Compartmentalization and Excretion of 2,4,6-Tribromophenol Sulfation and Glycosylation Conjugates in Rice Plants.

The most environmentally abundant bromophenol congener, 2,4,6-tribromophenol (2,4,6-TBP, 6.06 µmol/L), was exposed to rice for 5 d both in vivo (intact seedling) and in vitro (suspension cell) to systematically characterize the fate of its sulfation and glycosylation conjugates in rice. The 2,4,6-TBP was rapidly transformed to produce 6 [rice cells (3 h)] and 8 [rice seedlings (24 h)] sulfated and glycosylated conjugates. The predominant sulfation conjugate (TP408, 93.0-96.7%) and glycosylation conjugate (TP490, 77.1-90.2%) were excreted into the hydroponic solution after their formation in rice roots. However, the sulfation and glycosylation conjugates presented different translocation and compartmentalization behaviors during the subsequent Phase III metabolism. Specifically, the sulfated conjugate could be vertically transported into the leaf sheath and leaf, while the glycosylation conjugates were sequestered in cell vacuoles and walls, which resulted in exclusive compartmentalization within the rice roots. These results showed the micromechanisms of the different compartmentalization behaviors of 2,4,6-TBP conjugates in Phase III metabolism. Glycosylation and sulfation of the phenolic hydroxyl groups orchestrated by plant excretion and Phase III metabolism may reduce the accumulation of 2,4,6-TBP and its conjugates in rice plants.

Airborne Fine Particles Induce Hematological Effects through Regulating the Crosstalk of the Kallikrein-Kinin, Complement, and Coagulation Systems.

Particulate air pollution caused by human activities has drawn global attention due to its potential health risks. Considering the inevitable contact of inhaled airborne fine particulate matter (PM) with plasma, the hematological effects of PM are worthy of study. In this study, the potential effect of PM on hematological homeostasis through triggering the crosstalk of the kallikrein-kinin system (KKS), complement, and coagulation systems in plasma was investigated. The ex vivo, in vitro, and in vivo KKS activation assays confirmed that PM samples could efficiently cause the cascade activation of key zymogens in the KKS, wherein the particles coupled with lipopolysaccharide attachment provided substantial contribution. The binding of Hageman factor XII (FXII) with PM samples and its subsequent autoactivation initiated this process. The crucial elements in the complement cascade, including complement 3 (C3) and complement 5 (C5), and coagulation system (prothrombin) were also found to be actively induced by PM exposure, which was regulated by the interplay of KKS activation. The data provided solid evidence on hematological effects of airborne PM through inducing the activation of the KKS, complement, and coagulation systems, which would be valuable in the risk assessment on air-pollution-related cardiovascular diseases.

Identification of Emerging Brominated Chemicals as the Transformation Products of Tetrabromobisphenol A (TBBPA) Derivatives in Soil.

In contrast to the extensive investigation already conducted on tetrabromobisphenol A (TBBPA), the metabolism of TBBPA derivatives is still largely unknown. In this paper, we characterized unknown brominated compounds detected in 84 soil samples collected from sites around three brominated flame retardant production plants to determine possible transformation products of TBBPA derivatives. In addition to tribromobisphenol A (TriBBPA), dibromobisphenol A (DBBPA), and TBBPA, six novel transformation products, TriBBPA mono(allyl ether) (TriBBPA-MAE), DBBPA-MAE, hydroxyl TriBBPA-MAE, TBBPA mono(2-bromo-3-hydroxypropyl ether) (TBBPA-MBHPE), TBBPA mono(2,3-dihydroxypropyl ether) (TBBPA-MDHPE), and TBBPA mono(3-hydroxypropyl ether) (TBBPA-MHPE) were identified. The detection frequencies of these identified chemicals in soil samples ranged from 17% to 89%, indicating the widespread presence of the transformation products. To uncover the possible TBBPA derivative transformation pathways involved, super-reduced vitamin B12 (cyanocobalamin, (CCAs)) was used to treat TBBPA derivative and transformation products in this process were characterized. To our knowledge, this is the first study examining the transformation of TBBPA derivatives and the first to report several novel associated TBBPA and bisphenol A derivatives as transformation products. Our research suggests that ether bond breakage and debromination contribute to the transformation of TBBPA derivatives and the existence of the novel transformation products. These data provide new insights into the fate of TBBPA derivatives in environmental compartments.

Effect-directed analysis for revealing aryl hydrocarbon receptor agonists in sediment samples from an electronic waste recycling town in China.

Exposure to electronic and electrical waste (e-waste) has been related to a few adverse health effects. In this study, sediment samples from an e-waste recycling town in China were collected, and aryl hydrocarbon receptor (AhR) agonists in the samples were identified using an effect-directed analysis (EDA) strategy. The CBG2.8D cell line reporter gene bioassay was used as a toxicity test, while suspect screening against chemical databases was performed for potential AhR agonist identification where both gas chromatography- and liquid chromatography-high resolution mass spectrometry analyses were run. When the original sample extract showed high AhR-mediated activity, sample fractionation was performed, and fractions exhibiting high bioactivity were chemically analyzed again to reveal the corresponding AhR agonists. In total, 23 AhR agonists were identified, including 14 commonly known ones and 9 new ones. Benzo [k]fluoranthene and 6-nitrochrysene were the dominant AhR agonists, covering 16-71% and 2.7-12%, respectively, of the AhR activation effects measured in the parent extracts. The newly identified AhR-active chemicals combined explained 0.13-0.20% of the parent extracts' effects, with 7,12-dimethylbenz [a]anthracene and 8,9,11-trimethylbenz [a]anthracene being the major contributors. A diagnostic isomer ratio analysis of polycyclic aromatic hydrocarbons suggested that the major source of AhR agonists identified in these e-waste related sediment samples were probably petroleum product combustion and biomass combustion. In the future, for a more comprehensive AhR agonist investigation, in-house chemical synthesis and purification, and, when necessary, a secondary sample fractionation, would be beneficial.

Effect-directed analysis of estrogenic chemicals in sediments from an electronic-waste recycling area.

Electronic waste (e-waste) pollution is of great concern due to the release of hazardous chemicals during the improper e-waste disposal. Many chemicals leached from e-waste were reported to pose estrogenic effects. To date, little is known regarding the occurrence and biological effects of estrogenic chemicals in sediments near an e-waste area. In this study, an effect-directed analysis (EDA) is applied to determine the estrogenic chemicals in sediments of four sites collected from a typical e-waste recycling city in China. Following screening with the ER-CALUX assay, the extract of sample with the most potent effect was subjected in fractionation using reverse phase liquid chromatography. Based on a target analysis for the active fractions, four compounds, including estrone, 17ß-estradiol, 17α-ethinylestradiol and bisphenol A, were identified, and these contributed to 17% of the total toxic effects in the sample. A further nontarget analysis screened four candidates, namely diethylstilbestrol (DES), hexestrol (HES), nandrolone and durabolin, and the total contribution was found to be 48% from the active sample. Specifically, DES and HES were only detected in the active sample and were found to be the primary drivers of estrogenic effects. An examination of the identified chemicals in the four sites indicated that these estrogenic chemicals may originate from e-waste recycling, livestock excretion and domestic waste. These findings uncovered the estrogenic pollutants in sediments from an e-waste area. Considering single endpoint in biological assay is not abundant to screen chemicals with different toxic effects, further EDA studies with multiple endpoints are required to better understand the occurrence of representative or unknown chemicals in e-waste-polluted areas.

PM2.5 induces vascular permeability increase through activating MAPK/ERK signaling pathway and ROS generation.

Although in-vivo exposure of PM2.5 has been suggested to initiate a disorder on vascular permeability, the effects and related mechanism has not been well defined. In this work, an obvious increase on vascular permeability has been confirmed in vivo by vein injection of PM2.5 into Balb/c mouse. Human umbilical vein vascular endothelial cells and the consisted ex-vivo vascular endothelium were used as model to investigate the effects of PM2.5 on the vascular permeability and the underlying molecular mechanism. Upon PM2.5 exposure, the vascular endothelial growth factor receptor 2 on cell membrane phosphorylates and activates the downstream mitogen-activated protein kinase (MAPK)/ERK signaling. The adherens junction protein VE-cadherin sheds and the intercellular junction opens, damaging the integrity of vascular endothelium via paracellular pathway. Besides, PM2.5 induces the intracellular reactive oxygen species (ROS) production and triggers the oxidative stress including activity decrease of superoxide dismutase, lactate dehydrogenase release and permeability increase of cell membrane. Taken together, the paracellular and transcellular permeability enhancement jointly contributes to the significant increase of endothelium permeability and thus vascular permeability upon PM2.5 exposure. This work provides an insight into molecular mechanism of PM2.5 associated cardiovascular disease and offered a real-time screening method for the health risk of PM2.5.

Sensitive immunoassay for simultaneous determination of tetrabromobisphenol A bis(2-hydroxyethyl) ether and tetrabromobisphenol A mono(hydroxyethyl) ether: An effective and reliable strategy to estimate the typical tetrabromobisphenol A derivative and byproduct in aquatic environments.

Tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA DHEE), as one of the TBBPA derivatives, is frequently applied as a flame retardant. To date, however, little evidence has been gathered regarding its environmental behavior and fate. This is mainly attributed to the lack of an analytical approach available to measure it. Mass spectrometry cannot determine levels of TBBPA DHEE. LC-MS could not ionize TBBPA DHEE to yield enough fragments, while GC-MS could not be applied for the analysis either, due to the thermal degradation of TBBPA DHEE. We here designed a novel hapten, then conjugated it with a carrier protein and produced a type of polyclonal antibody capable of recognizing TBBPA DHEE. Based on this approach, a sensitive and high-throughput indirect competitive enzyme-linked immunosorbent assay (ELISA) was established. The respective detection limit (LOD, based on 90% B/B0) and IC50 calculated from the standard curve were 0.702 and 9.868 ng/mL for TBBPA DHEE. And the established method showed good tolerance to various matrix interferents. Using our ELISA, we measured the concentrations of these substances from environmental water samples with no pretreatment other than filtration. We found the presence of TBBPA DHEE in environmental water samples collected in Jiangsu province, and the detected concentrations ranging from 1.5 to 7.7 ng/mL. Our proposed method here could be applied to completely and systematically investigate TBBPA DHEE and TBBPA MHEE concentrations in environmental samples.

Toxicological and biochemical responses of the earthworm Eisenia fetida exposed to contaminated soil: Effects of arsenic species.

Arsenic is a pollutant that can be detected in different chemical forms in soil. However, the toxicological effects of different arsenic species on organisms have received little attention. In this study, we exposed earthworms Eisenia fetida to artificial soils contaminated by arsenite [As(III)], arsenate [As(V)], monomethylarsonate (MMA) and dimethylarsinate (DMA) for 28 and 56 days. Three biomarkers including lipid peroxidation (LPO), metallothioneins (MTs) and lysosomal membrane stability (LMS) were analyzed in the organisms. In addition, the contents of total arsenic and arsenic species in earthworms were also determined to investigate the effects of bioaccumulation and biotransformation of arsenic on biomarkers and to evaluate the dose-response relationships. The results showed that the relationship between the three biomarkers and the two inorganic arsenic species were dose dependent, and the correlation levels between the biomarkers and As(III) were higher than that between the biomarkers and As(V). Trivalent arsenic species shows more toxicity than pentavalent arsenic on the earthworms at molecular and subcellular level, including oxidative damage, MTs induction and lysosomal membrane damage. The toxicity of MMA and DMA was lower than inorganic arsenic species. However, the occurrence of demethylation of organic arsenics could lead to the generation of highly toxic inorganic arsenics and induce adverse effects on organisms. The biotransformation of highly toxic inorganic arsenics to the less toxic organic species in the earthworms was also validated in this study. The biomarker responses of the earthworm to different arsenic species found in this study could be helpful in future environment monitoring programs.