Occurrence and Prioritization of Human Androgen Receptor Disruptors in Sewage Sludges Across China.

The global practice of reusing sewage sludge in agriculture and its landfill disposal reintroduces environmental contaminants, posing risks to human and ecological health. This study screened sewage sludge from 30 Chinese cities for androgen receptor (AR) disruptors, utilizing a disruptor list from the Toxicology in the 21st Century program (Tox21), and identified 25 agonists and 33 antagonists across diverse use categories. Predominantly, natural products 5α-dihydrotestosterone and thymidine emerged as agonists, whereas the industrial intermediate caprolactam was the principal antagonist. In-house bioassays for identified disruptors displayed good alignment with Tox21 potency data, validating employing Tox21 toxicity data for theoretical toxicity estimations. Potency calculations revealed 5α-dihydrotestosterone and two pharmaceuticals (17ß-trenbolone and testosterone isocaproate) as the most potent AR agonists and three dyes (rhodamine 6G, Victoria blue BO, and gentian violet) as antagonists. Theoretical effect contribution evaluations prioritized 5α-dihydrotestosterone and testosterone isocaproate as high-risk AR agonists and caprolactam, rhodamine 6G, and 8-hydroxyquinoline (as a biocide and a preservative) as key antagonists. Notably, 16 agonists and 20 antagonists were newly reported in the sludge, many exhibiting significant detection frequencies, concentrations, and/or toxicities, demanding future scrutiny. Our study presents an efficient strategy for estimating environmental sample toxicity and identifying key toxicants, thereby supporting the development of appropriate sludge management strategies.

High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

Effect-directed analysis of androgenic compounds from sewage sludges in China.

The safety of municipal sewage sludge has raised great concerns because of the accumulation of large-scale endocrine disrupting chemicals in the sludge during wastewater treatment. The presence of contaminants in sludge can cause secondary pollution owing to inappropriate disposal mechanisms, posing potential risks to the environment and human health. Effect-directed analysis (EDA), involving an androgen receptor (AR) reporter gene bioassay, fractionation, and suspect and nontarget chemical analysis, were applied to identify causal AR agonists in sludge; 20 of the 30 sludge extracts exhibited significant androgenic activity. Among these, the extracts from Yinchuan, Kunming, and Shijiazhuang, which held the most polluted AR agonistic activities were prepared for extensive EDA, with the dihydrotestosterone (DHT)-equivalency of 2.5 - 4.5 ng DHT/g of sludge. Seven androgens, namely boldione, androstenedione, testosterone, megestrol, progesterone, and testosterone isocaproate, were identified in these strongest sludges together, along with testosterone cypionate, first reported in sludge media. These identified androgens together accounted for 55 %, 87 %, and 52 % of the effects on the sludge from Yinchuan, Shijiazhuang, and Kunming, respectively. This study elucidates the causative androgenic compounds in sewage sludge and provides a valuable reference for monitoring and managing androgens in wastewater treatment.

The perturbation of parabens on the neuroendocrine system in zebrafish larvae.

Parabens, as the synthetic preservatives, have caused universal environmental contamination and human exposure. Whether parabens could disturb neuroendocrine system was still ambiguous. In this study, the effects of four commonly-used parabens, i.e. methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP), were tested on the neuroendocrine system of zebrafish larvae by investigating the swimming behavior, the related hormones and biomarkers in the hypothalamic-pituitary-interrenal (HPI) axis. The results showed that all test chemicals significantly reduced the swimming distance and mean velocity of zebrafish larvae. The adrenocorticotropic hormone (ACTH) levels in zebrafish larvae were significantly increased, while the cortisol levels were obviously decreased by paraben exposure. The transcriptional analysis showed that the expressions of the target genes including gr, mr and crhr2 in the HPI axis were mostly down-regulated. The exploration of the initial molecular event showed that parabens could bind with the glucocorticoid receptor (GR) and trigger its transactivation, according to MDA-kb2 luciferase assay and molecular docking analysis. The interaction of parabens with the GR included the hydrogen bond and hydrophobic interaction. The findings herein revealed the potential deleterious effects of parabens on the neuroendocrine system of zebrafish larvae, thus accumulating the in vivo toxicological data on this kind of food preservatives.

Disposable Polypropylene Face Masks: A Potential Source of Micro/Nanoparticles and Organic Contaminates in Humans.

We have been effectively protected by disposable propylene face masks during the COVID-19 pandemic; however, they may pose health risks due to the release of fine particles and chemicals. We measured micro/nanoparticles and organic chemicals in disposable medical masks, surgical masks, and (K)N95 respirators. In the breathing-simulation experiment, no notable differences were found in the total number of particles among mask types or between breathing intensities. However, when considering subranges, <2.5 µm particles accounted for ∼90% of the total number of micro/nanoparticles. GC-HRMS-based suspect screening tentatively revealed 79 (semi)volatile organic compounds in masks, with 18 being detected in ≥80% of samples and 44 in ≤20% of samples. Three synthetic phenolic antioxidants were quantified, and AO168 reached a median concentration of 2968 ng/g. By screening particles collected from bulk mask fabrics, we detected 18 chemicals, including four commonly detected in masks, suggesting chemical partition between the particles and the fabric fibers and chemical exposure via particle inhalation. These particles and chemicals are believed to originate from raw materials, intentionally and nonintentionally added substances in mask production, and their transformation products. This study highlights the need to study the long-term health risks associated with mask wearing and raises concerns over mask quality control.

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.