the presence of dark spherites in the epithelium of bees collected from the sites with the highest lead levels. Finally, we found that honeybees with the highest lead content were smaller, and that wing fluctuating asymmetry increased in sites with increasing levels of mercury. To the best of our knowledge, this is the first comprehensive study of the concentration and effects on honeybees of trace elements potentially deriving from soil amendment practices.

Zinc Toxicity: Understanding the Limits.

Zinc, a vital trace element, holds significant importance in numerous physiological processes within the body. It participates in over 300 enzymatic reactions, metabolic functions, regulation of gene expression, apoptosis and immune modulation, thereby demonstrating its essential role in maintaining overall health and well-being. While zinc deficiency is associated with significant health risks, an excess of this trace element can also lead to harmful effects. According to the World Health Organization (WHO), 6.7 to 15 mg per day are referred to be the dietary reference value. An excess of the recommended daily intake may result in symptoms such as anemia, neutropenia and zinc-induced copper deficiency. The European Food Safety Authority (EFSA) defines the tolerable upper intake level (UL) as 25 mg per day, whereas the Food and Drug Administration (FDA) allows 40 mg per day. This review will summarize the current knowledge regarding the calculation of UL and other health risks associated with zinc. For example, zinc intake is not limited to oral consumption; other routes, such as inhalation or topical application, may also pose risks of zinc intoxication.

Assessment of macro, trace and toxic element intake from rice: differences between cultivars, pigmented and non-pigmented rice.

Pigmented and non-pigmented rice varieties (grown in different areas) were collected in China, Yunnan, to investigate the content of macro-, trace elements and potentially toxic elements (PTEs), and to assess the health risk associated with dietary intake. The order of elemental concentrations in rice was Mn > Zn > Fe > Cu > Se for trace elements, P > K > Mg > Ca > Na for macro elements, and Cr > As > Cd for PTEs. Rice with a high concentration of essential elements also associated with a high content of PTEs. In addition, higher content of Cr, Mn and Na were found in pigmented rice. The health risk assessment showed that the daily intake of all elements was below the tolerable limit (UL). Moreover the intake of Fe, Zn and Se was far from sufficient for the nutrient requirement. The PTEs in rice dominated the health risk. Of concern is that this rice consumption is likely to contribute to carcinogenic risks in the long term and that adults are at higher health risk from pigmented rice compared to non-pigmented rice. This study confirms that the lack of essential micronutrients in rice and the health risk associated with rice diets should remain a concern.

Essential and Toxic Elements in Infant Cereal in Brazil: Exposure Risk Assessment.

Infant cereals, one of the first solid foods introduced to infants, have been reported to pose risks to human health because they contain toxic elements and an excess of essential elements. The objective of this study was to assess the cancer and non-cancer risk of exposure to essential and toxic elements in infant cereal in Brazil. In our analyses, we included data from 18 samples of infant cereals made from different raw materials and estimated the incremental lifetime cancer risks and non-cancer hazard quotients (HQs) for their consumption. Rice cereal is particularly concerning because it is immensely popular and usually contains high levels of inorganic arsenic. In addition to arsenic, we assessed aluminum, boron, barium, cadmium, chromium, copper, lead, manganese, nickel, selenium, silver, strontium, and zinc. The cancer risk was highest for rice cereal, which was also found to have an HQ > 1 for most of the tested elements. Inorganic As was the element associated with the highest cancer risk in infant cereal. All of the infant cereals included in this research contained at least one element with an HQ > 1. The essential and non-essential elements that presented HQ > 1 more frequently were zinc and cadmium, respectively. The cancer and non-cancer risks could potentially be decreased by reducing the amount of toxic and essential elements (when in excess), and public policies could have a positive influence on risk management in this complex scenario.

Ocean acidification impact on the uptake of trace elements by mussels and their biochemical effects.

This study delves into the intricate interplay between ocean acidification (OA), metal bioaccumulation, and cellular responses using mussels (Mytilus galloprovincialis) as bioindicators. For this purpose, environmentally realistic concentrations of isotopically labelled metals (Cd, Cu, Ag, Ce) were added to investigate whether the OA increase would modify metal bioaccumulation and induce adverse effects at the cellular level. The study reveals that while certain elements like Cd and Ag might remain unaffected by OA, the bioavailability of Cu and Ce could potentially escalate, leading to amplified accumulation in marine organisms. The present findings highlight a significant rise in Ce concentrations within different mussel organs under elevated pCO2 conditions, accompanied by an increased isotopic fractionation of Ce (140/142Ce), suggesting a heightened potential for metal accumulation under OA. The results suggested that OA influenced metal accumulation in the gills of mussels. Conversely, metal accumulation in the digestive gland was unaffected by OA. The exposure to both trace metals and OA affects the biochemical responses of M. galloprovincialis, leading to increased metabolic capacity, changes in energy reserves, and alterations in oxidative stress markers, but the specific effects on other biomarkers (e.g., lipid peroxidation, some enzymatic responses or acetylcholinesterase activity) were not uniform, suggesting complex interactions between the stressors and the biochemical pathways in the mussels.

The significance of applying different factors for the evaluation of sediment contamination by toxic elements and estimation of the ecological risk.

The optimized three-step sequential extraction procedure for the fractionation of micro- and macroelements, was conducted to determine fractional characteristics of PTEs (potentially toxic elements) in surface sediments of rivers in the Vlasina watershed. The sequential extraction results, which enable the evaluation of mobility of the studied elements, have indicated that Zn, Ni, Cu, Cr, and As can be considered slightly mobile, whereas Pb, Mn, Cd, and Co were regarded as possibly mobile elements. Lead was dominantly bounded (specifically adsorbed or co-precipitated) to iron and manganese oxides (up to 80%) and may be released by reduction. Since the content of the exchangeable fraction (F1) is an indicator for anthropogenic impact on the aquatic environment, a low percentage (0-8%) of studied toxic elements in this fraction indicated that these elements have lithogenic origin in most sampling locations in the area of study. Except for Pb, the substantial positive correlations between Al and other elements showed that studied elements came primarily from terrigenous sources. Although the values obtained for the risk assessment code (RAC) indicated a slightly increased mobility of some elements (up to 22.44%), the values of the modified risk assessment code (mRAC), which include toxic effects on the environment, showed there is no danger of pollution by studied elements (all values were < 1%). Our recommendation is to use mRAC instead of RAC in ecochemical studies and assessment of the degree of sediment and soil pollution, because mRAC includes toxic effects of elements. Based on ATI values, river sediments show no toxic to a low toxic degree. Even though obtained results indicate that there was no considerable risk for river water contamination, the ecological risk for Fe and Pb should be monitored in the future.

Impact of potentially toxic elements on pines in a former ore processing mine: Exploitation of hyperspectral response from needle and canopy scales.

Anthropic potentially toxic element (PTE) releases can lead to persistent pollution in soil. Monitoring PTEs by their detection and quantification on large scale is of great interest. The vegetation exposed to PTEs can exhibit a reduction of physiological activities, structural damage … Such vegetation trait changes impact the spectral signature in the reflective domain 0.4-2.5 µm. The objective of this study is to characterize the impact of PTEs on the spectral signature of two pine species (Aleppo and Stone pines) in the reflective domain and ensure their assessment. The study focuses on nine PTEs: As, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Zn. The spectra are measured by an in-field spectrometer and an aerial hyperspectral instrument on a former ore processing site. They are completed by measurements related to vegetation traits at needle and tree scales (photosynthetic pigments, dry matter, morphometry …) to define the most sensitive vegetation parameter to each PTE in soil. A result of this study is that chlorophylls and carotenoids are the most correlated to PTE contents. Context-specific spectral indices are specified and used to assess metal contents in soil by regression. These new vegetation indices are compared at needle and canopy scales to literature indices. Most of the PTE contents are predicted at both scales with Pearson correlation scores between 0.6 and 0.9, depending on species and scale.

Trace element contamination in rice and its potential health risks to consumers in North-Central Vietnam.

Lead (Pb), cadmium (Cd), arsenic (As), chromium (Cr), and nickel (Ni) are poisonous, widely distributed, persistent, and transferable to crops, posing potential health risks. This study aims to assess the potential health risks of those elements in rice collected from North-Central Vietnam: Thanh Hoa, Nghe An, and Ha Tinh provinces. Element analysis was performed on rice harvested in November 2020 by ICP-MS. The estimated daily intake (EDI), target hazard quotient (THQ), non-carcinogenic hazard index (HI), and target carcinogenic risk (TR) were used to assess potential health risks for different population groups. The highest element levels (mg kg-1 dry weight) were observed for Cr (0.30 ± 0.11), As (0.17 ± 0.025) and for Pb (0.24 ± 0.013) in Thanh Hoa, and for Cd (0.088 ± 0.015) in Ha Tinh. Strong links were observed between geological formations, mining activities and Cr in rice (Thanh Hoa), or industrial activities and Ni accumulation in rice (Hung Nguyen and Ky Anh districts). Children had greater EDIs than adults, with As having a higher EDI than RfD. Rice THQs indicated a risk trend: Thanh Hoa > Ha Tinh > Nghe An, with As being a significant contributor to HIs. Cr and Cd were significant risk factors and HIs in female children were 1.5 times higher than in other groups. Based on TR values for Ni and Pb, a potential carcinogenic risk to rice eaters was observed, particularly Ni. The data revealed a significant human health risk (both non-carcinogenic and carcinogenic) connected with rice consumption. Therefore, crops and foods from North-Central Vietnam should be strictly regulated.

Ferroptosis As a Mechanism for Health Effects of Essential Trace Elements and Potentially Toxic Trace Elements.

Ferroptosis is a unique form of programmed cell death driven by iron-dependent phospholipid peroxidation that was proposed in recent years. It plays an important role in processes of various trace element-related diseases and is regulated by redox homeostasis and various cellular metabolic pathways (iron, amino acids, lipids, sugars), as well as disease-related signaling pathways. Some limited pioneering studies have demonstrated ferroptosis as a mechanism for the health effects of essential trace elements and potentially toxic trace elements, with crosstalk among them. The aim of this review is to bring together research articles and identify key direct and indirect evidence regarding essential trace elements (iron, selenium, zinc, copper, chromium, manganese) and potentially toxic trace elements (arsenic, aluminum, mercury) and their possible roles in ferroptosis. Our review may help determine future research priorities and opportunities.

Health threat of PM2.5-bound trace elements exposure on asthma hospital admission: A time-stratified case-crossover study.

Environmental pollution of trace elements has become of main concern due to the adverse effects. To estimate the impact of PM2.5-bound trace elements on human health, a time-stratified case-crossover study has been designed to examine the short-term associations between 28 elements and asthma hospitalizations from January 2019 to November 2021 in Xiamen, China. This research summarized the major components that pose health risks in different seasons and took risk assessment for different groups. We found that an inter-quartile range (IQR) increase of Ca, Fe, Mn, Pd, Si, and Ti was positively associated with the incidence of asthma in the lag of 0-4 days. In winter, the elements that predisposed the population to asthma attack were the most, such as Al, Ba, Ca, Cr, Cu, Fe, K, Mn, Pd, Si, and Ti, and these elements are at higher risk for longer periods of time. The discrepancy in risk levels and major elements of asthma diagnosis among various age groups were also found in this work. Our results provided insights into the development of specific policies to reduce the risk of asthma attacks due to exposure to PM2.5-bound trace elements.

The effect of arsenic on the structure and composition of stream hyphomycetes assemblages.

Aquatic hyphomycetes are fungi with a fundamental ecological role in forested streams. These organisms are responsible for cycling of nutrients in aquatic environments. However, their structure and composition can be affected when exposed to certain pollutants. Arsenic (As) is a trace element with high toxicity for the aquatic biota. Here we evaluated the effects of different concentrations of Arsenite (AsIII) and Arsenate (AsV) on aquatic hyphomycetes assemblages. To test As toxicity, we conditioned Nectandra megapotamica leaves in a stream and after this period, we incubated leaf discs with stream water and different concentrations of AsIII and AsV. Species richness was negatively affected by both As form. Likewise, the hyphomycetes assemblages presented variation in the composition of species. However, the sporulation rates were not influenced by As. The As showed toxicity on species of hyphomycetes more sensitive, remaining only in species tolerant to its toxicity. In this way, As generated a change in the aquatic hyphomycetes composition. We observed that As had a negative effect on the aquatic hyphomycetes assemblages, regardless of the chemical form. Our results point to the toxicity of this element and its effects on a group that is fundamental to the streams ecosystems functioning.

Interspecies differences in mammalian susceptibility to legacy POPs and trace metals using skin fibroblast cells.

The susceptibility to trace metals and legacy POPs is different between terrestrial and marine mammals. In this study, we established the first cell line from Indo-Pacific finless porpoises and compared the cellular responses of skin fibroblast cells from Pygmy killer whales, Pantropic spotted dolphins, Indo-Pacific finless porpoises, mice, and humans following exposure to copper, methylmercury, cadmium, PCB126, PCB153, and BDE47 to better understand the interspecies sensitivities of mammals to chemical pollutants. We conducted a risk assessment by comparing no-observed effect concentrations (NOEC), lowest-observed effect concentrations (LOEC), and half maximal effective concentrations (EC50) from cell viability assays and previously reported pollutant body burdens in mammals. Based on the in vitro data, Indo-Pacific finless porpoises were more sensitive to copper and methylmercury than other mammals. PCB153 exposure reduced cell viability in all mammals except humans, while PCB126 was more potent, with 13.33 µg/mL exposure reducing cell viability in all mammals. In contrast, BDE47 exposure reduced cell viability only in terrestrial mammals in addition to pantropic spotted dolphin. Based on the in vitro data and the natural context of metal concentrations, both methylmercury and cadmium posed a higher risk to cetaceans than human, while copper posed a lower risk to cetaceans. All three legacy POPs (PCB126, PCB153, and BDE47) posed minor risk to cetaceans for short-term exposure. This study demonstrated that a species-specific in vitro model may provide more accurate information on the potential risk of pollutants to mammals. However, due to the bioamplification of POPs and their potential impact on the endocrine system and immune system of cetaceans, risk assessment with long-term exposure with more in vitro models should be further studied.

Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements-A Focused Review.

Heavy metals and metalloids like cadmium, arsenic, mercury, and lead are frequently found in the soil, water, food, and atmosphere; trace amounts can cause serious health issues to the human organism. These toxic trace elements (TTE) affect almost all the organs, mainly the heart, kidney, liver, lungs, and the nervous system, through increased free radical formation, DNA damage, lipid peroxidation, and protein sulfhydryl depletion. This work aims to advance our understanding of the mechanisms behind lipid accumulation via increased free fatty acid levels in circulation due to TTEs. The increased lipid level in the myocardium worsens the heart function. This dysregulation of the lipid metabolism leads to damage in the structure of the myocardium, inclusive fibrosis in cardiac tissue, myocyte apoptosis, and decreased contractility due to mitochondrial dysfunction. Additionally, it is discussed herein how exposure to cadmium decreases the heart rate, contractile tension, the conductivity of the atrioventricular node, and coronary flow rate. Arsenic may induce atherosclerosis by increasing platelet aggregation and reducing fibrinolysis, as exposure interferes with apolipoprotein (Apo) levels, resulting in the rise of the Apo-B/Apo-A1 ratio and an elevated risk of acute cardiovascular events. Concerning mercury and lead, these toxicants can cause hypertension, myocardial infarction, and carotid atherosclerosis, in association with the generation of free radicals and oxidative stress. This review offers a complete overview of the critical factors and biomarkers of lipid and TTE-induced cardiotoxicity useful for developing future protective interventions.

Multiple trace elements exposure of Grey-cheeked Fulvettas Alcippe morrisonia, a nuclear member in bird mixed-species flocks, and implications for bioindicator.

Birds are vulnerable to metal pollution, which can serve as indicators of environmental safety monitoring. In this study, we evaluated three non-essential (Pb, Cd, and As) and two essential (Cu and Zn) trace elements of living (only feathers) and deceased (feathers and tissues) Grey-cheeked Fulvetta (Alcippe morrisonia) at a highly polluted mine tailings and a reference site. Five metal concentrations in the feathers of living Grey-cheeked Fulvettas were higher at the mine site. Among these, the levels of Cd and Pb in most feathers exceeded the threshold, resulting in an ecotoxicological concern. The correlation analysis suggested that feathers from Grey-cheeked Fulvettas might be useful bioindicators for local metal contamination assessment. The toxicological effects of trace metals on Grey-cheeked Fulvetta might affect its leadership ability. Therefore, understanding the effects of metal pollution on Grey-cheeked Fulvetta would show important practical implications for the conservation of bird communities.

Contamination and eco-risk assessment of toxic trace elements in lakebed surface sediments of Lake Yangzong, southwestern China.

Toxic trace elements represent an ongoing environmental problem in aquatic ecosystems. However, a lack of quantitative analysis and accurate evaluation has led to unguided control and water management strategies. Lake Yangzong is the main freshwater resource for nearly one million people in Yunnan Province in southwestern China. It has been heavily contaminated in recent years by significant anthropogenic activities including an industrial phosphor-gypsum spill, sewage effluent, and chemical remediation processes. Herein, we combine eco-environmental indices with multiple statistical analyses to determine the ecological risk and degree of contamination of 11 toxic trace elements in the upper sediments of the lakebed. Local geochemical background concentrations were determined using robust regression models developed from sediment core data. Pollution indices (EF/PLI) indicate that severe As contamination was centralized in the southwestern part of the lake. Other toxic trace elements (e.g., Cd, Cu, Pb) are slightly to moderately enriched, and progressively decrease from the northwestern to the southeastern areas of the lake. A more accurate and sensitive index (PCR) was proposed herein, suggesting that contamination was dominated by As and Pb in different lake sections. The northern section of the lake and the southwestern bay exhibited higher contaminant levels than other regions of the lake. Bio-toxic indices (ERF/PERI) indicate that As and Cd pose a high ecological risk, whereas Cu and Pb pose a low risk to biota. Statistical analyses (PCA/PMF) demonstrate that metal contaminants originated from three types of anthropogenic sources: the smelting of metal ores, the leakage of tailings effluent, and coal consumption.

Effects of trace elements contaminations on the larval development of Paracentrotus lividus using an innovative experimental approach.

Several experiments were performed using larvae of Paracentrotus lividus (Lamarck, 1816) in order to determine the consequences of different chronic contamination with mixtures of (i) fifteen trace elements from concentrations measured in the world ocean seawater, and (ii) seven trace elements from contamination resulting from mining. To predict the impact of increased marine pollution, higher concentrations were also used. These bioassays were conducted using spawners collected from Calvi (reference site, Corsica), and Albo (mining area, Corsica). The effects of trace elements have been studied on the entire larval development. The results show wider arms and delayed development as the number and concentration of trace elements increases. Therefore, the synergy between the different trace elements is of paramount importance with regard to the impact on organisms. Probably due to a hormesis phenomenon, larvae contaminated with seven trace elements at average concentrations developed more quickly. This work also highlighted the importance of the origin of spawners in ecotoxicological studies. To our knowledge, this is the first study to investigate the effects of such a broad combination of trace elements for chronic contamination on the entire larval stage of Paracentrotus lividus.

Dose-dependent effects of chronic lead toxicity in vivo: Focusing on trace elements and gut microbiota.

Dose-dependent effects of chronic Pb exposure-induced injuries, especially on the trace elements and gut microbiota in mice, have not been explored. In the present study, we investigated these aspects using C57BL/6 mouse models that were exposed to Pb via drinking water with Pb concentrations of 0.1, 0.5, and 1.0 g/L for 8 weeks. The results showed that with the increase in chronic Pb exposure dose, the Pb levels in the blood and tissues, Zn levels in the kidney and brain were elevated, and the levels of bone Zn, kidney Fe, brain Mg, Ca, and Fe, renal catalase activity, and glutathione levels, as well as the expression of colonic zonula occludens-1 and occludin, decreased with a strong linear correlation. Moreover, the relative abundance of Marvinbryantia and Ruminococcus 1 increased, while that of Lactobacillus and Roseburia decreased linearly with the Pb exposure dose. PICRUSt analysis revealed that chronic Pb exposure had a greater impact on the metabolism of macronutrients, trace elements, and neurodegenerative injury. These findings suggest that chronic Pb exposure disrupts trace element levels in tissues, especially in the brain, and induces gut dysbiosis in a dose-dependent manner, which is different from the dose-effect of acute Pb toxicity.

Effect of trace elements in the toxicity of copper to Chlamydomonas reinhardtii.

Copper sulfate (CuSO4) is widely used in the control of algal blooms. Cu can promote or inhibit algal growth, while also affecting trace element uptake, therefore, the response mechanisms of algae cells under Cu2+ interference should be studied. In this study, wild-type Chlamydomonas reinhardtii (C. reinhardtii) and wall-less mutant C. reinhardtii were selected as the research objects. Except for the cell wall, these two algae were physiologically the same. While manipulating the concentration of Cu, the accumulation of Cu, Fe, Zn, and Mn by the two algal cell types was studied. The cell wall hindered the accumulation of Cu by cells and alleviated the toxicity of Cu to C. reinhardtii. The addition of Cu increased the accumulation of Fe by both cell types. In an environment with excess Cu, the total amount of Zn and Mn accumulated by cells also increased. On the one hand, this may be due to the synergistic and antagonistic effects of trace elements in the adsorption and uptake process, and on the other hand, it may be due to the changes in metal speciation in the culture medium. In addition, the difference in the total accumulation of various trace elements between wild-type and wall-less-type C. reinhardtii may be due to the structure and function differences between cell wall and cell membrane. At the same time, by measuring the changes in the levels of glutathione (GSH) in algal cells, the relevant mechanisms underlying the algae's uptake of trace elements by algae were further explored.

Estimation of Target Hazard Quotients and Potential Health Risks for Toxic Metals and Other Trace Elements by Consumption of Female Fish Gonads and Testicles.

The aim of this study was to assess the risk to consumers associated with the intake of toxic metals and other trace elements in diets that include the female gonads, testicles, and muscles of four popular freshwater fish species in Poland­common bream (Abramis brama L.), European perch (Perca fluviatilis L.), common roach (Rutilus rutilus L.), and northern pike (Esox Lucius L.). The following methods were used to determine the elements: GF-AAS (Pb, Cd); CV-AAS (Hg); ICP-AES (Zn, Fe, Mn, Cu, Ni, Li, Cr, Al). The concentration of toxic elements (Hg, Cd, Pb) in the female gonads and testicles ranged from 0.004 ± 0.006 mg/kg (Cd) to 0.028 ± 0.018 mg/kg (Pb). Of the other elements, the lowest content was noted for Cr (0.122 ± 0.182 mg/kg) and the highest for Al (46.98 ± 31.89 mg/kg). The study confirmed that female gonads and testicles are a valuable source of essential trace elements (Zn, Fe). Considering the content of toxic elements, the raw material of female gonads and testicles posed no health risks (THQ < 1).

Ecological Risk Assessment Related to the Presence and Toxicity of Potentially Toxic Elements in Ashes from Household Furnaces.

The study material was comprised of 23 samples of ashes generated after the combustion of conventional and alternative fuels combined with selected fractions of municipal waste. The analyses performed involved determining the total concentration of As, Al, Cr, Fe, Ni, and their bioaccessible, ion-exchange, and carbonate-bound fractions. It was found that all of the samples analysed may display an elevated level of susceptibility to the reduction processes, which undoubtedly increases the mobility of trace elements, including the toxic ones. The predominant elements were Al and Fe, whereas considerably lower concentrations were observed for Ni, Cr, and As. The percentage share of the ion-exchange and carbonate-bound fraction ranged from 49% of the total concentration for As to as much as 0.35% in the case of Fe. The calculated Risk Assessment Code index points to a high risk related to the presence of As, medium to low risk related to the presence of Ni and Cr, and low to no risk related to the presence of Fe and Al. The calculated values of the Ecological Risk Index, associated with the combustion of selected municipal waste fractions and low-quality hard coals, combusted individually or in combination with different types of wood, point to a very high ecological risk. This is mainly related to the high concentrations and toxicity of As.