Unraveling the nexus: Microplastics, antibiotics, and ARGs interactions, threats and control in aquaculture - A review.

In recent years, aquaculture has expanded rapidly to address food scarcity and provides high-quality aquatic products. However, this growth has led to the release of significant effluents, containing emerging contaminants like antibiotics, microplastics (MPs), and antibiotic resistance genes (ARGs). This study investigated the occurrence and interactions of these pollutants in aquaculture environment. Combined pollutants, such as MPs and coexisting adsorbents, were widespread and could include antibiotics, heavy metals, resistance genes, and pathogens. Elevated levels of chemical pollutants on MPs could lead to the emergence of resistance genes under selective pressure, facilitated by bacterial communities and horizontal gene transfer (HGT). MPs acted as vectors, transferring pollutants into the food web. Various technologies, including membrane technology, coagulation, and advanced oxidation, have been trialed for pollutants removal, each with its benefits and drawbacks. Future research should focus on ecologically friendly treatment technologies for emerging contaminants in aquaculture wastewater. This review provided insights into understanding and addressing newly developing toxins, aiming to develop integrated systems for effective aquaculture wastewater treatment.

Interactive impacts of photoaged micro(nano)plastics and co-occurring chemicals in the environment.

In the environment, sunlight or ultraviolet (UV) radiation is considered to be the primary cause of plastic aging, leading to their fragmentation into particles, including micro(nano)plastics (MNPs). Photoaged MNPs possess diverse interactive properties and ecotoxicological implications substantially different from those of pristine plastic particles. This review aims to highlight the mechanisms and implications of UV-induced photoaging of MNPs, with an emphasis on various UV sources and their interactions with co-occurring organic and inorganic chemicals, as well as the associated ecological and health impacts and factors affecting those interactions. Compared to UV-B, UV-A and UV-C were more widely used in laboratory studies for MNP degradation. Photoaged MNPs act as vectors for the transportation of organic pollutants, organic matter, and inorganic chemicals in the environment. Literature showed that photoaged MNPs exhibit a higher sorption capacity for PPCPs, PAHs, PBDEs, pesticides, humic acid, fulvic acid, heavy metals, and metallic nanoparticles than pristine MNPs, potentially causing significant changes in associated ecological and health impacts. Combined exposure to photoaged MNPs and organic and inorganic pollutants significantly altered mortality rate, decreased growth rate, histological alterations, neurological impairments, reproductive toxicity, induced oxidative stress, thyroid disruption, hepatotoxicity, and genotoxicity in vivo, both in aquatic and terrestrial organisms. Limited studies were reported in vitro and found decreased cellular growth and survival, induced oxidative stress, and compromised the permeability and integrity of the cell membrane. In addition, several environmental factors (temperature, organic matter, ionic strength, time, and pH), MNP properties (polymer types, sizes, surface area, shapes, colour, and concentration), and chemical properties (pollutant type, concentration, and physiochemical properties) can influence the photoaging of MNPs and associated impacts. Lastly, the research gaps and prospects of MNP photoaging and associated implications were also summarized. Future research should focus on the photoaging of MNPs under environmentally relevant conditions, exploiting the polydisperse characteristics of environmental plastics, to make this process more realistic for mitigating plastic pollution.

A meta-analysis highlighting the increasing relevance of the hair matrix in exposure assessment to organic pollutants.

Owing to a wide range of advantages, such as stability, non-invasiveness, and ease of sampling, hair has been used progressively for comprehensive biomonitoring of organic pollutants for the last three decades. This has led to the development of new analytical and multi-class analysis methods for the assessment of a broad range of organic pollutants in various population groups, ranging from small-scale studies to advanced studies with a large number of participants based on different exposure settings. This meta-analysis summarizes the existing literature on the assessment of organic pollutants in hair in terms of residue levels, the correlation of hair residue levels with those of other biological matrices and socio-demographic factors, the reliability of hair versus other biomatrices for exposure assessment, the use of segmental hair analysis for chronic exposure evaluation and the effect of external contamination on hair residue levels. Significantly high concentrations of organic pollutants such as pesticides, flame retardants, polychlorinated biphenyls and polycyclic aromatic hydrocarbon were reported in human hair samples from different regions and under different exposure settings. Similarly, high concentrations of pesticides (from agricultural activities), flame retardants (E-waste dismantling activities), dioxins and furans were observed in various occupational settings. Moreover, significant correlations (p < 0.05) for hair and blood concentrations were observed in majority of studies featuring pesticides and flame retardants. While among sociodemographic factors, gender and age significantly affected the hair concentrations in females and children in general exposure settings, whereas adult workers in occupational settings. Furthermore, the assessment of the hair burden of persistent organic pollutants in domestic and wild animals showed high concentrations for pesticides such as HCHs and DDTs whereas the laboratory-based studies using animals demonstrated strong correlations between exposure dose, exposure duration, and measured organic pollutant levels, mainly for chlorpyrifos, diazinon, terbuthylazine, aldrin, dieldrin and pyrethroid metabolites. Considering the critical analysis of the results obtained from literature review, hair is regarded as a reliable matrix for organic pollutant assessment; however, some limitations, as discussed in this review, need to be overcome to reinforce the status of hair as a suitable matrix for exposure assessment.

PPARß/δ-ANGPTL4 axis mediates the promotion of mono-2-ethylhexyl phthalic acid on MYCN-amplified neuroblastoma development.

Di-2-ethylhexyl phthalic acid (DEHP) is one of the most widely used plasticizers in the industry, which can improve the flexibility and durability of plastics. It is prone to migrate from various daily plastic products through wear and leaching into the surrounding environment and decompose into the more toxic metabolite mono-2-ethylhexyl phthalic acid (MEHP) after entering the human body. However, the impacts and mechanisms of MEHP on neuroblastoma are unclear. We exposed MYCN-amplified neuroblastoma SK-N-BE(2)C cells to an environmentally related concentration of MEHP and found that MEHP increased the proliferation and migration ability of tumor cells. The peroxisome proliferator-activated receptor (PPAR) ß/δ pathway was identified as a pivotal signaling pathway in neuroblastoma, mediating the effects of MEHP through transcriptional sequencing analysis. Because MEHP can bind to the PPARß/δ protein and initiate the expression of the downstream gene angiopoietin-like 4 (ANGPTL4), the PPARß/δ-specific agonist GW501516 and antagonist GSK3787, the recombinant human ANGPTL4 protein, and the knockdown of gene expression confirmed the regulation of the PPARß/δ-ANGPTL4 axis on the malignant phenotype of neuroblastoma. Based on the critical role of PPARß/δ and ANGPTL4 in the metabolic process, a non-targeted metabolomics analysis revealed that MEHP altered multiple metabolic pathways, particularly lipid metabolites involving fatty acyls, glycerophospholipids, and sterol lipids, which may also be potential factors promoting tumor progression. We have demonstrated for the first time that MEHP can target binding to PPARß/δ and affect the progression of neuroblastoma by activating the PPARß/δ-ANGPTL4 axis. This mechanism confirms the health risks of plasticizers as tumor promoters and provides new data support for targeted prevention and treatment of neuroblastoma.

The untold story of PFAS alternatives: Insights into the occurrence, ecotoxicological impacts, and removal strategies in the aquatic environment.

Due to increasing regulations on the production and consumption of legacy per- and polyfluoroalkyl substances (PFAS), the global use of PFAS substitutes increased tremendously, posing serious environmental risks owing to their bioaccumulation, toxicity, and lack of removal strategies. This review summarized the spatial distribution of alternative PFAS and their ecological risks in global freshwater and marine ecosystems. Further, toxicological effects of novel PFAS in various freshwater and marine species were highlighted. Moreover, degradation mechanisms for alternative PFAS removal from aquatic environments were compared and discussed. The spatial distribution showed that 6:2 chlorinated polyfluorinated ether sulfonate (6:2 CI-PFAES, also known as F-53B) was the most dominant emerging PFAS found in freshwater. Additionally, the highest levels of PFBS and PFBA were observed in marine waters (West Pacific Ocean). Moreover, short-chain PFAS exhibited higher concentrations than long-chain congeners. The ecological risk quotients (RQs) for phytoplankton were relatively higher >1 than invertebrates, indicating a higher risk for freshwater phytoplankton species. Similarly, in marine water, the majority of PFAS substitutes exhibited negligible risk for invertebrates and fish, and posed elevated risks for phytoplanktons. Reviewed studies showed that alternative PFAS undergo bioaccumulation and cause deleterious effects such as oxidative stress, hepatoxicity, neurotoxicity, histopathological alterations, behavioral and growth abnormalities, reproductive toxicity and metabolism defects in freshwater and marine species. Regarding PFAS treatment methods, photodegradation, photocatalysis, and adsorption showed promising degradation approaches with efficiencies as high as 90%. Finally, research gaps and future perspectives for alternative PFAS toxicological implications and their removal were offered.

An integrated assessment of ecological and human health risks of per- and polyfluoroalkyl substances through toxicity prediction approaches.

Per- and polyfluoroalkyl substances (PFAS) are also known as "forever chemicals" due to their persistence and ubiquitous environmental distribution. This review aims to summarize the global PFAS distribution in surface water and identify its ecological and human risks through integrated assessment. Moreover, it provides a holistic insight into the studies highlighting the human biomonitoring and toxicological screening of PFAS in freshwater and marine species using quantitative structure-activity relationship (QSAR) based models. Literature showed that PFOA and PFOS were the most prevalent chemicals found in surface water. The highest PFAS levels were reported in the US, China, and Australia. The TEST model showed relatively low LC50 of PFDA and PFOS for Pimephales promelas (0.36 and 0.91 mg/L) and high bioaccumulation factors (518 and 921), revealing an elevated associated toxicity. The risk quotients (RQs) values for P. promelas and Daphnia magna were found to be 269 and 23.7 for PFOS. Studies confirmed that long-chain PFAS such as PFOS and PFOA undergo bioaccumulation in aquatic organisms and induce toxicological effects such as oxidative stress, transgenerational epigenetic effects, disturbed genetic and enzymatic responses, perturbed immune system, hepatotoxicity, neurobehavioral toxicity, altered genetic and enzymatic responses, and metabolism abnormalities. Human biomonitoring studies found the highest PFOS, PFOA, and PFHxS levels in urine, cerebrospinal fluid, and serum samples. Further, long-chain PFOA and PFOS exposure create severe health implications such as hyperuricemia, reduced birth weight, and immunotoxicity in humans. Molecular docking analysis revealed that short-chain PFBS (-11.84 Kcal/mol) and long-chain PFUnDA (-10.53 Kcal/mol) displayed the strongest binding interactions with human serum albumin protein. Lastly, research challenges and future perspectives for PFAS toxicological implications were also discussed, which helps to mitigate associated pollution and ecological risks.

Micro(nano)plastics in commercial foods: A review of their characterization and potential hazards to human health.

Micro (nano)plastics (MNPs) are pollutants of worldwide concern for their ubiquitous environmental presence and associated impacts. The higher consumption of MNPs contaminated commercial food can cause potential adverse human health effects. This review highlights the evidence of MNPs in commercial food items and summarizes different sampling, extraction, and digestion techniques for the isolation of MNPs, such as oxidizing digestion, enzymatic digestion, alkaline digestion and acidic digestion. Various methods for the characterization and quantification of microplastics (MPs) are also compared, including µ-Raman spectroscopy, µ-Fourier transform infrared spectroscopy (FTIR), thermal analysis and Scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX). Finally, we share our concerns about the risks of MNPs to human health through the consumption of commercial seafood. The knowledge of the potential human health impacts at a subcellular or molecular level of consuming mariculture products contaminated with MNPs is still limited. Moreover, MNPs are somewhat limited, hard to measure, and still contentious. Due to the nutritional significance of fish consumption, the risk of exposure to MNPs and the associated health effects are of the utmost importance.

Recent advances in micro (nano) plastics in the environment: Distribution, health risks, challenges and future prospects.

Environmental micro(nano)plastics have become a significant global pollution problem due to the widespread use of plastic products. In this review, we summarized the latest research advances on micro(nano)plastics in the environment, including their distribution, health risks, challenges, and future prospect. Micro(nano)plastics have been found in a variety of environmental media, such as the atmosphere, water bodies, sediment, and especially marine systems, even in remote places like Antarctica, mountain tops, and the deep sea. The accumulation of micro(nano)plastics in organisms or humans through ingestion or other passive ways poses a series of negative impacts on metabolism, immune function, and health. Moreover, due to their large specific surface area, micro(nano)plastics can also adsorb other pollutants, causing even more serious effects on animal and human health. Despite the significant health risks posed by micro(nano)plastics, there are limitations in the methods used to measure their dispersion in the environment and their potential health risks to organisms. Therefore, further research is needed to fully understand these risks and their impacts on the environment and human health. Taken together, the challenges of micro(nano)plastics analysis in the environment and organisms must be addressed, and future research prospects need to be identified. Governments and individuals must take action to reduce plastic waste and minimize the negative impact of micro(nano)plastics on the environment and human health.

Organochlorine pesticides (OCPs) in freshwater resources of Pakistan: A review on occurrence, spatial distribution and associated human health and ecological risk assessment.

The extensive use of organochlorine pesticides (OCPs) has resulted in the widespread contamination of different environmental matrices in Pakistan. Freshwater bodies are also prone to OCPs contamination as they receive agricultural and industrial runoff from different sources. In the present study, the data regarding OCPs' fate and distribution in freshwater resources of Pakistan was reviewed and associated risks to human and ecological health were assessed. Among all the OCPs, DDTs were more prevalent with the highest mean concentration of 2290 ng/L observed in River Ravi (Lahore and Sahiwal District). Human health risk assessment showed a higher risk to the children with high Hazard Quotient (HQ) values ranging between 4.1 × 10-9- 295 for Aldrin. The River Ravi (Lahore and Sahiwal District), the River Sutlej (Kasur & Bahawalpur District), and the River Kabul (Nowshehra District) were categorized as high-risk water bodies based on Hazard Index (HI) and Non-Cancer Risk (CRI) index values > 10. Ecological risk assessment revealed a higher risk posed to invertebrate species from DDT exposure. In summary, this review highlights the occurrence and distribution of OCPs and their associated human health and ecological risks in freshwater bodies of Pakistan and also contributes to signifying the need for proper management and regulation of banned pesticides and future research perspectives.

Current understanding of gliomagenesis: from model to mechanism.

Glioma, a kind of central nervous system (CNS) tumor, is hard to cure and accounts for 32% of all CNS tumors. Establishing a stable glioma model is critically important to investigate the underlying molecular mechanisms involved in tumorigenesis and tumor progression. Various core signaling pathways have been identified in gliomagenesis, such as RTK/RAS/PI3K, TP53, and RB1. Traditional methods of establishing glioma animal models have included chemical induction, xenotransplantation, and genetic modifications (RCAS/t-va system, Cre-loxP, and TALENs). Recently, CRISPR/Cas9 has emerged as an efficient gene editing tool with high germline transmission and has extended the scope of stable and efficient glioma models that can be generated. Therefore, this review will highlight the documented evidence about the molecular characteristics, critical genetic markers, and signaling pathways responsible for gliomagenesis and progression. Moreover, methods of establishing glioma models using gene editing techniques and therapeutic aspects will be discussed. Finally, the prospect of applying gene editing in glioma by using CRISPR/Cas9 strategy and future research directions to establish a stable glioma model are also included in this review. In-depth knowledge of glioma signaling pathways and use of CRISPR/Cas9 can greatly assist in the development of a stable, efficient, and spontaneous glioma model, which can ultimately improve the effectiveness of therapeutic responses and cure glioma patients.

Sulfonamide and tetracycline in landfill leachates from seven municipal solid waste (MSW) landfills: Seasonal variation and risk assessment.

Antibiotics have received increased attention as emerging contaminants due to their toxicity and potential risk. Landfills serve as one of the important reservoirs of antibiotics. The antibiotics in landfills leaching to nearby environment by leachate may threat ecosystem health. The present study aimed to evaluate the levels of tetracyclines (TCs) and sulfonamides (SAs) in seven Chinese Municipal Solid Waste (MSW) landfill leachates over two years (2017-2018). Seven target antibiotics, TC, oxytetracycline (OTC), doxycycline (DXC), sulfonamide sulfadiazine (SD), sulfamerazine (SM), sulfamethazine (SMX), and sulfamethoxazole (SMT), were detected in 56 landfill leachate samples. Among these, SMT had the highest mean concentration at 654 ng/L (n = 45), followed by OTC (219.58 ng/L, n = 47), and SD (209.98 ng/L, n = 49). The temporal trend showed that antibiotic concentrations were higher in 2017 than in 2018. Furthermore, physicochemical properties were significantly correlated with SAs (p < 0.05), whereas no significant correlation was found for TCs. Seasonal variation analysis revealed that antibiotic levels were higher in spring and winter compared to summer and fall seasons, which might be attributed to the higher waterfall levels in these seasons. Risk assessment revealed that SAs (SM, SMX, SMT) are associated with high risk, and the RQs follow the order of: SMX > SMT > SM. In contrast, TCs had insignificant risk. The findings of this two-year comprehensive monitoring project have produced positive results regarding antibiotic pollution at landfill sites, which can be applied to antibiotics management in landfill and further ensure public health.

Tissue distribution and endocrine disruption effects of chronic exposure to pharmaceuticals and personal care products mixture at environmentally relevant concentrations in zebrafish.

Pharmaceuticals and personal care products (PPCPs) as emerging contaminants are ubiquitously present in the aquatic environment. Using in vivo and in silico techniques, this study aims to elucidate tissue distribution and endocrine disruption effects of chronic exposure (120 days) to PPCP mixture at environmentally relevant concentrations (ERCs) in adult zebrafish. Results from UHPLC-MS/MS analyses showed elevated distribution of PPCPs in zebrafish tissues in the order of liver > gonad > brain. Upregulation of steroid hormone receptors, both gonadotropin, and steroidogenic genes perturb the HPG axis pathway in females, while male fish exhibited significantly downregulated expressions of vtg, cyp17, and 17ßhsd genes with inhibited fecundity. The Spearman correlation indicated a significant positive relationship between PPCPs bioaccumulation and mRNA levels of HPG axis genes. In silico molecular docking (MD) revealed specific amino acid residues of PPCPs binding with zebrafish estrogen receptors. Furthermore, the strongest binding energies of sulfamethoxazole, carbamazepine, and triclosan were discovered in erα and erß estrogen receptors, confirming PPCPs' xenoestrogenic behavior. To summarize, chronic exposure to ERCs resulted in a high accumulation of PPCPs in the liver and gonad tissues of adult zebrafish, as well as associated perturbed genetic responses. As a result, strict environmental regulations for the disposal of PPCPs should be ensured to protect ecological and public health.

Transcriptome and in silico approaches provide new insights into the mechanism of male reproductive toxicity induced by chronic exposure to DEHP.

Di-(2-ethylhexyl) phthalate (DEHP) can affect the male reproductive system in vertebrates, but the underlying molecular mechanism is still elusive. Therefore, in this study, we aimed to dig the in-depth mechanism of DEHP-induced reproductive toxicity on male zebrafish via testicular transcriptome using embryo exposed at the environmentally relevant concentration (ERC) of 100 µg/L for 111 days. Moreover, our results were further confirmed via in silico technique and bioassay experimental in vitro (cell lines) and in vivo (zebrafish). The results showed DEHP exposure could affect male spermatogenesis, altered gonad histology, and reduced egg fertilization rate. Transcriptome analysis identified 1879 significant differentially expressed genes enriched in the exposure group. Twenty-seven genes related to three pathways of reproduction behavior were further validated by qPCR. In silico molecular docking revealed that DEHP and its metabolism bind to the zebrafish progesterone receptor (Pgr), suggesting the potential disruption of DEHP to the normal Pgr signaling. To further validate it, a wild-type Pgr plasmid and its mutants on specific binding sites were constructed. The transfection and microinjection experiment demonstrated that these binding sites mutations of Pgr affected the expression levels of male reproductive toxicity. Taken together, our study provided new insight into the molecular mechanisms of male reproductive toxicity induced by DEHP, and Pgr may serve as an important target binding by DEHP pollution, which needs further study in the future.

Combined toxicity of endocrine-disrupting chemicals: A review.

The combined toxicological assessment provides a realistic approach for hazard evaluation of chemical cocktails that co-existed in the environment. This review provides a holistic insight into the studies highlighting the mixture toxicity of the endocrine-disrupting chemicals (EDCs), especially focusing on the screening of biochemical pathways and other toxicogenetic endpoints. Reviewed literature showed that numerous multiplexed toxicogenomic techniques were applied to determine reproductive effects in vertebrates, but limited studies were found in non-mammalian species after mixture chemical exposure. Further, we found that the experimental design and concentration selection are the two important parameters in mixture toxicity studies that should be time- and cost-effective, highly precise, and environmentally relevant. A summary of EDC mixtures affecting the thyroid axis, estrogen axis, androgen axis, growth stress, and immune system via in vivo bioassays was also presented. It is interesting to mention that majority of estrogenic effects of the mixtures were sex-dependent, particularly observed in male fish as compared to female fish. Further, the androgen axis was perturbed with serious malformations in male rat testis (epididymal or gubernacular lesions, and deciduous spermatids). Also, transgenerational epigenetic effects were promoted in the F3 and F4 generations in the form of DNA methylation epimutations in sperm, increasing polycystic ovaries and reducing the offspring. Similarly, increased oxidative stress, high antioxidant enzymatic activities, disturbed estrous cycle, and decreased steroidogenesis were the commonly found effects after acute or chronic exposure to EDC mixtures. Importantly, the concentration addition (CA) and independent action (IA) models became more prevalent and suitable predictive models to unveil the prominence of synergistic estrogenic and anti-androgenic effects of chemical mixtures. More importantly, this review encompasses the research challenges and gaps in the existing knowledge and specific future research perspectives on combined toxicity.

Atmospheric polycyclic aromatic hydrocarbons (PAHs) at urban settings in Pakistan: Spatial variations, sources and health risks.

For the first time, this study presents gaseous and particulate-bound (PM2.5) polycyclic aromatic hydrocarbons (PAHs) in ambient air samples collected from eight major cities of Pakistan. Diurnal air samples (gaseous and PM2.5) were collected in summer 2014 on polyurethane foam and quartz fiber filters using high volume-active air sampler. The US-EPA enlisted 16 priority PAHs in particulate and gaseous phase were measured on gas chromatograph equipped with mass spectrometer detector. The total PAHs concentrations ranged between 188 pg m-3 (in Gilgit), and 2340 pg m-3 (in Lahore). The decreasing order of PAHs concentrations in various cities was in the following order: Lahore > Rawalpindi > Multan > Faisalabad > Karachgi > Peshawar > Quetta > Gilgit. Phenanthrene showed the highest concentration, accounted 18% of total PAHs followed by fluoranthene (12% of total PAHs). This study showed that the gaseous fractions were predominant in the ambient air. Source apportionment analysis revealed that biomass combustion, vehicular emissions and diesel combustion in power generators were the potential PAHs emissions sources. The lifetime lungs cancer risk (LLCR) was in the range of 8.28 × 10-7 to 2.09 × 10-5 depicting mild cancer risk to the residents on exposure to atmospheric PAHs. Therefore, it is recommended to monitor atmospheric PAHs throughout the year and also adopt environmentally friendly fuels to reduce PAHs pollution and health risks in the country.

Chronic exposure to PPCPs mixture at environmentally relevant concentrations (ERCs) altered carbohydrate and lipid metabolism through gut and liver toxicity in zebrafish.

Pharmaceuticals and personal care products (PPCPs) have been widely distributed and posed ecotoxicological risks in the aquatic environment. This study aims to evaluate the toxic effects after chronic exposure to PPCPs mixture at the environment relevant concentrations (ERCs). Our results indicated that PPCPs induced serious metabolic effects by disturbing the carbohydrate and lipid metabolism pathways. Chronic exposure caused a significant reduction in the hepatosomatic index (HSI), the gut weight ratios, and histological alterations in liver and gut tissues. Further, exposure to the combined PPCPs disrupted the carbohydrate metabolism via significant upregulation of hk1, gk, pck1, and insr genes. The lipid metabolism was affected with higher ppars expression levels that increased the fatty acid ß-oxidation and ultimately decreased the lipidogenesis. Moreover, the altered responses of the insulin growth factor (IGF) pathway more in male gut tissue than that of female revealed sex-dependent disturbance in the gut homeostasis induced by PPCPs mixture. In conclusion, chronic exposure to PPCPs mixtures at ERCs can induce developmental effects and metabolic dysfunction in both male and female fish. The consumption and environmental disposal of these PPCPs should be regulated to ensure ecological health and environmental safety.

Prioritizing phthalate esters (PAEs) using experimental in vitro/vivo toxicity assays and computational in silico approaches.

Phthalate esters (PAEs) pose prominent ecological risks owing to their multiplex toxicity potentials and ubiquitous detection in the environment. Therefore, this study aims to prioritize the individual and mixtures of six PAEs based on their toxicological implications using in vitro and vivo models exposed at environmentally relevant concentrations. Results were further confirmed using in silico Combination index (CI) and Independent action (IA), and molecular docking models. Among PAEs, DEHP revealed prominent in vitro/vivo toxicity followed by DEP, DBP, and DMP. Importantly, binary mixtures particularly C2-C6 and C11-C15 exhibited greater developmental toxicity, apoptosis, and perturbed the HPG pathway. The CI and IA models forecasted antagonistic and additive effects at Fa = 0.5 and Fa = 0.9 using in vitro Acinetobacter sp. Tox2. Conversely, in zebrafish, the IA model predicted mixture effects in the following order: additive > synergistic > antagonistic on the regulation of the HPG pathway, which was consistent with experimental results from Acridine Orange (AO) staining and apoptosis gene expression. Molecular docking for estrogen receptors (ERα, ERß) revealed the highest binding energy scores for DEHP, compared to other PAEs. In short, our findings confirm that individual and mixtures of PAEs behave as xenoestrogens in the freshwater ecosystem with DEHP as a priority compound.

Individual and combined toxicogenetic effects of microplastics and heavy metals (Cd, Pb, and Zn) perturb gut microbiota homeostasis and gonadal development in marine medaka (Oryzias melastigma).

Currently, microplastics (MPs) attracted increased attention for their ubiquity and toxic properties. In this study, marine medaka was used to explore the individual and combined toxicity of heavy metals (HMs) and MPs on intestinal bacteria and gonadal development. After exposure to environmentally relevant concentrations of MPs and HMs, significant alterations of intestinal microbiota were found. The MPs treatment reduced the diversity and abundance of intestinal microbiota, while the HMs and MPs-HMs treatments increased them, which were confirmed by the abundance changes of Proteobacteria. According to the KEGG analysis, the metabolism and environmental information processing (EIP) pathways in the microbial community were significantly affected. This study showed that the MPs-HMs treatment caused a higher pollution load on the gut of the marine medaka, and triggered more significant changes of specific bacterial species and gut function in the males. However, during the gonadal development, HMs and MPs-HMs treatments resulted in empty follicles (EF) and follicular atresia (FA), and altered the gene expression levels related to hypothalamic-pituitary-gonadal (HPG) axis. In short, this study demonstrated that the reproductive disturbance was mainly due to HMs, but the combination of MPs and HMs did not strengthen the risk to the gonad development of the marine medaka.

Effects of phthalate acid esters on zebrafish larvae: Development and skeletal morphogenesis.

This study evaluated the acute developmental toxicity of six priority phthalic acid esters (PAEs) including dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DNOP), and benzyl butyl phthalate (BBP) in zebrafish embryos. A novel alcian blue and alizarin red double staining was performed to detect skeletal development of zebrafish larvae. Results revealed that all six PAEs could induce different developmental abnormalities in zebrafish larvae, including abnormal movement, decreased heart rate, spinal curvature, and pericardial edema. The bone development of zebrafish larvae exposed to PAEs was also affected by PAEs acute exposure. Among PAEs, DBP, and BBP even at low doses can cause mortality in zebrafish, implying their higher toxicity. Contrarily, DEHP and DNOP showed minor effects on the developmental morphology of zebrafish larvae. However, the gene expression levels of skeleton-related genes showed the upregulation of the runx2b and shha genes after DEHP and DBP exposure. Taken together, the strict use and release of PAEs in the environment should be supervised by the government for ecological and environmental safety.

Individual and combined mechanistic toxicity of sulfonamides and their implications for ecological risk assessment in the Three Gorges Reservoir Area (TGRA), China.

Sulfonamides (SAs) are conventional veterinary antibiotics that pose ecological risks in the aquatic environment. This study aims to evaluate the environmental concerns of SAs in the Three Gorges Reservoir Area (TGRA) and their toxicogenetic implications. Here, we employed various in vitro and in vivo bioassays to determine the combine toxicogenetic effects of SAs, which were further confirmed through applying Combination Index (CI) and Independent Action (IA) models. Among the investigated SAs, sulfamethoxazole (SMX) appeared as the individual chemical with relatively high environmental effects and elevated in vitro and in vivo toxicity. Importantly, exposure to the binary mixtures of SAs induced higher developmental toxicity and significantly perturbed the detoxification pathway in zebrafish, compared to that of individual compound exposure. Moreover, the CI and IA models indicated greater synergistic effects of SAs binary mixtures as SMX-SMR, SMX-ST, and SPY-ST on the Acinetobacter sp. Tox2 at Fa = 0.5. Contrarily, IA model predicted the additive, antagonistic and synergistic effects of SAs mixtures on the transcriptional responses of detoxification pathways in zebrafish, implying the different mode of actions (MoAs) for SAs to induce mixture toxicity in vivo. Thus, the nature of toxicological interactions of SAs should be considered while performing their ecological risk assessment.