Endocrine-disrupting Properties Research Articles

Chemical exposomics in biobanked plasma samples and associations with breast cancer risk factors.

The chemical exposome includes exposure to numerous environmental and endogenous molecules, many of which have been linked to reproductive outcomes due to their endocrine-disrupting properties. As several breast cancer risk factors, including age and parity, are related to reproduction, it is imperative to investigate the interplay between such factors and the chemical exposome prior to conducting large scale exposome-basedbreast cancer studies. This pilot study aimed to provide an overview of the chemical exposome in plasma samples from healthy women and identify associations between environmental exposures and three risk factors for breast cancer: age, parity, and age at menarche. Plasma samples (n = 161), were selected based on reproductive history from 100 women participating in the Northern Sweden Health and Disease Study, between 1987 and 2006. Samples were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) for 77 priority target analytes including contaminants and hormones, with simultaneous untargeted profiling of the chemical exposome and metabolome. Linear mixed effects models were applied to test associations between risk factors and chemical levels. Fifty-five target analytes were detected in at least one individual and over 94,000 untargeted features were detected across all samples. Among untargeted features, 430 could be annotated and were broadly classified as environmental (246), endogenous (167) or ambiguous (17). Applying mixed effect models to features detected in at least 70% of the samples (16,778), we found seven targeted analytes (including caffeine and various per- and poly-fluoroalkyl substances) and 38 untargeted features, positively associated with age. The directionality of these associations reversed for parity, decreasing with increasing births. Seven separate targeted analytes were associated with age at menarche. This study demonstrates how a comprehensive chemical exposome approach can be used to inform future research prioritization regarding associations between known and unknown substances, reproduction, and breast cancer risk. This study illustrates how chemical exposomics of long-term stored blood samples offers valuable insights to discover chemical exposures and their potential links to disease in humans, particularly those related to reproduction and breast cancer risk factors.

Pesticide Pollution in India: Environmental and Health Risks, and Policy Challenges

Intensive agriculture practices in India to meet the food demand of the increasing population have led to the use of agrochemicals such as pesticides in higher quantities to increase productivity resulting in contamination of the environment. Pesticides control pests, weeds, and diseases in plants, animals, and humans. Despite bans on pesticides such as organochlorides (OC), organophosphate (OP), or synthetic pyrethroids ranging from minimal to excessive, are detected in soil, surface water, and groundwater often exceeding WHO and BIS safety limits. The predominantly found pesticides were DDT, HCH, Endosulfan, malathion, chlorpyrifos, atrazine, endrin, cypermethrin, dichlorvos, etc. Different ranges of pesticides were detected in different states (Kashmir, UP, Tamil Nadu, Kerala, Rajasthan, Haryana, Assam, Madhya Pradesh, etc.) of India, which demonstrate that pesticides can persist in the environment and later can show bioaccumulation in the food chain. The article explores the consequences of this pollution such as biomagnification, bioaccumulation, and risks to human health and ecological integrity. This article also covers the adverse effects of pesticides such as carcinogenic, teratogenic, mutagenic, and endocrine-disrupting properties along with the importance of developing new policies or strengthening the current policies and regulations to monitor the use of pesticides.

Exploiting the Synergistic Effect of β-Cyclodextrin Functionalized-Multi-Walled Carbon Nanotubes and Zn-MOF for the Detection of Endocrine-Disrupting Chemical methylparaben

The buildup of methylparaben (MP), a broad-spectrum antimicrobial preservative with endocrine-disrupting properties, in aquatic systems has become a significant concern due to its adverse health effects. Hence, introducing inexpensive and easy-to-use monitoring devices for quantifying MP is highly desirable. Thus, Zn-BTC metal-organic framework (MOF) and multi-walled carbon nanotubes (MWCNTs) functionalized with β-Cyclodextrin (β-CD) were utilized to modify the matrix of a carbon paste electrode (CPE). The morphological and electrochemical characteristics of β-CD-MWCNTs/Zn-BTC/CPE were evaluated using conventional material characterization techniques and electroanalytical methods. The sensor exhibited two linear current responses in concentration ranges of 0.01 mM to 0.3 mM and 0.3 mM to 6 mM. The limit of detection (LOD) was calculated to be 3.8 μM. The device demonstrated excellent selectivity, repeatability, reproducibility, and stability over two weeks. Evaluating its applicability in real samples achieved recoveries in the range of 96.25% to 105%, proving its reliability in environmental and industrial applications.

Toxic effects of chronic exposure to BPAF and perturbation of gut microbiota homeostasis in marine medaka (Oryzias melastigma)

Bisphenol AF (BPAF), a substitute for bisphenol A (BPA), exhibits potent endocrine-disrupting properties that pose a serious health hazard to organisms. This study employed marine medaka as a model, subjecting them to different concentrations of BPAF (0.61, 6.65, and 91.88 μg/L) from the embryonic stage for a period of 160 days. Findings showed that 91.88 μg/L BPAF reduced survival rates and altered sex ratios. Furthermore, exposure to BPAF at all concentrations led to a significant increase in body length and weight. Behavioral analysis revealed that BPAF exposure impaired the swimming ability of the medaka. Histological changes included disrupted ovarian development, reduced sperm count, liver inflammation, and intestinal damage. Gene expression analysis revealed impacts on nervous system (e.g., gap43, itr, elavl3), HPG axis (e.g., gthα, erα, 3βhsd), and liver genes (e.g., chgl, vtg2). Additionally, BPAF altered the diversity and richness of gut microbes in marine medaka, leading to significant changes in specific bacterial species and intestinal functions. In conclusion, long-term BPAF exposure induced neurotoxicity, reproductive toxicity, and impaired digestive and immune systems in marine medaka, with sex-specific effects. These results provide further evidence of the potential hazards of BPAF as an environmental pollutant.

Endocrine-disrupting chemicals – pesticide regulatory issues from the EU perspective

Endocrine-disrupting chemicals (EDCs), including substances used in plant protection products (PPPs), are a source of ongoing concern for the EU society. Under the EC Regulation 1107/2009, the endocrine-disrupting (ED) properties of active substances, safeners, and synergists used in PPPs shall be investigated. The scientific criteria established by the Regulation (EU) 2018/605 and the joint guidance of the European Chemicals Agency (ECHA)/European Food Safety Authority (EFSA) provide the basis for this assessment. Data requirements for the approval of safeners and synergists have been recently published in Commission Regulation (EU) 2024/1487, allowing a consistent assessment of these substances. The approach to assessing co-formulant hazards is currently a subject of EU-wide discussion. It outlines the necessity to take into account information or evaluation data from other than pesticides' EU regulatory frameworks, such as REACH or SCCS applications for cosmetic ingredients. This paper outlines: a) current EU approach applied for identification of endocrine disrupting properties of pesticides; b) issues related to European regulations that may have an indirect impact on the safe use of plant protection products and c) an analysis of the European Commission's activities aimed to limit exposure to EDCs associated with use of PPPs in the society.

The impact of high exposure to perfluoroalkyl substances and risk for hormone receptor-positive breast cancer – A Swedish cohort study

IntroductionPerfluoroalkyl substances (PFAS) are persisting chemicals with endocrine disruptive and carcinogenic properties. Previous studies involving cohorts with high PFAS exposure have not shown an increased risk of breast cancer. Research on PFAS and breast cancer according to hormone receptor status is limited. This study aims to investigate the association between PFAS exposure and hormone receptor-positive breast cancer. Materials and MethodsIn 2013, high levels of PFAS (sum of PFAS > 10,000 ng/L), dominated by perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) were found in the drinking water from one of the two waterworks in Ronneby, Sweden. Breast cancer diagnoses and information of adjuvant endocrine therapy were retrieved from the Swedish Cancer Register and The Prescribed Drug Register 2006–2016 for a cohort of women residing in the municipality between 1985 and 2013 (n = 24,509). Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential addresses. Cox proportional hazards models were used in the analysis. The highest achieved educational level was used as an indicator of socioeconomic position. Sensitivity and subgroup analysis were performed for prepubertal exposure and diagnosis before or after age 50 (assumed menopause). ResultsThere were 313 cases of malignant breast cancer among women ≤ 85 years between 2006 and 2016. Of these, 224 cases (72 %) were considered hormone receptor-positive based on the first prescription of adjuvant endocrine therapy, antiestrogens (40 %) or aromatase inhibitor (60 %). Among women ever living at a residential address with high PFAS exposure, the hazard ratio (HR) for breast cancer classified as hormone receptor-positive was 0.84; 95 % confidence interval (CI) 0.61, 1.14. Findings were similar before and after menopause. ConclusionHigh PFAS exposure from drinking water, dominated by PFOS and PFHxS, was not associated with an elevated risk of hormone receptor-positive breast cancer.

A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters

The ubiquitous presence of organophosphate esters (OPEs) in the environment has prompted growing concerns about their potential health risks, particularly their endocrine-disrupting effects. This study comprehensively evaluated the endocrine-disrupting properties of six emerging OPEs: five aryl-OPEs (2-ethylhexyl diphenyl phosphate (EHDPP), tris (2-biphenylyl) phosphate (TBPP), resorcinol bis (diphenyl phosphate) (RDP), 4-hydroxyphenyl diphenyl phosphate (para-OH-TPHP), and 3-hydroxyphenyl diphenyl phosphate (meta-OH-TPHP)) and one alkyl-OPE, triallyl phosphate (TAP). Our findings revealed that all tested aryl-OPEs exhibited antagonistic effects on one or more hormone receptors. Importantly, para-OH-TPHP demonstrated the most potent antagonistic activity, inhibiting estrogen receptor α (ERα), thyroid hormone receptor β (TRβ), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) with the concentration of test compounds showing 20 % relative inhibitory concentration (RIC20) value below 10−6 mol/L (M). RDP antagonized ERα and cortical receptors (GR and MR), TBPP affected TRβ and GR, while EHDPP and meta-OH-TPHP targeted MR. Regarding steroidogenesis, para-OH-TPHP significantly inhibited genes for estrogen (cyp19) and cortisol synthesis (cyp11b2), and along with meta-OH-TPHP, EHDPP, TAP, and RDP downregulated cyp11a1, a rate-limiting enzyme in hormone synthesis. All compounds caused malformations and swimming abnormalities in zebrafish embryos/larvae at concentrations of 10−7 M or higher, with para-OH-TPHP showing nearly 50 % peak induction. Furthermore, the six compounds tested influenced genes associated with the hypothalamic-pituitary–gonadal (HPG) axis in both zebrafish larvae and adult female zebrafish, in addition to affecting the reproductive behavior of zebrafish. A weighted scoring system was employed to rank the endocrine-disrupting potency of the OPEs, with para-OH-TPHP exhibiting the highest risk, followed by EHDPP, RDP, TBPP, meta-OH-TPHP, and TAP. Collectively, our results highlight the significant endocrine-disrupting effects of emerging OPEs, underscoring the urgent need for further research to assess their potential health implications.

Prenatal exposure to neonicotinoid insecticides, fetal endocrine hormones and birth size: Findings from SMBCS

BackgroundNeonicotinoid insecticides (NNIs) were reported to be endocrine disruptors and cause adverse health effects in human. However, epidemiological evidence about the effect of prenatal NNIs exposure on birth outcome and hormones remains limited. ObjectivesThis study aimed to explore the effects of prenatal NNIs exposure on neonatal birth size and endocrine hormones, and assess the potential mediating role of hormones. MethodsThe study included 860 mother–child pairs from the Sheyang Mini Birth Cohort Study. 12 parent NNIs (p-NNIs) and 6 metabolites of NNIs (m-NNIs) were measured in maternal urine samples collected on their delivery days, and 5 thyroid hormones and 2 sex hormones were analyzed in cord serum. The concentrations of p-NNIs and its specific metabolite(s) were summed to characterize the role of each class of NNIs. Generalized linear model and weighted quantile sum regression were used to examine the impact of prenatal NNIs exposure on birth size and endocrine hormones, and potential mediating roles of hormones were further explored using mediation analysis. ResultsHigher detection frequencies of m-NNIs were observed than those in p-NNIs. A decrease in neonatal head circumference for gestation age z-score was associated with a 10-fold increase in 5-OH-IMI (β = -0.15, 95 %CI: −0.26, −0.03), ∑DIN (β = -0.22, 95 %CI: −0.40, −0.03), ∑IMI (β = -0.20, 95 %CI: −0.35, −0.06) and ∑NNIs (β = -0.23, 95 %CI: −0.42, −0.04). ∑IMI and ∑DIN were the major contributors to the significantly negative mixture effect and no sex-specific effect was observed. Negative associations were observed between ∑DIN and TT3 (β = -0.013, 95 %CI: −0.025, −0.002), ∑IMI and T (β = -0.035, 95 %CI: −0.065, −0.004), respectively. Furthermore, TT3 and T demonstrated 6.7 % and 6.1 % mediating effects on the negative association of prenatal ∑DIN and ∑IMI exposure with head circumference. ConclusionsOur findings suggested the potential endocrine disruptive properties of NNIs and their impacts on head circumference. Endocrine hormones may partly mediate these associations.

Exploring the use of gull eggs as bioindicators of phthalate esters exposure

Plastic pollution and associated plasticizers are a global threat affecting aquatic environments. Phthalates are among the most used plasticizers that can impact on fauna due to their endocrine-disrupting properties. The aim of this study was to investigate the use of eggs of Audouin's gull (Larus audouinii) and yellow-legged gull (Larus michahellis) as biomonitors of phthalate exposure. Sixteen phthalates were studied and the extraction and purification steps were optimized using various sorbents and clean-up processes to efficiently recover these contaminants in gull eggs. Analysis was performed using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) using multiple reaction monitoring to obtain high selectivity and sensitivity. Quality control parameters and a comprehensive analysis of blank contribution are provided. The best performance was obtained with Oasis PRiME HLB cartridges with recoveries from 61 to 138% for most of the compounds. Pooled gull-egg samples from seven breeding colonies collected over the period 2016–2021 within the Iberian Peninsula revealed the presence of dibutoxyethyl phthalate (DBEP), hexyl 2-ethylhexyl phthalate (HEHP), dimethyl phthalate (DMP), diethyl phthalate (DEP), and dibutyl phthalate (DBP) at mean concentrations ranging from 2.27 to 1330 ng/g ww in Audouin's gull and from 2.74 to 487 ng/g ww in yellow-legged gull (DBP not detected). The absence of other phthalates is likely attributable to their metabolism and excretion by female adults. Overall, this study provides an accurate method to analyse phthalates in gull eggs and supports their use as bioindicators of phthalate contamination.

Benzo(a)pyrene promotes autophagy to impair endometrial decidualization via inhibiting CXCL12/CXCR4 axis

Benzo(a)pyrene (BaP), a pervasive environmental pollutant with endocrine-disrupting properties, has been associated with detrimental effects on pregnancy. During early pregnancy, the endometrial decidualization process is critical for embryo implantation. Abnormal decidualization can lead to implantation failure, aberrant placental formation, and pregnancy loss. We previously revealed that BaP exposure impaired decidualization and implantation in mice, yet the underlying mechanisms remained elusive. Autophagy, a cellular mechanism pivotal for energy and material recycling, contributes to the decidualization process. The chemokine C-X-C motif chemokine ligand 12 (CXCL12), secreted by endometrium stromal cells (ESCs), is involved in regulating endometrial decidualization and autophagy. Therefore, this study aimed to explore the hypothesis that BaP disrupts the decidualization process by interfering with autophagic pathways via the CXCL12/CXCR4 axis during early pregnancy. We found that BaP inhibited CXCL12/CXCR4 expression, and induced autophagy by promoting autophagosome formation, which in turn impaired the decidualization in early pregnant mice uterus and decidual stromal cells (DSCs). Using autophagy inhibitors 3-methyladenine and chloroquine in combination with BaP to treat DSCs, successfully weakened BaP-induced autophagy, and relieved decidual injury. Additionally, activation of CXCL12/CXCR4 by recombinant protein CXCL12 attenuated BaP-induced autophagy, inhibited the PI3K/AKT signal activation caused by BaP, and partly rescued the expression of decidualization-related genes. In summary, this study demonstrates that BaP induces autophagy in DSCs by inhibiting the CXCL12/CXCR4 axis, leading to damage in endometrial decidualization during early pregnancy. The findings provide a critical chemokine-mediated regulatory mechanism involved in embryo implantation and contribute valuable knowledge to the reproductive toxicology of BaP.

Core-shell MIL-53(Al)–NH2@UiO-66 coated solid-phase microextraction Arrow for the selective enrichment of nine alkylphenols in milk

Metal-organic frameworks (MOFs) hold significant potential for sample preparation, but single-MOF materials often face limitations in selectivity and extraction efficiency. To overcome these, a mesoporous MIL-53(Al)–NH2@UiO-66 composites with a core–shell structure was synthesized using an epitaxial growth strategy. This composite leverages the complementary properties of both MOFs, offering enhanced active sites and interaction forces for analytes. The structure and integration of the composite were characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction, confirming their successful integration. To address the challenge of detecting alkylphenols (APs) in food matrices, known for their endocrine-disrupting properties and low concentrations, a new solid-phase microextraction (SPME) Arrow was fabricated using the MIL-53(Al)–NH2@UiO-66 composite combined with polyacrylonitrile as a binder. APs were detected using ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-ToF/MS). The developed SPME Arrow-UPLC-ESI-Q-ToF/MS method exhibits good linearity (R2 ≥ 0.9958), wide linear range (0.01–1000 μg L–1), and high sensitivity (limits of detection ranging from 0.005 to 0.01 μg L–1) for APs determination. This method was validated for determining nine APs in milk samples from various packing materials, with spiked recoveries ranging from 85.2 % to 115 % and relative standard deviations from 3.4 % to 13.6 %. This study demonstrates the potential of MOF-on-MOF composites in enhancing the performance of adsorbents for SPME pretreatment, offering a promising approach for improving analytical methodologies in food safety.

Profiling the endocrine-disrupting properties of triazines, triazoles, and short-chain PFAS.

Persistent, mobile, and toxic compounds released to the environment are likely to pollute drinking water sources due to their slow environmental degradation (persistency) and high water solubility (mobility). The aim of the present study was to create in vitro hazard profiles for 16 triazoles, 9 triazines, and 11 poly- and perfluoroalkyl substances (PFAS) based on their agonistic and antagonistic effects in estrogen receptor (ER), androgen receptor (AR), and thyroid hormone receptor (TR) reporter gene assays, their ability to bind human transthyretin (TTR), and their effects on steroidogenesis. The triazole fungicides tetraconazole, bitertanol, fenbuconazole, tebuconazole, cyproconazole, difenoconazole, propiconazole, paclobutrazol, and triadimenol had agonistic or antagonistic effects on the ER and AR. Difenoconazole, propiconazole, and triadimenol were also found to be TR antagonists. The triazine herbicide ametryn was an ER, AR, and TR antagonist. The same 9 triazole fungicides and the triazines atrazine, deethyl-atrazine, and ametryn affected the secretion of steroid hormones. Furthermore, PFAS compounds PFBS, PFHxS, PFHxA, PFOS, PFOA, and GenX and the triazoles bitertanol, difenoconazole, and 4-methyl benzotriazole were found to displace T4 from TTR. These results are in line with earlier in vitro and in vivo studies on the endocrine-disrupting properties of triazines, triazoles, and PFAS. The present study demonstrates that this battery of in vitro bioassays can be used to profile compounds from different classes based on their endocrine-disrupting properties as a first step to prioritize them for further research, emission reduction, environmental remediation, and regulatory purposes.

Effects of di-(2-ethylhexyl) phthalate and its metabolites on transcriptional activity via human nuclear receptors and gene expression in HepaRG cells

Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in polyvinyl chloride products. DEHP exposure in humans is of great concern due to its endocrine-disrupting properties. In this study, we characterized the agonistic activities of DEHP and its five metabolites, mono-(2-ethylhexyl) phthalate (MEHP), 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP and 2cx-MMHP against human nuclear receptors, peroxisome proliferator-activated receptor α (PPARα), pregnane X receptor (PXR), and constitutive androstane receptor (CAR) using transactivation assays. In the PPARα assay, the order of the agonistic activity was MEHP >> 5cx-MEPP >5OH-MEHP, 5oxo-MEHP >2cx-MMHP > DEHP, with DEHP significantly inhibiting MEHP-induced PPARα agonistic activity. This finding was compared to the results from in silico docking simulation. In the PXR assay, DEHP showed PXR agonistic activity more potent than that of MEHP, whereas the other metabolites showed little activity. In the CAR assay, none of the tested compounds showed agonistic activity. Moreover, the expression levels of PPARα-, PXR-, and CAR-target genes in HepaRG cells exposed to DEHP or MEHP were investigated using qRT-PCR analysis. As a result, exposure to these compounds significantly upregulated PXR/CAR target genes (CYP3A4 and CYP2B6), but not PPARα target genes (CYP4A11, etc.) in HepaRG cells. Taken together, these results suggest that direct PXR and/or indirect CAR activation by several DEHP metabolites may be involved in the endocrine disruption by altering hormone metabolism.

Association between phthalates exposure and non-alcoholic fatty liver disease under different diagnostic criteria: a cross-sectional study based on NHANES 2017 to 2018.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. Phthalates have been suggested to influence the development of NAFLD due to their endocrine-disrupting properties, but studies based on nationally representative populations are insufficient, and existing studies seem to have reached conflicting conclusions. Due to changes in legislation, the use of traditional phthalates has gradually decreased, and the phthalates substitutes is getting more attention. This study aims to delve deeper into how the choice of diagnostic approach influences observed correlations and concern about more alternatives of phthalates, thereby offering more precise references for the prevention and treatment of NAFLD. A cohort of 641 participants, sourced from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 database, was evaluated for NAFLD using three diagnostic methods: the Hepatic Steatosis Index (HSI), the US Fatty Liver Indicator (US.FLI), and Vibration Controlled Transient Elastography (VCTE). The urinary metabolite concentrations of Di-2-ethylhexyl phthalate (DEHP), Di-isodecyl phthalate (DIDP), Di-isononyl phthalate (DINP), Di-n-butyl phthalate (DnBP), Di-isobutyl phthalate (DIBP), Di-ethyl phthalate (DEP) and Di-n-octyl phthalate (DnOP) were detected. The association between NAFLD and urinary phthalate metabolites was evaluated through univariate and multivariate logistic regression analyses, considering different concentration gradients of urinary phthalates. Univariate logistic regression analysis found significant correlations between NAFLD and specific urinary phthalate metabolites, such as Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and Mono-(carboxyisoctyl) phthalate (MCiOP), across different diagnostic criteria. In a multivariate logistic regression analysis adjusting only for demographic data, MEOHP (OR = 3.26, 95% CI = 1.19-8.94, p = 0.029), MEHHP (OR = 3.98, 95% CI = 1.43-11.1, p = 0.016), MECPP (OR = 3.52, 95% CI = 1.01-12.2, p = 0.049), and MCiOP (OR = 4.55, 95% CI = 1.93-10.7, p = 0.005) were positively related to NAFLD defined by HSI and VCTE. The correlation strength varied with the concentration of phthalates, indicating a potential dose-response relationship. Adjusting for all covariates in multivariate logistic regression, only MCiOP (OR = 4.22, 95% CI = 1.10-16.2, p = 0.044), as an oxidative metabolite of DINP, remained significantly associated with NAFLD under the VCTE criterion, suggesting its potential role as a risk factor for NAFLD. This research highlights a significant association between DINP and NAFLD. These findings underscore the need for further investigation into the role of the phthalates substitutes in the pathogenesis of NAFLD and the importance of considering different diagnostic criteria in research.

Trajectories of long-term exposure to PCB153 and Benzo[a]pyrene (BaP) air pollution and risk of breast cancer

BackgroundWhile genetic, hormonal, and lifestyle factors partially elucidate the incidence of breast cancer, emerging research has underscored the potential contribution of air pollution. Polychlorinated biphenyls (PCBs) and benzo[a]pyrene (BaP) are of particular concern due to endocrine-disrupting properties and their carcinogenetic effect.ObjectiveTo identify distinct long term trajectories of exposure to PCB153 and BaP, and estimate their associations with breast cancer risk.MethodsWe used data from the XENAIR case–control study, nested within the ongoing prospective French E3N cohort which enrolled 98,995 women aged 40–65 years in 1990–1991. Cases were incident cases of primary invasive breast cancer diagnosed from cohort entry to 2011. Controls were randomly selected by incidence density sampling, and individually matched to cases on delay since cohort entry, and date, age, department of residence, and menopausal status at cohort entry. Annual mean outdoor PCB153 and BaP concentrations at residential addresses from 1990 to 2011 were estimated using the CHIMERE chemistry-transport model. Latent class mixed models were used to identify profiles of exposure trajectories from cohort entry to the index date, and conditional logistic regression to estimate their association with the odds of breast cancer.Results5058 cases and 5059 controls contributed to the analysis. Five profiles of trajectories of PCB153 exposure were identified. The class with the highest PCB153 concentrations had a 69% increased odds of breast cancer compared to the class with the lowest concentrations (95% CI 1.08, 2.64), after adjustment for education and matching factors. The association between identified BaP trajectories and breast cancer was weaker and suffered from large CI.ConclusionsOur results support an association between long term exposure to PCB153 and the risk of breast cancer, and encourage further studies to account for lifetime exposure to persistent organic pollutants.

Exposure to Per- and Polyfluoroalkyl Substances and Timing of Puberty in Norwegian Boys: Data from the Bergen Growth Study 2.

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with endocrine-disruptive properties. Their impact on puberty in boys is unclear. In this cross-sectional study, we investigated the association between PFAS exposure and pubertal timing in 300 Norwegian boys (9-16 years), enrolled in the Bergen Growth Study 2 during 2016. We measured 19 PFAS in serum samples and used objective pubertal markers, including ultrasound-measured testicular volume (USTV), Tanner staging of pubic hair development, and serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. In addition to logistic regression of single pollutants and the sum of PFAS, Bayesian and elastic net regression were used to estimate the contribution of the individual PFAS. Higher levels of the sum of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) were associated with later pubertal onset according to USTV (age-adjusted odds ratio (AOR): 2.20, 95% confidence interval (CI): 1.29, 3.93) and testosterone level (AOR: 2.35, 95% CI: 1.34, 4.36). Bayesian modeling showed that higher levels of PFNA and PFHxS were associated with later pubertal onset by USTV, while higher levels of PFNA and perfluoroundecanoic acid (PFUnDA) were associated with later pubertal onset by testosterone level. Our findings indicate that certain PFAS were associated with delay in male pubertal onset.

Liquid chromatography-high-resolution mass spectrometry-based metabolomics revealing the effects of zearalenone and alpha-zearalenol on human endometrial cancer cells.

Human exposure to mycotoxins through food involve a mixture of compounds, which can be harmful to human health. The Fusarium fungal species are known to produce zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, and its metabolite alpha-zearalenol (α-ZEL), both of which possess endocrine-disruptive properties. Given their potential harm to human health through food exposure, investigating the combined effects of ZEN and α-ZEL becomes crucial. Hence, the combined impact of ZEN and α-ZEL study hold significant importance. This in vitro study delves into the critical area, examining their combined impact on the proliferation and metabolic profile of endometrial cancer Ishikawa cells via sulforhodamine, clonogenic, proliferating cell nuclear antigen (PCNA) and liquid chromatography-high resolution mass spectrometry (LC-HRMS) based untargeted metabolomics. Low concentrations of ZEN (25nm), α-ZEL (10nm), or a combination of both were observed to significantly enhance cell proliferation of Ishikawa cells, as evidenced by PCNA immunostaining, immunoblotting as well and clonogenic assays. The metabolomics revealed the perturbations in glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and phenylalanine, tyrosine, tryptophan biosynthesis provides valuable insights into potential mechanism by which these mycotoxins may facilitate cell proliferation. However, further investigations are warranted to comprehensively understand the implications of these findings and their possible implications for human health.

The Association between Metals and Thyroid Cancer in Puerto Rico-A National Health and Nutrition Examination Survey Analysis and Ecological Study.

Thyroid cancer rates have risen globally over the past four decades, with Puerto Rico experiencing a particularly pronounced increase. This may be linked to higher metal exposure, as some metals are endocrine disruptors and carcinogens. Currently, certain regions of Puerto Rico have Superfund programs because of high concentrations of metals in the soil. Therefore, we investigated the association between thyroid cancer incidence and three metals (lead, cadmium, and mercury) with known endocrine-disrupting properties and increased levels in soil samples in Puerto Rico. We used the National Health and Nutrition Examination Survey (NHANES) data for heavy metal levels and the thyroglobulin antibody (TgAb) as a thyroid cancer marker. Additionally, we performed an ecological study using data from the Environmental Protection Agency (EPA) report on Metals from Natural and Anthropogenic Sources in Puerto Rico Soils and data from the Puerto Rico Central Cancer Registry on age-adjusted thyroid cancer incidence rates from 2015 to 2019. Through NHANES analysis, we found a significant negative association between mercury and TgAb. Through our ecological study, we observed higher thyroid cancer incidence rates and increased metal levels in the soil in the northern parts of Puerto Rico. Our heterogenous results necessitate further research on this topic.

High-throughput transcriptomics toxicity assessment of eleven data-poor bisphenol A alternatives

Bisphenol A (BPA), a widely used chemical in the production of plastics and epoxy resins, has garnered significant attention due to its association with adverse health effects, particularly its endocrine-disrupting properties. Regulatory measures aimed at reducing human exposure to BPA have led to a proliferation of alternative chemicals used in various consumer and industrial products. While these alternatives serve to reduce BPA exposure, concerns have arisen regarding their safety and potential toxicity as regrettable substitutes. Previous efforts have demonstrated that in vitro high-throughput transcriptomics (HTTr) studies can be used to assess the endocrine-disrupting potential of BPA alternatives, and this strategy produces transcriptomic points-of-departure (tPODs) that are protective of human health when compared to the PODs from traditional rodent studies. In this study, we used in vitro HTTr to assess the potential for toxicity of eleven data-poor legacy chemicals sharing structural similarities to BPA. Human breast cancer MCF-7 cells were exposed to BPA and 11 alternatives at concentrations ranging from 0.1 to 25 μM to assess toxicity. Analysis of global transcriptomic changes and a previously characterized estrogen receptor alpha (ERα) transcriptomic biomarker signature revealed that 9 of 11 chemicals altered gene expression relative to controls. One of the chemicals (2,4′-Bisphenol A) activated the ERα biomarker at the same concentration as BPA (i.e., 4,4′-BPA) but was deemed to be more potent as it induced global transcriptomic changes at lower concentrations. These results address data gaps in support of ongoing screening assessments to identify BPA alternatives with hazard potential and help to identify potential candidates that may serve as safer alternatives.

Bisphenol S Exposure Perturbs Epididymis Function of Adult Male Golden Hamster, <i>Mesocricetus auratus</i>

Bisphenols are widely used in industrial and commercial products that exhibit endocrine-disrupting properties. Bisphenol S (BPS) has been reported to show adverse impact on human health. The objective of the present study was to examine the effect of BPS on epididymal function in the adult male golden hamster Mesocricetus auratus. Different doses of BPS (25, 50 and 75mg/kg BW/day) were orally administered for 28 days. BPS administration caused a reduction in body and epididymis weight, sperm count and sperm viability. BPS exposure also caused a reduction in the serum testosterone levels, suggesting its impact on testicular steroidogenesis. Further, the activities of antioxidant enzymes (SOD and catalase) in the epididymis were markedly decreased, while the levels of lipid peroxidation increased significantly in epididymis of BPStreated hamsters. Epididymides obtained from BPS treated hamsters showed degenerative changes in the caput, corpus and cauda along with a decreased sperm count in the lumen. In conclusion, we demonstrate that exposure to BPS caused oxidative stress in the epididymis, which may lead to impaired reproductive function.