Global patterns of human exposure to flame retardants indoors.

To fill the knowledge gaps regarding the global patterns of human exposure to flame retardants (FRs) (i.e., brominated flame retardants (BFRs) and organophosphorus flame retardants (OPFRs)), data on the levels and distributions of FRs in external and internal exposure mediums, including indoor dust, indoor air, skin wipe, serum and urine, were summarized and analysed. Comparatively, FR levels were relatively higher in developed regions in all mediums, and significant positive correlations between FR contamination and economic development level were observed in indoor dust and air. Over time, the concentration of BFRs showed a slightly decreasing trend in all mediums worldwide, whereas OPFRs represented an upward tendency in some regions (e.g., the USA and China). The occurrence levels of FRs and their metabolites in all external and internal media were generally correlated, implying a mutual indicative role among them. Dermal absorption generally contributed >60% of the total exposure of most FR monomers, and dust ingestion was dominant for several low volatile compounds, while inhalation was found to be negligible. The high-risk FR monomers (BDE-47, BDE-99 and TCIPP) identified by external exposure assessment showed similarity to the major FRs or metabolites observed in internal exposure mediums, suggesting the feasibility of using these methods to characterize human exposure and the contribution of indoor exposure to the human burden of FRs. This review highlights the significant importance of exposure assessment based on multiple mediums for future studies.

Face mask as an indicator and shield of human exposure to traditional and novel organophosphate esters.

Herein, the trapping effectiveness of N95, filter KN95, medical surgical masks (MSMs), and disposable medical masks (DMMs) against 19 airborne traditional and novel organophosphate esters (OPEs) was evaluated. Laboratory simulations (n = 24 for each type of mask) showed that time-dependent accumulation of ∑19OPEs on the four types of masks ranged between 30.1 and 86.6 ng in 24 h, with the highest and lowest median amounts trapped by the N95 masks (53.3 ng) and DMMs (43.2 ng), respectively. The trapping efficiency of the four types of masks for ∑19OPEs decreased over time from 84 % to 39 % in 24 h, with N95 masks showing the highest median efficiency (70 %). Further, field investigations were conducted in five types of microenvironments (train, hospital, bus, supermarket, and canteen), and an analysis of 200 samples showed that ∑19OPEs were accumulated in the masks with a variable amount from 3.7 to 117 ng/mask. Consistent with the laboratory simulations, the N95 masks (29.0 ng/mask) exhibited the highest hourly median amount of trapped OPEs, followed by the KN95 masks (24.5 ng/mask), MSMSs (17.4 ng/mask), and DMMs (15.8 ng/mask). Triethyl phosphate (TEP), tris(1-chloro-2-propyl) phosphate (TCIPP), tri-n-butyl phosphate (TNBP), and cresyl diphenyl phosphate (CDP) as well as 4-isopropylphenyl diphenyl phosphate (4IPPDPP) and 2,4-diisopropylphenyl diphenyl phosphate (24DIPPDPP) were the most commonly detected traditional and novel OPEs. Based on the amount of OPEs trapped on the masks, we estimated the concentration of ∑19OPEs in the train microenvironment to be the highest (222 ng/m3), which is approximately 2-5 times higher than that in the other microenvironments. The results of this study prove that masks can effectively protect humans from exposure to OPEs and act as low-cost indicators of indoor contamination.

Methods for the characterisation of dermal uptake: Progress and perspectives for organophosphate esters.

Organophosphate esters (OPEs) are a group of pollutants that are widely detected in the environment at high concentrations. They can adversely affect human health through multiple routes of exposure, including dermal uptake. Although attention has been paid to achieving an accurate and complete quantification of the dermal uptake of OPEs, existing evaluation methods and parameters have obvious weaknesses. This study reviewed two main categories of methodologies, namely the relative absorption (RA) model and the permeability coefficient (PC) model, which are widely used to assess the dermal uptake of OPEs. Although the PC model is more accurate and is increasingly used, the most important parameter in this model, the permeability coefficient (Kp), has been poorly characterised for OPEs, resulting in considerable errors in the estimation of the dermal uptake of OPEs. Thus, the detailed in vitro methods for the determination of Kp are summarised and sorted. Furthermore, the commonly used skin membranes are identified and the factors affecting Kp and corresponding mechanisms are discussed. In addition, the experimental conditions, conclusions, and available data on Kp values of the OPEs are thoroughly summarised. Finally, the corresponding knowledge gaps are proposed, and a more accurate and sophisticated experimental system and unknown Kp values for OPEs are suggested.

Neurodegenerative disease and antioxidant biomarkers: A bidirectional Mendelian randomization study.

Objective: Previous observational studies have suggested that antioxidant imbalance is correlated with neurodegenerative diseases, while its cause-effect remains unclear. Thus, the goal of the present study is to explore the causal relationship between 11 antioxidant biomarkers and 3 most common neurodegenerative diseases [Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD)]. Methods: A bidirectional Mendelian randomization (MR) study was performed to investigate the causal effects by using 3 main methods (Variance Weighted (IVW), Weighted Median (WM), and MR-Egger regression) in the European population. The data of 11 antioxidant biomarkers were obtained from the open database by the most up-to-date Genome-Wide Association Studies (GWAS), the summary statistics of PD and ALS were obtained from the International Parkinson's Disease Genomics Consortium (IPDGC) (33,674 cases, and 449,056 controls), and the International Amyotrophic Lateral Sclerosis Genomics Consortium (IALSC) (20,806 cases and 59,804 controls), respectively. For AD, we specifically used two recently published GWAS data, one from the International Genomics of Alzheimer's Project (IGAP) (21,982 cases and 41,944 controls), and the other from a large meta-analysis (71,880 cases and 383,378 controls) as validation data. Results: Based on the Bonferroni correction p < 0.0015, there was no significant causal evidence for the antioxidant biomarkers on neurodegenerative diseases, however, the reverse analysis found that AD was significantly related to the decrease in retinol (IVW: beta = -0.023, p = 0.0007; WM: beta = -0.025, p = 0.0121), while the same analysis was carried out between the AD validation database and retinol, the results were consistent (IVW: beta = -0.064, p = 0.025). Moreover, AD on Glutathione S-transferase (GST), PD on Glutathione Peroxidase (GPX) as well as PD on uric acid (UA) also indicated potential causal-and-effect associations (IVW: p = 0.025; p = 0.027; p = 0.021, respectively). Conclusions: There was no sufficient evidence that antioxidant imbalance has a significant causal effect on neurodegenerative diseases. However, this study revealed that genetically predicted AD was significantly related to the decrease in retinol, which provides a new insight into previous research and indicates the possibility to regard retinol as potential biomarker for the diagnosis and progress of AD.

Phytotoxic effects on chloroplast and UHPLC-HRMS based untargeted metabolomic responses in Allium tuberosum Rottler ex Sprengel (Chinese leek) exposed to antibiotics.

Introduction of antibiotics into agricultural fields poses serious health risks to humans. This study investigated the uptake of antibiotics, their effects on metabolic pathways, and chloroplast structure changes of Allium tuberosum exposed to norfloxacin (NFL), oxytetracycline (OTC), and tetracycline (TC). Among all the antibiotic treatments, the highest accumulation of antibiotics in roots (4.15 mg/kg) and leaves (0.29 mg/kg) was TC, while in bulbs it was NFL (5.94 mg/kg). OTC was with the lowest accumulation in roots: 0.19 mg/kg, bulbs: 0.18 mg/kg, and leaves: 0.11 mg/kg. The number of mitochondira and the number of plastoglobulli increased. The chloroplast structure was disturbed under the stress of NFL, OTC, and TC. Disturbance in the chloroplast ultrastructure leads to altered chlorophyll fluorescence variables. Simultaneously, metabolomic profiling of leaves demonstrated that NFL stress regulated more of metabolic pathways than OTC and TC. Differences in metabolic pathways among the antibiotic treatments showed that each antibiotic has different impact even under the same experimental conditions. TC and NFL have more toxic effects than OTC antibiotic. Metabolic variations induced by antibiotics stress highlighted pools of metabolites that affect the metabolic activities, chlorophyll fluorescence, ultrastructural adjustments, and stimulate defensive impact in A. tubersoum. These findings provide an insight of metabolic destabilization as well as metabolic changes in defensive mechanism and stress response of A. tuberosum to different antibiotics.

Size-distribution-based assessment of human inhalation and dermal exposure to airborne parent, oxygenated and chlorinated PAHs during a regional heavy haze episode.

The adverse health effects of haze and particle-bound contaminants in China have recently caused increasing concern, and particle size plays a significant role in affecting human exposure to haze-correlated pollutants. To this background, size-segregated particulate samples (nine size fractions (<0.4, 0.4-0.7, 0.7-1.1, 1.1-2.1, 2.1-3.3, 3.3-4.7, 4.7-5.8, 5.8-9.0 and > 9.0 µm) were collected in three scale-gradient cities in northern China and analysed for a series of parent, oxygenated and chlorinated polycyclic aromatic hydrocarbons (PAHs, O-PAHs and Cl-PAHs). The total geometric mean concentrations of PAHs and O-PAHs for Beijing, Zhengzhou and Xinxiang were 98.1 and 27.2, 77.9 and 77.5, 41.0 and 30.7 ng m-3, respectively, which were 50-200 times higher than those for Cl-PAHs (0.5, 0.7 and 0.4 ng m-3). Though unimodal size-distribution patterns were found for all these contaminants for these three cities, PAHs represented distinctly higher concentration levels around the peak fraction (0.7-2.1 µm) than O-PAHs and Cl-PAHs. With 4-6 ring PAHs as dominant components in all samples, the percentage proportion of 2-3 ring PAHs (ranging from 1% to 26%) generally increased with particle size increasing, implying the sources of these compounds varied little among the 9 size fractions in all three cities. The International Commission on Radiological Protection (ICRP) model and permeability coefficient method were synchronously applied to the size-segregated data for inhalation and dermal exposure assessment to intensively estimate the human exposure doses to airborne PAHs. Further, the incremental lifetime cancer risk (ILCR) was calculated and it's found that ILCR from inhalation was higher than that from dermal uptake for children and adults in Beijing and Zhengzhou, while the ILCR for Xinxiang presented a contrary pattern, revealing dermal uptake to be an equally significant exposure pathway to airborne PAHs compared to inhalation.

Higher health risk resulted from dermal exposure to PCBs than HFRs and the influence of haze.

To investigate the influence of haze on human dermal exposure to a series of halogenated flame retardants (HFRs) and polychlorinated biphenyls (PCBs), paired forehead wipes were collected from 46 volunteers (23 males, 23 females) using gauze pads soaked in isopropyl alcohol under heavy and light haze pollution levels. The median levels of ∑27HFRs and ∑27PCBs in all 92 samples were 672 and 1300ng/m2, respectively. Decabromodiphenyl ether (BDE-209) (171ng/m2) and decabromodiphenylethane (DBDPE) (134ng/m2) were the dominant components of HFRs, indicating that dermal exposure may also be the significant pathway for non-volatile compounds. PCB-37 contributed the most to ∑27PCBs, with a median concentration of 194ng/m2, followed by PCB-60 (141ng/m2). Generally, PBDE, PCB and DD (dehalogenated derivatives of DPs) levels on the foreheads of female participants (291, 1340, 0.92ng/m2) were higher (p=0.037, 0.001, and 0.031, respectively) than those of male participants (226, 989, and 0.45ng/m2). A significant difference (p=0.001) in PCBs was found between light (1690ng/m2) and heavy (996ng/m2) haze pollution conditions. Nevertheless, HFR levels under heavy (median=595ng/m2, ranging from 295 to 1490ng/m2) and light haze pollution conditions (ranging from 205 to 1220ng/m2 with a median of 689ng/m2) did not show significant differences (p=0.269). The non-carcinogenic health risk resulting from dermal exposure to ∑8HFRs and ∑27PCBs was 8.72×10-5 and 1.63×10-2, respectively, raising more concern about populations' exposure to PCBs than HFRs.

SPOCK1 is up-regulated and promotes tumor growth via the PI3K/AKT signaling pathway in colorectal cancer.

SPOCK1 encodes a Ca2+-binding matricellular glycoprotein which plays an oncogenic role in cancer cells. However, the role of SPOCK1 in the pathogenesis of colorectal cancer (CRC) has not been determined. Here, SPOCK1 was found higher expressed in CRC tissues than that of adjacent normal tissues. Furthermore, up-regulated expression of SPOCK1 in CRC patients was associated with tumor size and TNM stage. In addition, we observed that the depletion of SPOCK1 inhibited proliferation in vitro and tumorigenicity in vivo and promoted apoptosis in cell culture. Our data suggest that inactivation of PI3K/Akt signaling pathway was involved in down-regulation of SPOCK1-mediated suppression of tumor cell proliferation. These results suggest that SPOCK1 expression is correlated with malignant features of CRC and may serve as potential therapeutic and preventive strategies for CRC.