Design and structure-activity relationships of ether-linked alkylides: Hybrids of 3-O-descladinosyl macrolides and quinolone motifs.

Ketolides (3-keto) such as TE-802 and acylides (3-O-acyl) like TEA0929 are ineffective against constitutively resistant pathogens harboring erythromycin ribosomal methylation (erm) genes. Following our previous work on alkylides (3-O-alkyl), we explored the structure-activity relationships of hybrids combining (R/S) 3-descladinosyl erythromycin with 6/7-quinolone motifs, featuring extended ether-linked spacers, with a focus on their efficacy against pathogens bearing constitutive erm gene resistance. Optimized compounds 17a and 31f not only reinstated efficacy against inducibly resistant pathogens but also demonstrated significantly augmented activities against constitutively resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, which are typically refractory to existing C-3 modified macrolides. Notably, hybrid 31f (coded ZN-51) represented a pioneering class of agents distinguished by its dual modes of action, with ribosomes as the primary target and topoisomerases as the secondary target. As a novel chemotype of macrolide-quinolone hybrids, alkylide 31f is a valuable addition to our armamentarium against macrolide-resistant bacteria.

Novel Method for in Situ Monitoring of Organophosphorus Flame Retardants in Waters.

Widespread use of organophosphorus flame retardants (OPFRs) and their ubiquity in water results in the need for a robust and reliable monitoring technique to better understand their fate and environmental impact. In situ passive sampling using the diffusive gradients in thin-films (DGT) technique provides time-integrated data and is developed for measuring OPFRs here. Ultrasonic extraction of binding gels in methanol provided reliable recoveries for all tested OPFRs. Diffusion coefficients of TCEP, TCPP, TDCPP, TPrP, TBP, and TBEP in the agarose diffusive gel (25 °C) were obtained. The capacity of an HLB binding gel for OPFRs was >115 µg per disc, and the binding performance did not deteriorate with time up to 131 days. DGT performance is independent of typical environmental ranges of pH (3.12-9.71), ionic strength (0.1-500 mmol L-1), and dissolved organic matter (0-20 mg L-1), and also of diffusive layer thickness (0.64-2.14 mm) and deployment time (3-168 h). Negligible competition effects between OPFRs was found. DGT-measured concentrations of OPFRs in a wastewater treatment plant (WWTP) effluent (12-16 days) were comparable to those obtained by grab sampling, further verifying DGT's reliability for measuring OPFRs in waters.

Impact of particle size on distribution and human exposure of flame retardants in indoor dust.

The effect of dust particle size on the distribution and bioaccessibility of flame retardants (FRs) in indoor dust remains unclear. In this study, we analyzed 20 FRs (including 6 organophosphate flame retardants (OPFRs), 8 polybrominated diphenyl ethers (PBDEs), 4 novel brominated flame retardants (NBFRs), and 2 dechlorane plus (DPs)) in composite dust samples from offices, public microenvironments (PME), and cars in Nanjing, China. Each composite sample (one per microenvironment) was separated into 6 size fractions (F1-F6: 200-2000µm, 150-200µm, 100-150µm, 63-100µm, 43-63µm, and <43µm). FRs concentrations were the highest in car dust, being 16 and 6 times higher than those in offices and PME. The distribution of FRs in different size fractions was Kow-dependent and affected by surface area (Log Kow=1-4), total organic carbon (Log Kow=4-9), and FR migration pathways into dust (Log Kow>9). Bioaccessibility of FRs was measured by the physiologically-based extraction test, with OPFR bioaccessibility being 1.8-82% while bioaccessible PBDEs, NBFRs, and DPs were under detection limits due to their high hydrophobicity. The OPFR bioaccessibility in 200-2000µm fraction was significantly higher than that of <43µm fraction, but with no difference among the other four fractions. Risk assessment was performed for the most abundant OPFR-tris(2-chloroethyl) phosphate. The average daily dose (ADD) values were the highest for the <43µm fraction for all three types of dust using total concentrations, but no consistent trend was found among the three types of dust if based on bioaccessible concentrations. Our results indicated that dust size impacted human exposure estimation of FRs due to their variability in distribution and bioaccessibility among different fractions. For future risk assessment, size selection for dust sampling should be standardized and bioaccessibility of FRs should not be overlooked.

Effects of novel brominated flame retardant TBPH and its metabolite TBMEHP on human vascular endothelial cells: Implication for human health risks.

As a replacement for polybrominated diphenyl ethers, bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a novel flame retardant and has been detected in many environmental matrix including human blood. TBPH can be metabolized into mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) by carboxylesterase. However, their adverse effects on human vascular endothelium and their potential impacts on human cardiovascular disease are unknown. In this study, their adverse effects and associated molecular mechanisms on human vascular endothelial cells (HUVECs) were investigated. A concentration-dependent inhibition on HUVECs' viability and growth was observed for TBMEHP but not for TBPH. TBMEHP induced a marked G0/G1 cell cycle arrest and robust cell apoptosis at 1µg/mL by inducing expression of p53, GADD45α and cyclin dependent kinase (CDK) inhibitors (p21and p27) while suppressing the expression of cyclin D1, CDK2, CDK6, and Bcl-2. Unlike TBMEHP, TBPH caused early apoptosis after G2/M phase arrest only at 10µg/mL via up-regulation of p21 and down-regulation of CDK2 and CDK4. TBMEHP decreased mitochondrial membrane potential and increased caspase-3 activity at 1µg/mL, suggesting that activation of p53 and mitochondrial pathway were involved in the cell apoptosis. The data showed that TBPH and TBMEHP induced different cell cycle arrest and apoptosis through different molecular mechanisms with much higher toxicity for TBMEHP. Our study implies that the metabolites of TBPH, possibly other novel brominated flame retardants, may be of potential concern for human cardiovascular disease.

Activated charcoal based diffusive gradients in thin films for in situ monitoring of bisphenols in waters.

Widespread use of bisphenols (BPs) in our daily life results in their elevated concentrations in waters and the need to study their environmental impact, which demands reliable and robust measurement techniques. Diffusive gradients in thin films (DGT) is an in situ passive sampling approach which provides time-integrated data. In this study we developed a new methodology, based on DGT with activated charcoal (AC) as a binding agent, for measuring three BPs (BPA, BPB, and BPF) which incorporated and tested its performance characteristics. Consistent elution efficiencies were obtained using methanol when concentrations of BPs were low and a methanol-NaOH mixture at high concentrations. The diffusion coefficients of BPA, BPB, and BPF in the diffusive gel, measured using an independent diffusion cell, were 5.03 × 10(-6), 5.64 × 10(-6), and 4.44 × 10(-6) cm(2) s(-1) at 25 °C, respectively. DGT with an AC binding gel had a high capacity for BPA, BPB, and BPF at 192, 140, and 194 µg/binding gel disk, respectively, and the binding performance did not deteriorate with time, up to 254 d after production. Time-integrated concentrations of BPs measured in natural waters using DGT devices with AC gels deployed in situ for 7 d were comparable to concentrations measured by an active sampling method. This study demonstrates that AC-based DGT is an effective tool for in situ monitoring of BPs in waters.

In vivo bioavailability and in vitro bioaccessibility of perfluorooctanoic acid (PFOA) in food matrices: correlation analysis and method development.

Food is a major source of human exposure to perfluorooctanoic acid (PFOA), however, PFOA bioavailability in food has not been studied. An in vivo mouse model and three in vitro methods (unified BARGE method, UBM; physiologically based extraction test, PBET; and in vitro digestion method, IVD) were used to determine the relative bioavailability and bioaccessibility of PFOA in the presence of 17 foods. PFOA was mixed with foods of different nutritional compositions and fed to mice over a 7-d period. PFOA relative bioavailability was determined by comparing PFOA accumulation in the liver following PFOA exposure via food to that in water. PFOA bioavailability relative to water ranged from 4.30 ± 0.80 to 69.0 ± 11.9% and was negatively correlated with lipid content (r = 0.76). This was possibly due to competitive sorption of free fatty acids with PFOA onto transporters on intestine epithelial cells. Besides, cations in the gastrointestinal tract, such as Ca(2+) and Mg(2+), are capable of complexing PFOA and partitioning to the lipid phase. On the other hand, when assessed using in vitro assays, PFOA bioaccessibility varied with methods, being 8.7-73% (UBM), 9.8-99% (PBET), and 21-114% (IVD). PFOA bioaccessibility was negatively correlated with lipid content when assessed using UBM (r = 0.82); however, a poor correlation with food composition was observed for PBET and IVD (r = 0.01-0.50). When in vivo and in vitro data were compared, a strong correlation was observed for UBM (r = 0.79), but poor relationships were observed for PBET and IVD (r = 0.11-0.22). This was probably because the higher lipolysis ability and presence of Ca(2+) and Mg(2+) in the gastrointestinal fluid of UBM resulted in a lower potential to form stable micelles compared to PBET and IVD. These results indicated that PFOA relative bioavailability was mainly affected by lipid content in foods, and UBM has the potential to determine PFOA bioaccessibility in food samples.

Assessment of in vitro lead bioaccessibility in house dust and its relationship to in vivo lead relative bioavailability.

House dust samples containing 25-738 mg of Pb kg(-1) from 15 cities in China were assessed for in vitro Pb bioaccessibility and in vivo Pb relative bioavailability. On the basis of stable Pb isotope ratios, the Pb in dust samples mainly originated from coal combustion. Lead bioaccessibility was determined using gastric (GP) and intestinal phase (IP) of solubility bioaccessibility research consortium (SBRC), in vitro gastrointestinal (IVG), Deutsches Institut für Normunge.V. (DIN), and physiologically based extraction test methods (PBET), while Pb relative bioavailability (RBA) was determined using a mouse blood model. Lead bioaccessibility in 24 house dust samples varied significantly (23-99%) depending on the methods. Values from the IP were considerably lower than those from the GP because of the co-precipitation of Pb with iron and re-adsorption onto the dust matrix. The SBRC assay with lower GP pH produced higher Pb bioaccessibility because of enhanced Pb dissolution. When compared to mouse blood data using 12 dust samples (29-60%), SBRC-GP and DIN-GP data were correlated with Pb RBA with r(2) values of 0.68 and 0.85 and intercepts 3.15 and 17.4, respectively. Overall, SBRC-GP had potential to predict Pb RBA in dust samples. However, our data suggested that more research is needed to develop a valid in vitro method for predicting Pb RBA in house dust.

[Application of EMD and SPA algorithm in the detection of benzoyl peroxide addition in flour by spectroscopy].

In order to improve the accuracy of spectroscopy analysis and reduce the modeling wavelength numbers, empirical mode decomposition (EMD) and successive projections algorithm (SPA) were applied together in the measurement of benzoyl peroxide (BPO) additive amount in flour by near infrared spectroscopy. Spectra of flour samples into which BPO were added were collected. Firstly, EMD was implemented to eliminate the noise of original spectra, and then SPA was employed to select the characteristic wavelengths. The precision of the model based on the processed spectra by EMD was greatly improved compared with the model based on the original spectra, with the calibration determination coefficient Rcal2 increased from 0.81 to 0.899 and the prediction determination coefficient R2pred increased from 0. 755 4 to 0. 86. Seven characteristic variables were selected from 512 wavelength variables by SPA. And the performance of the model built by the selected characteristic variables (Rcal2 is 0.863, Rpred2 is 0.86) was as good as full-spectrum model's, while the number of modeling variables was greatly reduced by 96.4%. The results indicated that empirical mode decomposition and successive projections algorithm can be effectively used to denoise the spectra and selected characteristic wavelengths for the detection of BPO addition in flour. The seven selected wavelengths in this paper can be a reference for designing portable BPO detection meter.

Chemical compositions and source apportionment of PM2.5 during clear and hazy days: Seasonal changes and impacts of Youth Olympic Games.

Seasonal changes in chemical compositions and source apportionment of PM2.5 during clear and hazy days help to develop effective control policy, but limited information is available in megacity Nanjing. In this study, 102 PM2.5 samples were collected during clear and hazy days from 4 seasons in 2014-2015. Their chemical compositions (organic and elemental carbon, 8 water-soluble ions, and 22 inorganic elements) were determined, which were used for PM2.5 source apportionment using the PMF model. The mean PM2.5 concentration was lower during clear days than hazy days (42 vs. 122 µg m-3), so were mean concentrations of metals (0.48 vs. 0.82 ng m-3 for Co and 2.0 vs. 2.4 µg m-3 for Na), water soluble ions (0.10 vs. 0.16 µg m-3 for Mg2+ and 12 vs. 23 µg m-3 for SO42-), and carbon species (3.2 vs. 5.4 µg m-3 for elemetal C and 20 vs. 35 µg m-3 for organic C). Based on the PMF model, five main sources of PM2.5 were identified including secondary aerosols (31%), coal combustion (27%), road & construction dust (26%), oil combustion (8.5%), and iron & steel industry (5.1%) for all samples. The PM2.5 concentrations from the 5 sources were 0.01-46.5, averaging 9.8 µg m-3 during clear days (PM2.5 < 75 µg m-3), which increased to 1.83-60.1, averaging 18 µg m-3 during hazy days. However, based on their contributions to PM2.5, only secondary aerosols increased during hazy days compared to clear days in all seasons (11 vs. 42%), indicating its dominant contribution to haze in Nanjing. For different seasons, road & construction dust was a major contributor to PM2.5 in the summer, while oil combustion (4.86 vs.16.8%) contributed more in spring. However, coal combustion became the main source of PM2.5 during the summer (44-85%) due to the pollution controls for the Youth Olympic Games. Our results suggest that secondary aerosols play an important role in haze formation and season-dependent pollution measures should be implemented for effective control of air pollution.

Physical and chemical characteristics of PM2.5 and its toxicity to human bronchial cells BEAS-2B in the winter and summer.

With the increasing occurrence of haze during the summer, the physicochemical characteristics and toxicity differences in PM2.5 in different seasons are of great concern. Hangzhou is located in an area that has a subtropical monsoon climate where the humidity is very high during both the summer and winter. However, there are limited studies on the seasonal differences in PM2.5 in these weather conditions. In this test, PM2.5 samples were collected in the winter and summer, the morphology and chemical composition of PM2.5 were analyzed, the toxicity of PM2.5 to human bronchial cells BEAS-2B was compared, and the correlation between PM2.5 toxicity and the chemical composition was discussed. The results showed that during both the winter and summer, the main compounds in the PM2.5 samples were water-soluble ions, particularly SO42-, NO3-, and NH4+, followed by organic components, while heavy metals were present at lower levels. The higher the mass concentration of PM2.5, the greater its impact on cell viability and ROS levels. However, when the mass concentration of PM2.5 was similar, the water extraction from the summer samples showed a greater impact on BEAS-2B than that from the winter samples. The cytotoxicity of PM2.5 was closely associated with heavy metals and organic pollutants but less related to water-soluble ions.

Food influence on lead relative bioavailability in contaminated soils: Mechanisms and health implications.

To determine the effects of dietary constituents on soil Pb oral bioavailability, Pb relative bioavailability (RBA) in 3 soils contaminated by zinc smelting (ZS), wire-rope production (WR), and metal mining (MM) was measured under fasted and fed states with 9 foods. Under fasted state, Pb-RBA was 84.4 ±â€¯10.3, 82.6 ±â€¯4.70, and 32.3 ±â€¯1.10% for ZS, WR, and MM soils; however, it decreased by 1.3-3.5 fold to 23.9-58.8, 25.6-49.9, and 14.8-24.2% under fed states with foods excluding Pb-RBA with egg in WR soil (97.3 ±â€¯4.46%), and with cabbage and egg in MM soil (40.0 ±â€¯8.62 and 44.4 ±â€¯0.96%). In the presence of foods, egg and pork with significantly higher protein and fat contents leaded to the highest soil Pb-RBA (44.4-97.3%), while Pb-RBA determined with mineral-rich mouse feed was 1.6-7.9 fold lower (9.41-13.5%), suggesting high fat and protein foods tended to increase soil Pb-RBA, while high mineral diets decreased soil Pb-RBA. The increased Pb-RBA of MM soil with cabbage compared to fasted state was due to high organic content in cabbage, which could increase soil Pb solubility by inhibiting Fe and Pb co-precipitation in the intestine. For accurate assessment of health risks of contaminated soils, dietary influence on soil Pb-RBA should be considered.

In situ measurement of perfluoroalkyl substances in aquatic systems using diffusive gradients in thin-films technique.

To better understand the environmental impact of ubiquitous perfluoroalkyl substances (PFASs) in waters, reliable and robust measurement techniques are needed. As one of the most widely used passive sampling approaches, diffusive gradients in thin-films (DGT) is not only easy to handle but also provides time-weighted analyte concentrations. Based on DGT with XAD18 as a binding agent, we developed a new methodology to measure two frequently detected PFASs in surface waters and wastewaters, i.e. perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Their diffusion coefficients in the diffusive gel, measured using an independent diffusion cell, were 4.37 × 10-6 and 5.08 × 10-6 cm2 s-1 at 25 °C, respectively. DGT had a high capacity for PFOA and PFOS at 196 and 246 µg per gel disk, suggesting the DGT sampler was suitable for deployment of several weeks. Time-integrated concentrations of PFOA and PFOS in a natural lake and river, and a municipal wastewater treatment plant effluent using DGT samplers deployed in situ for 12-33 d were comparable to those measured by a solid-phase extraction method coupled with high-frequency grab sampling. This study demonstrates that DGT is an effective tool for in situ monitoring of PFASs in natural waters and wastewaters.

Cellular responses of normal (HL-7702) and cancerous (HepG2) hepatic cells to dust extract exposure.

Cancerous human liver cell line has been used to test the hepatic toxicity of indoor dust, showing its organic extract decreases cell viability. However, little is known about its impact on normal human liver cell line. In the present study, we compared the cellular responses between carcinoma cell line (HepG2) and normal cell line (HL-7702) after exposing to 10-640 µg/100 µL organic dust extract for 24 h. The dust extract caused cytotoxicity, oxidative damage, inflammatory response and loss of mitochondrial transmembrane potential (MMP) in both cells. The inhibition of cell viability in HL-7702 cells was stronger than that in HepG2 cells, with HL-7702 cells having lower LC50. Higher production of oxidative stress, more loss of MMP and stronger suppression of antioxidant enzymes mRNA level occurred in HepG2 cells, while mRNA expression and hepcidin secretion were enhanced in HL-7702 cells at 40/100 µL, indicating the dust extract probably perturbed their liver Fe homeostasis. Our data showed considerable differences in cellular responses between normal and cancerous cell lines. To obtain accurate data, normal hepatocytes should be employed as they better match with the in vivo tissue than cancerous cell lines.

Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: Implications for human health.

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC50 at 202 µg/mL. A concentration-dependent apoptotic sign was observed in HCECs after exposing to ≥2 µg/mL TDCPP. Endoplasmic reticulum stress induction was evidenced by up-regulation of its biomarker genes (ATF-4, CHOP, BiP, and XBP1). Furthermore, alternation of Bcl-2/Bax expression, mitochondrial membrane potential loss, cellular ATP content decrease, and caspase-3 and -9 activity increase were observed after exposing to 2 or 20 µg/mL TDCPP. Taken together, the data implicated the involvement of endoplasmic reticulum stress in TDCPP-induced HCEC apoptosis, probably mediated by mitochondrial apoptotic pathway. Our findings showed TDCPP exposure induced toxicity to human cornea. Due to TDCPP's presence at high levels in indoor dust, further study is warranted to evaluate its health risk on human corneas.

Lead relative bioavailability in soils based on different endpoints of a mouse model.

Mouse is an acceptable animal model to measure lead (Pb) relative bioavailability (RBA) in contaminated soils; however, there is a lack of comparisons among Pb-RBA measurements based on different endpoints and dosing approaches. In this study, 12 soils (47.8-8123mg Pbkg-1) were assessed for Pb-RBA using Pb accumulation in mouse liver, kidneys, and/or femur following a 10-d steady state soil dose via diet, with 6 soils being measured using mouse bioassays with area under the mouse blood Pb concentration time curve (AUC) following a single gavaged dose as the endpoint. Based on individual endpoints of the steady state method, Pb-RBA in soils was 2.1-83.4%, being generally consistent among liver, kidneys, and femur with strong linear correlations between them (r2=0.74-0.89). To compensate variation in Pb distribution among different tissues, Pb-RBA was further calculated using a combined endpoint (e.g., sum of Pb accumulation in liver, kidneys, and femur). Compared to Pb-RBA based on individual tissue showing relative standard deviation (RSD) of 11.9-15.8%, Pb-RBA using the combined endpoint showed lower RSD (10.8%), thereby being more robust. For the 6 soils with Pb-RBA based on both mouse single gavaged and steady state dosing approach, no significant difference was observed; however, steady state approach was more repeatable among animals with lower RSD (11.4% vs. 34.5%). To ensure robustness of in vivo data, the steady state dosing approach with Pb accumulation in combined tissues is recommended.

Advances in in vitro methods to evaluate oral bioaccessibility of PAHs and PBDEs in environmental matrices.

Cleanup goals for sites contaminated with persistent organic pollutants (POPs) are often established based on total contaminant concentrations. However, mounting evidence suggests that understanding contaminant bioavailability in soils is necessary for accurate assessment of contaminant exposure to humans via oral ingestion pathway. Animal-based in vivo tests have been used to assess contaminant bioavailability in soils; however, due to ethical issues and cost, it is desirable to use in vitro assays as alternatives. Various in vitro methods have been developed, which simulate human gastrointestinal (GI) tract using different digestion fluids. These methods can be used to predict POP bioavailability in soils, foods, and indoor dust after showing good correlation with in vivo animal data. Here, five common in vitro methods are evaluated and compared using PAHs and PBDEs as an example of traditional and emerging POPs. Their applications and limitations are discussed while focusing on method improvements and future challenges to predict POP bioavailability in different matrices. The discussions should shed light for future research to accurately assess human exposure to POPs via oral ingestion pathway.

Mechanisms of housedust-induced toxicity in primary human corneal epithelial cells: Oxidative stress, proinflammatory response and mitochondrial dysfunction.

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-1ß, 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.

Influence of pollution control on lead inhalation bioaccessibility in PM2.5: A case study of 2014 Youth Olympic Games in Nanjing.

Pollution controls were implemented to improve the air quality for the 2014 Youth Olympic Games (YOG) in Nanjing. To investigate the influence of pollution control on Pb inhalation bioaccessibility in PM2.5, samples were collected before, during, and after YOG. The objectives were to identify Pb sources in PM2.5 using stable isotope fingerprinting technique and compare Pb inhalation bioaccessibility in PM2.5 using two simulated lung fluids. While artificial lysosomal fluid (ALF) simulates interstitial fluid at pH 7.4, Gamble's solution simulates fluid in alveolar macrophages at pH 4.5. The Pb concentration in PM2.5 samples during YOG (88.2ngm(-3)) was 44-48% lower than that in non-YOG samples. Based on stable Pb isotope ratios, Pb in YOG samples was mainly from coal combustion while Pb in non-YOG samples was from coal combustion and smelting activities. While Pb bioaccessibility in YOG samples was lower than those in non-YOG samples (59-79% vs. 55-87%) by ALF, it was higher than those in non-YOG samples (11-29% vs. 5.3-21%) based on Gamble's solution, attributing to the lower pH and organic acids in ALF. Different Pb bioaccessibility in PM2.5 between samples resulted from changes in Pb species due to pollution control. PbSO4 was the main Pb species in PM2.5 from coal combustion, which was less soluble in ALF than PbO from smelting activities, but more soluble in Gamble's solution. This study showed it is important to consider Pb bioaccessibility during pollution control as source control not only reduced Pb contamination in PM2.5 but also influenced Pb bioaccessibility.

Molecular mechanisms of dust-induced toxicity in human corneal epithelial cells: Water and organic extract of office and house dust.

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-1ß, 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.

Toxic metals in children's toys and jewelry: coupling bioaccessibility with risk assessment.

A total of 45 children's toys and jewelry were tested for total and bioaccessible metal concentrations. Total As, Cd, Sb, Cr, Ni, and Pb concentrations were 0.22-19, 0.01-139, 0.1-189, 0.06-846, 0.14-2894 and 0.08-860,000 mg kg(-1). Metallic products had the highest concentrations, with 3-7 out of 13 samples exceeding the European Union safety limit for Cd, Pb, Cr, or Ni. However, assessment based on hazard index >1 and bioaccessible metal showed different trends. Under saliva mobilization or gastric ingestion, 11 out of 45 samples showed HI >1 for As, Cd, Sb, Cr, or Ni. Pb with the highest total concentration showed HI <1 for all samples while Ni showed the most hazard with HI up to 113. Our data suggest the importance of using bioaccessibility to evaluate health hazard of metals in children's toys and jewelry, and besides Pb and Cd, As, Ni, Cr, and Sb in children's products also deserve attention.