Strategies for Removing Endocrine Disrupting Chemicals (EDCs) from Wastewater.

INTRODUCTION: Endocrine-disrupting drugs, also called endocrine disruptors or micropollutants, cause serious environmental and public health problems due to their ability to disrupt the endocrine functions of organisms and humans, even at low concentrations. This report provides a summary of current removal techniques, such as activated sludge processes, membrane filtration, adsorption, and membrane bioreactor techniques for endocrine-disrupting chemicals, including their efficiency, limitations, and practical implementation. METHODS: This review evaluates these methods by considering their treatment efficiency, costs, and environmental impact. To curb this menace, several developed countries have distinct strategies, such as physical remediation techniques, biological processes, phytoremediation, and chemical processes to remove endocrine disruptors. RESULTS: In developing nations, most conventional wastewater treatment plants do not even monitor those contaminants due to the low biodegradability and high complexity of such compounds. CONCLUSION: Hence, in this review work, potential endocrine-disrupting chemicals, their impacts, mechanisms of action, consequences for human health, and bio-mitigation strategies reported so far have been discussed in the context of the relevant literature.

Indian and global scenarios of Bisphenol A distribution and its new analogues: Prevalence & probability exceedance.

We compare, the prevalence, fate, and sources of Bisphenol A both globally and in India. India has the highest concentration of BPA and Bisphenol S(BPS) in general, with vegetables, particularly corn, beans, strings, and raw or canned vegetables, being the largest contributors. Among all the matrices, bisphenols (BPs) are found in the highest concentration in food, followed by surface water, wastewater, and indoor dust. BPA, BPS, and BPF are the most commonly reported analogues in India, with BPA being the most dominant category used worldwide. The highest concentration of BPs is observed in Uttar Pradesh, Punjab and Haryana that are three major agricultural states of India however, there is still a research gap regarding the dietary exposure to BPs on an individual level. Environmentally detected BPA occurs in a range of below detection to 10636 ng. L-1, with significant geographic variations. Interestingly, the order of abundance in India was maximum for BPS, which is contrary to the global average, where BPA is observed as most abundant. BPS is found to be the most common BPs analogue in surface water worldwide, with limited removal efficiency by both naturally remediation and conventional treatment methods. Similar patterns were observed in the US-India and Japan-Korea regions in terms of their source-sink-prevalence-fate dynamics. The probability of exceeding safe concentrations of BPs is higher in India and Korea, suggesting that these countries are more vulnerable to high prevalence concentrations and the subsequent public health hazards.

Aptamer biosensor design for the detection of endocrine-disrupting chemicals small organic molecules using novel bioinformatics methods.

Endocrine-disrupting chemicals (EDCs) are substances that can disrupt the normal functioning of hormones.Using aptamers, which are biological recognition elements, biosensors can quickly and accurately detect EDCs in environmental samples. However, the elucidation of aptamer structures by conventional methods is highly challenging due to their complexity. This has led to the development of three-dimensional aptamer structures based on different models and techniques. To do this, we developed a way to predict the 3D structures of the SS DNA needed for this sequence by starting with an aptamer sequence that has biosensor properties specific to bisphenol-A (BPA), one of the chemicals found in water samples that can interfere with hormones. In addition, we will elucidate the intermolecular mechanisms and binding affinity between aptamers and endocrine disruptors using bioinformatics techniques such as molecular docking, molecular dynamics simulation, and binding energies. The outcomes of our study are to compare modeling programs and force fields to see how reliable they are and how well they agree with results found in the existing literature, to understand the intermolecular mechanisms and affinity of aptamer-based biosensors, and to find a new way to make aptamers that takes less time and costs less.

Thyroid cancer and endocrine disruptive chemicals: a case-control study on per-fluoroalkyl substances and other persistent organic pollutants.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Per- and Polyfluoroalkyl Substances (PFAS) in Community Water Systems (CWS) and the Risk of Thyroid Cancer: An Ecological Study.

Thyroid cancer incidence has been steadily increasing over the past decade in the United States (US). A discussion exists regarding the potential contribution of exposure to endocrine-disrupting chemicals, encompassing certain per- and poly-fluoroalkyl substances (PFASs). This ecological study evaluated the potential correlation between PFAS levels in drinking water and thyroid cancer incidence in the US. Data on age-adjusted thyroid cancer incidence rate (per 100,000 persons) by county were obtained from the Centers for Disease Control and Prevention (CDC) for US counties with available data in 2015-2019. Data on PFAS concentrations in the drinking water of selected community water systems (CWSs) were obtained from the CDC National Environmental Public Health Tracking Network in 2013-2015. The correlation between PFASs in CWSs and thyroid cancer incidence was calculated using Spearman correlation. A statistically significant correlation was found between perfluorooctanoic acid (PFOA) (r = 0.031; p = 0.043), perfluorononanoic acid (PFNA) (r = 0.058; p ≤ 0.001), and thyroid cancer incidence. The results suggest a potential link between certain PFAS exposures and thyroid cancer risk. However, due to the nature of an ecological study, no conclusions can be drawn at the individual level or causality. More research is needed, particularly on an individual level to allow for more detailed exposure assessment.

Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer.

Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men in the world. Its prevention has been limited because of an incomplete understanding of how environmental exposures to chemicals contribute to the molecular pathogenesis of aggressive PCa. Environmental exposures to endocrine-disrupting chemicals (EDCs) may mimic hormones involved in PCa development. This research aims to identify EDCs associated with PCa hub genes and/or transcription factors (TF) of these hub genes in addition to their protein-protein interaction (PPI) network. We are expanding upon the scope of our previous work, using six PCa microarray datasets, namely, GSE46602, GSE38241, GSE69223, GSE32571, GSE55945, and GSE26126, from the NCBI/GEO, to select differentially expressed genes based on |log2FC| (fold change) ≥ 1 and an adjusted p-value < 0.05. An integrated bioinformatics analysis was used for enrichment analysis (using DAVID.6.8, GO, KEGG, STRING, MCODE, CytoHubba, and GeneMANIA). Next, we validated the association of these PCa hub genes in RNA-seq PCa cases and controls from TCGA. The influence of environmental chemical exposures, including EDCs, was extrapolated using the chemical toxicogenomic database (CTD). A total of 369 overlapping DEGs were identified associated with biological processes, such as cancer pathways, cell division, response to estradiol, peptide hormone processing, and the p53 signaling pathway. Enrichment analysis revealed five up-regulated (NCAPG, MKI67, TPX2, CCNA2, CCNB1) and seven down-regulated (CDK1, CCNB2, AURKA, UBE2C, BUB1B, CENPF, RRM2) hub gene expressions. Expression levels of these hub genes were significant in PCa tissues with high Gleason scores ≥ 7. These identified hub genes influenced disease-free survival and overall survival of patients 60-80 years of age. The CTD studies showed 17 recognized EDCs that affect TFs (NFY, CETS1P54, OLF1, SRF, COMP1) that are known to bind to our PCa hub genes, namely, NCAPG, MKI67, CCNA2, CDK1, UBE2C, and CENPF. These validated differentially expressed hub genes can be potentially developed as molecular biomarkers with a systems perspective for risk assessment of a wide-ranging list of EDCs that may play overlapping and important role(s) in the prognosis of aggressive PCa.

Correlation between Lindane Use and the Incidence of Thyroid Cancer in the United States: An Ecological Study.

The increasing rate of thyroid cancer may be attributable to endocrine disruptive chemicals. Lindane is a persistent organochlorine pesticide with endocrine disruptive properties that has been classified as carcinogenic to humans. The aim of this ecological study was to evaluate potential correlation between lindane exposure and thyroid cancer incidence in the United States (US). Data on statewide age-adjusted thyroid cancer incidence rate (per 100,000 people) was obtained from the Centers for Disease Control and Prevention for all US states for 2019. Lindane use estimates per cropland (kg/acres cropland) were then overlaid on the map of age-adjusted thyroid cancer incidence rate using ArcGIS. The trend of lindane use in the US between 1992 and 2007 was calculated using the Mann Kendall correlation test. The correlation between statewide lindane use and age-adjusted thyroid cancer incidence rates was calculated using Spearman correlation. Lindane use in the US decreased significantly between 1992 and 2007 (T = -0.617; p < 0.001). There was no statistically significant correlation between lindane use in 1992 and thyroid cancer incidence rate for any of the years between 1999 and 2019. Our results suggest that restrictions clearly seem to be effective in reducing lindane use, however, more research is needed for individual pesticides and thyroid cancer.

Minireview: Parabens Exposure and Breast Cancer.

There is increasing recognition that environmental exposure to chemicals, such as endocrine-disruptive chemicals (EDCs), contributes to the development of breast cancer. Parabens are a group of EDCs commonly found in personal care products, foods, and pharmaceuticals. Systemic exposure to parabens has been confirmed by the ubiquitous detection of parabens in human blood and urine samples. Although evidence from in vivo and epidemiological studies linking parabens exposure to breast cancer is limited, the current evidence suggests that parabens may negatively interfere with some endocrine and intracrine targets relevant to breast carcinogenesis. So far, most studies have focused on a single paraben's effects and the direct modulating effects on estrogen receptors or the androgen receptor in vitro. Recent studies have revealed that parabens can modulate local estrogen-converting enzymes, 17ß-hydroxysteroid dehydrogenase 1 and 2 and increase local estrogen levels. Also, parabens can crosstalk with the human epidermal growth factor receptor 2 (HER2) pathway and work with ER signaling to increase pro-oncogenic c-Myc expression in ER+/HER2+ breast cancer cells. Future studies investigating paraben mixtures and their crosstalk with other EDCs or signaling pathways both in vitro and in vivo in the context of breast cancer development are warranted.

Novel use of coactivators to enhance sensitivity of SEAP-based reporter assay system for visual monitoring and quantitation of androgens and antiandrogens in water.

Every year thousands of chemicals get discharged into the waterbodies of the world. These chemicals cause endocrine disruption and induce adverse health effects in human and aquatic life. Global environmental protection agencies emphasise the need to develop rapid and specific tests for identification of these endocrine disruptive chemicals (EDCs) in water. Detection of chemicals that disrupt androgen signaling is especially important because androgen input at specific phases of life is critical for proper male development. Effect-based methods such as reporter assays are suitable tools for identification of EDCs in mixtures of unknown composition. The current study describes a stable, secreted alkaline protease (SEAP)-based reporter assay system, for visual detection of androgenic/antiandrogenic activity present in water samples. A novel feature of this system is the inclusion of coactivators, GRIP1, CARM1, p300 and mZac1b, in addition to an optimal combination of androgen response element (3× HRE), androgen receptor (AR) and the SEAP reporter gene. Incorporation of the coactivators resulted in a transcriptional fold change of 162 folds, enabling visual detection at much lower concentrations of androgen (1 picomolar) within 1 h of addition of test sample. Also, non-androgenic steroids such as estrogen, progesterone and Dexamethasone did not induce significant reporter activity, except at very high concentrations. This reporter assay can be readily converted into a high throughput format for investigation in multiple samples simultaneously, and reflects the changes that can be expected to occur inside a mammalian cell. The androgenic activity in six different water sources was evaluated using this assay. The results reveal significant androgenic activity in rivers and lakes close to Industrial areas, whereas the highest androgenic activity was observed in water containing paper and pulp mill effluents. This bioassay therefore provides a rapid, visual detection tool for effect-directed analysis of androgenic/antiandrogenic compounds in water. IMPACT STATEMENT: The current SEAP-based assay allows visual detection of androgens/antiandrogens in water, at concentrations as low as 1 picomolar, within a 1 h time period, in a high throughput format, providing a very useful technique for field users and regulatory bodies.

Endocrine Disrupting Chemicals and Thyroid Cancer: An Overview.

Endocrine disruptive chemicals (EDC) are known to alter thyroid function and have been associated with increased risk of certain cancers. The present study aims to provide a comprehensive overview of available studies on the association between EDC exposure and thyroid cancer. Relevant studies were identified via a literature search in the National Library of Medicine and National Institutes of Health PubMed as well as a review of reference lists of all retrieved articles and of previously published relevant reviews. Overall, the current literature suggests that exposure to certain congeners of flame retardants, polychlorinated biphenyls (PCBs), and phthalates as well as certain pesticides may potentially be associated with an increased risk of thyroid cancer. However, future research is urgently needed to evaluate the different EDCs and their potential carcinogenic effect on the thyroid gland in humans as most EDCs have been studied sporadically and results are not consistent.

Endocrine-disruptive chemicals as contaminants of emerging concern in wastewater and surface water: A review.

Population growth followed by rapid development of industrialisation has caused serious environmental pollution with contaminants of emerging concern found in wastewater and surface water. As one of the most important resources for human survival, water is daily polluted by endocrine-disruptive chemicals (EDCs) including pharmaceuticals and personal care products, organic pollutants and heavy metals. Even at low concentrations in water bodies, chronic exposure to EDCs can cause adverse effects on human and environment health. The main concern with EDCs is the diseases they can generate in humans or wildlife by affecting the function of hormones in the body. Problems in the reproductive system, thyroid problems, Alzheimer's, cancer and obesity are some of the major effects of EDCs in humans. In wildlife, the reproductive system may be affected, including its levels of hatchability and vitellogenin. The efforts of the present review are on emphasising on the environmental concern on the occurrence and risk assessment of EDCs, their harmful effects in the ecosystem, human life, and wildlife, as a result of their incomplete removal from wastewater treatment plants. The review focuses on studies conducted in South Africa highlights the use of fungal bioreactors as a low-cost and eco-effective environmentally friendly wastewater treatment processes.

Grouping of endocrine disrupting chemicals for mixture risk assessment - Evidence from a rat study.

Exposure to mixtures of endocrine disrupting chemicals may contribute to the rising incidence of hormone-related diseases in humans. Real-life mixtures are complex, comprised of chemicals with mixed modes of action, and essential knowledge is often lacking on how to group such chemicals into cumulative assessment groups, which is an essential prerequisite to conduct a chemical mixture risk assessment. We investigated if mixtures of chemicals with diverse endocrine modes of action can cause mixture effects on hormone sensitive endpoints in developing and adult rat offspring after perinatal exposure. Wistar rats were exposed during pregnancy and lactation simultaneously to either bisphenol A and butylparaben (Emix), diethylhexyl phthalate and procymidone (Amix), or a mixture of all four substances (Totalmix). In male offspring, the anogenital distance was significantly reduced and nipple retention increased in animals exposed to Amix and Totalmix, and the mixture effects were well approximated by the dose addition model. The combination of Amix and Emix responded with more marked changes on these and other endocrine-sensitive endpoints than each binary mixture on its own. Sperm counts were reduced by all exposures. These experimental outcomes suggest that the grouping of chemicals for mixture risk assessment should be based on common health outcomes rather than only similar modes or mechanisms of action. Mechanistic-based approaches such as the concept of Adverse Outcome Pathway (AOP) can provide important guidance if both the information on shared target tissues and the information on shared mode/mechanism of action are taken into account.

Identifying Greener and Safer Plasticizers: A 4-Step Approach.

The health and economic burden of endocrine disrupting chemicals, such as the plasticizer di(2-ethylhexyl) phthalate (DEHP), is prompting industry to develop alternatives. However, the absence of requirements for manufacturers to ensure the safety of these alternatives has led to the generation of replacements that may have similar or worse effects than the original chemicals. Consequently, there is increasing recognition by scientists, regulators and industry that proactive approaches are needed to develop safe chemical substitutes. We propose a 4-step approach for the design, characterization and toxicological testing of responsible alternative chemicals that we illustrate with our ongoing studies on DEHP replacements. Our approach is comprised of: (1) the design and characterization of alternative chemicals based on innovative chemical structures and environmental considerations; (2) large-scale in vitro cell-based high throughput and selective ex vivo studies to preselect the most innocuous alternatives; (3) an acute toxicity in vivo study to rule out overt toxicity of the selected candidates; and (4) an in utero and lactational exposure study comparing the effects of selected candidates to those currently in use, emphasizing commonly described phenotypes after exposure to the latter. Using this 4-step approach, we have identified 2 alternative chemicals displaying good plasticizing properties, better biodegradability, and less leaching than DEHP without any apparent toxicity in vivo. This process has thus far proven useful in the proactive identification of responsible chemical replacements for DEHP.

Impact of butyl benzyl phthalate on development of the reproductive system of European pikeperch, Sander lucioperca (L.).

The effect of butyl benzyl phthalate (BBP) on the sex differentiation process of fish is practically unknown. The experimental material of this study was juvenile European pikeperch [Sander lucioperca (L.)], which is gonochoristic, undergoes immediate sex differentiation, and has a fixed gonad differentiation period. The fish were fed a diet supplemented with BBP (during the sex differentiation phase: age 61-96 days post hatch) in the following quantities: 1.0; 2.0; 4.0; 8.0; 16.0 g BBP kg-1 feed. The control feed was a xenobiotic-free base feed. In the present experiment lasting 10 weeks, the survival and growth of fish, the histopathological changes of the fish gonads and the sex ratio were evaluated. After administration of the two highest doses of BBP, growth inhibition of the fish was observed. BBP also seriously disturbed the gonadal differentiation process of pikeperch. All analysed concentrations of BBP delayed testicular development and, at concentrations of 4.0, 8.0 and 16.0 g BBP kg-1, induction of the feminisation process was observed. The sex ratio was distinctly disrupted in groups receiving 8.0 and 16.0 g BBP kg-1.