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Atrazine is currently one of the most commonly used agrochemicals in the United States and elsewhere. Here, we studied the immunoexpression of molecular markers of mammalian testicular functions: androgen receptor (AR), promyelocytic leukemia zinc finger (PLZF), GDNF family receptor alpha-1 (GFRA1), VASA/DDX4 (DEAD-Box Helicase 4) as well as the levels of intratesticular and intra-epididymal estradiol (E2) and dihydrotestosterone (DHT), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins (IL-1β and IL-6, IL-10) and testicular chemokines (CXCL-1, CCL-2 and CCL3) in BalB/c mice after a sub-acute gavage treatment with a gonado-toxin, atrazine (50 mg/kg body wt.) for three days. We found high numbers of AR immunopositive Sertoli cells and low numbers of GFRA1, PLZF and VASA/DDX4-positive germ cells in the seminiferous tubule regions of the testes. While TNF-α level in the testes fell and remained unchanged in the epididymides, IFN-γ levels in the testes remained constant but increased in the epididymides. E2 and DHT concentrations remained unaltered in the testes but were changed in the epididymides. There were no significant changes in the levels of interleukins in the testis and epididymis. Intratesticular chemokines were also not significantly altered, except for CCL-4, which was increased in the testis. Light microscopy of the epididymis showed detached epithelium and some detached cells in the lumen. It is concluded that atrazine changed the inflammatory status of the gonads and highlighted Sertoli and undifferentiated spermatogonia as important targets for atrazine's toxic effects in the testis of mice. Concerning the epididymis, atrazine altered the epididymal hormonal concentrations and promoted histopathological modifications in its parenchyma. [Display omitted] • Acute exposure to atrazine has detrimental effects on the testis and epididymis. • Atrazine decreased VASA/DDX4, GFRA1 and PLZF expression in germ cells. • Atrazine increased AR expression in Sertoli cells. • Atrazine increased aromatase immunofluorescence in epididymides. • Epididymides are highly affected by atrazine's inflammatory and hormonal effects. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are widespread across the environment and humans are unavoidably and constantly exposed to them. As lipophilic contaminants, these substances tend to accumulate in fatty tissues as adipose tissue and exposure to these endocrine disruptors has been associated with severe health hazards including prevalence and incidence of obesity. Previous studies have shown significantly higher concentrations of PAHs in adipose tissue compared to other human samples, such as urine and plasma, which are typically used for PAHs assessment. Therefore, conducting biomonitoring studies in adipose tissue is essential, although such studies are currently limited. In this study, the concentrations of 18 PAHs were measured in subcutaneous (scAT) and visceral adipose tissue (vAT) of 188 Portuguese obese females by high performance liquid chromatography (HPLC). The obtained results were then associated with the patient's data namely: 13 clinical, 4 social, and 42 biochemical parameters. Seventeen PAHs were present, at least, in one sample of both scAT and vAT, most of them with detection frequencies higher than 80%. Indeno [1,2,3-cd]pyrene (InP) was the only PAH never detected. Overall higher concentrations of PAHs were observed in scAT. Median concentrations of ∑PAHs were 32.2 ± 10.0 ng/g in scAT and 24.6 ± 10.0 ng/g in vAT. Thirty-six significant associations (7 with social, 18 with clinical, and 11 with biochemical parameters), including 21 Spearman's correlations were identified (12 positive and 9 negative correlations). Indicating the potential effects of PAHs on various parameters such as obesity evolution, body fat, number of adipocytes, total cholesterol, alkaline phosphatase, macrominerals, uric acid, sedimentation velocity, and luteinizing hormone. This study underscores the significance of biomonitoring PAH levels in adipose tissue and their potential effects on metabolic health. Further research is essential to fully comprehend the metabolic implications of PAHs in the human body and to develop strategies for obesity prevention and treatment. [Display omitted] • 18 PAHs were measured in adipose tissue of 188 obese women. • 17 PAHs were detected and most of PAHs had detection frequencies higher than 80%. • Median concentrations of PAHs were 32.2 ng/g in scAT and 24.6 ng/g in vAT. • Overall higher concentrations of PAHs were observed in scAT. • PAHs alter metabolic processes of obese females (36 associations identified). [ABSTRACT FROM AUTHOR]

As the most heavily used herbicide globally, glyphosate (GLY) has been detected in a variety of environments and has raised concerns about its ecological and health effects. There is debate as to whether GLY may disrupt the endocrine system. Here, we investigated the developmental toxicity of GLY in zebrafish based on deep learning-enabled morphometric analysis (DLMA). In addition, the estrogenic activity of GLY was assessed by endocrine disruption prediction, docking study and in vivo experiments. Results showed that exposure to environmental concentrations of GLY negatively impacted zebrafish development, causing yolk edema and pericardial edema. Endocrine disruption prediction suggested that GLY may target estrogen receptors (ER). Molecular docking analysis revealed binding of GLY to three zebrafish ER. In vivo zebrafish experiment, GLY enhanced the protein levels of ERα and the mRNA levels of cyp19a, HSD17b1, vtg1, vtg2, esr1, esr2a and esr2b. These results suggest that GLY may act as an endocrine disruptor by targeting ER, which warrants further attention for its potential toxicity to aquatic animals. [Display omitted] • Glyphosate caused yolk sac oedema and pericardial oedema in zebrafish. • Glyphosate may target estrogen receptors. • Glyphosate poses the estrogenic effect both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

In recent decades, male infertility has been on the rise, largely attributed to exposure to chemicals with endocrine-disrupting properties. The adverse effects of disrupting androgen actions on the development and reproductive health of children and adolescents have been extensively studied. Flame retardants (FRs), used in consumer products to delay flammability, have been identified as antagonists of the androgen receptor (AR), potentially leading to adverse outcomes in male reproductive health later in life. This study examined the interaction of eight novel FRs with the AR, employing an in vitro AR-dependent luciferase reporter gene assay utilizing MDA-kb2 cells. The investigation revealed the anti-androgenic activity of tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), a frequently detected FR in the environment. Furthermore, TDBP-TAZTO contributed to anti-androgenic activity when combined with six other anti-androgenic FRs. The mixture effects were predicted by three commonly employed models: concentration addition (CA), generalized CA, and independent action, with the CA model showcasing the highest accuracy. This suggests that all FRs act through a similar mechanism, as further confirmed by in silico molecular docking, indicating limited synergy or antagonism. Importantly, in the mixtures, each FR contributed to the induction of anti-androgenic effects at concentrations below their individual effective concentrations in single exposures. This raises concern for public health, especially considering the co-detection of these FRs and their potential co-occurrence with other anti-androgenic chemicals like bisphenols. Therefore, our findings, along with previous research, strongly support the incorporation of combined effects of mixtures in risk assessment to efficiently safeguard population health. [Display omitted] • Androgen receptor (AR) agonist and antagonist activities were explored for eight novel flame retardants (FRs) • TDBP-TAZTO (tris (2,3-dibromopropyl) isocyanurate) is anti-androgenic • Four mixtures with different ratios of six anti-androgenic FRs, with or without TDBP-TAZTO, have anti-androgenic activity • The concentration of each FR at the mixture's inhibiting concentrations (IC) is several times lower than the individual ICs • The mixture effect is best predicted by the additivity model, with no clear evidence of synergy or antagonism [ABSTRACT FROM AUTHOR]

In this work, an evaluation of the occurrence of fifteen phthalates, four metabolites and one adipate in different groundwater, seawater and wastewater samples has been carried out due to their relevance on human health as they act as endocrine disruptors. For this purpose, a sustainable, fast and easy-handling vortex-assisted liquid-liquid microextraction method using a natural hydrophobic deep eutectic solvent based on menthol and carvacrol as extraction agent, combined with ultra-high performance liquid chromatography-mass spectrometry technique, has been developed and applied for the first time. An optimization was performed to evaluate four important factors affecting the extraction performance, and an analytical validation was carried out in terms of matrix effect, linearity, extraction efficiency, and sensitivity. Recovery values were obtained in the range 72–119% for all analytes (except for monoethyl phthalate: 61.1–72.3%) with relative standard deviation values lower than 17%. Limits of quantification were found between 0.91 and 8.09 μg L−1. As a result of the assessment of 31 different environmental water samples, monoethyl phthalate, diethyl phthalate, dibutyl phthalate and bis (2-ethylhexyl) phthalate were detected and quantified at different concentrations in the range 2.59–21.17 μg L−1 in 6 samples, and diallyl phthalate, butyl benzyl phthalate, dipentyl phthalate, dicyclohexyl phthalate, dihexyl phthalate and bis (2-ethylhexyl) adipate were detected in 20 more, showing the exposition of the population to these hazardous substances. [Display omitted] • Occurrence of endocrine disruptors was evaluated in 31 environmental water samples. • A NAHDES-based VA-LLME was used to extract PAEs, MPEs and DEHA for the first time. • The method was validated in groundwater, seawater, and wastewater matrices. • Recovery in the range 61–119% and LOQ in the range 0.91–8.09 μg L−1 were obtained. • MEP, DEP, DBP and DEHP were found at concentrations between 2.59 and 21.17 μg/L. [ABSTRACT FROM AUTHOR]

Despite the increasing concern regarding bisphenol A (BPA) as an endocrine disrupting chemical (EDC) upon environmental or human exposure, development of simple method for BPA detection has been hampered, due to the lack of a stable bioreceptor and signal generator. Here, we report a nucleic acid-based rapid and sensitive method for BPA detection, which constitutes a ssDNA aptamer and ssDNAzyme. When the peroxidase-like DNAzyme sequence was split into two parts (one incorporated into the anti-BPA aptamer as a target recognition element and the other into the complementary sequence as a bait), the presence of BPA hindered the association of the split DNA sequence, leading to a reduced signal in the DNAzyme-triggered chemiluminescence (CL). Thus, this NA-based CL measurement permitted the detection of BPA at as low as 5 nM with a broad dynamic range of five orders and with high selectivity towards BPA over other EDCs with structural similarity. With the development of aptamers, our detection method is expected to facilitate studies to monitor EDCs with high simplicity and sensitivity in the field of environmental science. • Rapid and sensitive detection of BPA was developed using coupled nucleic acids. • Split peroxidase-like ssDNAzyme was used with an anti-BPA ssDNA aptamer. • BPA-induced chemiluminescence showed high detection sensitivity and selectivity. • This method will promote applications for monitoring EDCs. [ABSTRACT FROM AUTHOR]

Abstract The present study evaluates the effects of adult exposure to low doses of a mixture of di-(2-ethylexyl)phthalate (DEHP) and nonylphenol (NP) on reproductive neuroendocrine function and behavior. The neural circuitry that processes male sexual behavior is tightly regulated by testosterone and its neural metabolite estradiol. In previous studies, we showed that adult exposure of mice to low doses of each of these widespread environmental contaminants resulted in altered sexual behavior, without any effect on the regulation of the gonadotropic axis. Here, adult C57BL/6J male mice were exposed to DEHP/NP (0.5 or 5 μg/kg body weight/day) for 4 weeks before starting the analyses. Mice treated with DEHP/NP at 0.5 μg/kg/day show altered olfactory preference, and fewer of them emit ultrasonic vocalization compared to the other treatment groups. These mice also exhibit a lower number of mounts and thrusts, increased locomotor activity and unaffected anxiety-state level, along with unaltered testosterone levels and kisspeptin system, a key regulator of the gonadotropic axis. Analysis of the neural circuitry that underlies sexual behavior showed that the number of cells expressing androgen and estrogen receptors is comparable between control and DEHP/NP-exposed males. The comparison of these data with those obtained in males exposed to each molecule separately highlights synergistic effects at the lower dose of contaminants of 0.5 μg/kg/day. In contrast, the effects previously observed for each molecule at 5 μg/kg/day were not detected. A detailed comparison of the effects triggered by separate or combined exposure to DEHP and NP is discussed. Highlights • Adult co-exposure to DEHP/NP alters male sexual behavior. • DEHP/NP mixture increases locomotor activity and reduces anxiety-state level. • The lower dose of DEHP/NP mixture triggers the majority of behavioral effects. • No effects of DEHP/NP mixture on the gonadotropic axis. • Unaltered number of AR- and ERα-immunoreactive cells in exposed males. [ABSTRACT FROM AUTHOR]

Abstract The aim of our study was to evaluate the bidirectional transfer of Bisphenol S (BPS) and its main metabolite, BPS Glucuronide (BPSG), using the model of perfused human placenta and to compare the obtained values with those of Bisphenol A (BPA) and BPA Glucuronide. Fourteen placentas at term were perfused in an open dual circuit with deuterated BPS (1 and 5 μM) and non-labelled BPSG (2.5 μM) and a freely diffusing marker antipyrine (800 ng/ml) in the presence of albumin (25 mg/ml). In a second experiment, the potential role of P-glycoprotein in the active efflux of BPS across the placental barrier was studied using the well-established P-glycoprotein inhibitor, PSC833 (2 and 4 μM). Placental transfer of BPS was much lower than that of BPA in both directions. The placental clearance index of BPS in the materno-fetal direction was three times lower than in the opposite direction, strongly suggesting some active efflux transport. However, our results show that P-glycoprotein is not involved in limiting the materno-fetal transfer of BPS. Placental transfer of BPSG in the fetal compartment was almost non-existent indicating that, in the fetal compartment, BPSG originates mainly from feto-placental metabolism. The feto-maternal clearance index for BPSG was 20-fold higher than the materno-fetal index. We conclude that the blood-placental barrier is much more efficient in limiting fetal exposure to BPS than to BPA, indicating that the placenta has a crucial role in protecting the human fetus from BPS exposure. Graphical abstract Image 1 Highlights • The placenta is more efficient to restrict fetal exposure to BPS than to BPA. • Materno-fetal transfer of Bisphenol S glucuronide was almost non-existent. • It is likely that BPS and its metabolite are effluxed out of the fetal compartment. [ABSTRACT FROM AUTHOR]

Clethodim is a widely used and approved class II herbicide, with little information about its impact on the reproductive system. Herein, we investigated the male reproductive toxicity of clethodim using a mouse model. GrassOut Max (26% clethodim-equivalent) or analytical grade clethodim (≥90%) were given orally to male mice for 10 d in varying doses. All parameters were assessed at 35 d post-treatment. Significant decrease in testicular weight, decreased germ cell population, elevated DNA damage in testicular cells and lower serum testosterone level was observed post clethodim based herbicide exposure. Epididymal spermatozoa were characterized with significant decrease in motility, elevated DNA damage, abnormal morphology, chromatin immaturity and, decreased acetylated-lysine of sperm proteins. In the testicular cells of clethodim-based herbicide treated mice, the expression of Erβ and Gper was significantly higher. Proteomic analysis revealed lower metabolic activity, poor sperm-oocyte binding potential and defective mitochondrial electron transport in spermatozoa of clethodim-based herbicide treated mice. Further, fertilizing ability of spermatozoa was compromised and resulted in defective preimplantation embryo development. Together, our data suggest that clethodim exposure risks male reproductive function and early embryogenesis in Swiss albino mice via endocrine disrupting function. [Display omitted] • Clethodim affects spermatogenesis and produces poor quality sperm. • Clethodim acts as a potential endocrine disruptor. • Decreased fertilization potential of spermatozoa observed post clethodim exposure. • Paternal exposure to clethodim leads to defective embryo development. [ABSTRACT FROM AUTHOR]

The widely used herbicide atrazine is a potent endocrine disruptor known to cause increased aromatase expression and transient increase in testicular weight followed by remarkable testis atrophy. However, whether the effects of atrazine on the testes are primary or secondary to dysfunctions in other components of male reproductive tract remains unknown. Given the high sensitivity of the efferent ductules to estrogen imbalance and the similarity to alterations previously described for other disruptors of these ductules function, and the testicular alterations observed after atrazine exposure, we hypothesized that the efferent ductules could be a target for atrazine. Herein we characterized the efferent ductules and the ventral prostate of adult Wistar rats treated with 200 mg/kg/day of atrazine for 7, 15, and 40 days. Additionally, we evaluated if the effects of atrazine in these organs could be reduced after discontinuation of the treatment. Atrazine exposure resulted in mild effects on the ventral prostate, but remarkable alterations on the efferent ductules, including luminal dilation, reduced epithelial height, and disruption of the epithelial homeostasis, which coincides with increased aromatase expression. Together with our previous data, these results suggest that at least part of the testicular effects of atrazine may be secondary to the alterations in the efferent ductules. [ABSTRACT FROM AUTHOR]

Phthalates are plasticizers commonly detected in human urine due to widespread exposure from PVC plastics, food packaging, and personal care products. Several phthalates are known antiandrogenic endocrine disruptors, which raises concern for prenatal exposure during critical windows of fetal development. While phthalate exposure is ubiquitous, certain demographics are subject to greater or lesser exposure. We sampled urine from 378 pregnant women during the second trimester of gestation living in Charleston, SC, and measured eight urinary phthalate metabolites as biomarkers of phthalate exposure: monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and monomethyl phthalate (MMP). Demographic data was collected from questionnaires administered at the time of specimen collection. All phthalate metabolites were detected in over 93% of urine samples. On average, concentrations were highest for MEP (median = 47.0 ng/mL) and lowest for MMP (median = 1.92 ng/mL). Sociodemographic characteristics associated with elevated phthalate concentrations included being unmarried, less educated, having a low income, high body mass index (BMI), and/or being African American. After racial stratification, age, BMI, education, and income were significantly associated with phthalate concentrations in African American women. Marital status was associated with phthalate concentrations in Caucasian women only, with greater concentrations of MBP, MEHHP, MiBP, and MMP in unmarried versus married women. Results of this cross-sectional study provide evidence for significant racial and demographic variations in phthalate exposure. [ABSTRACT FROM AUTHOR]

Cypermethrin (CYP) is a widely used synthetic pyrethroid insecticide and regarded as a potential endocrine disruptor. CYP exposure may pose a great risk to human health including adverse effect on their reproductive functions. This study aimed to delineate the effects of perinatal exposure of rats to CYP on the sexual maturation and fertility of F1 male progeny. Pregnant rats (F0) were gavaged daily with CYP (0, 1, 10, 25 mg/kg BW/day) and Diethylestilbestrol (DES, 10 μg/kg BW/day), as positive control from gestation day 6 to postnatal day 21. The effects of CYP on body weight gain and reproductive functions were evaluated at the Juvenile (PND 22), peri-pubertal (PND 45) and adult (PND 75) stages of development. A significant delay in the age of testicular descent and prepuce separation was observed at 1 and 25 mg/kg doses of CYP. At the same dose level, reproductive organ development and their functions were also affected. A significant alteration in testicular histology, expression of steroid hormone receptors, and circulatory steroid hormones was observed throughout development. Reduced sperm count and motility were observed at PND 75 leading to subfertility and reduced litter size. These adult male rats when cohabitated with unexposed normal cycling females, the F2 fetuses exhibited developmental defects. Taken together, CYP perinatal exposure caused significant long lasting effects of the reproductive functions of F1 generation male rats, which were vertically transmitted to F2 generation leading to developmental defects. The mechanism of transgenerational effects needs to be explored in details. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is widely used in industry, and is released in large amounts into the environment. BPA is a teratogen and an estrogen receptor agonist and negatively affects reproduction, particularly in aquatic animals, which is of concern for the aquaculture industry. Although there is a large body of literature on the mechanisms that underlie BPA disruption and the effects of different toxicities on invertebrate reproduction, many of the mechanisms involved in invertebrate responses to BPA remain unknown. In this study, we investigated the effects of BPA on the reproduction of female and male oysters ( Crassostrea angulata ), and measured BPA bioaccumulation, the gonad-somatic index (GSI), and gonadal protein profiles in oysters exposed to BPA. Compared to controls, approximately 160-times more BPA accumulated in the gonads of male and female oysters after exposure to 2 mg L −1 BPA for 16 days. Gonadal development was negatively affected in males, but was accelerated in females when exposed to BPA, based on GSI analysis and a visual inspection of histological sections of the gonads. BPA exposure induced the differential expression of many important proteins such as vitellogenin, periostin, phosphoglucomutase, collagen alpha-1(XII) chain, and zinc transporter 9, which are involved in energy metabolism, oxidative stress, gene transcription regulation, the vitellogenin interaction network, and zinc transportation. A functional analysis of these proteins indicated that BPA has different effects on gonadal development in male and female oysters. [ABSTRACT FROM AUTHOR]

Composite resin has been increasingly used in an effort to remove minimal amount of tooth structure and are used for restoring not just carious cavities but also cervical abrasion. To synthesize composite resin, bisphenol A (BPA) is used. The aim of the study was to measure the changes in salivary BPA level related with composite resin restoration. ELISA was used to examine the BPA levels in the saliva collected from 30 volunteers whose teeth were filled with composite resin. Salivary samples were collected immediately before filling and 5 min and 7 d after filling. Wilcoxon signed-ranks test and linear regression were performed to test the significant differences of the changes in BPA levels in saliva. Before a new composite resin filling, there was no significant difference between with and without existing filling of composite resin and BPA level in the saliva was not correlated to the number of filled surfaces with composite resin. However, BPA level in the saliva increased to average 3.64 μg/L from average 0.15 μg/L after filling 5 min. BPA level increased in proportion with the number of filled surfaces. BPA level decreased to average 0.59 after filling 7 d. However it was higher than the BPA level before a new composite resin filling. Considering 50 μg/kg/day as the Tolerable Daily Intake of BPA suggested by European Food Safety Authority, the amount of BPA eluted in saliva after the composite resin filling is considered a safe level that is not a hazard to health at all. [ABSTRACT FROM AUTHOR]

Inorganic minerals are important compositions in biochars, but their roles in biochar functions are investigated limitedly, which restricted our understanding on biochar applications. This study applied different biomasses to produce biochars. Their properties as well as sorption to bisphenol A (BPA) were studied, with a major focus on the role of inorganic compositions. Oxalates, carbonates, as well as KCl crystals were observed in the produced biochars depending on the feedstocks and temperatures. Oxalates and KCl formed at relatively low temperature (200–300 °C), while carbonates generally formed at pyrolysis temperature above 400 °C. The separated insoluble crystal particles and the dissolved salts have limited contribution to the apparent BPA sorption, but ash content removal altered BPA sorption. The potential impact of inorganic composition to BPA sorption should be resulted from biochar properties. Based on biochar characterization and sorption comparison before and after ash removal, we proposed that the formation of inorganic mineral compositions in biochar particles may have blocked the inner pores, which limited the significance of these sorption sites. As a result, the interactions of BPA and biochars were mostly determined by biochar surface functional groups. The acid treatment removed most of the inorganic compositions, and exposed more sorption sites, which consequently increased BPA sorption. Biochar sorption capacity may be further increased if the accessibility of the inner pores could be enhanced. [ABSTRACT FROM AUTHOR]

Glyphosate-based herbicides (GBHs) are one of the most commonly used herbicides worldwide. Numerous in vitro and in vivo model system studies have demonstrated endocrine-disrupting chemical (EDC) properties associated with glyphosate/GBH exposure. The present hypothesis-testing study evaluated the potential inverse dose-dependent relationship between increasing urinary glyphosate and decreasing concentrations of blood sex hormones. Demographic and newly available lab test data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) were analyzed with survey regression modeling (adjusted for age, gender, race, and country of birth) in Statistical Analysis System (SAS) software. A total of 225, 615, 858 weighted-persons (sample n = 2130 persons) were examined for concentrations of urinary glyphosate and serum sex hormones (including: total testosterone, total estradiol, and sex hormone binding globulin (SHBG)) among males and females, 6 years-old or older. This study revealed about 82% of the population of the United States examined had detectable urinary concentrations of glyphosate. A significant inverse correlation between concentrations of glyphosate and total estradiol and a trend towards an inverse correlation between concentrations of glyphosate and total testosterone were observed. Concentrations of SHBG and glyphosate did not correlate. Ratios of total testosterone:SHBG and total estradiol:SHBG (estimating the fraction of active sex hormones in the blood) were significantly inversely correlated with urinary concentrations of glyphosate. This epidemiological study associates widespread and ongoing glyphosate/GBH exposures with human endocrine-disruptions. Future studies should examine these phenomena in other databases and other endocrine-related disorders. [Display omitted] • Glyphosate-based herbicides are among the most commonly used herbicides. • Glyphosate is widely present in the environment. • Glyphosate exposure was linked to endocrine-disruption. • Urinary glyphosate is detectable in ∼82% of the US population. • Urinary glyphosate is inversely related to blood sex hormones amounts. [ABSTRACT FROM AUTHOR]

Triclosan (TCS) is an antibacterial compound used mainly in personal care products. Its widespread use for decades has made it one of the most widely detected compounds in environmental matrices and in biological fluids. Although it has been shown to be an endocrine disruptor in rats and aquatic species, its safe use by humans is unclear. The aim of the present study was to evaluate the effects of exposure to TCS in female rats. To this end, 14 rats were divided into two groups and fed daily as follows: the control group with sesame oil and the TCS group at a dose of 50 mg/kg/day for 28 days. Any signs of toxicity in the rats were observed daily, and the weight and phase of the estrous cycle were recorded. At the end, the rats were decapitated, the serum and ovaries were collected. The levels of testosterone and progesterone in serum were determined by immunoassay and mass spectrometry. Estradiol (in serum) and kisspeptin-10 (in serum and ovary) were measured only by immunoassays. Trace elements were determined by inductively coupled plasma–mass spectrometry (ICP–MS). The weight gain study of the rats showed a significant decrease by exposure to TCS, while the estrous cycle was not significantly affected compared to the control. The optimized methods based on mass spectrometry showed a significant decrease in the levels of progesterone and testosterone due to exposure to TCS. In addition, elements determined by ICP–MS in rat serum showed significant changes in calcium, lithium and aluminum due to TCS treatment. Finally, the kisspeptin-10 levels did not show a negative effect due to the treatment by TCS. The results suggest that medium-term exposure to TCS did not significantly alter estrous cyclicity but caused alterations in growth, sex hormone levels and some elements in the rat serum. [Display omitted] • The exposure to triclosán in rats caused alterations in animal growth, steroid hormone levels and in the contents of calcium, lithium and aluminum. [ABSTRACT FROM AUTHOR]

Sex hormone disorders can cause adverse health consequences. While experimental data suggests that cadmium (Cd) disrupts the endocrine system, little is known about the link between Cd exposure and sex hormones in men. We measured blood cadmium (B-Cd), urine cadmium (U-Cd), serum testosterone and serum estradiol in men aged ≥18 years old participating in the China National Human Biomonitoring program, from 2017 to 2018. Urine cadmium adjusted for creatinine (Ucr-Cd) and the serum testosterone to serum estradiol ratio (T/E 2) were calculated. The association of Cd exposure to serum testosterone and T/E 2 in men was analyzed with multiple linear regression models. Among Chinese men ≥18 years old, the weighted geometric mean (95% CI) of B-Cd and Ucr-Cd levels were 1.23 (1.12-1.35) μg/L and 0.53 (0.47-0.59) μg/g, respectively. The geometric means (95% CI) of serum testosterone and T/E 2 were 18.56 (17.92-19.22) nmol/L and 143.86 (137.24-150.80). After adjusting for all covariates, each doubling of B-Cd level was associated with a 5.04% increase in serum testosterone levels (β = 0.071; 95%CI: 0.057-0.086) and a 4.03% increase in T/E 2 (β = 0.057; 95%CI: 0.040-0.075); similar findings were found in Ucr-Cd. In Chinese men, Cd may be an endocrine disruptor, which is positively associated with serum testosterone and T/E 2. [Display omitted] • Cadmium exposure was positively associated with testosterone in Chinese men. • Cadmium exposure was positively associated with T/E 2 in Chinese men. • Cadmium can act as an endocrine disruptor to affect hormone homeostasis in men. [ABSTRACT FROM AUTHOR]

The aim of the study was to develop a rapid, cost-effective combined testing method to assess the indirect effect of compounds interfering with sex steroid synthesis and to determine complex effects of atrazine on estrogen and androgen synthesis in vitro on H295R human cell line. Steroidogenic assay was performed on H295R human adrenocortical carcinoma cell line. Instead of standard analytical methods, bioluminescence bioreporter assays ( Saccharomyces cerevisiae BLYES and BLYAS) were used to measure estrogenic and androgenic effects of sex steroid hormones released by human cells in response to atrazine. Atrazine resulted in elevated estrogen production presumably due to its well documented inductive effect on aromatase on H295R cell line, detected by BLYES. Interestingly, results of BLYAS test showed concentration-dependent increase of androgen production in H295R cells. That indicates that atrazine can not only increase estrogen level via aromatase induction, but may interfere in androgen synthesis as well. The combined method allows us to assess the androgenic and estrogenic effect of sex steroids produced by human cells in increased or decreased quantity as a result of the different chemicals, without determining specific analytical measurement endpoints, by using the yeast based bioluminescent bioreporter test. [ABSTRACT FROM AUTHOR]

A considerable amount of scientific evidence indicates that a number of pharmaceuticals that could be detected in the environment can contribute towards the development of problems associated with human reproductive systems, as well as those of wildlife. We investigated the estrogenic and androgenic effects of select pharmaceuticals with high production volume and environmental relevance. We examined the receptor-binding activities of these pharmaceuticals in the T47D human cell line using altered secretion of cytokine CXCL12. Functional yeast-luciferase reporter gene assays were also employed to confirm the mechanism of receptor binding by estrogen and androgen. Non-steroidal anti-inflammatory drugs, namely ibuprofen, diclofenac and antiarrhythmic agent amiodarone showed strong anti-estrogenic effects in the T47D cell line. In the yeast-luciferase assay, these anti-inflammatory drugs also demonstrated anti-estrogenic potency and inhibited the E2 response in a concentration-dependent manner. Amiodarone did not exhibit any response in the yeast-luciferase assay; therefore, the endocrine disruption presumably occurred at a different level without directly involving the receptor. All the anti-inflammatory drugs considered in this study, including ketoprofen, naproxen and clofibrate, exhibited a dose-dependent antagonism towards the androgen receptor in the yeast-luciferase assays. Several other drugs, including the stimulant caffeine, did not show any response in the tests that were employed. A risk assessment analysis using ‘Hazard Quotient’ suggested a potential risk, especially in the cases of ibuprofen, ketoprofen, diclofenac and clofibrate. The results reveal the intrinsic endocrine disrupting nature of several pharmaceuticals and thus could contribute towards explaining a number of adverse health effects on humans and wildlife. [ABSTRACT FROM AUTHOR]

Due to phasing out of additive flame retardants such as polybrominated diphenyl ethers (PBDEs), Tris (2-butoxyethyl) phosphate (TBOEP) is widely used as a substitute. TBOEP is ubiquitous in the environment and has been measured at concentrations of micrograms per liter (μg L −1 ) in surface waters and wastewater. Information on potential adverse effects on development of aquatic organisms caused by exposure to environmentally relevant concentrations of TBOEP is limited, especially for effects that may be caused through impairment of endocrine-modulated homeostasis. Therefore, this study was conducted to determine effects of TBOEP on ontogeny and transcription profiles of genes along the hypothalamus–pituitary–thyroidal (HPT), hypothalamus–pituitary–adrenal (HPA), and hypothalamus–pituitary–gonadal (HPG) axes in embryos/larvae of zebrafish ( Danio rerio ). Exposure to TBOEP (2–5,000 μg L −1 ) from 3 h post-fertilization (hpf) to 120 hpf induced developmental malformations in zebrafish with a LC 50 of 288.54 μg L −1 at both 96 hpf and 120 hpf. The predicted no observed effect concentration (PNOEC) was 2.40 μg L −1 . Exposure to 2, 20, or 200 μg TBOEP L −1 altered expression of genes involved in three major molecular pathways in a concentration-dependent manner after 120 hpf. TBOEP caused lesser expression of some genes involved in synthesis of hormones, such as ( pomc and fshβ ) as well as upregulating expression of some genes coding for receptors ( thr, tshr, gr, mr, er and ar ) in zebrafish larvae. These changes at the molecular level could result in alterations of endocrine function, which could result in edema or deformity and ultimately death. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) occurs widely in natural waters with both traditional and reproductive toxicity to various aquatic species. The water quality criteria (WQC), however, have not been established in China, which hinders the ecological risk assessment for the pollutant. This study therefore aims to derive the water quality criteria for BPA based on both acute and chronic toxicity endpoints and to assess the ecological risk in surface waters of China. A total of 15 acute toxicity values tested with aquatic species resident in China were found in published literature, which were simulated with the species sensitivity distribution (SSD) model for the derivation of criterion maximum concentration (CMC). 18 chronic toxicity values with traditional endpoints were simulated for the derivation of traditional criterion continuous concentration (CCC) and 12 chronic toxicity values with reproductive endpoints were for reproductive CCC. Based on the derived WQC, the ecological risk of BPA in surface waters of China was assessed with risk quotient (RQ) method. The results showed that the CMC, traditional CCC and reproductive CCC were 1518 μg L −1 , 2.19 μg L −1 and 0.86 μg L −1 , respectively. The acute risk of BPA was negligible with RQ values much lower than 0.1. The chronic risk was however much higher with RQ values of between 0.01–3.76 and 0.03–9.57 based on traditional and reproductive CCC, respectively. The chronic RQ values on reproductive endpoints were about threefold as high as those on traditional endpoints, indicating that ecological risk assessment based on traditional effects may not guarantee the safety of aquatic biota. [ABSTRACT FROM AUTHOR]

The aim of this study was to improve the identification of endocrine disrupting chemicals (EDCs) by developing and evaluating in silico tools that predict interactions at the estrogen (E) and androgen (A) receptors, and binding to transthyretin (T). In particular, the study focuses on evaluating the use of the EAT models in combination with a metabolism simulator to study the significance of bioactivation for endocrine disruption. Balanced accuracies of the EAT models ranged from 77–87%, 62–77%, and 65–89% for E-, A-, and T-binding respectively. The developed models were applied on a set of more than 6000 commonly used industrial chemicals of which 9% were predicted E- and/or A-binders and 1% were predicted T-binders. The numbers of E- and T-binders increased 2- and 3-fold, respectively, after metabolic transformation, while the number of A-binders marginally changed. In-depth validation confirmed that several of the predicted bioactivated E- or T-binders demonstrated in vivo estrogenic activity or influenced blood levels of thyroxine in vivo . The metabolite simulator was evaluated using in vivo data from the literature which showed a 50% accuracy for studied chemicals. The study stresses, in summary, the importance of including metabolic activation in prioritization activities of potentially emerging contaminants. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals (EDCs). Their presence in the environment is particularly concerning in cases of fetal exposure, which is the most vulnerable period of life for both human and animals who share the same environment. Placenta, as a sample collected using noninvasive methods to screen EDCs, is a good indicator for potential fetal exposure. Although recent studies indicate that companion animal may correspond to human exposure, species-specific anatomo-morphological and metabolic differences are controversial. In this study, placenta samples of 60 women and 25 dogs living and giving birth within the same region were evaluated for the presence of PCB, OCP, PBDE, and PAH residues; where, socio-demographic factors were also assessed to identify the possible sources. Gas chromatography-mass spectrometry method was validated for the matrix, and among 45 screened and targeted pollutants, only 18 were found in human placentas. While the most frequently detected pollutants were DDTs, followed by PAHs and PCBs in decreasing order, the pollutants with the highest concentrations were PAHs, followed by PCBs and DDTs. Only five of the target contaminants were detected in the dog placentas. These results indicate that; as dogs have different bioaccumulation capacities and higher excretion rates than humans, the life-long effects of exposure to endocrine compound and possible consequences related to adverse health outcomes are expected to vary and concentrations cannot be directly correlated. [Display omitted] • Tested that dogs could be used as sentinels for human exposure to pollutants. • PCBs, OCPs, PBDEs, and PAHs in dog and human placentas were analyzed using GC-MS. • Dogs have a lower bioaccumulation capacity and a higher excretion rate than humans. • Socio-demographic factors can affect exposure to environmental pollutants. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) has become a topic of increasing concern for its environmental and health risks. However, studies on the potential toxic effects of GO, especially as an endocrine disrupting chemical (EDC), are very limited. In the present study we have used Japanese medaka fish as a model to assess the endocrine disruption potential of GO by evaluating its toxic and histopathologic effects on thyroid follicles and the gas gland (GG) of medaka larvae. One day post-hatch (dph) starved medaka fries were exposed to GO (2.5, 5.0, 10.0, and 20 mg/L) for 96 h, followed by 6 weeks depuration in a GO-free environment with feeding. Larvae were sacrificed and histopathological evaluation of thyroid follicles and the GG cells were done microscopically. Different sizes of spherical/oval shape thyroid follicles containing PAS positive colloids, surrounded by single-layered squamous/cuboidal epithelium, were found to be scattered predominantly throughout the pharyngeal region near the ventral aorta. We have apparently observed a sex-specific difference in the follicular size and thyrocytes height and a non-linear effect of GO exposure on the larvae on 47th day post hatch (dph). The GG is composed of large uniform epithelial cells with eosinophilic cytoplasm. Like thyroids, our studies on GG cells indicate a sex-specific difference and GO exposure non-linearly reduced the GG cell numbers in males and females as well as in XY and XX genotypes. Our data further confirm that sex effect should be carefully considered while assessing the toxicity of EDCs on the thyroid gland. [Display omitted] • Compared to XX genotype, XY males have large thyroid follicles and long thyrocytes. • Phenotypic females and XX males have increased number of GG cells than XY males. • GO exposure apparently showed sex-specific effects on follicles and thyrocytes. • GO reduced GG cell numbers in male and female phenotypes, and XY and XX genotypes. • Agglomeration of GO in thyroid disruption was demonstrated in medaka. [ABSTRACT FROM AUTHOR]

Several studies have reported exposure of humans to various endocrine disrupting chemicals (EDCs) worldwide. However, there is a lack of data regarding EDC exposures in humans living in Southeast Asian countries, such as the Philippines. Hence, this study measured levels of 41 EDCs in women residing in the Greater Manila Area, home to the second largest city in Southeast Asia. Urine samples from women with versus without breast cancer were analyzed for 11 phthalate metabolites, 8 environmental phenols, and 10 bisphenols, while serum samples were analyzed for 12 perfluoroalkyl substances (PFAS). Out of the four groups of EDCs analyzed, PFAS were significantly associated with breast cancer (adjusted OR = 13.63, 95% CI: 3.24–94.88 p -trend = 0.001 for PFDoA; adjusted OR = 9.26, 95% CI 2.54–45.10, p -trend = 0.002 for PFDA; and adjusted OR = 2.66, 95% CI: 0.95–7.66, p -trend = 0.004 for PFHxA). Long-chain PFAS levels were positively correlated with age and were significantly higher in women from Region IV-A, a heavily industrialized region, than from the National Capital Region. Overall, this study showed baseline information regarding the level of EDCs in Filipinas, providing a glimpse of EDC exposure in women living in a megalopolis city in Southeast Asia. • Endocrine disrupting chemicals were detected in women from the Greater Manila Area. • High PFAS levels were observed in Filipinas with breast cancer. • Long-chain PFAS concentration was positively correlated with age in Filipinas. • Long-chain PFAS levels were higher in women from Region IV-A versus NCR. [ABSTRACT FROM AUTHOR]

Highlights: [•] Pyriproxyfen induces male production in adult Daphnia magna with an EC50 of 156pM. [•] Pyriproxyfen primarily reduces reproduction and slows development in juveniles. [•] Pyriproxyfen’s effects on fecundity are more pronounced in juveniles than adults. [•] Recovery takes longer in juveniles than adults. [•] The length of exposure is crucial as daphnids can recover from acute exposures. [Copyright &y& Elsevier]

Abstract: Organochlorine compounds (OCCs), like pesticides (OCPs) and polychlorinated biphenyls (PCBs), are persistent lipophilic chemicals classified as endocrine-disruptors. Caiman latirostris inhabits wetlands throughout north-eastern Argentina and may accumulate OCCs. The aims of this study were to determine OCC residues in the eggs of C. latirostris and to correlate OCC burden with clutch size, hatching success and hatchling survival as measures of reproductive performance. Fourteen caiman clutches were harvested from sites with different degrees of anthropogenic intervention on wetlands surrounding Paraná River tributaries. Two to four eggs by clutch were used to quantify OCCs. OCP residues were found in all clutches. The principal contributors to the OCPs burden were the DDT family (range BDL-153.0ngg−1 lipid) and oxychlordane (range BDL-34.3ngg−1 lipid). PCBs were present in 92.9% of the clutches (range BDL-136.6ngg−1 lipid). Both higher concentrations and higher diversity of pesticides, including endosulfan sulfate, were found in the nests harvested close to croplands. A negative correlation was found between clutch size and ∑OCCs (p =0.02, Pearson r =−0.53, r 2 =0.28), mainly due to the ∑OCPs (p =0.04, Pearson r =−0.54, r 2 =0.30). Since egg OCCs concentrations predict maternal burden, present findings suggest that higher OCCs exposure could lead to smaller clutches. Although, other factors like mother age could influence clutch size. Additionally, as caimans are a long-lived and non-migratory species, the maternal OCCs burden reflects the environmental status throughout their home range; thus, caiman eggs could be useful as a biomonitor of local contamination. [Copyright &y& Elsevier]

Abstract: Bisphenol A is an endocrine disrupting compound, which is ubiquitous in the environment due to its wide use in plastic and resin production. Seven day old cultures of the litter-decomposing fungus Stropharia coronilla removed the estrogenic activity of bisphenol A (BPA) rapidly and enduringly. Treatment of BPA with purified neutral manganese peroxidase (MnP) from this fungus also resulted in 100% reduction of estrogenic activity, as analyzed using a bioluminescent yeast assay, and in the formation of polymeric compounds. In cultures of Stropharia rugosoannulata, estrogenic activity also quickly disappeared but temporarily re-emerged in the further course of cultivation. LC–MS analysis of the extracted estrogenic culture liquid revealed [M−H]− ions with m/z values of 219 and 235. We hypothesize that these compounds are ring fission products of BPA, which still exhibit one intact hydroxyphenyl group to interact with estrogen receptors displayed by the yeast. [Copyright &y& Elsevier]