The impact of endocrine-disrupting chemicals on stem cells: Mechanisms and implications for human health.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

Diagnostic screening of private well water using gas chromatography with high resolution mass spectrometry to support well water management.

In the US, private well users are responsible for their own water quality testing, but local health officials are often uncertain what tests to recommend, particularly for regulated organic chemical contaminants. This study evaluated the utility of suspect and non-target screening (NTS) high resolution mass spectrometry (HRMS) as a tool to identify a wide range of organic chemicals of emerging concern in private well water and to inform well water management decisions. Qualitative NTS, which detects chemicals without providing concentrations, was used to analyze 25 private well water samples from Wake County, North Carolina. Using the NIST 20 mass spectral database (M1), NTS tentatively identified 106 unique organic chemicals across the 25 samples and an average of 11 organic chemicals per sample. At least one USEPA ToxCast chemical was identified in each private well water sample. Private well water users were interviewed prior to and after their sample's NTS results were reported back; four county groundwater managers were interviewed after aggregated results for all 25 water samples were reported back. All but one well user participant chose to participate in the reporting-back post-interview. The 24 private well users found NTS results useful and valued the contextualization of their results using NTS results for other well users and a local municipal water sample. Most private well users (67 %) were surprised by their well water results, especially regarding the number of tentatively identified organic chemicals detected. All the groundwater managers believed the NTS results were useful and could help improve their testing recommendations to private well users. Even with qualitative limitations, NTS results can be an effective and valuable tool to inform the public and governance stakeholders in decisions around groundwater quality management.

Leveraging New Approach Methodologies: Ecotoxicological Modelling of Endocrine Disrupting Chemicals to Danio rerio through Machine Learning and Toxicity Studies.

Emerging endocrine-disrupting chemicals (EDCs) are a diverse group of toxic substances that disrupt the endocrine system. These substances can only be approved after obtaining concrete evidence of their toxicity. New approach methodologies (NAMs) offer information tailored to the intended application while reducing the use of animals. NAMs aim to develop quantitative structure-activity relationship (QSAR) and quantitive-Read-Across structure-activity relationship (q-RASAR) models to predict and categorize the acute toxicity of known and unknown EDCs. The q-RASAR model was constructed and verified using validation metrics (R2 = 0.886 and Q2 = 0.814). The substructure fingerprint was well-fitted for the classification model and the model was validated using 10-fold average accuracy (Q = 86.88%), specificity (Sp = 88.89%), Matthew's correlation curve (MCC = 0.621) and receiver operating characteristics (ROC = 0.828). The dataset of unknown substances revealed that phenolphthalein (Php) exhibited a significant level of toxicity. The docking and simulation study results indicated that the computationally derived important features successfully bound to the target zebrafish sex hormone binding globulin (zfSHBG). The experimental LC50 value of 0.790 mg L-1 was very close to the predicted value of 0.763 mg L-1, which provides high confidence to the developed model.

Parabens, bisphenols, and triclosan in coral polyps, algae, and sediments from sanya, China: Occurrence, profiles, and environmental implications.

Parabens, bisphenols (BPs), and triclosan (TCS) are common environmental phenols widely applied in industrial products, pharmaceuticals, and personal care products. They are endocrine disruptors and pervade the natural environment, causing significant detrimental impacts on ecosystems, including marine habitats. Therefore, in this study, 40 samples comprising coral polyps, algae, and sediments were collected from Sanya, Hainan Province, China, in which the presence and compositional profiles of parabens, BPs, and TCS were examined to identify their fate in the oceans. The results unveiled the ubiquitous occurrence of at least one paraben or bisphenol in all samples, with TCS detected in over 80% of cases. Notably, coral samples contained the most contaminants (median concentration: 9.42 ng/g dry weight-dw), followed by sediment samples (5.95 ng/g dw) and algal samples (3.58 ng/g dw). Attributed to their broadest application, methylparaben (MeP) and propylparaben (PrP) emerged as the primary paraben constituents. MeP displayed the highest median concentration in coral samples (4.42 ng/g dw), probably related to its high-water solubility and the filtration mechanism employed by the coral polyps during seawater intake. Intriguingly, bisphenol P (BPP) superseded bisphenol A (BPA) as the dominant bisphenol, especially in the algal samples, probably owing to the lipophilic character of BPP and the enhanced biodegradability of BPA within aquatic environments. The highest concentration of TCS (3.44 ng/g dw) was found in the sediment samples, associated with its long half-life in the sediments. Furthermore, the correlation between multiple parabens and TCS implies their co-use to augment antimicrobial efficacy. Future research should prioritize the examination of these phenols in diverse marine environmental media. Corresponding toxicological experiments should be conducted to visualize their transport dynamics, degradation byproducts, and toxicity to marine biota to gain insights into the risks they pose to the marine ecosystem.

Persistent endocrine-disrupting chemicals and incident uterine leiomyomata: A mixtures analysis.

BACKGROUND: Uterine leiomyomata (UL; fibroids) are hormone-dependent neoplasms that can cause significant gynecologic morbidity. Studies have documented associations between concentrations of persistent endocrine-disrupting chemicals (EDCs) and UL incidence; however, few have assessed the effects of EDC mixtures on UL. METHODS: In the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study, participants attended study visits at baseline and approximately every 20 months for up to 10 years; at each visit, they completed questionnaires, provided blood samples, and underwent standardized ultrasound examinations. In baseline plasma samples (n = 1155), we quantified concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides using high-resolution mass spectrometry. We selected nine EDCs detected in >60 % of samples (4 PCBs, 4 PBDEs, and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE)) and conducted probit Bayesian kernel machine regression with hierarchical variable selection to estimate effects of the EDC mixture and individual EDCs on UL incidence, adjusting for potential confounders. RESULTS: During 10 years of follow-up, 32 % of participants developed ultrasound-detected UL. The EDC mixture was not appreciably associated with the probit of UL (ß comparing all EDCs at their 75th vs. 50th percentile:= - 0.01, 95 % credible interval [CrI]: -0.11, 0.10). However, individual EDC concentrations were associated with UL in opposing directions: PCB138/158 was positively associated with UL (ß for 25th-to-75th-percentile increase when all other chemicals were set to their 50th percentile = 0.18, 95 % CrI: -0.09, 0.44), whereas PBDE99 and p,p'-DDE were inversely associated with UL (ß = -0.06, 95 % CrI: -0.21, 0.10 and ß = -0.12, 95 % CrI: -0.34, 0.10, respectively). There was little evidence of interaction between EDCs. CONCLUSION: In this prospective ultrasound study, a mixture of persistent EDCs was not appreciably associated with incident UL during 10 years of follow-up, but individual EDCs were associated with UL in opposite directions.

Placenta Extracellular Vesicles: Messengers Connecting Maternal and Fetal Systems.

The placenta operates during gestation as the primary communication organ between the mother and fetus. It is essential for gas, nutrient exchange, and fetal waste transfer. The placenta also produces a wide range of hormones and other factors that influence maternal physiology, including survival and activity of the corpus luteum of the ovary, but the means whereby the placenta shapes fetal development remain less clear, although the fetal brain is thought to be dependent upon the placenta for factors that play roles in its early differentiation and growth, giving rise to the term "placenta-brain axis". Placental hormones transit via the maternal and fetal vasculature, but smaller placental molecules require protection from fetal and maternal metabolism. Such biomolecules include small RNA, mRNA, peptides, lipids, and catecholamines that include serotonin and dopamine. These compounds presumably shuttle to maternal and fetal systems via protective extracellular vesicles (EVs). Placental EVs (pEVs) and their components, in particular miRNA (miRs), are known to play important roles in regulating maternal systems, such as immune, cardiovascular, and reproductive functions. A scant amount is known about how pEVs affect fetal cells and tissues. The composition of pEVs can be influenced by gestational diseases. This review will provide critical insight into the roles of pEVs as the intermediary link between maternal and fetal systems, the impact of maternal pathologies on pEV cargo contents, and how an understanding of biomolecular changes within pEVs in health and disease might be utilized to design early diagnostic and mitigation strategies to prevent gestational diseases and later offspring disorders.

Pharmaceuticals in biota: The impact of wastewater treatment plant effluents on fish in Australia.

Globally, pharmaceuticals and personal care products (PPCPs) are detected in surface waters receiving wastewater, yet their presence in biota, remain largely understudied. To address this, we conducted a study that measured 46 PPCPs in spot water samples and fish caught up- and downstream from wastewater treatment plants (WWTPs) in Victoria, Australia. We sampled 15 sites located along four waterways following a 3-site design: WWTP-discharge('hotspot'), 'upstream'(∼2 km) and 'downstream'(∼2 km). Spot water and fish were also sampled at reference sites >100 km from WWTP discharge (n = 3). Additionally, spot water samples were taken from WWTP effluent outflows (n = 3). From each locality, we analysed 3-12 fish (n = 131 total). In waterways, passive samplers (POCIS; ∼28d, n = 19 PPCPs) were also deployed. Individual fish (axial muscle) and water were analysed with LC-MS-MS. We found that PPCP concentrations in environmental surface water ranged from<0.02-0.97 µg/L. In WWTP effluent, the range was <0.02-1.4 µg/L. Of the 46 PPCPs analysed, 12 were detected in spot water samples and five in fish. In water, the highest concentration detected was for antidepressant venlafaxine (3 µg/L). The most frequently detected PPCPs: venlafaxine (54.9%), metoprolol (41.2%), propranolol (29.4%), carbamazepine (29.4%), caffeine (17.6%) and sulfamethoxazole (17.6%). Out of 131 fish analysed, 35 fish had detectable levels of PPCPs in the muscle tissue. The highest muscle concentrations were: venlafaxine (150 µg/kg, redfin perch), and sertraline (100 µg/kg, eel). Bioaccumulation factors ranged from 104 to 341L/kg for venlafaxine in redfins, 21-1,260L/kg for carbamazepine in redfins and eels, and 367-3,333L/kg for sertraline in eels. Based on our human health risk calculations for venlafaxine, carbamazepine, sertraline, triclosan, and caffeine, consumption of fish does not pose a significant risk to human health. Despite this, most of the detected PPCPs in surface waters exceeded 10 ng/L trigger value, which has led to further investigations by EPA. Our study highlights the need for using multiple lines of evidence for estimating risks of PPCPs.

Healthy lifestyles ameliorate an increased risk of periodontitis associated with polycyclic aromatic hydrocarbons.

The risk of chronic inflammatory diseases has been linked to exposure to polycyclic aromatic hydrocarbons (PAHs). However, limited data are available regarding their impact on periodontitis. This study aims to explore the association between PAHs and periodontitis while also evaluating the potential modifying effects of healthy lifestyles. We included 17,031 participants from the US National Health and Nutrition Examination Survey (NHANES, 2001-2004 and 2009-2014). A meta-analysis-based environment-wide association study (EWAS) was adopted to identify environmental chemicals for the mean probing pocket depth (PPD) and the mean attachment loss (AL). PAHs were further evaluated concerning the cross-sectional association with Mod/Sev periodontitis using multivariable logistic regression models. Moreover, healthy lifestyle scores were estimated to assess their modifying effect on the PAH-periodontitis association. EWAS analysis identified several urinary PAH metabolites as significant risk factors for the mean PPD and AL (false discovery rate <0.05, Q > 0.05). Periodontitis severity was positively associated with eight individual and total PAH concentrations. Stratifying the participants in terms of healthy lifestyle scores did not reveal any association in the healthy group. Moreover, the association weakened in never-smokers and individuals with sufficient physical activity and normal weight. PAH exposure was a risk factor for periodontitis. A healthier lifestyle was observed to offset the risk potentials of PAHs for periodontitis. Smoking cessation, physical activity, and weight loss might be recommended as a healthy lifestyle strategy for ameliorating PAH-related periodontitis.

Inhalation Toxicity Screening of Consumer Products Chemicals using OECD Test Guideline Data-based Machine Learning Models.

This study aimed to screen the inhalation toxicity of chemicals found in consumer products such as air fresheners, fragrances, and anti-fogging agents submitted to K-REACH using machine learning models. We manually curated inhalation toxicity data based on OECD test guideline 403 (Acute inhalation), 412 (Sub-acute inhalation), and 413 (Sub-chronic inhalation) for 1709 chemicals from the OECD eChemPortal database. Machine learning models were trained using ten algorithms, along with four molecular fingerprints (MACCS, Morgan, Topo, RDKit) and molecular descriptors, achieving F1 scores ranging from 51 % to 91 % in test dataset. Leveraging the high-performing models, we conducted a virtual screening of chemicals, initially applying them to data-rich chemicals generally used in occupational settings to determine the prediction uncertainty. Results showed high sensitivity (75 %) but low specificity (23 %), suggesting that our models can contribute to conservative screening of chemicals. Subsequently, we applied the models to consumer product chemicals, identifying 79 as of high concern. Most of the prioritized chemicals lacked GHS classifications related to inhalation toxicity, even though they were predicted to be used in many consumer products. This study highlights a potential regulatory blind spot concerning the inhalation risk of consumer product chemicals while also indicating the potential of artificial intelligence (AI) models to aid in prioritizing chemicals at the screening level.

Pesticide-induced transgenerational alterations of genome-wide DNA methylation patterns in the pancreas of Xenopus tropicalis correlate with metabolic phenotypes.

The unsustainable use of manmade chemicals poses significant threats to biodiversity and human health. Emerging evidence highlights the potential of certain chemicals to cause transgenerational impacts on metabolic health. Here, we investigate male transmitted epigenetic transgenerational effects of the anti-androgenic herbicide linuron in the pancreas of Xenopus tropicalis frogs, and their association with metabolic phenotypes. Reduced representation bisulfite sequencing (RRBS) was used to assess genome-wide DNA methylation patterns in the pancreas of adult male F2 generation ancestrally exposed to environmentally relevant linuron levels (44 ± 4.7 µg/L). We identified 1117 differentially methylated regions (DMRs) distributed across the X. tropicalis genome, revealing potential regulatory mechanisms underlying metabolic disturbances. DMRs were identified in genes crucial for pancreatic function, including calcium signalling (clstn2, cacna1d and cadps2), genes associated with type 2 diabetes (tcf7l2 and adcy5) and a biomarker for pancreatic ductal adenocarcinoma (plec). Correlation analysis revealed associations between DNA methylation levels in these genes and metabolic phenotypes, indicating epigenetic regulation of glucose metabolism. Moreover, differential methylation in genes related to histone modifications suggests alterations in the epigenetic machinery. These findings underscore the long-term consequences of environmental contamination on pancreatic function and raise concerns about the health risks associated with transgenerational effects of pesticides.

Assessment and characterization of solid and hazardous waste from inorganic chemical industry: Potential for energy recovery and environmental sustainability.

Rapid global urbanization and economic growth have significantly increased solid waste volumes, with hazardous waste posing substantial health and environmental risks. Co-processing strategies for industrial solid and hazardous waste as alternative fuels highlight the importance of integrated waste management for energy and material recovery. This study identifies and characterizes solid and hazardous industrial wastes with high calorific values from various industrial processes at Nirma Industries Limited. Nine types of combustible industrial wastes were analyzed: discarded containers (W1), plastic waste (W2), spent ion exchange resins from RO plants (W3), sludge from effluent treatment in soap plants (W4), glycerine foot from soap plants (W5), rock wool puff material (W6), fiber-reinforced plastic waste (W7), spent activated carbon (W8), and spent cartridges from reverse osmosis plants (W9). Physical characterization, proximate and ultimate analysis, heavy metal concentration evaluation, and thermogravimetric analysis were conducted to assess their properties, revealing high calorific values exceeding 2500 kcal/kg. Notably, W1 and W2 exhibited the highest calorific values (∼10,870 kcal/kg), followed by W6 and W8 (∼6000 kcal/kg) and W9 (∼8727 kcal/kg). Safe heavy metal levels are safe, and high calorific values support the prospects of energy recovery and economic and environmental benefits, reducing landfill reliance and enhancing sustainable waste management.

Cytotoxicity by endocrine disruptors through effects on ER Ca2+ transporters, aberrations in Ca2+ signalling pathways and ER stress.

Concerns regarding man-made organic chemicals pervading our ecosystem and having adverse and detrimental effects upon organisms, including man, have now been studied for several decades. Since the 1970s, some environmental pollutants were identified as having endocrine disrupting affects. These endocrine disrupting chemicals (EDC) were initially shown to have estrogenic or anti-estrogenic properties and some were also shown to bind to a variety of hormone receptors. However, since the 1990s it has also been identified that many of these EDC additionally, have the ability of causing abnormal alterations in Ca2+ signalling pathways (also commonly involved in hormone signalling), leading to exaggerated elevations in cytosolic [Ca2+] levels, that is known to cause activation of a number of cell death pathways. The major emphasis of this review is to present a personal perspective of the evidence for some types of EDC, specifically alkylphenols and brominated flame retardants (BFRs), causing direct effects on Ca2+ transporters (mainly the SERCA Ca2+ ATPases), culminating in acute cytotoxicity and cell death. Evidence is also presented to indicate that this Ca2+ATPase inhibition, which leads to abnormally elevated cytosolic [Ca2+], as well as a decreased luminal ER [Ca2+], which triggers the ER stress response, are both involved in acute cytotoxicity.

Differences in impact on disease or lung injury depending on the physicochemical characteristics of harmful chemicals in the PAH model.

The number of individuals with underlying medical conditions has been increasing steadily. These individuals are relatively vulnerable to harmful external factors. But it has not been proven that the effects of hazardous chemicals may differ depending on their physicochemical properties. This study determines the toxic effects of two chemicals with high indoor exposure risk and different physicochemical properties on an underlying disease model. A pulmonary arterial hypertension (PAH) model was constructed by a single subcutaneous injection of monocrotaline (MCT; 60 mg/kg) into Sprague-Dawley rats. After three weeks, formaldehyde (FA; 2.5 mg/kg) and polyhexamethylene guanidine (PHMG; 0.05 mg/kg) were administered once via intratracheal instillation, and rats were necropsied one week later. Exposure to FA and PHMG affected organ weight and the Fulton and toxicity indices in rats induced with PAH. FA promoted bronchial injury and aggravated PAH, while PHMG only induced alveolar injury. Additionally, the differentially expressed genes were altered following exposure to FA and PHMG, as were the associated diseases (cardiovascular disease and pulmonary fibrosis, respectively). In conclusion, inhaled chemicals with different physicochemical properties can cause damage to organs, such as the lungs and heart, and can aggravate underlying diseases. This study elucidates indoor inhaled exposure-induced toxicities and alerts patients with pre-existing diseases to the harmful chemicals.

Trend of soil salinization in Africa and implications for agro-chemical use in semi-arid croplands.

Soil salinization is a gradual degradation process that begins as a minor problem and grows to become a significant economic loss if no control action is taken. It progressively alters the soil environment which eventually negatively affects plants and organism that were not originally adapted for saline conditions. Soil salinization arises from diverse sources such as side-effects of long-term use of agro-chemicals, saline parent rocks, periodic inundation of soil with saline water, etc. In Africa, soil salinization has not been adequately documented particularly in the croplands. The objective of this study was to identify trends of cropland salinization in Africa and how its relationship with long-term land use practices affected the soil environment. The study analysed soil salinization between 1965 and 2020 using measured electrical conductivity (EC), spatial modelling with environmental covariates, and national statistics on cropland expansion and application of mineral fertilizers, herbicides, and pesticides. The results showed increasing trends of EC in Africa due to climatic and land use drivers. Increasing trends of EC, which evidenced salinization, was found in 31 million hectares of topsoils and 18 million hectares of subsoils. About 2 million hectares of croplands were depicted with salinization and >25 million hectares at the risk of salinization in the arid and semi-arid areas. The study also found statistical relationships between semi-arid cropland salinization and trends of agro-chemical use and cropland sizes. There were significant (p < 0.001) positive correlations between semi-arid cropland salinization and trends of cropland expansion and applied nitrogenous fertilizers. It found that increasing trend of applied mineral nitrogenous fertilizers could double the odds of salinization in semi-arid croplands while cropland expansion could increase the odds of semi-arid cropland salinization by >10 %. These findings present ground-breaking baseline information for future works on sustainable land-use practices that can control cropland soil salinization in Africa.

The effect of endocrine-disrupting chemicals in follicular fluid: The insights from oocyte to fertilization.

Endocrine-disrupting chemicals (EDCs) exhibited the detriment in female reproductive health. Our objective was to investigate the individual and mixture effects of EDCs present in follicular fluid, the environment in which oocytes grow and develop, on early reproductive outcomes. We recruited 188 women seeking reproduction examination from the Study of Exposure and Reproductive Health (SEARCH) cohort between December 2020 and November 2021. We assessed the concentrations of 7 categories of 64 EDCs in follicular fluid, and measured early reproductive outcomes, including retrieved oocytes, mature oocytes, normal fertilized oocytes, and high-quality embryos. In this study Monomethyl phthalate (MMP) (2.17 ng/ml) were the compounds found in the highest median concentrations in follicular fluid. After adjusting for multiple testing, multivariate regression showed that multiple EDCs were significantly negatively associated with early assisted reproduction outcomes. For example, MMP showed a significant negative correlation with the number of high quality embryos (ß: -0.1, 95 % CI: -0.15, -0.04). Specifically, eight types of EDCs were significantly negatively associated with four early assisted reproductive outcomes (ß range: -0.2 âˆ¼ -0.03). In the mixed exposure model, we found that mixtures of EDC were significantly negatively correlated with all four outcomes. In the quantile g-computation (QGCOMP) model, for each interquartile range increase in the concentration of EDC mixtures, the number of oocytes retrieved, mature oocytes, normally fertilized oocytes, and high-quality embryos decreased by 0.46, 0.52, 0.77, and 1.2, respectively. Moreover, we identified that phthalates (PAEs) predominantly contributed to the negative effects. Future research should validate our findings.

Human skin absorption of three plasticizers: Diisononyl-1,2-cyclohexanedicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), and di(2-ethylhexyl) adipate (DEHA).

Alternative plasticizers such as diisononyl-1,2-cyclohexanedicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), and di(2-ethylhexyl) adipate (DEHA) are progressively replacing phthalates in many consumer and professional products because of adverse effects on reproduction associated with some phthalates. Human exposures to these phthalate substitutes can occur through ingestion, skin absorption and inhalation. Skin uptake can lead to greater concentration at the target organs compared to ingestion because the skin exposure route bypasses the first-pass effect. Skin absorption studies are almost absent for these alternative plasticizers. We therefore wanted first, to characterize skin absorption of a mixture containing DINCH, DEHA and DEHTP in vitro using a flow-through diffusion cell system with ex vivo human skin, quantifying their respective monoester metabolites (mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH), mono-2-ethylhexyl adipate (MEHA), mono-2-ethylhexyl terephthalate (MEHTP), respectively); second, to validate these results by exposing five human volunteers to this mixture on their forearm and quantifying the corresponding urinary metabolites (including the monoesters and their oxidation products). Our study showed that two of these alternative plasticizers, DEHTP and DINCH, did not permeate skin showing as quantifiable metabolite levels in vitro and only traces of DEHA were quantified as its monoester metabolite, MEHA. Permeation coefficient (Kp) 0.06 and 55.8*10-7 cm/h for neat and emulsified DEHA, respectively, while the permeation rate (J) remained low for both (0.005 and 0.001 µg/cm2/h, respectively). Participants exposed to a mixture of these three plasticizers did not have noteworthy urinary concentrations of their respective metabolites after 24 hours post-application. However, the alternative plasticizer mixture was completely absorbed after six hours post-application on the forearms of the human volunteers, and the urinary elimination curves showed a slight increase after 24 hours post-application. Further studies on skin absorption of these substances should follow the urinary elimination kinetics of these metabolites more than 24 hours post-application. We also recommend quantifying the parent compounds in the in vitro diffusion experiments.

Do dietary exposures to multi-class endocrine disrupting chemicals translate into health risks for Gangetic dolphins? An assessment and way forward.

Dietary exposure risks of 39 multi-class Endocrine Disrupting Chemicals (EDCs) to the threatened Gangetic dolphins (Platanista gangetica) were investigated in a conservation-priority segment of the Ganga River. Elevated EDCs bioaccumulation was observed across prey fish species, with di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) significantly contributing to the EDC burden. The concentrations of persistent organochlorines in prey revealed a shift from dioxin-like polychlorinated biphenyls (PCBs) to non-dioxin-like PCBs. The prevalence of regulated p,p' DDT (Dichlorodiphenyltrichloroethane) and γ-HCH (Lindane) residues suggests regional non-compliance with regulatory standards. The concentration of some EDCs is dependent on the habitat, foraging behavior, trophic level and fish growth. The potential drivers of EDCs contamination in catchment includes agriculture, vehicular emissions, poor solid waste management, textile industry, and high tourist influx. Risk quotients (RQs) based on toxicity reference value were generally below 1, while the RQ derived from the reference dose highlighted a high risk to Gangetic dolphins from DEHP, DDT, DnBP, arsenic, PCBs, mercury, and cadmium, emphasizing the need for their prioritization within monitoring programs. The study also proposes a monitoring framework to provide guidance on monitoring and assessment of chemical contamination in Gangetic dolphin and habitats.

Reduced ovarian cholesterol and steroid biosynthesis along with increased inflammation are associated with high DEHP metabolite levels in human ovarian follicular fluids.

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is known to have endocrine-disrupting properties mediated by its many metabolites that form upon exposure in biological systems. In a previous study, we reported an inverse association between DEHP metabolites in the human ovarian follicular fluid (FF) and the responsiveness of the follicles to controlled ovarian stimulation during in vitro fertilization (IVF) treatments. Here, we explored this association further through molecular analysis of the ovarian FF samples. Ninety-six IVF patients from Swedish (N = 48) and Estonian (N = 48) infertility clinics were selected from the previous cohort (N = 333) based on the molar sum of DEHP metabolites in their FF samples to arrive at "high" (mean 7.7 ± SD 2.3 nM, N = 48) and "low" (0.8 ± 0.4 nM, N = 48) exposure groups. Extracellular miRNA levels and concentrations of 15 steroid hormones were measured across FF samples. In addition, FF somatic cells, available for the Estonian patients, were used for RNA sequencing. Differential expression (DE) and interactions between miRNA and mRNA networks revealed that the expression levels of genes in the cholesterol biosynthesis and steroidogenesis pathways were significantly decreased in the high compared to the low DEHP group. In addition, the DE miRNAs were predicted to target key enzymes within these pathways (FDR < 0.05). A decreased 17-OH-progesterone to progesterone ratio was observed in the FF of the high DEHP group (p < 0.05). Additionally, the expression levels of genes associated with inflammatory processes were elevated in the FF somatic cells, and a computational cell-type deconvolution analysis suggested an increased immune cell infiltration into the high DEHP follicles (p < 0.05). In conclusion, elevated DEHP levels in FF were associated with a significantly altered follicular milieu within human ovaries, involving a pro-inflammatory environment and reduced cholesterol metabolism, including steroid synthesis. These results contribute to our understanding of the molecular mechanisms of female reprotoxic effects of DEHP.

[Microbial production of food compounds with carbon dioxide and derived low-carbon molecules as substrates].

The construction and optimization of microbial cell factories are crucial steps and key technologies in achieving green biomanufacturing. As concern has been aroused regarding the excessive carbon dioxide (CO2) emissions and food security, a new and promising research field, microbial conversion of CO2 into food compounds, has emerged. The research in this field not only holds significant implications for achieving the carbon peaking and carbon neutrality goals but also plays a role in maintaining food security. This paper provides a comprehensive review and outlook of the research on utilizing CO2 and its derived low-carbon chemicals for the production of food compounds, focusing on the production of glucose, sugar derivatives, and single-cell proteins and the development of artificial CO2 fixation pathways.

High value-added chemical production through anaerobic codigestion of corn straw with a microbial consortium, cow manure and cow digestion solution.

OBJECTIVES: This study investigated the codigestion of corn straw (CS) with cow manure (CM), cow digestion solution (CD), and a strain consortium (SC) for enhanced volatile fatty acid (VFA) production. The aims of this study were to develop a sustainable technique to increase VFA yields, examine how combining microbial reagents with CS affects VFA production by functional microorganisms, and assess the feasibility of improving microbial diversity through codigestion. METHODS: Batch experiments evaluated VFA production dynamics and microbial community changes with different combinations of CS substrates with CM, CD, and SC. Analytical methods included measuring VFAs by GC, ammonia and chemical oxygen demand (COD) by standard methods and microbial community analysis by 16S rRNA gene sequencing. RESULTS: Codigesting CS with the strain consortium yielded initial VFA concentrations ranging from 0.6 to 1.0 g/L, which were greater than those of the other combinations (0.05-0.3 g/L). Including CM, and CD further increased VFA production to 1.0-2.0 g/L, with the highest value of 2.0 g/L occurring when all four substrates were codigested. Significant ammonium reduction (194-241 mg/L to 29-37 mg/L) and COD reduction (3310-5250 mg/L to 730-1210 mg/L) were observed. Codigestion with CM and CD had greater Shannon diversity indices (3.19-3.24) than did codigestion with the other consortia (2.26). Bacillota dominated (96.5-99.6 %), with Clostridiales playing key roles in organic matter breakdown. CONCLUSIONS: This study demonstrated the feasibility of improving VFA yields and harnessing microbial diversity through anaerobic codigestion of lignocellulosic and animal waste streams. Codigestion substantially enhanced VFA production, which was dominated by butyrate, reduced ammonium and COD, and enriched fiber-degrading and fermentative bacteria. These findings can help optimize codigestion for sustainable waste management and high-value chemical production.