Potential Endocrine-disrupting Effects Research Articles

Polystyrene microplastics exacerbate acetochlor-induced reproductive toxicity and transgenerational effects in zebrafish.

Microplastic (MPs) can adsorb co-existing pollutants, and alter their behavior and toxicity. Meanwhile, amide herbicides like acetochlor (ACT) are widely used in agriculture, with potential endocrine-disrupting effects that raise ecological concerns. The aim of this research was to examine the effects of MPs on the reproductive endocrine disruption caused by ACT and the effects of maternal transmission. Zebrafish were employed in this study to assess the reproductive toxicity of ACT alone and in combination with polystyrene microplastics (PS-MPs) of different sizes (200 nm and 2 μm) and concentrations (0.1 and 1 mg/L) over a 63-day exposure experiment. The results indicated that ACT was concentrated in zebrafish tissues in the order: intestine > liver > gill > brain > gonad > muscle. PS-MPs increased ACT bioaccumulation, worsened gonadal damage, led to abnormalities in hormone levels, and caused disruptions in HPG axis gene expression, further exacerbating the reproductive toxicity. Maternal transfer of ACT affected offspring growth, thyroid function, and HPT axis gene expression, with nanoplastics (NPS) amplifying these adverse effects. This study offers crucial insights into the ecological hazards posed by ACT and PS-MPs, emphasizing the increased toxicity due to PS-MPs.

Predicting in vivo concentrations of dietary hop phytoestrogens by physiologically based kinetic modeling.

Hop extracts containing prenylated polyphenols such as 8-prenylnaringenin (8-PN) and its precursor isoxanthohumol (iXN) are popular among women seeking natural alternatives to hormone therapy for postmenopausal symptoms. Due to structural similarities with estrogens, these compounds act as estrogen receptor agonists. Especially 8-PN, described as the most potent phytoestrogen known to date, poses a potential risk for endocrine disruption. Therefore, its use as a hormone replacement raises concerns for human health. However, a significant challenge in assessing the potential endocrine-disruptive effects of hop polyphenols is the lack of data on their toxicokinetics. Particularly, information on in vivo concentrations in target tissues is lacking. To address this gap, we developed a physiologically based kinetic (PBK) model tailored to female physiology. The model was used to predict the levels of hop polyphenols in human blood and target tissues under realistic exposure scenarios. The predictions suggest that iXN and 8-PN concentrations in target tissues reach the low nanomolar range after dietary supplementation. This study enhances our understanding of internal concentrations of iXN and 8-PN after dietary consumption and is of direct applicability for respective risk assessment.

In Silico, In Vitro, and In Vivo Studies Indicate the Endocrine-Disrupting Effects of Cyproconazole Stereoisomers.

The widespread use of chiral triazole fungicide cyproconazole (CPZ) in agricultural fields has led to frequent detection of CPZ in the environment. The restriction of CPZ in the EU raised wide concerns regarding its potential endocrine-disrupting effects (EDEs). The present study was conducted to evaluate EDEs of CPZ stereoisomers in vitro, in silico, and in vivo. The reporter gene assay indicated that all CPZ stereoisomers were agonists to the human estrogenic receptor α. (2S,3S)-(+)- and (2R,3S)-(-)-CPZ exhibited stronger binding capacities to ERα compared with (2R,3R)-(-)- and (2S,3R)-(+)-CPZ. Our computational studies showed consistent results with reporter gene assay, elucidating the stereoselective binding mode of CPZ to estrogen receptor. In zebrafish embryos, the 96h-lethality of CPZ stereoisomers ordered (2R,3R)-(-)- > (2R,3S)-(-)- > (2S,3S)-(+)- > Rac- > (2S,3R)-(+)-CPZ. Stereoselective developmental toxicity of CPZ was observed while (2R,3S)-(-)-CPZ is the most toxic isomer. The estrogenic hormones were significantly decreased in (2S,3R)-(+)- and (2R,3S)-(-)-CPZ groups and enhanced in (2S,3S)-(+)- and (2R,3R)-(-)-CPZ, along with the gene expression in hypothalamic-pituitary-gonad axis altered. CPZ shows no thyroid hormone activity. These data clarified that CPZ is a new-found endocrine disruptor threatening human health and each stereoisomer of CPZ showed stereoselective EDEs by regulating the nuclear receptor-mediated gene expression.

Endocrine-Disrupting Effects of Salicylate Preservatives on Neurosteroidogenesis: Targeting 5α-Reductase Type 1.

Salicylate preservatives are widely used in consumer products and pharmaceuticals. This study investigates their potential endocrine-disrupting effects on neurosteroidogenesis, focusing on 5α-reductase type 1 (SRD5A1). We evaluated the effects of 13 salicylates on human SRD5A1 using SF126 glioblastoma cell microsomes and rat brain microsomes, examining dihydrotestosterone production in SF126 cells. Results revealed a hierarchy of inhibitory potency against human SRD5A1, with methyl salicylate (IC50, 71.93 μM) to menthyl salicylate (2.41 μM), indicating increasing potency. Kinetic analysis indicates their mixed/noncompetitive inhibitions. In SF126 cells, all salicylates at 100 μM significantly reduced dihydrotestosterone production. Rat SRD5A1 showed reduced sensitivity, with menthyl salicylate as the most potent inhibitor (IC50, 17.12 μM). Docking analysis suggests salicylates bind to the reduced nicotinamide adenine dinucleotide phosphate site of both human and rat SRD5A1. Bivariate correlation analysis highlights the influence of LogP, molecular weight, carbon number in the alcohol moiety, and pKa on inhibitory potency. 3D-QSAR revealed the importance of hydrophobic aromatic regions in SRD5A1 binding. This study delineates the inhibitory effects of salicylates and binding mechanisms on human and rat SRD5A1, providing insights into their impact on neurosteroid production.

Toxicokinetic Profiles and Potential Endocrine Disruption Effects at the Reproductive Level Promoted by Siloxanes Used in Consumer Products.

Siloxanes, commonly known as silicones, are polymeric compounds made up of silicon and oxygen atoms bonded together alternately. Within this group of substances are linear methyl-siloxanes and cyclic methyl-siloxanes, with octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) being the most produced and used industrially. Due to their versatility, high production volume, stability, and local presence in environmental matrices and biological fluids such as breast milk, fat, and plasma, siloxanes have been considered persistent organic pollutants, representing a public health problem. This represents a public health concern, especially when different investigations have reported potential endocrine effects at the reproductive level in experimental animals exposed to D4 and D5. The objective of this study was to review the potential reproductive and endocrine effects derived from siloxanes present in personal care products (PCPs). The results of the literature review confirmed that D4 and D5 were the most used siloxanes as additives in PCP because they improve the emollient properties of the cosmetic and the physical appearance of hair and skin. Similarly the toxicological effects of siloxanes, particularly D4, D5, and D6 included significant endocrine disruption, reproductive toxicity, and liver toxicity. Studies in SD and F-344 rats, commonly used to assess these effects, have shown that D4 has low estrogenic activity, binding to ER-α receptors, whereas D5 does not bind to estrogen receptors. D4 exposure has been associated with increased uterine weight and estrous cycle alterations, leading to prolonged exposure to estrogens, which raises the risk of endometrial hyperproliferation and carcinogenesis. Recent research highlights that D5 exposure disrupts follicle growth, endometrial receptivity, and steroidogenesis, resulting in infertility and hormonal imbalances, potentially causing disorders like endometriosis and increased cancer risk. Chronic exposure to D5 has been linked to the development of uterine endometrial adenocarcinoma, with higher doses further elevating this risk.

Low concentrations of the food contaminant Deoxynivalenol trigger apoptosis and impair GnRH-induced LH secretion in pituitary gonadotrope-like cells.

AbstractTheFusariummycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. Nearly all individuals are exposed to DON, due to it widespread presence in grains and grain-based products. Chronic DON poisoning is associated with growth retardation, immunotoxicity as well as impaired reproduction and fetal development. At the molecular level, DON alters intracellular signaling by activating mitogen-activated protein kinases (MAPKs) that modulate cell growth, differentiation, and apoptosis. Of note, these MAPKs are also critical mediators of gonadotrophin-releasing hormone (GnRH)-induced synthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by pituitary gonadotrope cells. So far, no research has explored the potential endocrine-disrupting effects of DON on pituitary gonadotropins production. Herein, we show the first evidence that DON affects LH production by the immortalized gonadotrope-like cell line LβT2 in a concentration-dependent manner. Taken together, our experiments demonstrated that low concentrations of DON affect GnRH-induced signaling through a mechanism that, at least in part, involves apoptosis and inhibition of GnRH-induced phosphorylation of ERK-MAPK. Consequently, DON also affects the GnRH-induced expression ofCgaandLhb, two critical genes for LH synthesis and secretion by gonadotrope cells in mammals. This research broadens our knowledge of the toxicity of DON and brings a new depth to the potential neuroendocrine implications for reproduction.Graphical abstract

Potential endocrine-disrupting effects of iprodione via estrogen and androgen receptors: evaluation using in vitro assay and an in silico model

This study was conducted to provide evidence, using in vitro and in silico testing methods, regarding the adverse effects of iprodione, a representative dichlorophenyl dicarboxamide fungicide, on the endocrine system. In the present study, we used the HeLa9903 stably transfected transactivation assay (OECD TG 455), 22Rv1/MMTV_GR‒KO androgen receptor transcriptional activation assay (OECD TG 458), and toxicity prediction using VEGA QSAR. Our results showed that iprodione had no estrogen receptor antagonistic or androgen receptor agonistic effects; however, iprodione was determined to be an estrogen receptor agonist (log PC10 value is less than − 9) and androgen receptor antagonist (log IC30 value is − 4.58) without intrinsic toxicity against the human cell lines used in this study. VEGA QSAR was used to evaluate five substances with structures similar to that of iprodione. Among them, four chemicals were found to have positive androgen receptor and aromatase activities and have been observed to be developmental toxicants. These results suggest that iprodione regulates steroid hormone receptor interactions and is a potential reproductive toxicant.

Identification and quantification of acetyl tributyl citrate (ATBC) metabolites using human liver microsomes and human urine

Plasticizers are chemicals that make plastics flexible, and phthalates are commonly used. Due to the toxic effects of phthalates, there is increasing use of non-phthalate plasticizers like acetyl tributyl citrate (ATBC). ATBC has emerged as a safer alternative, yet concerns about its long-term safety persist due to its high leachability and potential endocrine-disrupting effects. This study aims to identify ATBC metabolites using human liver microsomes and suspect screening methods, and to explore potential urinary biomarkers for ATBC exposure. Using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we identified ATBC metabolites, including acetyl dibutyl citrate (ADBC), tributyl citrate (TBC), and dibutyl citrate (DBC). Urine samples from 15 participants revealed the presence of ADBC in 5, TBC in 11, and DBC in all samples, with DBC concentrations pointedly higher than the other metabolites. These metabolites show promise as biomarkers for ATBC exposure, though further validation with human data is required. Our results underscore the need for comprehensive studies on ATBC metabolism, exposure pathways, and urinary excretion to accurately assess human exposure levels.

Melatonin's protective role against Bisphenol F and S-induced skeletal damage: A morphometric and histological study in rat

This study aimed to evaluate the potential effects of Bisphenol F and S exposure on the skeletal structures of Sprague-Dawley rats. Given the increasing concern about the potential endocrine-disrupting effects of Bisphenol analogs on bone health, this research sought to elucidate their impact in conjunction with Melatonin. Using 80 male Sprague Dawley rats, bones were subjected to a 3-point bending test to assess mechanical properties, and histopathological evaluation was conducted after fixation and decalcification. Statistical analysis was performed using SPSS. The results of the mechanical tests revealed significant differences in deformation and elastic modulus values between groups treated with Bisphenol F+Melatonin and Bisphenol S+Melatonin compared to the control groups. However, the histological images showed no significant differences between the groups. In the discussion, it was noted that the injection of Bisphenol F and Melatonin together increased bone hardness, suggesting that Bisphenol F and Bisphenol S may mitigate the negative effects of melatonin on bone. We attributed the absence of histological differences to the male gender of the studied rats and previous exposure considerations. This study shows that Melatonin can reduce Bisphenol F and Bisphenol S′ rapid adjustment effects and increase bone elasticity. The side effects of Bisphenol F and S, as well as the prophylactic effects of Melatonin, can be observed and improved by carefully adjusting the duration, dose, and gender selection.

Structure-based modeling to assess binding and endocrine disrupting potential of polycyclic aromatic hydrocarbons in Daniorerio

Environmental contaminants, such as polycyclic aromatic hydrocarbons (PAHs), have raised concerns regarding their potential endocrine-disrupting effects on aquatic organisms, including fish. In this study, molecular docking and molecular dynamics techniques were employed to evaluate the endocrine-disrupting potential of PAHs in zebrafish, as a model organism. A virtual screening with 72 PAHs revealed a correlation between the number of PAH aromatic rings and their binding affinity to proteins involved in endocrine regulation. Furthermore, PAHs with the highest binding affinities for each protein were identified: cyclopenta[cd]pyrene for AR (−9.7 kcal/mol), benzo(g)chrysene for ERα (−11.5 kcal/mol), dibenzo(a,e)pyrene for SHBG (−8.7 kcal/mol), dibenz(a,h)anthracene for StAR (−11.2 kcal/mol), and 2,3-benzofluorene for TRα (−9.8 kcal/mol). Molecular dynamics simulations confirmed the stability of the protein-ligand complexes formed by the PAHs with the highest binding affinities throughout the simulations. Additionally, the effectiveness of the protocol used in this study was demonstrated by the receiver operating characteristic curve (ROC) analysis, which effectively distinguished decoys from true ligands. Therefore, this research provides valuable insights into the endocrine-disrupting potential of PAHs in fish, highlighting the importance of assessing their impact on aquatic ecosystems.

Temporal trends in exposure to parabens, benzophenones, triclosan, and triclocarban in adult females in Kyoto, Japan, from 1993 to 2016.

Products used in daily life can contain chemicals such as parabens, benzophenones, triclosan, and triclocarban that have potential endocrine-disrupting effects. Little is known about the temporal trends of exposure levels to some of these chemicals in Japan. Our study assessed the intake and risk associated with exposure to commonly used chemicals. We measured the concentrations of five parabens, four benzophenones, and triclosan and triclocarban in 133 single spot urine samples. The urine samples were collected in 1993, 2000, 2003, 2009, 2011, and 2016 from healthy female residents in Kyoto, Japan. With the exception of methylparaben, ethylparaben, and butylparaben, there were no significant fluctuations in the concentrations of target chemicals over the study period; however, methylparaben, ethylparaben, and butylparaben showed temporal changes in concentrations. Methylparaben concentrations peaked in 2003 with a median value of 309μg/g creatinine, ethylparaben concentrations peaked in 1993 with a median value of 17.3μg/g creatinine, and butylparaben showed a decline, with the median values becoming non-detectable in 2009 and 2016. We calculated estimated daily intakes and hazard quotients for each chemical. In the analysis of total samples, 2.3% (3 samples) for butylparaben and 0.8% (1 sample) for propylparaben were found to surpass a hazard quotient of 1. Overall, 3% (n = 4) of the study participants exceeded a hazard index of 1. The potential health risks associated with exposure to butylparaben and propylparaben emphasize the need for further monitoring and research.

Recognizing high-priority disinfection byproducts based on experimental and predicted endocrine disrupting data: Virtual screening and in vitro study

So far, about 130 disinfection by-products (DBPs) and several DBPs-groups have had their potential endocrine-disrupting effects tested on some endocrine endpoints. However, it is still not clear which specific DBPs, DBPs-groups/subgroups may be the most toxic substances or groups/subgroups for any given endocrine endpoint. In this study, we attempt to address this issue. First, a list of relevant DBPs was updated, and 1187 DBPs belonging to 4 main-groups (aliphatic, aromatic, alicyclic, heterocyclic) and 84 subgroups were described. Then, the high-priority endocrine endpoints, DBPs-groups/subgroups, and specific DBPs were determined from 18 endpoints, 4 main-groups, 84 subgroups, and 1187 specific DBPs by a virtual-screening method. The results demonstrate that most of DBPs could not disturb the endocrine endpoints in question because the proportion of active compounds associated with the endocrine endpoints ranged from 0 (human thyroid receptor beta) to 32% (human transthyretin (hTTR)). All the endpoints with a proportion of active compounds greater than 10% belonged to the thyroid system, highlighting that the potential disrupting effects of DBPs on the thyroid system should be given more attention. The aromatic and alicyclic DBPs may have higher priority than that of aliphatic and heterocyclic DBPs by considering the activity rate and potential for disrupting effects. There were 2 (halophenols and estrogen DBPs), 12, and 24 subgroups that belonged to high, moderate, and low priority classes, respectively. For individual DBPs, there were 23 (2%), 193 (16%), and 971 (82%) DBPs belonging to the high, moderate, and low priority groups, respectively. Lastly, the hTTR binding affinity of 4 DBPs was determined by an in vitro assay and all the tested DBPs exhibited dose-dependent binding potency with hTTR, which was consistent with the predicted result. Thus, more efforts should be performed to reveal the potential endocrine disruption of those high research-priority main-groups, subgroups, and individual DBPs.

Multiplex analysis platform for evaluation of endocrine disruption of emerging contaminants against human steroid hormone receptors using autobioluminescent yeast bioassay: Application to bisphenols

Emerging synthetic or derivative chemicals have drawn global concern due to their potential endocrine-disrupting effects, either as agonists or antagonists or through indirect effects on enzymes of signal transduction pathways. Currently, in vitro screening models are limited to poor tolerance, robustness, high cost and need for sphisticated equipment or complex procedures that require high levels of expertise. Herein, a multiplex analysis platform based on autobioluminescent yeast strains, including BLYhERαS, BLYhERβS, BLYhPRS, BLYhARS, BLYhMRS, and BLYhGRS, was developed for use in easy, rapid, robust, and sensitive screening for potential modulation of endocrine systems. Methods were applied to assess endocrine-disrupting effects of Bisphenol A (BPA) and its alternatives. Disrupting activities of bisphenols (BPs) varied greatly, and some BPA substitutes exerted more potent activities than those of BPA. Most BPs were primarily agonists of ERα and ERβ, while others were antagonists to AR, PR, GR, and MR. BPP and BPM exhibited non-monotonic dose-response relationships toward ERα and ERβ, and BHPF and BPG displayed converse disrupting activities to ERα and ERβ. Overall, the bioassay system provides an efficient tool for comprehensive evaluation of endocrine-disrupting activities of emerging contaminants.

Comprehensive Characterization of Organic Light-Emitting Materials in Breast Milk by Target and Suspect Screening.

Organic light-emitting materials (OLEMs) are emerging contaminants in the environment and have been detected in various environment samples. However, limited information is available regarding their contamination within the human body. Here, we developed a novel QuEChERS (quick, easy, cheap, effective, rugged, and safe) method coupled with triple quadrupole/high-resolution mass spectrometry to determine OLEMs in breast milk samples, employing both target and suspect screening strategies. Our analysis uncovered the presence of seven out of the 39 targeted OLEMs in breast milk samples, comprising five liquid crystal monomers and two OLEMs commonly used in organic light-emitting diode displays. The cumulative concentrations of the seven OLEMs in each breast milk sample ranged from ND to 1.67 × 103 ng/g lipid weight, with a mean and median concentration of 78.76 and 0.71 ng/g lipid weight, respectively, which were higher compared to that of typical organic pollutants such as polychlorinated biphenyls and polybrominated diphenyl ethers. We calculated the estimated daily intake (EDI) rates of OLEMs for infants aged 0-12 months, and the mean EDI rates during lactation were estimated to range from 30.37 to 54.89 ng/kg bw/day. Employing a suspect screening approach, we additionally identified 66 potential OLEMs, and two of them, cholesteryl hydrogen phthalate and cholesteryl benzoate, were further confirmed using pure reference standards. These two substances belong to cholesteric liquid crystal materials and raise concerns about potential endocrine-disrupting effects, as indicated by in silico predictive models. Overall, our present study established a robust method for the identification of OLEMs in breast milk samples, shedding light on their presence in the human body. These findings indicate human exposure to OLEMs that should be further investigated, including their health risks.

Association between prenatal exposure to per- and polyfluoroalkyl substances and infant anthropometry: A prospective cohort study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are a group of synthetic organic chemicals with potential endocrine-disrupting effects, and have been found to impair the physical growth of offspring in both experimental and epidemiological studies. We aimed to investigate the effects of prenatal PFAS exposure on repeated measurements of multiple anthropometric indicators in infants. MethodPFAS were measured in serum samples collected from pregnant women at 12–16 gestational weeks. We calculated z-scores for the weight-for-age (WAZ), weight-for-length (WLZ), head circumference-for-age (HCZ), arm circumference-for-age (ACZ), triceps skinfold-for-age (TSZ), and subscapular skinfold-for-age (SSZ) at birth, 6 months, and 12 months of age according to the child growth standards of the World Health Organization (WHO) for anthropometric indicators. A total of 964 mother–infant pairs were included. A multivariate linear regression was performed to examine the associations between prenatal PFAS concentrations and anthropometric indicators at each time point. A generalized estimating equation (GEE) model was used to examine the longitudinal effects of PFAS exposure on repeated measurements of anthropometric indicators. Ultimately, a Bayesian kernel machine regression (BKMR) model was used to assess the joint effects of the PFAS mixture on anthropometric indicators. ResultsIn GEE models, perfluorododecanoic acid (PFDoA) in the high tertile group was associated with increased WAZ/WLZ, with β values (95% confidence intervals (CI)) of 0.12 (0.00, 0.23) and 0.18 (0.03, 0.32), respectively. Perfluorononanoic acid (PFNA) was associated with increased ACZ in the middle and high tertile groups. The BKMR models also presented the associations of the PFAS mixture with increased WAZ/WLZ throughout infancy, with more profound effects in females. Meanwhile, a pattern of inverse associations was observed between the perfluorooctanoic acid (PFOA) concentrations in the high tertile group and decreased WAZ, WLZ, and HCZ in males. In addition, the associations between PFAS and increased TSZ/SSZ at birth were identified by both linear regression and BKMR models. ConclusionPrenatal PFAS exposure (PFNA and PFDoA) was associated with increased infant anthropometry, especially in female infants, while prenatal PFOA exposure was associated with decreased weight, and head and arm circumference in male infants. The findings indicate that prenatal PFAS exposure may impair the growth trajectory of offspring.

Enantioselective Toxicity and Potential Endocrine-Disruptive Effects of the Insecticides Flufiprole and Ethiprole on Danio rerio.

Phenylpyrazole insecticides are widely used as chiral pesticides. However, the enantioselective toxicity and potential endocrine-disrupting effects of these insecticides on aquatic organisms remain unclear. Herein, the enantioselective toxicity and potential endocrine-disrupting effects of flufiprole and ethiprole were investigated by using zebrafish embryos/larvae as a model. The acute toxicity of R-flufiprole and R-ethiprole toward zebrafish embryos and larvae was 1.8-3.1-fold higher than that of the S-configuration. Additionally, R-flufiprole and R-ethiprole had a greater effect on the expression of genes related to the hypothalamus-pituitary-gonad axis in zebrafish compared with the S-configuration. Nevertheless, both S-flufiprole and S-ethiprole exhibited a greater interference effect on the expression of genes related to the hypothalamus-pituitary-thyroid axis and a greater teratogenic effect on zebrafish than the R-configuration. Thus, this study demonstrates that both flufiprole and ethiprole exhibit enantioselective acute toxicity and developmental toxicity toward zebrafish. Furthermore, those pesticides potentially possess enantioselective endocrine-disrupting effects.

Highly dispersed Ru immobilized on Ni-modified Al2O3 for selective hydrogenation of bisphenol A to hydrogenated bisphenol A

Bisphenol A (BPA) is ubiquitous in industrial production and daily life. However, BPA is harmful to the health of fetuses and children due to its potential endocrine-disrupting effects. Hydrogenated bisphenol...

Polystyrene microplastic exposure in mice: oxidative stress-induced testicular damage, AR gene suppression, and histopathological alterations

ABSTRACT Aim: Microplastics (MPs), widespread environmental contaminants, pose a growing risk to livestock and other animals by potentially polluting their feed and ecosystems. This study aims to investigate the impact of MP exposure on oxidative stress, testicular function, and androgen receptor gene expression in mice, providing insights into the potential reproductive health risks for animals. Methods: Adult male mice were divided into three groups: a control group and two groups exposed to polystyrene microplastics (PS-MPs) at concentrations of 0.1 mg/0.5 mL and 0.2 mg/1 mL, respectively. We evaluated antioxidant enzyme levels (CAT, SOD, POD), reactive oxygen species (ROS) levels in testes, sperm count, viability, and motility, as well as histological changes in the testicular tissue. Furthermore, the gene expression levels of AR were assessed using qRT-PCR. Results: Exposure to PS-MPs led to a dose-dependent decrease in antioxidant enzyme levels and an increase in ROS levels in the testes. Similarly, sperm count, viability, and motility were significantly reduced in the PS-MPs treated groups. Histological examinations revealed a noticeable adverse effects on testicular development, with a marked reduction in germ cell populations. The analysis of gene expression showed significant downregulation of AR genes in mice exposed to PS-MPs, indicating the potential endocrine-disrupting effects of MP exposure. Conclusion: This study reveals that polystyrene MP exposure causes oxidative stress and reproductive damage in mice. These findings highlight the potential risks for livestock and other animals through contaminated feed, emphasizing the need for further research on microplastics' impact on animal health in agricultural ecosystems.

Assessing Metabolic Differences Associated with Exposure to Polybrominated Biphenyl and Polychlorinated Biphenyls in the Michigan PBB Registry.

Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB in utero or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. Mean levels were [standard deviation (SD): 13.9] for PBB-153 and (SD: 0.788) for . Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) ], respectively. There were 2,861 features associated with (FDR ). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with levels (level 1 evidence). Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657.

P09-44: Placental Toxicity assessment of Five Essential Oils and Their Potential Endocrine-Disrupting Effects with hPLACENTOX protocol

P09-44: Placental Toxicity assessment of Five Essential Oils and Their Potential Endocrine-Disrupting Effects with hPLACENTOX protocol