Health risks associated with phthalate esters depend on exposure level, individual sensitivities, and other contributing factors.

This study employed artificial intelligence algorithms while applying data mining techniques to identify correlations between phthalate esters [di(2-ethylhexyl) phthalate, DEHP], lifestyle factors, and disease outcomes.

We conducted exploratory analysis using demographic and laboratory data collected from the Taiwan Biobank. The study developed a prediction model to examine the relationship between phthalate esters and the risk of developing certain diseases based on various artificial intelligence algorithms, including logistic regression, artificial neural networks, and Bayesian networks.

The results indicate that phthalate esters exhibited a greater impact on bone and joint issues than heart problems. We observed that DEHP metabolites, such as mono(2-carboxymethylhexyl) phthalate, mono-n-butyl phthalate, and monoethylphthalate, leave higher residue in females than in males, with statistically significant differences. Monoethylphthalate levels were lower in individuals who exercised regularly than those who did not, indicating statistically significant differences.

This study's findings can serve as a valuable reference for clinical nursing assessments regarding diseases related to osteoporosis, arthritis, and musculoskeletal pain. Medical professionals can enhance care quality by considering factors beyond patients' essential physical assessment items.Trial Registration: This study was registered under NCT05892029 on May 5, 2023, retrospectively.

Endocrine-disrupting compounds (EDCs) include ubiquitous and persistent environmental contaminants that interfere with the endocrine system's functions. Many of these compounds are used as acaricides, fungicides, herbicides, and insecticides in agricultural fields worldwide. Considering the serious implications of exposure to EDCs in the first months of life and the few works on pesticide residues in infant formulas, the present research focused exclusively on endocrine-disrupting pesticides in infant formulas intended for babies below 1 year old available in the Brazilian market. An accurate, sensitive, and selective gas chromatography-mass spectrometry (GC-MS) method was successfully validated, and then, applied to infant formula samples. The limits of detection and quantification were low enough to meet the maximum residue level (MRL) of 10.0 μg/kg established for infant formula. Recoveries varied from 86.3 to 119.8 % and precision values, under repeatability and within-laboratory reproducibility, were ≤ 19.7 %. Another unique feature of the study was the detection and strategies to remove a potential matrix-interfering compound, which shared the same ions monitored for malathion in GC-MS analysis, thus preventing false positives. Among the 60 infant formula samples analysed, dimethoate, an organophosphate insecticide, was detected in five samples, with one soy-based infant formula exceeding the MRL. Based on a deterministic approach, the estimated daily intakes were within the acceptable daily intake (ADI) values and below the acute reference dose (ARfD), indicating no major health concerns.

The evidence linking endocrine-disrupting chemicals (EDCs) to anxiety in adults is currently sparse, while the effects of various categories of EDCs on the risk of anxiety, along with the underlying mechanisms, remain poorly understood.

Four EDCs-polycyclic aromatic hydrocarbons (PAHs), phenols, pesticides, and phthalates-were quantified in 3927 adults from the National Health and Nutrition Examination Survey (NHANES) (2007-2012). We employed five statistical models to assess the individual and joint impacts of EDCs on anxiety risk. Causal mediation analysis frameworks were constructed to explore the mediating role of oxidative stress (OS). We identified potential biological mechanisms linking analytes to outcomes using the Comparative Toxicogenomics Database (CTD), MalaCards, and Open Targets, followed by enrichment analyses with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG).

In individual chemical analyses, nine PAHs were significantly associated with increased anxiety risk (P < 0.05). Mixed-effects analyses showed that co-exposure to EDCs positively correlated with anxiety, primarily due to 2-hydroxyfluorene (2-FLU) and 3-hydroxyfluorene (3-FLU). Bilirubin mediated 5.42 % of the anxiety linked to the PAH mixture. The inflammatory genes TNF and IL-6 were identified as key biological stressors, with enrichment analysis indicating significant involvement in reactive oxygen species metabolic processes and the AGE-RAGE signaling pathway.

This study highlights the association between EDCs and anxiety in a representative U.S. population, indicating that exposure to PAHs may elevate anxiety risk through OS, inflammation, and the AGE-RAGE signaling pathway. Further longitudinal study were merited to support our results.

Bisphenol A (BPA) poses longstanding environmental concerns due to its widespread presence and recognized toxicity; however, its multigenerational ecotoxicity, in aquatic models such as water fleas, remains incompletely understood. This study examined the impact of sublethal BPA exposure on Daphnia magna across six generations, tracking changes in both life-history and population traits. Over the first five generations, BPA exposure produced minor and inconsistent effects on age at first oogenesis, age at first offspring production, growth rate, and fertility. The sixth generation exhibited prolonged oogenesis, delayed first offspring production, reduced body size, and decreased fertility, indicating delayed adverse effects. These multigenerational effects did not significantly alter population size or dynamics. Furthermore, BPA exposure did not affect feeding behavior in D. magna over six days, suggesting that food consumption-mediated mechanisms were unlikely a contributing factor. Our findings reveal BPA's delayed adverse effects on D. magna fitness, underscoring potential vulnerabilities for D. magna and other species under additional environmental stressors. These results support literature indicating that endocrine-disrupting chemicals can cause delayed and cumulative adverse effects on zooplankton descendants. Broadening multigenerational research to include a wider range of species, alongside sub-organismal analyses, is crucial to advancing regulatory frameworks and understanding underlying mechanisms.

The large-scale industrial production characteristic of the last century led to an increase in man-made compounds and mobilization of natural compounds, many of which can accumulate in the environment and organisms due to their bioaccumulation and biomagnification properties. The endocrine system is especially vulnerable to these compounds that are known as endocrine disruptor chemicals (EDCs). Thyroid hormones (THs) are essential for normal development and growth, besides being the main regulators of basal metabolic rate. Thus, compounds able to affect THs synthesis, transport, and action could produce important deleterious effects, impacting the development of metabolic and endocrine diseases. Herein, we will review the main effects of EDCs on the thyroid axis, with special emphasis on the widely used substances bisphenol A (BPA), employed in the synthesis of polycarbonate plastics and epoxy resins; tributyltin (TBT), an organotin chemical substance widely used in several agro-industrial applications; and lead (Pb), a ubiquitous environmental and occupational polluting heavy metal. Exposure to these EDCs occurs mainly from the ingestion of contaminated food and beverages. Furthermore, there are few epidemiological studies evaluating human risk, and experimental studies employ different exposure models, making it difficult to integrate results. However, even low doses of these EDCs warn of thyrotoxicity. Since THs homeostasis is essential for health and humans are increasingly being exposed to EDCs, it is important to clarify which substances might act as thyroid hormone system disrupting chemicals and how they act in order to try to overcome their deleterious effects and limit the exposure to these compounds.

The pervasive use of dicofol in agricultural settings has been linked to biomolecular perturbations, posing significant threats to environmental sustainability and human health. Therefore, it is crucial to investigate the interactions between dicofol and biomacromolecules, such as proteins. This study employed a range of molecular modeling approaches and spectroscopic techniques to examine the binding interaction between dicofol and lysozyme to elucidate the underlying mechanisms of these toxic effects. Molecular docking studies identified the most optimal binding site for dicofol on the lysozyme structure, highlighting the precise region within the protein where dicofol binds most effectively. Molecular dynamic simulations showed that the dicofol-lysozyme system was stable throughout the entire simulation period. UV-vis absorption and fluorescence emission studies confirmed that dicofol interacts with lysozyme to form a complex. FT-IR analysis revealed that this interaction alters lysozyme's conformation, decreasing alpha-helical content while increasing β-sheet content. Furthermore, a direct relationship was observed between dicofol concentration and lysozyme's activity and stability, with higher dicofol levels causing a notable decline in both factors. In conclusion, this research deepens our understanding of the specific interactions between dicofol and lysozyme while also highlighting the importance of studying such interactions to evaluate the environmental and health risks linked to pesticide usage.

Chemicals in personal care and consumer products are suspected to disrupt endocrine function and affect reproductive health. However, the link between mixed exposure and long-term amenorrhea is not well understood. This study analyzed data from 684 women (2013-2018 National Health and Nutrition Examination Survey) to assess exposure to eight polyfluorinated alkyl substances (PFASs), 15 phthalates (PAEs), six phenols, and four parabens. Various statistical models for robustness tests and mediation analysis were used to explore associations with long-term amenorrhea and the role of serum globulin. Biological mechanisms were identified through an integrated strategy involving target analysis of key chemicals and long-term amenorrhea intersections, pathway analysis, and target validation. Results showed that women with long-term amenorrhea had higher exposure levels of Perfluorodecanoic acid, Perfluorohexane sulfonic acid (PFHxS), Perfluorononanoic acid, n-perfluorooctanoic acid (n_PFOA), n-perfluorooctane sulfonic acid, and Perfluoromethylheptane sulfonic acid isomers. Logistic regression with different adjustments consistently found significant associations between elevated PFAS concentrations and increased long-term amenorrhea risk, confirmed by Partial Least Squares Discriminant Analysis. Mediation analysis revealed that serum globulin partially mediated the relationship between PFAS exposure and long-term amenorrhea. Network and target analysis suggested that PFHxS and n_PFOA may interact with Signal Transducer and Activator of Transcription 3 (STAT3). This study highlights significant associations between PFAS exposure, particularly PFHxS and n_PFOA, and long-term amenorrhea, with serum globulin and STAT3 serving as mediators in the underlying mechanisms.

This study investigated the relationship between exposure to endocrine-disrupting chemicals (EDCs), specifically phthalates, bisphenol A, bisphenol F, and bisphenol S, and the severity of attention-deficit/hyperactivity disorder (ADHD) symptoms using neuropsychological tests in children diagnosed with ADHD.

This study included 67 medication-naïve children with ADHD aged 6-16 years. The urinary concentrations of EDCs were measured, and ADHD symptom severity was evaluated using neuropsychological tests and clinical symptom scale measurements. The Jonckheere-Terpstra test, Pearson and Spearman correlation analyses, linear regression models, and multiple regression models were used to examine the relationship between EDC exposure and ADHD symptoms.

A significant correlation was observed between urinary phthalate metabolite concentrations and commission error T-scores in the visual Advanced Test of Attention test. No significant associations were found with other neuropsychological indicators or bisphenol levels.

Phthalate exposure affects impulsivity in children with ADHD, which is consistent with the results of previous studies that used parental surveys. However, bisphenols are not clearly associated with ADHD symptoms, which is consistent with the results of previous studies.

With the rapid progression of industrialization, the application and release of endocrine disruptors (EDCs), including bisphenol A (BPA), octylphenol and nonylphenol have significantly increased, presenting substantial health hazards. Conventional analytical techniques, such as high-performance liquid chromatography and gas chromatography-mass spectrometry, are highly sophisticated but suffer from complex procedures and high costs. To overcome these limitations, this study introduces an innovative spectral methodology for the simultaneous detection of multiple aquatic multicomponent EDCs. By leveraging chemical machine vision, specifically with convolutional neural network (CNN) models, we employed a long-path holographic spectrometer for rapid, cost-effective identification of BPA, 4-tert-octylphenol, and 4-nonylphenol in aqueous samples. The CNN, refined with the ResNet-50 architecture, demonstrated superior predictive performance, achieving detection limits as low as 3.34, 3.71 and 4.36 μg/L, respectively. The sensitivity and quantification capability of our approach were confirmed through the analysis of spectral image Euclidean distances, while its universality and resistance properties were validated by assessments of environmental samples. This technology offers significantly advantages over conventional techniques in terms of efficiency and cost, offering a novel solution for EDC monitoring in aquatic environments. The implications of this research extend beyond improved detection speed and cost reduction, presenting new methodologies for analyzing complex chemical systems and contributing to environmental protection and public health.

Endocrine disrupting chemicals (EDCs) can cross the placenta and thereby expose the fetus, which may lead to developmental consequences. It is still unclear which chemicals are of concern regarding neurodevelopment and specifically behaviour, when being exposed to a mixture.

The objective is to determine associations between prenatal exposure to EDCs and behavioural difficulties. Furthermore, we investigated sex-specific associations and determined chemicals of concern in significant regressions.

Associations between prenatal exposure to EDCs (both as single compounds and their mixtures) and behavioural outcomes using the Strengths and Difficulties Questionnaire (SDQ) were estimated in 607 mother-child pairs in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study. Levels for chemical compounds were measured in either urine or serum (median of 10 weeks of gestation). Associations were estimated for the total SDQ score (quasipoisson regression) and a 90th percentile cut-off (logistic regression). Exposure for EDC mixtures (phenols, phthalates, PFAS and persistent chlorinated) was studied using weighted quantile sum (WQS) regression with deciles and with and without repeated holdout validation techniques. The models were adjusted for selected covariates.

The odds for behavioural difficulties increased in girls with higher chemical exposures (OR 1.77, 95% CI 1.67, 1.87) using the full sample and borderline for the validation set (OR 1.31, 95% CI 0.93, 1.85) with 94/100 positive betas in the 100 repeated holdout validations. Chemicals of concern for girls are mostly short-lived chemicals and more specifically plasticizers. No pattern of significant associations was detected for boys.

There is an indication of increased behavioural difficulties for girls in the SELMA population with higher exposure to mixtures of EDCs. Using the repeated holdout validation techniques, the inference is more stable, reproducible and generalisable. Prenatal exposure to mixtures of environmental chemicals should be considered when assessing the safety of chemicals.

Growing evidence points towards a "mixture effect" where different environmental chemicals might act jointly where individual compounds may be below a level of concern, but the combination may have an effect on human health. We are constantly exposed to a complicated mixture pattern that is individual for every person as this mixture depends on personal choices of lifestyle, diet and housing to name a few. Our study suggests that prenatal exposure to EDCs might adversely affect the behaviour of children and especially girls. Hence, risk assessment needs to improve and sex-specific mechanisms should be included in assessments.

The increasing use of industrial chemicals has raised concerns regarding exposure to endocrine-disrupting chemicals (EDCs), which interfere with developmental, reproductive and metabolic processes. Of particular concern is their interaction with adipose tissue, a vital component of the endocrine system regulating metabolic and hormonal functions. The SGBS (Simpson Golabi Behmel Syndrome) cell line, a well-established human-relevant model for adipocyte research, closely mimics native adipocytes' properties. It responds to hormonal stimuli, undergoes adipogenesis and has been successfully used to study the impact of EDCs on adipose biology. In this study, we screened human exposure-relevant doses of various EDCs on the SGBS cell line to investigate their effects on viability, lipid accumulation and adipogenesis-related protein expression. Submicromolar doses were generally well tolerated; however, at higher doses, EDCs compromised cell viability, with cadmium chloride (CdCl2) showing the most pronounced effects. Intracellular lipid levels remained unaffected by EDCs, except for tributyltin (TBT), used as a positive control, which induced a significant increase. Analysis of adipogenesis-related protein expression revealed several effects, including downregulation of fatty acid-binding protein 4 (FABP4) by dibutyl phthalate, upregulation by CdCl2 and downregulation of perilipin 1 and FABP4 by perfluorooctanoic acid. Additionally, TBT induced dose-dependent upregulation of C/EBPα, perilipin 1 and FABP4 protein expression. These findings underscore the importance of employing appropriate models to study EDC-adipocyte interactions. Conclusions from this research could guide strategies to reduce the negative impacts of EDC exposure on adipose tissue.

The human body is regularly exposed to simple catechols and small phenols originating from our diet or as a consequence of exposure to various industrial products. Several biological properties have been associated with these compounds such as antioxidant, anti-inflammatory, or antiplatelet activity. Less explored is their potential impact on the endocrine system, in particular through interaction with the alpha isoform of the estrogen receptor (ERα). In this study, human breast cancer cell line MCF-7/S0.5 was employed to investigate the effects on ERα of 22 closely chemically related compounds (15 catechols and 7 phenols and their methoxy derivatives), to which humans are widely exposed. ERα targets genes ESR1 (ERα) and TFF1, both on mRNA and protein level, were chosen to study the effect of the tested compounds on the mentioned receptor. A total of 7 compounds seemed to impact mRNA and protein expression similarly to estradiol (E2). The direct interaction of the most active compounds with the ERα ligand binding domain (LBD) was further tested in cell-free experiments using the recombinant form of the LBD, and 4-chloropyrocatechol was shown to behave like E2 with about 1/3 of the potency of E2. Our results provide evidence that some of these compounds can be considered potential endocrine disruptors interacting with ERα.

Retinoic acid receptors (RARs) are known as crucial endocrine receptors that could mediate a broad diversity of biological processes. However, the data on endocrine disrupting effects of emerging chemicals by targeting RAR (ant)agonism are far from sufficient. Herein, we investigated the RARα agonistic or antagonistic activities for 75 emerging chemicals of concern, and explored their interactions with this receptor. A recombinant two-hybrid yeast assay was used to examine the RARα activities of the test chemicals, wherein 7 showed effects of RARα agonism and 54 exerted potentials of RARα antagonism. The representative chemicals with RARα agonistic activities, i.e. 4-hydroxylphenol (4-HP) and bisphenol AF (BPAF), significantly increased the mRNA levels of CRABP2 and CYP26A1, while 4 select chemicals with RARα antagonistic potentials, including bisphenol A (BPA), tetrabromobisphenol A (TBBPA), 4-tert-octylphenol (4-t-OP), and 4-n-nonylphenol (4-n-NP), conversely decreased the transcriptional levels of the test genes. The in silico molecular docking analysis using 3 different approaches further confirmed the substantial binding between the chemicals with RARα activities and this nuclear receptor protein. This work highlights the promising strategy for screening endocrine-disrupting effects of emerging chemicals of concern by targeting RARα (ant)agonism.

Chemical risk assessments typically focus on single substances, often overlooking real-world co-exposures to chemical mixtures. Mixture toxicology studies using representative mixtures can reveal potential chemical interactions, but these do not account for the unique chemical profiles that occur in the blood of diverse individuals. Here we used the H295R steroidogenesis assay to screen personalized mixtures of 24 persistent organic pollutants (POPs) for cytotoxicity and endocrine disruption. Each mixture was reconstructed at a human exposure relevant concentration (1×), as well as at 10- and 100-fold higher concentration (10×, 100×) by acoustic liquid handling based on measured blood concentrations in a Swedish cohort. Among the twelve mixtures tested, nine mixtures decreased the cell viability by 4-18%, primarily at the highest concentration. While the median and maximum mixtures based on the whole study population induced no measurable effects on steroidogenesis at any concentration, the personalized mixture from an individual with the lowest total POPs concentration was the only mixture that affected estradiol synthesis (35% increase at the 100× concentration). Mixtures reconstructed from blood levels of three different individuals stimulated testosterone synthesis at the 1× (11-15%) and 10× concentrations (12-16%), but not at the 100× concentration. This proof-of-principle personalized toxicity study illustrates that population-based representative chemical mixtures may not adequately account for the toxicological risks posed to individuals. It highlights the importance of testing a range of real-world mixtures at relevant concentrations to explore potential interactions and non-monotonic effects. Further toxicological studies of personalized contaminant mixtures could improve chemical risk assessment and advance the understanding of human health, as chemical exposome data become increasingly available.

Active ingredients of pesticides or biocides and industrial chemicals can negatively affect environmental organisms, potentially endangering populations and ecosystems. European legislation mandates that chemical manufacturers provide data for the environmental risk assessment of substances to obtain registration. Endocrine disruptors, substances that interfere with the hormone system, are not granted marketing authorization due to their adverse effects. Current methods for identifying disruptors targeting the thyroid hormone system are costly and require many amphibians. Consequently, alternative methods compliant with the 3R principle (replacement, reduction, refinement) are essential to prioritize risk assessment using reliable biomarkers at non-protected life stages. Our study focused on detecting robust biomarkers for thyroid-disrupting mechanisms of action (MoA) by analyzing molecular signatures in zebrafish embryos induced by deiodinase inhibitor iopanoic acid and thyroid peroxidase inhibitor methimazole. We exposed freshly fertilized zebrafish eggs to these compounds, measuring lethality, hatching rate, swim bladder size and transcriptomic responses. Both compounds significantly reduced swim bladder size, aligning with prior findings. Transcriptome analysis revealed specific molecular fingerprints consistent with the MoA under investigation. This analysis confirmed regulation directions seen in other studies involving thyroid disruptors and allowed us to identify genes like tg, scl2a11b, guca1d, cthrc1a, si:ch211-226h7.5, soul5, nnt2, cox6a2 and mep1a as biomarker genes for thyroid disrupting MoA in zebrafish embryos as per OECD test guideline 236. Future screening methods based on our findings will enable precise identification of thyroid-related activity in chemicals, promoting the development of environmentally safer substances. Additionally, these biomarkers could potentially be incorporated into legally mandated chronic toxicity tests in fish, potentially replacing amphibian tests for thyroid disruption screening in the future.

This comprehensive review examines the complex interplay between endocrine disrupting chemicals (EDCs) and the development of testicular germ cell tumors (TGCTs). Despite the high cure rates of TGCTs, challenges in diagnosis and treatment remain, necessitating a deeper understanding of the etiology of the disease. Here, we emphasize current knowledge on the role of EDCs as potential risk factors for TGCTs, focusing on pesticides and perfluorinated and polyfluoroalkyl substances (PFAs/PFCs). Evidence suggests that EDCs disrupt endocrine pathways and induce epigenetic changes that contribute to the development of TGCTs. However, the direct link between EDCs and TGCTs remains elusive and requires further investigation of the molecular mechanisms. We also highlighted the importance of studying nuclear receptors as potential targets for understanding TGCT etiology. In addition, recent evidence implicates PFAs/PFCs in TGCT incidence, highlighting the need for further research into their impact on human health. Overall, this review provides valuable insights into the potential role of EDCs in TGCT development and suggests avenues for future research, while also highlighting how understanding their influence may pave the way for novel therapeutic approaches to improve disease management.

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.

Photocatalytic degradation is a highly efficient technique for eliminating organic pollutants such as antibiotics, organic dyes, toluene, nitrobenzene, cyclohexane, and refinery oil from the environment. The effects of operating conditions, concentrations of contaminants and catalysts, and their impact on the rate of deterioration are the key focuses of this review. This method utilizes light-activated semiconductor catalysts to generate reactive oxygen species that break down contaminants. Modified photocatalysts, such as metal oxides, doped metal oxides, and composite materials, enhance the effectiveness of photocatalytic degradation by improving light absorption and charge separation. Furthermore, operational conditions such as pH, temperature, and light intensity also play a crucial role in enhancing the degradation process. The results indicated that both high pollutant and catalyst concentrations improve the degradation rate up to a threshold, beyond which no significant benefits are observed. The optimal operational conditions were found to significantly enhance photocatalytic efficiency, with a marked increase in degradation rates under ideal settings. Antibiotics and organic dyes generally follow intricate degradation pathways, resulting in the breakdown of these substances into smaller, less detrimental compounds. On the other hand, hydrocarbons such as toluene and cyclohexane, along with nitrobenzene, may necessitate many stages to achieve complete mineralization. Several factors that affect the efficiency of degradation are the characteristics of the photocatalyst, pollutant concentration, light intensity, and the existence of co-catalysts. This approach offers a sustainable alternative for minimizing the amount of organic pollutants present in the environment, contributing to cleaner air and water. Photocatalytic degradation hence holds tremendous potential for remediation of the environment.

Many persistent organic pollutants (POPs) are suspected endocrine disruptors and it is important to investigate their effects at low concentrations relevant to human exposure. Here, the OECD test guideline #456 steroidogenesis assay was downscaled to a 96-well microplate format to screen 24 POPs for their effects on viability, and testosterone and estradiol synthesis using the human adrenocortical cell line H295R. The compounds (six polyfluoroalkyl substances, five organochlorine pesticides, ten polychlorinated biphenyls and three polybrominated diphenyl ethers) were tested at human-relevant levels (1 nM to 10 µM). Increased estradiol synthesis, above the OECD guideline threshold of 1.5-fold solvent control, was shown after exposure to 10 µM PCB-156 (153%) and PCB-180 (196%). Interestingly, the base hormone synthesis varied depending on the cell batch. An alternative data analysis using a linear mixed-effects model that include multiple independent experiments and considers batch-dependent variation was therefore applied. This approach revealed small but statistically significant effects on estradiol or testosterone synthesis for 17 compounds. Increased testosterone levels were demonstrated even at 1 nM for PCB-74 (18%), PCB-99 (29%), PCB-118 (16%), PCB-138 (19%), PCB-180 (22%), and PBDE-153 (21%). The MTT assay revealed significant effects on cell viability after exposure to 1 nM of perfluoroundecanoic acid (12%), 3 nM PBDE-153 (9%), and 10 µM of PCB-156 (6%). This shows that some POPs can interfere with endocrine signaling at concentrations found in human blood, highlighting the need for further investigation into the toxicological mechanisms of POPs and their mixtures at low concentrations relevant to human exposure.

The mitigation of cadmium (Cd) pollution, a significant ecological threat, is of paramount importance. Pseudomonas aeruginosa harbors 2 Cd resistance genes, namely, cadR and cadA. Presently, our focus is on the identification and characterization of the cation-transporting P-type ATPase (cadA) in Pseudomonas aeruginosa BC15 through in silico methods. The CadA protein and its binding capacities remain poorly understood, with no available structural elucidation. The presence of the cadA gene in P aeruginosa was confirmed, showing a striking 99% sequence similarity with both P aeruginosa and P putida. Phylogenetic analysis unveiled the evolutionary relationship between CadA protein sequences from various Pseudomonas species. Physicochemical analysis demonstrated the stability of CadA, revealing a composition of 690 amino acids, a molecular weight of 73 352.85, and a predicted isoelectric point (PI) of 5.39. Swiss-Model homology modelling unveiled a 33.73% sequence homology with CopA (3J09), and the projected structure indicated that 89.3% of amino acid residues were situated favourably within the Ramachandran plot, signifying energetic stability. Notably, the study identified metal-binding sites in CadA, namely, H3, C30, C32, C35, H48, C89, and C106. Docking studies revealed a higher efficiency of Cd binding with CadA compared to other heavy metals. This underscores the crucial role of N-terminal cysteine residues in Cd removal. It is evident that CadA of P aeruginosa BC15 plays a crucial role in Cd tolerance, rendering it a potential microorganism for Cd toxicity bioremediation. The structural and functional elucidation of CadA, facilitated by this study, holds promise for advancing cost-effective strategies in the remediation of cadmium-contaminated environments.

Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens.

Steroid receptors (SRs) are transcription factors activated by steroid hormones (SHs) that belong to the nuclear receptors (NRs) superfamily. Several studies have shown that SRs are targets of endocrine disrupting chemicals (EDCs), widespread substances in the environment capable of interfering with the endogenous hormonal pathways and causing adverse health effects in living organisms and/or their progeny. Cell lines with SRs reporter gene are currently used for in vitro screening of large quantities of chemicals with suspected endocrine-disrupting activities. However, most of these cell lines express human SRs and therefore the toxicological data obtained are also extrapolated to non-mammalian species. In parallel, in vivo tests have recently been developed on fish species whose data are also extrapolated to mammalian species. As some species-specific differences in SRs activation by natural and synthetic chemicals have been recently reported, the aim of this review is to summarize those between human and fish SRs, as representatives of mammalian and non-mammalian toxicology, respectively. Overall, this literature study aims to improve inter-species extrapolation of toxicological data on EDCs and to understand which reporter gene cell lines expressing human SRs are relevant for the assessment of effects in fish and whether in vivo tests on fish can be properly used in the assessment of adverse effects on human health.

This is the first attempt that investigate the abundance of plasticizers in leachate sediment in the scientific literature, alongside the debut effort to explore the abundance of microplastics and plasticizers in landfill leachate and sediment in Sri Lanka. Microplastics in sizes ranging from ≥2.0-5.0, ≥1.0-2.0, and ≥ 0.5-1.0 mm were extracted from the leachate draining from ten municipal solid waste open dump sites and sediment samples covering seven districts. Microplastics were extracted by density separation (Saturated ZnCl2) followed by wet peroxide digestion and the chemical identification was conducted by Fourier Transform Infrared spectroscopy. Plasticizers were extracted to hexane and analyzed by high-performance liquid chromatography. The total mean microplastic abundance in leachate was 2.06 ± 0.62 mg/L whereas it was 363 ± 111 mg/kg for leachate sediments. The most frequently found polymer type was polyethylene (>50%), and white color was dominant. The average concentration of bisphenol A (BPA), benzophenone (BP) and diethyl-hydrogen phthalate (DHEP) in leachate was 158 ± 84.4, 0.75 ± 0.16 and 170 ± 85.8 μg/L respectively. Furthermore, BP and DHEP in leachate sediment was 100 ± 68.3 and 1034 ± 455 μg/kg respectively. As landfill leachate is directly discharged into nearby surface and groundwater bodies that serve as sources of drinking water, the study highlights the potential concerns of microplastic and plasticizer exposure to the surrounding Sri Lankan community through consumption of contaminated drinking water. Therefore, there is a timely need of develop the effective waste management and pollution control measures to minimize the possible threats to both the environment and human health.

Wastewater-based epidemiology (WBE) is considered an innovative and promising tool for estimating community exposure to a wide range of chemical and biological compounds by analyzing wastewater. Despite scholars' interest in WBE studies, there are uncertainties and limitations associated with this approach. This current review focuses on the feasibility of the WBE approach in assessing environmental pollutants, including pesticides, heavy metals, phthalates, bisphenols, and personal care products (PCPs). Limitations and challenges of WBE studies are initially discussed, and then future perspectives, gaps, and recommendations are presented in this review. One of the key limitations of this approach is the selection and identification of appropriate biomarkers in studies. Selecting biomarkers considering the basic requirements of a human exposure biomarker is the most important criterion for validating this new approach. Assessing the stability of biomarkers in wastewater is crucial for reliable comparisons of substance consumption in the population. However, directly analyzing wastewater does not provide a clear picture of biomarker stability. This uncertainty affects the reliability of temporal and spatial comparisons. Various uncertainties also arise from different steps involved in WBE. These uncertainties include sewage sampling, exogenous sources, analytical measurements, back-calculation, and estimation of the population under investigation. Further research is necessary to ensure that measured pollutant levels accurately reflect human excretion. Utilizing data from WBE can support healthcare policy in assessing exposure to environmental pollutants in the general population. Moreover, WBE seems to be a valuable tool for biomarkers that indicate healthy conditions, lifestyle, disease identification, and exposure to pollutants. Although this approach has the potential to serve as a biomonitoring tool in large communities, it is necessary to monitor more metabolites from wastewater to enhance future studies.

Plastics, while providing modern conveniences, have become an inescapable source of global concern due to their role in environmental pollution. Particularly, the focus on bisphenol A (BPA) reveals its biohazardous nature and association with liver issues, specifically steatosis. However, research indicates that BPA is just one facet of the problem, as other bisphenol analogues, microplastics, nanoplastics and additional plastic derivatives also pose potential risks. Notably, BPA is implicated in every stage of non-alcoholic fatty liver disease (NAFLD) onset and progression, surpassing hepatitis B virus as a primary cause of chronic liver disease worldwide. As plastic contamination tops the environmental contaminants list, urgent action is needed to assess causative factors and mitigate their impact. This review delves into the molecular disruptions linking plastic pollutant exposure to liver diseases, emphasizing the broader connection between plastics and the rising prevalence of NAFLD.

There has been increasing interest in endocrine-disrupting chemicals (EDCs) among scientists and public authorities over the last 30 years, notably because of their wide use and the increasing evidence of detrimental effects on humans and the environment. However, test systems for the detection of potential EDCs as well as testing strategies still require optimization. Thus, the aim of the present project was the development of an integrated test protocol that merges the existing OECD test guidelines (TGs) 229 (fish short-term reproduction assay) and 234 (fish sexual development test) and implements thyroid-related endpoints for fish. The integrated fish endocrine disruptor test (iFEDT) represents a comprehensive approach for fish testing, which covers reproduction, early development, and sexual differentiation, and will thus allow the identification of multiple endocrine-disruptive effects in fish. Using zebrafish (Danio rerio) as a model organism, two exposure tests were performed with well-studied EDCs: 6-propyl-2-thiouracil (PTU), an inhibitor of thyroid hormone synthesis, and 17α-ethinylestradiol (EE2), an estrogen receptor agonist. In part A of this article, the effects of PTU and EE2 on established endpoints of the two existing TGs are reported, whereas part B focuses on the novel thyroid-related endpoints. Results of part A document that, as expected, both PTU and EE2 had strong effects on various endocrine-related endpoints in zebrafish and their offspring. Merging of TGs 229 and 234 proved feasible, and all established biomarkers and endpoints were responsive as expected, including reproductive and morphometric changes (PTU and EE2), vitellogenin levels, sex ratio, gonad maturation, and histopathology (only for EE2) of different life stages. A validation of the iFEDT with other well-known EDCs will allow verification of the sensitivity and usability and confirm its capacity to improve the existing testing strategy for EDCs in fish. Integr Environ Assess Manag 2024;20:817-829. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

In the present systematic review and meta-analysis, the association of maternal exposure to the endocrine disrupting chemicals (EDCs) with cardio-metabolic risk factors in children during childhood for the first time.

The PubMed, Scopus, EMBASE, and Web of Science databases were systematically searched, up to Feb 2023. In total 30 cohort studies had our inclusion criteria. A random-effects model was used for the variables that had considerable heterogeneity between studies. The Newcastle-Ottawa Scale (NOS) tool was used to classify the quality score of studies. All statistical analyses were conducted using Stata 14 and P-value < 0.05 considered as a significant level.

In the meta-analysis, maternal exposure to the EDCs was weakly associated with higher SBP (Fisher_Z: 0.06, CI: 0.04, 0.08), BMI (Fisher_Z: 0.07, CI: 0.06, 0.08), and WC (Fisher_Z: 0.06, CI: 0.03, 0.08) z-scores in children. A significant linear association was found between maternal exposure to the bisphenol-A and pesticides with BMI and WC z-score in children (p < 0.001). Subgroup analysis showed significant linear association of BPA and pesticides, in the urine samples of mothers at the first trimester of pregnancy, with BMI and WC z-score in children from 2-8 years (p < 0.05).

Prenatal exposure to the EDCs in the uterine period could increase the risk of obesity in children. Maternal exposure to bisphenol-A and pesticides showed the strongest association with the obesity, especially visceral form, in the next generation.

There is a lack of comprehensive reviews tracking emerging organic contaminants (EOCs) within the soil-plant continuum using the source-pathway-receptor-impact-mitigation (SPRIM) framework. Therefore, this review examines existing literature to gain insights into the occurrence, behaviour, fate, health hazards, and strategies for mitigating EOCs within the soil-plant system. EOCs identified in the soil-plant system encompass endocrine-disrupting chemicals, surfactants, pharmaceuticals, personal care products, plasticizers, gasoline additives, flame retardants, and per- and poly-fluoroalkyl substances (PFAS). Sources of EOCs in the soil-plant system include the land application of biosolids, wastewater, and solid wastes rich in EOCs. However, less-studied sources encompass plastics and atmospheric deposition. EOCs are transported from their sources to the soil-plant system and other receptors through human activities, wind-driven processes, and hydrological pathways. The behaviour, persistence, and fate of EOCs within the soil-plant system are discussed, including sorption, degradation, phase partitioning, (bio)transformation, biouptake, translocation, and bioaccumulation in plants. Factors governing the behaviour, persistence, and fate of EOCs in the soil-plant system include pH, redox potential, texture, temperature, and soil organic matter content. The review also discusses the environmental receptors of EOCs, including their exchange with other environmental compartments (aquatic and atmospheric), and interactions with soil organisms. The ecological health risks, human exposure via inhalation of particulate matter and consumption of contaminated food, and hazards associated with various EOCs in the soil-plant system are discussed. Various mitigation measures including removal technologies of EOCs in the soil are discussed. Finally, future research directions are presented.

Microplastics (MPs) have entered drinking water (DW) via various pathways, raising concerns about their potential health impacts. This study provides a comprehensive review of MP-associated chemicals, such as oligomers, plasticizers, stabilizers, and ultraviolet (UV) filters that can be leached out during DW treatment and distribution. The leaching of these chemicals is influenced by various environmental and operating factors, with three major ones identified: MP concentration and polymer type, pH, and contact time. The leaching process is substantially enhanced during the disinfection step of DW treatment, due to ultraviolet light and/or disinfectant-triggered reactions. The study also reviewed human exposure to MPs and associated chemicals in DW, as well as their health impacts on the human nervous, digestive, reproductive, and hepatic systems, especially the neuroendocrine toxicity of endocrine-disrupting chemicals. An overview of MPs in DW, including tap water and bottled water, was also presented to enable a background understanding of MPs-associated chemicals. In short, certain chemicals leached from MPs in DW can have significant implications for human health and demand further research on their long-term health impacts, mitigation strategies, and interactions with other pollutants such as disinfection byproducts (DBPs) and per- and polyfluoroalkyl substances (PFASs). This study is anticipated to facilitate the research and management of MPs in DW and beverages.

The human population of Galapagos has rapidly increased in the last decades accelerating the anthropogenic pressures on the archipelago's natural resources. The growing human footprint, including inadequate management of garbage, may lead to conservation conflicts. Here, we assessed the ingestion of debris by Western Santa Cruz giant tortoises (Chelonoidis porteri) within human-modified and protected areas. Additionally, we characterized environmental debris and quantified tortoise abundance together with tortoise fecal samples. We processed a total of 6629 fecal samples along a gradient of anthropogenic disturbance based on human debris presence. We found 590 pieces of debris in samples within human-modified areas (mean of 3.97 items/kg of feces) and only two pieces in the protected area (mean of 0.08 items/kg of feces). Plastic waste was the predominant category in feces within the anthropic area (86.3%; n = 511), followed by cloth, metal, paper, synthetic rubber, construction materials, and glass. On average, the proportion of plastic was higher in feces (84%) than it was in environmental debris (67%), denoting that plastics are more readily ingested than other types of debris. We also found that green, white, and light blue plastics were consumed more often than their prevalence in the environment, suggesting color discrimination. Tortoise abundance was higher in the protected area when compared to the human-modified area; however, recapture rates were higher in anthropized landscapes which increases tortoise exposure to plastics and other human associated threats. Our results indicate that plastics are frequently consumed by tortoises in the polluted anthropic areas of western Santa Cruz, but scarce in protected areas. More research is needed to understand the negative impacts associated with plastics for Galapagos terrestrial species. We encourage local stakeholders to implement current policies limiting expansion of urban areas, plastic use, and improving waste management systems to minimize threats to human and animal health.

PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erβ, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.

Xenobiotics, radiation, and other environmental health risk factors leave their mark on human organs. This can be demonstrated through the use of pathology museum specimens. Upon completing two semesters of postgraduate studies in environmental health, a tour of the Museum of Pathology is offered to postgraduate students at Athens Medical School who are being trained in environmental health. A structured questionnaire is employed to assess the specimens' impact on several aspects: improving students' observational skills, reinforcing the taught material, acquiring new relevant knowledge, and cultivate the social-cognitive ability of empathy. Additionally, students are asked to evaluate the necessity of preserving metadata associated mainly with the social context of the specimens. This research-educational initiative, a component of an ongoing larger project, underscores the significant educational and research value of museum specimens pertaining to environmental health. Furthermore, effectively utilizing such exhibits can enrich the museum experience for visitors and increase public awareness of environmental health issues.

Humans are continuously exposed to a variety of toxicants and chemicals which is exacerbated during and after environmental catastrophes such as floods, earthquakes, and hurricanes. The hazardous chemical mixtures generated during these events threaten the health and safety of humans and other living organisms. This necessitates the development of rapid decision-making tools to facilitate mitigating the adverse effects of exposure on the key modulators of the endocrine system, such as the estrogen receptor alpha (ERα), for example. The mechanistic stages of the estrogenic transcriptional activity can be measured with high content/high throughput microscopy-based biosensor assays at the single-cell level, which generates millions of object-based minable data points. By combining computational modeling and experimental analysis, we built a highly accurate data-driven classification framework to assess the endocrine disrupting potential of environmental compounds. The effects of these compounds on the ERα pathway are predicted as being receptor agonists or antagonists using the principal component analysis (PCA) projections of high throughput, high content image analysis descriptors. The framework also combines rigorous preprocessing steps and nonlinear machine learning algorithms, such as the Support Vector Machines and Random Forest classifiers, to develop highly accurate mathematical representations of the separation between ERα agonists and antagonists. The results show that Support Vector Machines classify the unseen chemicals correctly with more than 96% accuracy using the proposed framework, where the preprocessing and the PCA steps play a key role in suppressing experimental noise and unraveling hidden patterns in the dataset.

The organosulfur compound propyl-propane thiosulfonate (PTSO), mainly found in Allium cepa, has a promising use in the agrifood industry. To confirm its safety for livestock, consumers, and environment, toxicological assessment is needed. In this regard, endocrine-disrupting chemicals (EDCs) are in the spotlight of research. Therefore, as part of the risk assessment of PTSO, in the present work, an in vivo study was performed in mice exposed to PTSO to investigate its potential reproductive toxicity considering fertility, genetic and endocrine endpoints. Five-weeks-old CD1 mice (80 males, 80 females) were exposed for 11 or 16 weeks (males or females, respectively) to different doses of PTSO (0, 14, 28 and 55 mg PTSO/kg b.w./day; 20 animals per group and sex) through the food pellets. No clinical observations or mortality and no changes in absolute organ weights and relative organ weights/body weight or brain ratios occurred during the study. The estrous cycle did not undergo any significant toxicologically relevant change. Most of the sex hormones displayed normal values. Some alterations in the expression of some genes related to reproduction is only observed in females, but they do not appear to have consequences in the development of sex organs. Docking results showed the impossibility of stable binding to estrogen and androgen receptors. Considering all the results obtained, the safe profile of PTSO can be confirmed for different agrifood applications at the conditions assayed.

Endocrine-disrupting chemicals (EDCs) are substances generated by human industrial activities that are detrimental to human health through their effects on the endocrine system. The global societal and economic burden posed by EDCs is substantial. Poorly defined or unenforced policies can increase human exposure to EDCs, thereby contributing to human disease, disability and economic damage. Researchers have shown that policies and interventions implemented at both individual and government levels have the potential to reduce exposure to EDCs. This Review describes a set of evidence-based policy actions to manage, minimize or even eliminate the widespread use of these chemicals and better protect human health and society. A number of specific challenges exist: defining, identifying and prioritizing EDCs; considering the non-linear or non-monotonic properties of EDCs; accounting for EDC exposure effects that are latent and do not appear until later in life; and updating testing paradigms to reflect 'real-world' mixtures of chemicals and cumulative exposure. A sound strategy also requires partnering with health-care providers to integrate strategies to prevent EDC exposure in clinical care. Critical next steps include addressing EDCs within global policy frameworks by integrating EDC exposure prevention into emerging climate policy.

Endocrine-disrupting chemicals (EDCs) can cause serious harm to human health and the environment; therefore, it is important to rapidly and correctly identify EDCs. Different computational models have been proposed for the prediction of EDCs over the past few decades, but the reported models are not always easily available, and few studies have investigated the structural characteristics of EDCs. In the present study, we have developed a series of artificial intelligence models targeting EDC receptors: the androgen receptor (AR); estrogen receptor (ER); and pregnane X receptor (PXR). The consensus models achieved good predictive results for validation sets with balanced accuracy values of 87.37%, 90.13%, and 79.21% for AR, ER, and PXR binding assays, respectively. Analysis of the physical-chemical properties suggested that several chemical properties were significantly (p < 0.05) different between EDCs and non-EDCs. We also identified structural alerts that can indicate an EDC, which were integrated into the web server SApredictor. These models and structural characteristics can provide useful tools and information in the discrimination and mechanistic understanding of EDCs in drug discovery and environmental risk assessment.

Objective: We aimed to explore the correlations between and possible mechanisms of common environmental endocrine disruptors, phthalates, and ovarian dysfunction in endometriosis. Methods: Subjects were included in the case group (n = 107) who were diagnosed with endometriosis by postoperative pathology in Fujian Maternal and Child Hospital from February 2018 to February 2021, and the women who were excluded from endometriosis by surgery were as the control group (n = 70). The demographic information of the subjects were evaluated by questionnaire, and the clinical characteristics were evaluated by medical records and 3-year follow-up results. Gas chromatography‒mass spectrometry was used to quantify 10 metabolites of phthalates, including dimethyl ortho-phthalate (DMP), mono-n-methyl phthalate (MMP), dioctyl ortho-phthalate (DEP), mono-ethyl phthalate (MEP), di-n-butyl ortho-phthalate (DBP), mono-butyl phthalate (MBP), benzylbutyl phthalate (BBzP), mono-benzyl; phthalate (MBzP), diethylhexyl phthalate (DEHP) and mono-ethylhexyl phthalate (MEHP), in the urine samples of the subjects. Furthermore, a total of 54 SD rats were exposed to DEHP 0, 5, 50, 100, 250, 500, 1,000, 2000, and 3,000 mg/kg/day for 2 weeks. The SD rats' body weight, oestrus cycle changes, and serum anti-mullerian hormone (AMH) levels were evaluated. After sacrifice, the mass index of the rat uterus and bilateral ovaries were calculated. Finally, bioinformatics analysis of rat ovarian tissues was performed to explore the possible mechanism. SPSS 24.0 (IBM, United States) was used for data analysis. p-value <0.05 was considered statistically significant. Results: The human urinary levels of DMP (p < 0.001), MMP (p = 0.001), DEP (p = 0.003), MEP (p = 0.002), DBP (p = 0.041), MBP (p < 0.001), BBzP (p = 0.009), DEHP (p < 0.001), and MEHP (p < 0.001) were significantly higher in women with endometriosis than in controls. Notably, DEHP was a significant risk factor for endometriosis (OR: 11.0, 95% CI: 5.4-22.6). The area under the ROC curve increased when multiple phthalates were diagnosed jointly, reaching 0.974 as the highest value, which was helpful for the diagnosis of endometriosis. In vivo experiments showed that after DEHP exposure in rats, the mass index of the ovary and uterus decreased in a dose-dependent manner; the oestrus cycle of SD rats was irregularly prolonged and disordered; and the serum AMH level was negatively correlated with the DEHP exposure dose (Rho = -0.8, p < 0.001). Bioinformatics analysis of rat ovarian tissues showed that seven genes involved in the steroid biosynthesis pathway were upregulated and may play a negative role in ovarian function. Conclusion: Exposure to phthalates, especially DEHP, is associated with the occurrence of endometriosis and affects women's reproductive prognosis and ovarian function. The steroid biosynthesis pathway may be related to ovarian dysfunction. The detection of phthalate in urine may become a new biological target for the diagnosis of endometriosis.

Globally, there has been a significant increase in awareness of the adverse effects of chemicals with known or suspected endocrine-acting properties on human health. Human exposure to endocrine disrupting compounds (EDCs) mainly occurs by ingestion and to some extent by inhalation and dermal uptake. Although it is difficult to assess the full impact of human exposure to EDCs, it is well known that timing of exposure is of importance and therefore infants are more vulnerable to EDCs and are at greater risk compared to adults. In this regard, infant safety and assessment of associations between prenatal exposure to EDCs and growth during infancy and childhood has been received considerable attention in the last years. Hence, the purpose of this review is to provide a current update on the evidence from biomonitoring studies on the exposure of infants to EDCs and a comprehensive view of the uptake, the mechanisms of action and biotransformation in baby/human body. Analytical methods used and concentration levels of EDCs in different biological matrices (e.g., placenta, cord plasma, amniotic fluid, breast milk, urine, and blood of pregnant women) are also discussed. Finally, key issues and recommendations were provided to avoid hazardous exposure to these chemicals, taking into account family and lifestyle factors related to this exposure.

The increase in the surface and groundwater contamination due to global population growth, industrialization, proliferation of pathogens, emerging pollutants, heavy metals, and scarcity of drinking water represents a critical problem. Because of this problem, particular emphasis will be placed on wastewater recycling. Conventional wastewater treatment methods may be limited due to high investment costs or, in some cases, poor treatment efficiency. To address these issues, it is necessary to continuously evaluate novel technologies that complement and improve these traditional wastewater treatment processes. In this regard, technologies based on nanomaterials are also being studied. These technologies improve wastewater management and constitute one of the main focuses of nanotechnology. The following review describes wastewater's primary biological, organic, and inorganic contaminants. Subsequently, it focuses on the potential of different nanomaterials (metal oxides, carbon-based nanomaterials, cellulose-based nanomaterials), membrane, and nanobioremediation processes for wastewater treatment. The above is evident from the review of various publications. However, nanomaterials' cost, toxicity, and biodegradability need to be addressed before their commercial distribution and scale-up. The development of nanomaterials and nanoproducts must be sustainable and safe throughout the nanoproduct life cycle to meet the requirements of the circular economy.

Early vertebrate development is partially regulated by thyroid hormones (THs). Environmental pollutants that interact with the TH system (TH system-disrupting chemicals [THSDCs]) can have massively disrupting effects on this essential phase. Eye development of fish is directly regulated by THs and can, therefore, be used as a thyroid-related endpoint in endocrine disruptor testing. To evaluate the effects of THSDC-induced eye malformations during early development, zebrafish (Danio rerio) embryos were exposed for 5 days postfertilization (dpf) to either propylthiouracil, a TH synthesis inhibitor, or tetrabromobisphenol A, which interacts with TH receptors. Subsequently, one half of the embryos were exposed further to the THSDCs until 8 dpf, while the other half of the embryos were raised in clean water for 3 days to check for reversibility of effects. Continued THSDC exposure altered eye size and pigmentation and induced changes in the cellular structure of the retina. This correlated with morphological alterations of thyroid follicles as revealed by use of a transgenic zebrafish line. Interestingly, effects were partly reversible after a recovery period as short as 3 days. Results are consistent with changes in TH levels measured in different tissues of the embryos, for example, in the eyes. The results show that eye development in zebrafish embryos is very sensitive to THSDC treatment but able to recover quickly from early exposure by effective repair mechanisms. Environ Toxicol Chem 2023;42:1276-1292. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Human adrenocortical H295R cells have been validated by the OECD Test Guideline 456 to detect chemicals disrupting testosterone and 17β-estradiol (estradiol) biosynthesis. This study evaluated a novel approach to detect disturbances of steroidogenesis in H295R cells, exemplified by prochloraz and five anabolic steroids. Steroid profiles were assessed by an untargeted LC-MS-based method, providing a relative quantification of 57 steroids annotated according to their accurate masses and retention times. Such a panel of steroids included several mineralocorticoids, glucocorticoids, progestins and adrenal androgens. The coverage of a high number of metabolites in this extended steroid profiling facilitated grouping of chemicals with similar effects and detecting subtler differences between chemicals. It allowed, for example, distinguishing between the effects of turinabol and oxymetholone, supposed to act similarly in a previous characterization including only nine adrenal steroids. Furthermore, the results revealed that product/substrate ratios can provide superior information on altered enzyme activities compared to individual metabolite levels. For example, the 17α-hydroxypregnenolone/pregnenolone ratio was found to be a more sensitive marker for detecting 17α-hydroxylase inhibition by prochloraz than the corresponding individual steroids. These results illustrate that chemical grouping and calculation of product/substrate ratios can provide valuable information on mode-of-action and help prioritizing further experimental work.

The oestrogen receptor (ER) from the nuclear receptor family is involved in different physiological processes, which can be affected by multiple xenobiotics. Some of these compounds, such as bisphenols, pesticides, and phthalates, are widespread as consequence of human activities and are commonly present also in human organism. Xenobiotics able to interact with ER and trigger a hormone-like response, are known as endocrine disruptors. In this review, we aim to summarize the available knowledge on products derived from human industrial activity and other xenobiotics reported to interact with ER. ER-disrupting chemicals behave differently towards oestrogen-dependent cell lines than endogenous oestradiol. In low concentrations, they stimulate proliferation, whereas at higher concentrations, are toxic to cells. In addition, most of the knowledge on the topic is based on individual compound testing, and only a few studies assess xenobiotic combinations, which better resemble real circumstances. Confirmation from in vivo models is lacking also.

Bisphenol P (BPP), structurally similar to bisphenol A, is commonly identified in the samples of environment, food, and humans. Unfortunately, very little information is currently available on adverse effects of BPP. The obesogenic effects and underlying mechanisms of BPP on mice were investigated in this study. Compared with the control, high-resolution microcomputed tomography (micro-CT) scans displayed that the visceral fat volume of mice was significantly increased at a dose of 5 mg/kg/day after BPP exposure for 14 days, whereas the subcutaneous fat volume remained unchanged. Nontargeted metabolomic analysis revealed that BPP significantly perturbed the metabolic pathways of mouse livers, and acetyl-CoA was identified as the potential key metabolite responsible for the visceral fat induced by BPP. These findings recommend that a great deal of attention should be paid to the obesogenic properties of BPP as a result of its widely utilized and persistence in the environment.

The marine ecosystem around the Island of Newfoundland is contaminated by thyroid disrupting chemicals (TDCs). Coastal inhabitants may be exposed to TDCs through consumption of contaminated local seafood products and affecting thyroid functions. The aim of this study was to explore: (1) consumption frequency of local seafood products consumed by rural residents, (2) thyroid hormones (THs) and TDCs concentrations in residents, (3) relationships between local seafood consumption, TDC concentrations, and THs. Participants (n = 80) were recruited from two rural Newfoundland communities. Seafood consumption was measured through a validated seafood consumption questionnaire. Blood samples were collected from all participants and tested for THs (thyroid stimulating hormone, free thyroxine, free triiodothyronine) and TDCs, including polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), and dichlorodiphenyldichloroethylene (p,p'-DDE). Cod was the most frequently consumed local species, but there was a wide range of other local species consumed. Older participants (>50 years) had greater plasma concentrations of PBB-153, PCBs and p,p'-DDE, and males had higher concentrations of all TDCs than females. The consumption frequency of local cod was found to be positively associated with several PCB congeners, p,p'-DDE and ∑14TDCs. There was no significant relationship between TDCs and THs in either simple or multivariate linear regression analyses.

Individuals are exposed to environmental pollutants with endocrine disrupting activity (endocrine disruptors, EDCs) and the early stages of life are particularly susceptible to these exposures. Previous studies have focused on identifying molecular signatures associated with EDCs, but none have used repeated sampling strategy and integrated multiple omics. We aimed to identify multi-omic signatures associated with childhood exposure to non-persistent EDCs.

We used data from the HELIX Child Panel Study, which included 156 children aged 6 to 11. Children were followed for one week, in two time periods. Twenty-two non-persistent EDCs (10 phthalate, 7 phenol, and 5 organophosphate pesticide metabolites) were measured in two weekly pools of 15 urine samples each. Multi-omic profiles (methylome, serum and urinary metabolome, proteome) were measured in blood and in a pool urine samples. We developed visit-specific Gaussian Graphical Models based on pairwise partial correlations. The visit-specific networks were then merged to identify reproducible associations. Independent biological evidence was systematically sought to confirm some of these associations and assess their potential health implications.

950 reproducible associations were found among which 23 were direct associations between EDCs and omics. For 9 of them, we were able to find corroborating evidence from previous literature: DEP - serotonin, OXBE - cg27466129, OXBE - dimethylamine, triclosan - leptin, triclosan - serotonin, MBzP - Neu5AC, MEHP - cg20080548, oh-MiNP - kynurenine, oxo-MiNP - 5-oxoproline. We used these associations to explore possible mechanisms between EDCs and health outcomes, and found links to health outcomes for 3 analytes: serotonin and kynurenine in relation to neuro-behavioural development, and leptin in relation to obesity and insulin resistance.

This multi-omics network analysis at two time points identified biologically relevant molecular signatures related to non-persistent EDC exposure in childhood, suggesting pathways related to neurological and metabolic outcomes.