Exploring Prenatal Exposure to Halogenated Compounds and Its Relationship with Birth Outcomes Using Nontarget Analysis.

Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks.

Association between famine exposure during infancy and childhood and the risk of chronic kidney disease in adulthood.

BACKGROUND: Famine exposure in childhood is proven to be associated with multiple chornic disease in adult but has not been studied with chronic kidney disease (CKD). AIMS: This study was conducted to identify the relationship between famine exposure during infancy and childhood - specifically, the Chinese famine of 1959-1961 - and the risk of adult-onset chronic kidney disease (CKD) among Chinese individuals. METHODS: This study included 2937 individuals from the Qingdao Diabetes Prevention Program. They were stratified by birth year into infancy-exposed (1956-1958), childhood-exposed (1950-1955) and unexposed (1963-1971) groups. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR of <90 mL/min/1.73 m2 . RESULTS: The mean eGFR values for the infancy-exposed and childhood-exposed groups were 107.23 ± 12.53 and 103.23 ± 12.44 mL/min/1.73 m2 , respectively, both of which were lower than that of the unexposed group (114.82 ± 13.39 mL/min/1.73 m2 ; P < 0.05). In the crude model, the odds ratio (OR) for CKD was 2.00 (95% confidence interval (CI): 1.39-2.88) in the infancy-exposed group and 2.92 (95% CI: 2.17-3.93) in the childhood-exposed group. Further adjustments for urban/rural residence, body mass index, age, current smoking, type 2 diabetes, systolic blood pressure, diastolic blood pressure and total cholesterol did not significantly alter the association between famine exposure and CKD. The corresponding ORs were 1.71 (95% CI: 1.17-2.50) and 2.48 (95% CI: 1.81-3.40) for the infancy-exposed and childhood-exposed groups respectively. CONCLUSIONS: Famine exposure during infancy and childhood is associated with a long-term decline in eGFR and an increased adult-onset CKD risk. Early intervention for high-risk individuals may mitigate the risk of adult-onset CKD.

Developmental 6:2 FTCA exposure impairs renal development in chicken embryos via IGF signaling.

6:2 fluorotelomer carboxylic acid (6:2 FTCA) is a perfluorooctanoic acid (PFOA) substitute, which is supposedly less accumulative and toxic than PFOA. However, 6:2 FTCA is structurally similar to PFOA, and there had already been reports about its toxicities comparable to PFOA. The aim of the current study is to assess potential effects of developmental exposure to 6:2 FTCA on the development of kidney in chicken embryo and to investigate underlying mechanism. Fertile chicken eggs were exposed to 1.25 mg/kg, 2.5 mg/kg or 5 mg/kg doses of 6:2 FTCA, or 2 mg/kg PFOA, then incubated to hatch. Serum and kidney of hatchling chickens were collected. Blood urea nitrogen (BUN) and creatinine (Cre) levels were measured with commercially available kits. Morphology of kidney was assessed with histopathology. To further reveal molecular mechanism of observed endpoints, IGF signaling molecules were assessed in the kidney samples with qRT-PCR, results indicated that IGFBP3 is a potentially crucial molecule. Lentiviruses overexpressing or silencing IGFBP3 were designed and applied to enhance/suppress the expression of IGFBP3 in developing chicken embryo for further verification of its role in the observed effects. Disrupted nephron formation, in the manifestation of decreased glomeruli number/area and increased serum BUN/Cre levels, was observed in the animals developmentally exposed to 6:2 FTCA. Correspondingly, IGF signaling molecules (IGF1, IGF1R and IGFBP3) were affected by 6:2 FTCA exposure. Meanwhile, overexpression of IGFBP3 effectively alleviated such changes, while silencing of IGFBP3 mimicked observed effects. In conclusion, developmental exposure to 6:2 FTCA is associated with disrupted chicken embryo renal development, in which IGFBP3 seems to be a remarkable contributor, suggesting potential health risks for human and other species. Further risk assessments and mechanistic works are necessary.

Hepatotoxicity assessment investigations on PFASs targeting L-FABP using binding affinity data and machine learning-based QSAR model.

Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants that have been detected in various environmental media and human serum, but their safety assessment remains challenging. PFASs may accumulate in liver tissues and cause hepatotoxicity by binding to liver fatty acid binding protein (L-FABP). Therefore, evaluating the binding affinity of PFASs to L-FABP is crucial in assessing the potential hepatotoxic effects. In this study, two binding sites of L-FABP were evaluated, results suggested that the outer site possessed high affinity to polyfluoroalkyl sulfates and the inner site preferred perfluoroalkyl sulfonamides, overall, the inner site of L-FABP was more sensitive to PFASs. The binding affinity data of PFASs to L-FABP were used as training set to develop a machine learning model-based quantitative structure-activity relationship (QSAR) for efficient prediction of potentially hazardous PFASs. Further Bayesian Kernel Machine Regression (BKMR) model disclosed flexibility as the determinant molecular property on PFASs-induced hepatotoxicity. It can influence affinity of PFASs to target protein through affecting binding conformations directly (individual effect) as well as integrating with other molecular properties (joint effect). Our present work provided more understanding on hepatotoxicity of PFASs, which could be significative in hepatotoxicity gradation, administration guidance, and safer alternatives development of PFASs.

Nontarget Identification of Novel Per- and Polyfluoroalkyl Substances in Cord Blood Samples.

Per- and polyfluoroalkyl substances (PFASs) can penetrate the placental barrier and reach embryos through cord blood, probably causing adverse birth outcomes. Therefore, novel PFASs identification in cord blood and their relationships with birth outcomes are essential to evaluate prenatal exposure risk of PFASs. Herein, 16 legacy and 12 novel PFASs were identified in 326 cord blood samples collected from pregnant women in Jinan, Shandong, China. The presence of perfluoropolyether carboxylic acids, hydrogen-substituted polyfluoroetherpropane sulfate, and 3:3 chlorinated polyfluoroalkyl ether alcohol in cord blood was reported for the first time. Two extensive OECD (Organization for Economic Co-operation and Development)-defined PFASs named fipronil sulfone and 2-chloro-6-(trifluoromethyl)pyridine-3-ol were also identified. Quantification results showed that the emerging and OECD-defined PFASs separately accounted for 9.4 and 9.7% of the total quantified PFASs, while the legacy PFOA, PFOS, and PFHxS were still the most abundant PFASs with median concentrations of 2.12, 0.58, and 0.37 ng/mL, respectively. Several PFASs (C9-C12 PFCAs, C6-C8 PFSAs, and 6:2 Cl-PFESA) showed significantly higher levels for older maternities than younger ones. PFHxS levels were positively associated with birth weight and ponderal index (p < 0.05). The results provide comprehensive information on the presence and exposure risks of several novel PFASs during the early life stage.

Identification of N-Nitrosamines and Nitrogenous Heterocyclic Byproducts during Chloramination of Aromatic Secondary Amine Precursors.

With diminishing pristine water, wastewater-affected waters that contain complex anthropogenic compounds are becoming important sources of drinking water and the compounds will inevitably react with disinfectants to form disinfection byproducts (DBPs). Secondary amines such as diphenylamine (DPA) analogues are considered as potential precursors of N-nitrosamines. In this study, an in situ 14N/15N-labeling and screening workflow was used to systematically investigate the formation of nitrogenous DBPs (N-DBPs) and putative reaction pathways. Twenty-four pairs of N-DBPs were generated and identified from chloramination of DPA through two main pathways, in which chloramines reacted with the amino and phenyl functional groups to form N-nitrosodiphenylamine and monochlorinated 5,10-dihydro-phenazine (Cl-DiH-Phe), respectively. Cl-DiH-Phe could further produce phenazine and the coupling products with another DPA molecule. Selective N-DBP formation was pH and dose-dependent, and the same reactions were observed for additional two aromatic DPA analogues. Effects of alkyl substituents on the formation pathways were investigated using a series of dialkyl and N-alkyl aromatic analogues. Only the amino pathway to form nitrosamines was noticed for dialkyl amines, nevertheless, both the main reactions occurred for N-alkyl aromatic amines. These findings suggested that the reaction with chloramines through a phenyl pathway was likely to be crucial for novel nitrogenous heterocyclic byproducts.

Exploring the Occurrence and Temporal Variation of ToxCast Chemicals in Fine Particulate Matter Using Suspect Screening Strategy.

Existence of emerging contaminants in the environment is of great importance for health risk assessment. The consensus on categories and numbers of the emerging contaminants in airborne fine particulate matter (PM2.5) is still extremely deficient. In this study, an in-house data set was constructed containing 890 unique ToxCast (Phase I and Phase II) chemicals. Occurrence and temporal variation of the chemicals was investigated by a suspect screening workflow in 60 PM2.5 samples from January to December of 2016 in Beijing. Eighty-nine compounds were identified in 12 substance categories, which covered a broad range of physicochemical properties. Quantification/semiquantification results showed that phthalates, phenols, and carboxylic esters were the three most predominant categories, with mean concentrations of 7.82, 4.42, and 4.11 ng/m3, respectively. Four diverse temporal variation patterns were discerned, which could be explained by correlations of chemical concentrations (or instrumental responses) with meteorological parameters. An extended retrospective suspect screening was also performed to reveal the presence of several analogues of the identified chemicals that were not included in the data set. Another 75 pollutants were tentatively recognized, and comparison of estimated composition profiles based on instrumental responses suggested the identified ToxCast chemicals are a notable subset of typical emerging contaminants. The results might facilitate ranking of organic pollutants with active biological effects in PM2.5 samples.

Occurrence and Degradation Potential of Fluoroalkylsilane Substances as Precursors of Perfluoroalkyl Carboxylic Acids.

Polyfluoroalkylsilanes (PFASis) are a class of artificial chemicals with wide applications in surface coating, which arouse attention due to their hydrophobic/oleophobic properties and potential biological effects. In this study, a robust high-resolution mass spectrometry method through direct injection into a Fourier transform ion cyclotron resonance instrument was established, with the aid of CF2-scaled Kendrick mass defect analysis and isotope fine structure elucidation. The occurrence of 8:2 polyfluoroalkyl trimethoxysilane (8:2 PTrMeOSi) and 8:2 polyfluoroalkyl triethoxysilane (8:2 PTrEtOSi), as well as their cationic adducts, solvent substitutions, and other compound analogues, were identified in commercial antifingerprint liquid products. In the hydroxyl radical-based total oxidizable precursor assay, differential molar yields of products were observed with regard to varied PFASi carbon-chain lengths and terminal groups. The yields of perfluoroalkyl carboxylic acids (PFCAs) from 8:2 PTrMeOSi conversion were the highest (92 ± 9%, n = 3), with the C ( n - 1) perfluoroheptanoic acid (PFHpA, 49 ± 11%, n = 3) as the dominating product. Distinct conversion of 8:2 PTrMeOSi in the simulated solar exposure experiments found that C ( n) perfluorooctanoic acid (PFOA, 0.6 ± 0.04 ‰, n = 3) was predominant, and 8:2 fluorotelomer carboxylic acid (8:2 FTCA, 0.59 ± 0.08‰, n = 3), 8:2 fluorotelomer unsaturated carboxylic acid (8:2 FTUCA, 0.09 ± 0.00‰, n = 3) intermediates were also observed. To our knowledge, this is the first report regarding the occurrence and degradation potential of several fluoroalkylsilane substances as PFCA precursors.

Multiple Metabolic Pathways of 2,4,6-Tribromophenol in Rice Plants.

Bromophenols occur naturally and are used globally as man-made additives in various industrial products. They are decomposition products of many emerging organic pollutants, such as tetrabromobisphenol A, polybrominated dibenzo- p-dioxin (PBDD), polybrominated diphenyl ethers (PBDE), and others. To characterize their biotransformation pathways, bromophenol congener 2,4,6-tribromophenol, being used most frequently in the synthesis of brominated flame retardants and having the greatest environmental abundance, was selected to hydroponically expose rice plants. After exposure for 5 days, 99.2% of 2,4,6-tribromophenol was metabolized by rice. Because of the lack of relative reference standards, an effective screening strategy was used to screen for potential metabolites that were further qualitatively identified by gas and liquid chromatography combined with high-resolution mass spectrometry. Forty transformation products were confirmed or tentatively identified at different confidence levels, including 9 phase I and 31 phase II metabolites. A large number of metabolites (39) were found in rice root, and 10 of them could be translocated and detected in rice stems or leaves. Many transformation pathways were proposed, including debromination, hydroxylation, methylation, coupling reactions, sulfation, and glycosylation. It was remarkable that a total of seven hydrophobic, persistent, and toxic OH-PBDEs and PBDD/Fs were found, indicating the biotic dimeric reactions of 2,4,6-tribromophenol that occurred in the rice plants. These results improve our understanding of the transformation and environmental fates of bromophenols, and they indicate new potential sources for OH-PBDEs and PBDD/Fs in the environment, especially in food chains.

Emerging aromatic secondary amine contaminants and related derivatives in various dust matrices in China.

Aromatic secondary amines (Ar-SAs), constituted of several analogues with varied substitutions in molecular structure, are among the most frequently used anthropogenic antioxidants. Despite the reported toxicity effects, little information is available on their environmental contamination, except for few particular congeners such as diphenylamine. In this study, the occurrence of two kinds of Ar-SAs, substituted diphenylamines (S-DPAs) and novel substituted p-phenylenediamines (S-PPDs), was investigated in dust samples collected from outdoor rubber playgrounds and residential houses. Seven S-DPAs (GM: 102 ng/g) and two S-PPDs (GM: 20.9 ng/g) were detected in indoor dust. Significantly higher concentrations of S-DPAs (GM: 422 ng/g) and S-PPDs (GM: 31.6 ng/g) were observed in playground dust (p < 0.05). Different dominant Ar-SA congeners were found for indoor dust (low molecular weight Ar-SAs) and playground dust (high molecular weight Ar-SAs), indicating varied sources of Ar-SAs for different dust matrices. Apart from these parent chemicals, three diphenylamine derivatives, including N-nitrosodiphenylamine, 2-nitrodiphenylamine, and 4-nitrodiphenylamine, were also confirmed in indoor dust (GM: 35.7 ng/g) and playground dust (GM: 7.88 ng/g). A preliminary estimated daily intake calculation via dust ingestion indicated no immediate health risk to Chinese population. To our knowledge, this is the first report on the occurrence of a wide range of Ar-SAs and related derivates in dust matrices.

Identification of Unknown Brominated Bisphenol S Congeners in Contaminated Soils as the Transformation Products of Tetrabromobisphenol S Derivatives.

Compared with tetrabromobisphenol A (TBBPA) and its derivatives, the skeletally similar chemicals tetrabromobisphenol S (TBBPS) and its derivatives have been rarely studied, and very little is known about their structures, environmental occurrence, and behaviors. In this study, a total of 84 soil samples from a chemical industrial park have been collected and analyzed to investigate the occurrence of TBBPS and its derivatives and to identify novel TBBPS analogs. TBBPS, TBBPS bis(2,3-dibromopropyl ether) (TBBPS-BDBPE), and three byproducts, TBBPS mono(allyl ether) (TBBPS-MAE), TBBPS mono(2-bromoallyl ether) (TBBPS-MBAE), and TBBPS mono(2,3-dibromopropyl ether) (TBBPS-MDBPE), have been detected with contents ranging from below detection limits to 1934.6 ng/g dw and with detection frequencies of 21.4-97.6%. In addition, another 5 unknown TBBPS analogs, tribromobisphenol S (TriBBPS), 2,2',6'-TriBBPS-MAE (TriBBPS-MAE3.2), 2,6,2'-TriBBPS-MAE (TriBBPS-MAE3.4), 2',6'-DBBPS-MAE (DBBPS-MAE2.0), and 2,6-DBBPS-MAE (DBBPS-MAE2.6), have been identified in these soil samples by untargeted mass spectrometry screening. These unknown analogs have also been observed in laboratory transformation experiments of TBBPS-MDBPE conducted under reducing conditions. TriBBPS-MAE3.4 and DBBPS-MAE2.6 were more likely to be produced than TriBBPS-MAE3.2 and DBBPS-MAE2.0 due to the stereoselectivity of the transformation. TriBBPS-MAE3.4 and DBBPS-MAE2.0 were more stable, resulting in higher detection frequencies of these compounds in soil samples. Ether bond breakage and debromination contributed to the generation of these novel products. The results provide new information on the behaviors of TBBPS and its derivatives in the environment.

Identification of Novel Hydrogen-Substituted Polyfluoroalkyl Ether Sulfonates in Environmental Matrices near Metal-Plating Facilities.

Environmental occurrence and behaviors of 6:2 chlorinated polyfluoroalkyl ether sulfonate (Cl-6:2 PFESA, with trade name F-53B) have been receiving increased attention recently. Nevertheless, its potential fates under diversified conditions remain concealed. In this study, susceptibility of Cl-6:2 PFESA to reductive dehalogenation was tested in an anaerobic super-reduced cyanocobalamin assay. A rapid transformation of dosed Cl-6:2 PFESA was observed, with a hydrogen-substituted polyfluoroalkyl ether sulfonate (1H-6:2 PFESA) identified as the predominant product by a nontarget screening workflow. With the aid of laboratory-purified standards, hydrogen-substituted PFESA analogues (i.e., 1H-6:2 and 1H-8:2 PFESA) were further found in river water and sediment samples collected from two separate regions near metal-plating facilities. Geometric mean concentrations of 560 pg/L (river water) and 11.1 pg/g (sediment) for 1H-6:2 PFESA and 11.0 pg/L (river water) and 7.69 pg/g (sediment) for 1H-8:2 PFESA were measured, and both analytes consisted average compositions of 1% and 0.1% among the 18 monitored per- and polyfluoroalkyl sulfonate and carboxylate pollutants, respectively. To our knowledge, this is the first to report existence of polyfluoroalkyl sulfonates with both hydrogen and ether functional group in the environment.

Chlorinated Polyfluoroalkyl Ether Sulfonic Acids in Marine Organisms from Bohai Sea, China: Occurrence, Temporal Variations, and Trophic Transfer Behavior.

F-53B, the commercial product of chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs), has been used in Chinese chrome plating industry for 30 years, and was recently identified in the environment, which caused great concerns. So far, limited investigations have been performed on their environmental occurrence, fate and impact. In this study, we demonstrated the wide occurrence of Cl-PFESAs and their trophic transfer behavior in marine organisms from Chinese Bohai Sea. 6:2 Cl-PFESA (<0.016-0.575 ng/g wet weight) was the dominant congener, and 8:2 Cl-PFESA (<0.022-0.040 ng/g) was occasionally detected. Compared to other perfluoroalkyl and polyfluoroalkyl substances (PFASs) of concern, the levels of Cl-PFESAs were relatively lower in marine organisms. Based on the comparative analysis of Cl-PFESA contamination in mollusk samples collected in 2010-2014, both the concentrations and detection frequencies of Cl-PFESAs tended to increase in this region. And this kind of chemicals were more vulnerable to be accumulated in marine organisms at relatively higher trophic levels. Similar to perfluorooctanesulfonate (PFOS) and the long chain perfluorinated carboxylates (PFCAs), 6:2 Cl-PFESA could be magnified along the food chain. Accordingly, the potential threat might be posed to the wildlife and human beings due to unintended exposure to Cl-PFESAs.

Observation of Emerging Photoinitiator Additives in Household Environment and Sewage Sludge in China.

Photoinitiators (PIs) are widely used additives in industrial polymerization process, the contamination of which through migration into foodstuffs has been subjected to increasing public scrutiny. Nevertheless, little attention has been paid to the PI residue levels and potential exposure pathways from other environmental compartments. In the present study, the occurrence of PI additives with discrete molecular structures, that is, nine benzophenones (BZPs), four thioxanthones (TXs), and eight amine co-initiators (ACIs), was investigated in commercial products, indoor dust and sewage sludge samples. Nine PI compounds were positively detected in ultraviolet curable resins with concentrations of ∑PIs (sum of the detected PIs) up to 2.51 × 10(4) ng/g, and 20 PIs can be found in food contact materials with concentrations of ∑PIs varying from 65.9 to 6.93 × 10(3) ng/g. The wide usage of PIs in commercial products led to the occurrence of 19 PIs in indoor dust, with concentrations of ∑PIs in the range of 245-5.68 × 10(3) ng/g. Meanwhile, all 21 targeted PIs could be identified in the sewage sludge, with concentrations from 67.6 to 2.03 × 10(3) ng/g. Distinct PI composition profiles were observed in different investigated compartments, and BZPs were the dominant homologues in all samples. Most of the target PIs were further identified as class III chemicals by toxic hazard estimation algorithm (Toxtree), which indicates the compounds might be of significant toxicity or have reactive functional groups.

Identification of Novel Polyfluorinated Ether Sulfonates as PFOS Alternatives in Municipal Sewage Sludge in China.

A 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFAES) with the trade name F-53B, is an alternative to perfluorooctanesulfonate (PFOS) in electroplating industry that is uniquely used in China. It was developed as a mist suppressant initially in the 1970s, but the environmental behaviors and potential adverse effects of the 6:2 Cl-PFAES have only recently been investigated. In this work, the occurrence and distribution of perfluoroalkyl sulfonate (PFSA), fluorotelomer sulfonate (FTSA), and PFAES analogues were investigated in municipal sewage sludge samples collected around China. Perfluorobutane, perfluorohexane, perfluorooctane, and perfluorodecanesulfonates, 6:2 and 8:2 FTSAs, and the emerging 6:2 Cl-PFAES were detected. Moreover, 8:2 and 10:2 Cl-PFAESs were identified for the first time as new polyfluorinated contaminants using high resolution mass spectrometry. These fluorinated analytes were further quantified with the aid of commercial and laboratory-purified standards. PFOS was the predominant contaminant with a geometric mean (GM) value of 3.19 ng/g dry weight (d.w.), which was subsequently followed by 6:2 Cl-PFAES and 8:2 Cl-PFAES (GM: 2.15 and 0.50 ng/g d.w., respectively). Both 6:2 and 8:2 Cl-PFAES were positively detected as the major components in the F-53B commercial product, and discrete 6:2 Cl-PFAES/8:2 Cl-PFAES ratios in the product and sludge samples might suggest 8:2 Cl-PFAES had enhanced sorption behavior in the sludge due to the increase in hydrophobicity.

Occurrence of synthetic phenolic antioxidants and major metabolites in municipal sewage sludge in China.

Synthetic phenolic antioxidants (SPAs) are one group of widely used additive chemicals, which have not yet had focused attention except for a few compounds such as 2,6-di-tert-butyl-4-methylphenol (BHT). In this study, the occurrence and composition profiles of 12 frequently used SPAs and three BHT metabolites were investigated in fifty-six sludge samples collected from individual wastewater treatment plants in China. Eleven SPAs were positively found in the sludge samples, in which, to our knowledge, eight SPA compounds were identified for the first time in the environment. BHT, 4-tert-octylphenol (4-tOP), and 2,4,6-tri-tert-bultylphenol (AO 246) were the most dominant SPAs in the sludge at mean concentrations of 4.14 µg/g, 374 ng/g, and 98.1 ng/g d.w. (dry weight). Meanwhile, three BHT metabolites, including 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q), and 2,6-di-tert-butyl-4-hydroxy-4-methyl-2,5-cyclohexadienone (BHT-quinol), were also found in most of the samples (>98.2%) with mean concentrations of 141, 562, and 225 ng/g d.w., respectively. The activated sludge system (anaerobic, anoxic, and oxic tanks) of a wastewater treatment plant was further investigated for the removal efficiencies of the SPAs. High removal efficiencies (80.1-89.2%) were found for the six detected SPAs in the aqueous phase, while generation of large proportions of the three BHT metabolites was also observed.

Identification and composition of emerging quaternary ammonium compounds in municipal sewage sludge in China.

Quaternary ammonium compounds (QACs) have raised considerable attention due to their wide commercial applications and recent discovery of unknown persistent analogues in aqueous environment. In this work, the occurrence and distribution of alkyltrimethylammonium (ATMAC), benzylakyldimethylethylammonium (BAC) and dialkyldimethylammonium (DADMAC) homologues were investigated in fifty-two municipal sewage sludge samples. ATMAC C10-18, BAC C8-18 and paired DADMAC C8:8-C18:18 as well as emerging homologues such as ATMAC-20, 22 and mixed DADMAC-16:18 and 14:16 were present. Furthermore, paired DADMAC-20:20 and mixed DADMAC-14:18, 18:20 were identified for the first time by nontarget qualitative strategies. A triple quadruple mass spectrometer quantification method was also initially verified with the aid of laboratory synthesized standards for the analysis of the mixed DADMACs with no certificated commercial standards currently available. The total concentrations of ATMACs, BACs and DADMACs were in the range of 0.38-293, 0.09-191 and 0.64-344 µg/g dry weight, respectively, and particularly, mixed DADMACs constituted 39 ± 7% of total DADMAC concentrations. The concentrations and profiles of individual homologues further suggested different QAC applications and fate in China. Significant correlations were also found among the concentrations of various QAC homologues as well as wastewater treatment plant (WWTP) characteristics (total organic carbon contents and daily treatment volumes).

Association between phthalate metabolite mixture in neonatal cord serum and birth outcomes.

Prenatal exposure to phthalates (PAEs) is ubiquitous among Chinese neonates. PAEs entering the body will be transformed to various hydrolyzed and oxidated PAE metabolites (mPAEs). PAEs and mPAEs exposure may lead to adverse birth outcomes through disruption of multiple hormone signaling pathways, induction of oxidative stress, and alterations in intracellular signaling processes. In this study, the concentrations of 11 mPAEs in 318 umbilical cord serum samples from neonates in Jinan were quantified with HPLC-ESI-MS. Multiple linear regression, Bayesian kernel machine regression, and quantile g-computation models were utilized to investigate the effects of both individual mPAE and mPAE mixture on birth outcomes. Stratified analysis was performed to explore whether these effects were gender-specific. mPAE mixture was negatively associated with birth length (BL) z-score, birth weight (BW) z-score, head circumference (HC) z-score, and ponderal index (PI). Mono(2-ethylhexyl) phthalate (MEHP) manifested negative associations with BL(z-score), BW(z-score), HC(z-score), and PI, whereas mono(2-carboxymethylhexyl) phthalate (MCMHP) was negatively associated with BW(z-score) and PI within the mPAE mixture. Stratified analysis revealed that the negative associations between mPAE mixture and four birth outcomes were attenuated in female infants, while the positive impact of mono(2-ethyl-5carboxypentyl) phthalate (MECPP) on BL(z-score) and BW(z-score) could be detected only in females. In summary, our findings suggest that prenatal exposure to phthalates may be associated with intrauterine growth restriction, and these effects vary according to the gender of the infant.

Competitive-like binding between carbon black and CTNNB1 to ΔNp63 interpreting the abnormal respiratory epithelial repair after injury.

Airway epithelium is extraordinary vulnerable to damage owning to continuous environment exposure. Subsequent repair is therefore essential to restore the homeostasis of respiratory system. Disruptions in respiratory epithelial repair caused by nanoparticles exposure have been linked to various human diseases, yet implications in repair process remain incompletely elucidated. This study aims to elucidate the key stage in epithelial repair disturbed by carbon black (CB) nanoparticles, highlighting the pivotal role of ΔNp63 in mediating the epithelium repair. A competitive-like binding between CB and beta-catenin 1 (CTNNB1) to ΔNp63 is proposed to elaborate the underlying toxicity mechanism. Specifically, CB exhibits a remarkable inhibitory effect on cell proliferation, leading to aberrant airway epithelial repair, as validated in air-liquid culture. ΔNp63 drives efficient epithelial proliferation during CB exposure, and CTNNB1 was identified as a target of ΔNp63 by bioinformatics analysis. Further molecular dynamics simulation reveals that oxygen-containing functional groups on CB disrupt the native interaction of CTNNB1 with ΔNp63 through competitive-like binding pattern. This process modulates CTNNB1 expression, ultimately restraining proliferation during respiratory epithelial repair. Overall, the current study elucidates that the diminished interaction between CTNNB1 and ΔNp63 impedes respiratory epithelial repair in response to CB exposure, thereby enriching the public health risk assessment on CB-related respiratory diseases.