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Because of rampant concern that estrogenic chemicals in the environment may be adversely affecting the health of humans and wildlife, reliable methods for detecting and characterizing estrogenic chemicals are needed. It is important that general agreement be reached on which tests to use and that these tests then be applied to the testing of both m...
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With the aid of such systems as the E-screen assay (MCF-7 human breast cancer cells) and/or estrogen receptor (ER) binding assays, estrogenic activity has been identified in a wide variety of nonsteroidal substances, such as polychlorobiphenyls, alkylphenols, bisphenols, pesticides (e.g., DDT derivatives, methoxychlor, kepone), pharmaceutical agent...
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... Reported encounters are other people or the estimated number of times a person remembers a warning (Vaske and Donnelly, 2002). In measuring intensity, encounter norms typically consume as standards for consumption to restrict individuals from accepting more encounters with other people or objects (Manning, 2007;Shelby et al., 1996). As a result of the increasing number of ecotourism destinations, it is subject to extensive negative impacts. ...
National parks are at the forefront where city people can satisfy their longing for nature. While the increase in the demands for green and soul has caused some questions for these areas, it has also prepared the ground for local governments to take protective-preventive measures. Yozgat Çamlık National Park has the title of being the first national park of Turkey and is characterized as a rare piece of nature. This study calculated the carrying capacities of the scenic cruise route and picnic roads, the most intensive-use areas of Yozgat Çamlık National Park. To make the calculations, the National Park was visited frequently between January and December 2021-2022, and the most intense usage points were determined. Photographs of the determined points were taken, and six simulation images were created. The visitors using the National Park were asked to score between 1-6 on the simulation images that they felt comfortable and uncomfortable within the simulation images created by a survey study. The National Park's Social Carrying Capacity and Social Norm levels were calculated according to the scoring status. When the findings are evaluated, the Social carrying capacity of the Picnic area is 524 people, the Social Norms level is nine people, the Social Capacity is 84 people on the Scenic cruise route, and the Social Norms level is determined as ten people.
... Estrogenicity assay In vivo uterotrophic assay using rodents Growth of uterine tissue under the control of estrogen and recording and evaluating the response Shelby et al. (1996); OECD. Test No. 440 (2007) In vivo vitellogenin assay using fish Vitellogenin is a hallmark of female protein and its occurrence or high concentration in male fish is considered estrogenic effect of endocrine disruption Heppell et al. (1995); Denslow et al. (1999); Matozzo et al. (2008) In vitro MCF-7 focus assay MCF-7 cells are known to propagate in response to estrogen and chemicals having similar estrogenic activity Arcaro and Gierthy (2001); Ssempebwa et al. (2004) In vitro estrogen screen assay in yeast Screening of Lac Z gene activity involving β-galactosidase in yeast Saccharomyces cerevisiae Bistan et al. (2012) In vitro luciferase reporter gene assay Monitoring of transcription of certain genes in cells and generation of light by the action of enzyme luciferase Naylor (1999) In vitro aryl hydrocarbon (dioxin) receptor (AHR) test Binding of AHR to dioxin like substance that activates cytochrome enzyme and decreases intracellular concentration of estrogen ...
Environmental Endocrine Toxicants: Biology, Effects, and Management presents important knowledge of human exposure to endocrine toxicants and the related harmful effects. The book highlights the cutting-edge research currently being conducted on the subject and focuses on the challenges of dealing with increasing pollution levels, increased use of synthetic chemicals, and environmental endocrine disruptors that endanger the human endocrine system and its respective hormones.
Found in various man-made and natural substances and materials, endocrine toxicants include pesticides, herbicides, industrial chemicals, solvents and by-products, phytoestrogens, nanomaterials, and chemicals used in personal care products. These endocrine disruptors may mimic or interfere with the body’s hormones and are linked with developmental, reproductive, brain, immune, and other problems.
The volume discusses the many potential endocrine toxicants and the pathways through which they disrupt the endocrine system.
Key features:
Provides an overview of the chemical nature and mechanisms of endocrine disruptors
Discusses the sources of endocrine toxicants
Assesses the impact of endocrine toxicants on a sustainable environment
Looks at endocrine toxicants and their effect on human health, such as on thyroid glands, on human reproduction, etc.
... The antioxidant potential of Amaranthus betalains has been shown to have stronger antioxidant properties compared with vitamin C and other interesting components of antioxidants like catechins (Cai et al., 2003). Even though some in vitro analyses of antioxidant activity of betalains by using the DPPH and TEAC tests provide the imperative acumens with the mode of action of their antioxidant activity, they are limited in their ability to impressionist on the entire metabolism and circulation of the animal (Shelby et al., 1996). By avoiding fat degradation and heme disintegration at lower concentrations, the quantification of antioxidant action of betalains in vitro condition needs to vigilant elucidation from beetroot and cacti fruits betalains showed the robust antioxidant property in the biological atmosphere. ...
... The pigment betalains have the capacity for fundamental inequality among oxidant species and organisms' antioxidant protection mechanism and can form a favorable situation for cells to combat oxidative stress (Esatbeyoglu et al., 2014). The application of in vivo analysis of betalains permits the detection of total effects consequential from numerous regulations of antioxidant activity (Shelby et al., 1996). An in vivo and in vitro study of betalains antioxidant activity can explore more effectively to determine it. ...
Betalains are pigments of red-violet and yellow colors derived from tyrosine that attract scientific and economic interest. In comparison with other major plant pigments, the findings of betalain related to biochemistry, chemistry, and function were minimal. Genetic engineering in plants and microbes for the development of betalains, opening up the current scenario since in recent years the large analysis of this pigment's main synthetic pathway has been elucidated. With the current survey, we address the health impact through regulatory mechanism and alternative source of betalains in this chapter. A broad view of current use and a possible new source of betalains, including a natural source or genetic engineering, bioavailability, and stability, will be given in addition to a summary of potential applications of betalains for research and commercial use.
... Our findings are in agreement with the study conducted previously in India (Anand and Taneja, 2020) and China (Guo et al., 2014), who showed that as the cord serum concentration of OCPs increases, the child birth weight decreases, whereas there are other reports which did not find any association between birth weight and the contamination to DDT and DDE (Tan et al., 2009). Probable mechanism of action for decrease in birth weight following OCPs and its metabolites contamination, may be that these OCPs interfere with endogenous hormones, like estrogens, androgens, and thyroid hormones (Li et al., 2008;Yaglova and Yaglov, 2015), as they bind to specific binding receptors by mimicking them (Shelby et al., 1996). OCPs could inhibit androgen binding to the androgen receptor by the antagonist action, which may interfere with the synthesis, metabolism and elimination of hormones (Kelce et al., 1995). ...
The present study was aimed to assess the correlation between transplacental transfer of xenobiotics and resulting biochemical alterations (including genotoxicity and oxidative stress) in non-occupational pregnant women of North India along with the effect on pregnancy outcomes. Maternal and cord blood samples were collected from 221 healthy mother-infant couples and divided according to their gestational age and birth weight. Genotoxic effects in mother and cord blood were examined using comet assay. The quantitative determination of Organo-chlorine pesticides in blood serum of study population was carried out using gas chromatography-mass spectrometry (GC-MS). Notably higher Organo-chlorine pesticides levels were observed in maternal blood of preterm than term subjects for almost all of the compounds detected, with the maximum concentration found for aldrin (3.26 mg/l) in maternal blood and dieldrin (2.69 mg/l) in cord blood. The results showed a significant increment in olive tail moment, tail full length, catalase, super-oxide dismutase, and malondialdehyde levels whereas lower glutathione reductase and peroxidase were found in preterm babies when compared with term group and it varied in the order: maternal blood > cord blood. A clear trend was observed for preterm babies with their lower birth weight and cesarean mode of delivery. Therefore, reduction in birth weight in newborns may be the consequence of increased oxidative damage and genotoxicity brought about by pesticides and these markers could be employed for early detection of pesticides related ailments and toxicities. To the best of our knowledge, this was a pioneering study and it may help to increase our knowledge with regard to xenobiotic exposure in biological system and the need for stringent guidelines for agricultural use of pesticides.
... In addition, the number of effects identified for the thyroid or adrenal glands depends directly on the organs studied by EFSA via the cumulative risks evaluation groups. The high prevalence of overweight status and type II diabetes among farmers and their potential relationship with exposure to pesticides is a strong argument for further investigation into the effects of PAS on carbohydrate and lipid metabolism [20][21][22]. ...
Studying the human health impacts of pesticides and their endocrine disruptor (ED) effects is a public health concern. The aim of this study is to identify phytopharmaceutical active substances (PAS) that are an ED or are toxic on endocrine glands (TEG), and to propose an ED/TEG effect indicator. Five international official databases were analyzed to identify the occurrence of health outcomes for 458 PAS. Health outcomes targeting seven endocrine systems were selected. For each substance, the level of evidence of the collected information and the number of outcomes were used to affect a level of concern about ED/TEG effects. Among the substances studied, 10% had a global ED/TEG effect classified as ‘high concern’, 55% as ‘medium concern’, 9% as ‘low concern’, and 26% as ‘unknown’. Ten of the high ED/TEG concern substances and 170 medium or low concern substances were licensed in 2018 in France. The outcomes were mainly on the reproductive organs, thyroid, and adrenal glands. Eight of the 41 biocontrol products studied were classified: 5 were ‘high’ or ‘medium concern’ and 3 had ‘unknown effect’. Although the proposed ED/TEG indicator is not an official classification, it can be used as an epidemiological tool for classifying the occupational and environmental risks of substances in retrospective population studies and be useful for occupational health physicians.
... These results are consistent with results from ERα reporter gene and cell proliferation data for ERα positive cells reported in the literature (Kalach et al. 2005;Sotoca et al. 2008). However, the binding affinity of DES to ERα has been reported to be slightly greater than that of E2 (Blair et al. 2000;Bolger et al. 1998;Okulicz and Johnson 1987;Shelby et al. 1996). ...
Diethylstilbestrol (DES) is a synthetic estrogen and proven human teratogen and carcinogen reported to act via the estrogen receptor α (ERα). Since the endogenous ERα ligand 17β-estradiol (E2) does not show these adverse effects to a similar extent, we hypothesized that DES’ interaction with the ERα differs from that of E2. The current study aimed to investigate possible differences between DES and E2 using in vitro assays that detect ERα-mediated effects, including ERα-mediated reporter gene expression, ERα-mediated breast cancer cell (T47D) proliferation and ERα-coregulator interactions and gene expression in T47D cells. Results obtained indicate that DES and E2 activate ERα-mediated reporter gene transcription and T47D cell proliferation in a similar way. However, significant differences between DES- and E2-induced binding of the ERα to 15 coregulator motifs and in transcriptomic signatures obtained in the T47D cells were observed. It is concluded that differences observed in binding of the ERα with several co-repressor motifs, in downregulation of genes involved in histone deacetylation and DNA methylation and in upregulation of CYP26A1 and CYP26B1 contribute to the differential effects reported for DES and E2.
... Reference chemicals for the VM7Luc ERTA assay were identified from OECD Test Guideline 455 (OECD, 2016) and 457 (OECD, 2012) (referenced hereafter as "test guideline"): one assay reference standard (17b-estradiol [E2]), 6 ER agonists (17a-ethinylestradiol, bisphenol A, coumestrol, ethylparaben, genistein, daidzein); 3 ER antagonists (tamoxifen, 4-hydroxytamoxifen, fulvestrant); 3 agonist negative controls (atrazine, corticosterone, spironolactone); and 1 antagonist negative control (resveratrol). The organochlorine pesticide methoxychlor (MXC) was included as a prototypical chemical requiring metabolic activation to produce the potent estrogenic metabolite 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) (Bulger et al., 1978a,b,c;Gaido et al., 1999;Ousterhout et al., 1981;Shelby et al., 1996). Both MXC and HPTE were included to monitor the metabolism-dependent range of MXC ERTA bioactivity. ...
... The proestrogenic control compound, MXC, also exhibited a decrease in efficacy when transitioned from test guideline to metabolism negative conditions, but exhibited an increase in efficacy from 29% to 64% of E2 controls in metabolism positive mode ( Figure 3D). MXC is metabolized to the potent metabolite HPTE and is well known to exhibit bioactivation for ER agonism (Mollergues et al., 2017;Shelby et al., 1996;van Vugt-Lussenburg et al., 2018). Hence, the coupling of metabolizing systems to existing in vitro assays should be carefully monitored for target assay variability, as well as any biotransformation effects on reference control compounds because performance may not fully conform to test guideline expectations. ...
The U.S. EPA Endocrine Disruptor Screening Program utilizes data across the ToxCast/Tox21 high-throughput screening (HTS) programs to evaluate the biological effects of potential endocrine active substances (EAS). A potential limitation to the use of in vitro assay data in regulatory decision-making is the lack of coverage for xenobiotic metabolic processes. Both hepatic- and peripheral-tissue metabolism can yield metabolites that exhibit greater activity than the parent compound (bioactivation) or are inactive (bioinactivation) for a given biological target. Interpretation of biological effect data for both putative EAS, as well as other chemicals, screened in HTS assays may benefit from the addition of xenobiotic metabolic capabilities to decrease the uncertainty in predicting potential hazards to human health. The objective of this study was to develop an approach to retrofit existing HTS assays with hepatic metabolism. The Alginate Immobilization of Metabolic Enzymes (AIME) platform encapsulates hepatic S9 fractions in alginate microspheres attached to 96-well peg lids. Functional characterization across a panel of reference substrates for phase I cytochrome P450 enzymes revealed substrate depletion with expected metabolite accumulation. Performance of the AIME method in the VM7Luc estrogen receptor (ER) transactivation assay was evaluated across 15 reference chemicals and 48 test chemicals that yield metabolites previously identified as ER active or inactive. The results demonstrate the utility of applying the AIME method for identification of false positive and false negative target assay effects, reprioritization of hazard based on metabolism-dependent bioactivity, and enhanced in vivo concordance with the rodent uterotrophic bioassay. Integration of the AIME metabolism method may prove useful for future biochemical and cell-based HTS applications.
... A target can be applied to a wide range of biological entities which includes proteins, genes and RNA. A good target needs to be efficacious, safe, meet clinical and commercial needs and, above all, be druggable [82][83][84][85][86][87][88][89][90][91][92][93]. ...
Drug discovery is one of the most complicated processes and establishment of a single drug may require multidisciplinary attempts to design efficient and commercially viable drugs. The main purpose of drug design is to identify a chemical compound or inhibitor that can bind to an active site of a specific cavity on a target protein. The traditional drug design methods involved various experimental based approaches including random screening of chemicals found in nature or can be synthesized directly in chemical laboratories. Except for the long cycle design and time, high cost is also the major issue of concern. Modernized computer-based algorithm including structure-based drug design has accelerated the drug design and discovery process adequately. Surprisingly from the past decade remarkable progress has been made concerned with all area of drug design and discovery. CADD (Computer Aided Drug Designing) based tools shorten the conventional cycle size and also generate chemically more stable and worthy compounds and hence reduce the drug discovery cost. This special edition of editorial comprises the combination of seven research and review articles set emphasis especially on the computational approaches along with the experimental approaches using a chemical synthesizing for the binding affinity in chemical biology and discovery as a salient used in de-novo drug designing. This set of articles exfoliates the role that systems biology and the evaluation of ligand affinity in drug design and discovery for the future.
... : Endocrine mechanism of action-As described above and in Table 2, DDT is widely acknowledged to be an ER agonist (142,143). Considering the key characteristics of EDCs, DDT is a androgen receptor antagonist (144), and it alters steroidogenic enzymes including aromatase (145,146). Circulating DDT exposures are associated with decreased serum testosterone levels in adult men living in a heavily contaminated area (147). ...
... Summary of effects of three model agrochemicals in Tier 1 EDSP assays, or similar assays examining comparable outcomes Assay DDT Endosulfan Atrazine ER binding assay Positive for ER binding (143) Negative for ER binding (143) Negative for ER binding (198) Aromatase DDT only affects aromatase at cytotoxic concentrations (96) but DDE appears to induce hepatic aromatase in vivo (146) Positive for weak inhibition of aromatase (199) Positive for aromatase upregulation (200) AR binding Positive for AR antagonism (144) Negative for AR binding (201) Steroidogenesis Positive for multiple effects on steroidogenesis in ovarian follicles (145) Positive for indirect effect on aromatase activity (200) ER transcriptional activation ...
... Summary of effects of three model agrochemicals in Tier 1 EDSP assays, or similar assays examining comparable outcomes Assay DDT Endosulfan Atrazine ER binding assay Positive for ER binding (143) Negative for ER binding (143) Negative for ER binding (198) Aromatase DDT only affects aromatase at cytotoxic concentrations (96) but DDE appears to induce hepatic aromatase in vivo (146) Positive for weak inhibition of aromatase (199) Positive for aromatase upregulation (200) AR binding Positive for AR antagonism (144) Negative for AR binding (201) Steroidogenesis Positive for multiple effects on steroidogenesis in ovarian follicles (145) Positive for indirect effect on aromatase activity (200) ER transcriptional activation ...
Many agrochemicals have endocrine disrupting properties. A subset of these chemicals is characterized as “estrogenic”. In this review, we describe several distinct ways that chemicals used in crop production can affect estrogen signaling. Using three agrochemicals as examples (DDT, endosulfan, and atrazine), we illustrate how screening tests such as the US EPA's EDSP Tier 1 assays can be used as a first-pass approach to evaluate agrochemicals for endocrine activity. We then apply the “Key Characteristics” approach to illustrate how chemicals like DDT can be evaluated, together with the World Health Organization's definition of an endocrine disruptor, to identify data gaps. We conclude by describing important issues that must be addressed in the evaluation and regulation of hormonally active agrochemicals including mixture effects, efforts to reduce vertebrate animal use, chemical prioritization, and improvements in hazard, exposure, and risk assessments.
... In vivo estrogenicity assay Uterotrophic assay is an internationally recognized short-term screening method to determine estrogenic and anti-estrogenic properties of chemicals in vivo [188,189]. It is based on the development of uterine tissue under the influence of estrogen. ...
Endocrine Disrupting Chemicals (EDCs) are a global problem for environmental and human health. They are defined as "an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action". It is estimated that there are about 1000 chemicals with endocrine-acting properties. EDCs comprise pesticides, fungicides, industrial chemicals, plasticizers, nonylphenols, metals, pharmaceutical agents and phytoestrogens. Human exposure to EDCs mainly occurs by ingestion and to some extent by inhalation and dermal uptake. Most EDCs are lipophilic and bioaccumulate in the adipose tissue, thus they have a very long half-life in the body. It is difficult to assess the full impact of human exposure to EDCs because adverse effects develop latently and manifest at later ages, and in some people do not present. Timing of exposure is of importance. Developing fetus and neonates are the most vulnerable to endocrine disruption. EDCs may interfere with synthesis, action and metabolism of sex steroid hormones that in turn cause developmental and fertility problems, infertility and hormone-sensitive cancers in women and men. Some EDCs exert obesogenic effects that result in disturbance in energy homeostasis. Interference with hypothalamo-pituitary-thyroid and adrenal axes has also been reported. In this review, potential EDCs, their effects and mechanisms of action, epidemiological studies to analyze their effects on human health, bio-detection and chemical identification methods, difficulties in extrapolating experimental findings and studying endocrine disruptors in humans and recommendations for endocrinologists, individuals and policy makers will be discussed in view of the relevant literature.
