•Halonitromethanes (HNMs) exposure increased oxidative DNA damage in mouse liver.•Amino acid, carbohydrate and lipid metabolisms were disturbed by HNMs exposure.•Bromo-HNMs are more toxic than chloro-HNMs.•Induction of oxidative stress is one of the toxicity mechanisms of HNMs.Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection byproducts have been widely found in drinking water. In vitro test found HNMs could induce higher cytotoxicity and genotoxicity than trihalomethanes and haloacetic acids. However, data on toxic effect from in vivo experiment is limited. In this study, bromonitromethane (BNM), bromochloronitromethane (BCNM) and trichloronitromethane (TCNM) were chosen as target HNMs, and exposed to mice for 30 d. Hepatic toxicity and serum metabolic profiles were determined to reveal toxic effects and mechanisms of the three HNMs. Results showed the three HNMs significantly decreased relative liver weight, indicating liver is one of the target organs. Further, the three HNMs exposure damaged hepatic antioxidant defense system, and increased oxidative DNA damage. Nuclear magnetic resonance based metabolomics analysis found amino acid metabolism and carbohydrate metabolism were disturbed by HNMs exposure. Some metabolites in these metabolisms are related to oxidative stress and damage. Combined with above results, BNM had the highest toxicity, followed by BCNM and TCNM, indicating bromo-HNMs had higher toxicity than chloro-HNMs. Induction of oxidative stress is one of the toxicity mechanisms of HNMs. This study firstly provides the insight into in vivo toxicity of HNMs and their underlying mechanisms based on metabolomics methods, which is very useful for their health risk assessment in drinking water.

Chronic exposure to inorganic arsenic (iAs) or a high-fat diet (HFD) can produce liver injury. However, effects of HFD on risk assessment of iAs in drinking water are unclear. In this study, we examined how HFD and iAs interact to alter iAs-induced liver injury in C57BL/6 mice. Mice fed low-fat diet (LFD) or HFD were exposed to 3 mg/L iAs or deionized water for 10 weeks. Results showed that HFD changed intake and excretion of iAs by mice. Then, HFD increased the amount of iAs-induced hepatic DNA damage and amplified changes in pathways related to cell death and growth, signal transduction, lipid metabolism, and insulin signaling. Compared to gene expression profiles caused by iAs alone or HFD alone, insulin signaling pathway might play important roles in the interactive effects of iAs and HFD. Our data suggest that HFD increases sensitivity of mice to iAs in drinking water, resulting in increased hepatotoxicity. This study highlight that HFD might enhance the risk of iAs hepatotoxicity in iAs-polluted regions. The diet should be considered during risk assessment of iAs in drinking water.

Experimental studies indicate that multiwalled carbon nanotubes (MWCNTs) have the potential to induce cytotoxicity. However, the reports are often inconsistent and even contradictory. Additionally, adverse effects of MWCNTs at low concentration are not well understood. In this study, we systemically compared adverse effects of six MWCNTs including pristine MWCNTs, hydroxyl-MWCNTs and carboxyl-MWCNTs of two different lengths (0.5–2 μm and 10–30 μm) on human hepatoma cell line HepG2. Results showed that MWCNTs induced cytotoxicity by increasing reactive oxygen species (ROS) generation and damaging cell function. Pristine short MWCNTs induced higher cytotoxicity than pristine long MWCNTs. Functionalization increased cytotoxicity of long MWCNTs, but reduced cytotoxicity of short MWCNTs. Further, our results indicated that the six MWCNTs, at nontoxic concentration, might not be environmentally safe as they inhibited ABC transporters’ efflux capabilities. This inhibition was observed even at very low concentrations, which were 40–1000 times lower than their effective concentrations on cytotoxicity. The inhibition of ABC transporters significantly increased cytotoxicity of arsenic, a known substrate of ABC transporters, indicating a chemosensitizing effect of MWCNTs. Plasma membrane damage was likely the mechanism by which the six MWCNTs inhibited ABC transporter activity. This study provides insight into risk assessments of low levels of MWCNTs in the environment.

Iron (Fe) is a common trace element in drinking water. However, little is known about how environmental concentrations of Fe affect the metabolism and toxicity of arsenic (As) in drinking water. In this study, influence of Fe at drinking water-related concentrations (0.1, 0.3, and 3 mg Fe (total)/L) on As metabolism and toxicity, and the roles of gut microbiota during this process were investigated by using in vitro Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Results showed that Fe had ability to decrease bioaccessible As by coflocculation in small intestine. 0.1 and 0.3 mg/L Fe significantly increased As methylation in simulated transverse and descending colon. Gut microbiota played an important role in alteration of As species, and Fe could affect As metabolism by changing the gut microbiota. Bacteroides, Clostridium, Alistipes, and Bilophila had As resistance and potential ability to methylate As. Cytotoxicity assays of effluents from simulated colons showed that the low levels of Fe decreased As toxicity on human hepatoma cell line HepG2, which might be due to the increase of methylated As. When assessing the health risk of As in drinking water, the residual Fe should be considered.

Health risk of arsenic (As) has received increasing attention. Acute and chronic exposure to As could cause several detrimental effects on human health. As toxicity is closely related to its bioaccessibility and metabolism. In real environment, many factors, such as diet and nutrition, can influence As bioaccessibility, metabolism and toxicity. This paper mainly reviews the influences of diets and elements on As bioaccessibility, metabolism and toxicity and their underlying mechanisms to provide suggestions for future investigations. Vitamins, jaggery, fruit, tea, glutathione, N-acetylcysteine and zinc could reduce the As-induced toxicity by increasing antioxidative enzymes to antagonize oxidative stress caused by As and/or increasing As methylation. However, bean and betel nut could increase risk of skin lesions caused by As. Interestingly, high-fat diet, selenium and iron have incompatible effects on As bioaccessibility, metabolism and toxicity in different experimental conditions. Based on current literatures, the As methylation and As-induced oxidative damage might be two main ways that the diets and elements influence As toxicity. Combined application of in vitro human cell lines and gastrointestinal models might be useful tools to simultaneously characterize the changes in As bioaccessibility and toxicity in the future research.

Removing arsenic (As) from drinking water is widely dependent on iron (Fe)-based coagulation/flocculation techniques. However, little is known about the influence of Fe precipitant on As toxicity. In this present study, the influence of Fe on As toxicity was determined at systems biology level by in vitro and in vivo experiments. In vitro study based on HepG2 cell line found that Fe increased the As toxicity on cell viability and DNA damage, indicating the synergetic toxic effects. However, when the Fe and As were simultaneously exposed to mice by drinking water for 90 days, the results showed that Fe reduced the changes of hepatic transcriptomic profiles and serum and urine metabolic profiles caused by As exposure, showing the antagonistic toxic effects. The antagonistic effects might be because Fe reduced As bioavailability and accumulation, which was verified by As and Fe levels in feces and liver. The results of this study indicate that Fe precipitant can influence the As toxicity. The interactions between As and Fe and their bioavailability might play important roles in the As toxicity. When assessing the safety of As in drinking water, it is necessary to fully consider the combined effects of As and Fe.

Dechlorane plus (DP), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for DP have seldom been reported. In the present study, we investigated hepatic oxidative stress, DNA damage, and transcriptomic and metabonomic responses of male mice administered 500 mg/kg, 2000 mg/kg, and 5000 mg/kg of DP by gavage for 10 days. The results showed that DP exposure increased the level of superoxide dismutase (SOD) and 8-hydroxy-2-deoxyguanosine (8-OHdG). The microarray-based transcriptomic results demonstrated that DP exposure led to significant alteration of gene expression involved in carbohydrate, lipid, nucleotide, and energy metabolism, as well as signal transduction processes. The NMR-based metabonomic analyses corroborated these results showing changes of metabolites associated with the above altered mechanisms. Our results demonstrate that an oral exposure to DP can induce hepatic oxidative damage and perturbations of metabolism and signal transduction. These observations provide novel insight into toxicological effects and mechanisms of action of DP at the transcriptomic and metabonomic levels.

•Trivalent metal induced longer recovery on removal performance than bivalent metal.•Trivalent metal cations reduced trans-membrane pressure by binding EPS and SMP.•Fe(III)-tolerance genera were positively correlated and interacted with SMP.•Inhibited genera and binding bridge reduced membrane fouling under Ca(II) stress.•Microorganisms and EPS/SMP interacted and affected with each other.Five lab-scale membrane bioreactors (MBRs) were continuously operated to investigate the mechanisms and linkages of the microbial community and membrane fouling with trivalent metal cations (Fe(III) and Al(III)) and bivalent metal cations (Ca(II) and Mg(II)) shock loads. COD and NH4+-N removals showed recovery trends along with treatment process in the presence of metals. Trivalent metal cations reduced trans-membrane pressure (TMP) as well as fouling rate (dTMP/dt) and extended membrane module replacement period by binding activated sludge extracellular polymeric substance (EPS) and effluent soluble microbial product (SMP) productions. Illunima sequencing of 16S rRNA gene showed that metal stress stimulated specific metal-tolerance bacteria in the MBRs. Canonical correspondence analysis indicated that EPS and SMP made different contributions to the distribution of microbial community structure in Fe(III) and Al (III) systems, respectively. Under bivalent metal conditions, microbial community shifts and Ca(II) binding bridge worked together to inhibit EPS and SMP, while filamentous bacteria stimulated by Mg(II) that mainly controlled membrane fouling. This study has shown that the comparison of tri- and bivalent metals for membrane fouling control with binding bridge and functional microorganisms can provide a strategy for practical membrane bioreactor applications.