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Due to its toxicity as a carcinogen and wide distribution in the environment, arsenic (As) exposure in humans is of public concern globally. Many studies have manifested that As exposure induces cancers besides pathological effects in humans. Animal studies showed that chronic As exposure induces serious neurological effects. Based on recent studies, researchers proposed that As, including arsenate (AsV) and arsenite (AsIII), is also an endocrine disruptor. This review discusses the mechanisms of As toxicity on three endocrine systems including gonadal, adrenal and thyroid endocrine systems. Arsenic methylation and oxidative stress are responsible for As-induced disorders of endocrine systems, however, strong binding of AsIII to thiols also play an important role. Some studies showed AsV toxicity on endocrine systems, but mechanistic investigation is lacking. Research is needed to look into their toxicity mechanisms to help cure the illnesses caused by As-induced endocrine system disorders., (Published by Elsevier Ltd.)

In vitro assays have been developed to determine metal bioaccessibility in contaminated soils; however, their application to Cd is limited. To assess their suitability to determine Cd relative bioavailability (RBA), Cd-RBA in 12 contaminated soils containing 3.00-296mgkg(-1) Cd were determined using a mouse model and compared with Cd bioaccessibility data based on four assays including the UBM, SBRC, IVG, and PBET. After being administered feed amended with soil or CdCl2 for 10-day, the Cd concentrations in the mouse liver and/or kidneys were used as biomarkers to estimate Cd-RBA. Cd-RBA was comparable at 34-90% and 40-78% based on mouse liver and kidneys with RSD of 7.10-8.99%, and 37-84% based on mouse liver plus kidneys with lower RSD of 5.8%. Cadmium bioaccessibility in soils varied with assays, with 61-99, 59-103, 54-107, and 35-97% in the gastric phase and 20-56, 38-77, 42-88, and 19-64% in the intestinal phase of the UBM, SBRC, IVG and PBET assays. Based on the combined biomarker of liver plus kidneys, better correlation was observed for PBET (r(2)=0.61-0.70) than those for IVG, UBM and SBRC assays (0.12-0.52). The monthly Cd intake in children was 0.24-23.9μgkg(-1) using total Cd concentration in soils, which was reduced by 43% to 0.18-12.3μgkg(-1) using bioavailable Cd. Our data suggest it is important to consider Cd-RBA to assess risk associated with contaminated soils and the PBET may have potential to predict Cd-RBA in contaminated soils., (Published by Elsevier Ltd.)

Human corneal epithelial (HCE) cells are continually exposed to dust in the air, which may cause corneal epithelium damage. Both water and organic soluble contaminants in dust may contribute to cytotoxicity in HCE cells, however, the associated toxicity mechanisms are not fully elucidated. In this study, indoor dust from residential houses and commercial offices in Nanjing, China was collected and the effects of organic and water soluble fraction of dust on primary HCE cells were examined. The concentrations of heavy metals in the dust and dust extracts were determined by ICP-MS and PAHs by GC-MS, with office dust having greater concentrations of heavy metals and PAHs than house dust. Based on LC50, organic extract was more toxic than water extract, and office dust was more toxic than house dust. Accordingly, the organic extracts induced more ROS, malondialdehyde, and 8-Hydroxydeoxyguanosine and higher expression of inflammatory mediators (IL-1β, IL-6, and IL-8), and AhR inducible genes (CYP1A1, and CYP1B1) than water extracts (p<0.05). Extracts of office dust presented greater suppression of superoxide dismutase and catalase activity than those of house dust. In addition, exposure to dust extracts activated NF-κB signal pathway except water extract of house dust. The results suggested that both water and organic soluble fractions of dust caused cytotoxicity, oxidative damage, inflammatory response, and activation of AhR inducible genes, with organic extracts having higher potential to induce adverse effects on primary HCE cells. The results based on primary HCE cells demonstrated the importance of reducing contaminants in indoor dust to reduce their adverse impacts on human eyes., (Published by Elsevier Ltd.)

Human cornea is highly susceptible to damage by dust. Continued daily exposure to housedust has been associated with increasing risks of corneal injury, however, the underlying mechanism has not been elucidated. In this study, a composite housedust sample was tested for its cytotoxicity on primary human corneal epithelial (PHCE) cells, which were exposed to dust at 5-320μg/100μL for 24h. PHCE cell viability showed a concentration-dependent toxic effect, attributing to elevated intracellular ROS. Moreover, when exposed at >20-80μg/100μL, dust-induced oxidative damage was evidenced by increased malondialdehyde and 8-hydroxy-2-deoxyguanosine (1.3-2.3-fold) and decreased antioxidative capacity (1.6-3.5-fold). Alteration of mRNA expression of antioxidant enzymes (SOD1, CAT, HO-1, TRXR1, GSTM1, GSTP1, and GPX1) and pro-inflammatory mediators (IL-1β, IL-6, IL-8, TNF-α, and MCP-1) were also observed. Furthermore, the mitochondrial transmembrane potential was dissipated from 9.2 to 82%. Our results suggested that dust-induced oxidative stress probably played a vital role in the cytotoxicity in PHCE cells, which may have contributed to dust-induced impairment of human cornea., (Published by Elsevier Ltd.)

Arsenic (As) and selenium (Se) are unusual metalloids as they both induce and cure cancer. They both cause carcinogenesis, pathology, cytotoxicity, and genotoxicity in humans, with reactive oxygen species playing an important role. While As induces adverse effects by decreasing DNA methylation and affecting protein 53 expression, Se induces adverse effects by modifying thioredoxin reductase. However, they can react with glutathione and S-adenosylmethionine by forming an As-Se complex, which can be secreted extracellularly. We hypothesize that there are two types of interactions between As and Se. At low concentration, Se can decrease As toxicity via excretion of As-Se compound [(GS3)2AsSe](-), but at high concentration, excessive Se can enhance As toxicity by reacting with S-adenosylmethionine and glutathione, and modifying the structure and activity of arsenite methyltransferase. This review is to summarize their toxicity mechanisms and the interaction between As and Se toxicity, and to provide suggestions for future investigations., (Published by Elsevier Ltd.)