A study on assessing the toxic effects of ethyl paraben on rohu (Labeo rohita) using different biomarkers; hemato-biochemical assays, histology, oxidant and antioxidant activity and genotoxicity.

Parabens are being used as preservatives due to their antifungal and antimicrobial effects. They are emerging as aquatic pollutants due to their excessive use in many products. The purpose of this study was to determine the toxic effect of ethyl paraben (C9H10O3) on the hematobiochemical, histological, oxidative, and anti-oxidant enzymatic and non-enzymatic activity; the study also evaluates the potential of ethyl paraben to cause genotoxicity in Rohu Labeo rohita. A number of 15 fish with an average weight of 35.45±1.34g were placed in each group and exposed to ethyl paraben for 21 days. Three different concentrations of ethyl paraben, i.e., T1 (2000µg/L), T2 (4000 µg/L), andT3 (6000 µg/L) on which fish were exposed as compared to the control T0 (0.00 µg/L). Blood was used for hematobiochemical and comet assay. Gills, kidneys, and liver were removed for histological alterations. The results showed a significant rise in all hemato-biochemical parameters such as RBCs, WBCs, PLT count, blood sugar, albumin, globulin, and cholesterol. An increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels directed the hepatocytic damage. Histological alterations in the liver, gills and kidneys of fish were found. Ethylparaben induces oxidative stress by suppressing antioxidant enzyme activity such as SOD, GSH, CAT and POD. Based on the comet assay, DNA damage was also observed in blood cells, resulting in genotoxicity. Findings from the present study indicate that ethyl paraben induces hemato-biochemical alterations, tissue damage, oxidative stress, and genotoxicity.

The combined effects of preservative chemicals in consumer products: An analysis using embryonic and adult zebrafish.

Benzisothiazolinone (BIT) and propyl paraben (PP) are preservatives in cleaning products; however, their toxicities are not well understood. In this study, zebrafish embryos were exposed to BIT, PP, and mixtures of both for 96 h to investigate the effects on growth hormone (GH), insulin-like growth factor-1 (IGF-1), and the transcription of 19 genes related to the GH/IGFs axis. Concentrations of BIT and PP were measured in the whole body of larvae. Zebrafish pairs were also exposed to BIT, PP, and mixtures for 21 d to evaluate the effects on sex hormones, histology in gonad, and transcription of 22 genes related to the hypothalamus-pituitary-gonad axis and vitellogenin. The mixtures had potentiation effects on development, reproduction, hormones, and gene transcripts than individual exposure. Larvae exposed to 229 µg L-1 BIT, 64.5 µg L-1 PP, and mixtures showed reduced growth. Decreased GH and IGF-1 levels were supported by gene regulation associated with the GH/IGFs axis. In larvae, reactive oxygen species, superoxide dismutase, catalase, and glutathione peroxidase levels were increased under all exposures. The gonadosomatic index in males and number of eggs decreased after mixture exposure. In females exposed to mixtures, the percentage of atretic follicle in ovary was significantly increased. The significant decrease in testosterone in males and significant decrease in 17ß-estradiol in females exposed to mixtures suggest anti-estrogenic and anti-androgenic potential. Thus, preservative mixtures in consumer products may be more toxic than the individual substances, which is important for managing the risks of mixing preservatives.

Butylparaben induced zebrafish (Danio rerio) kidney injury by down-regulating the PI3K-AKT pathway.

Butylparaben, a common endocrine disruptor in the environment, is known to be toxic to the reproductive system, heart, and intestines, but its nephrotoxicity has rarely been reported. In order to study the nephrotoxicity and mechanism of butylparaben, we examined the acute and chronic effects on human embryonic kidney cells (HEK293T) and zebrafish. Additionally, we assessed the potential remedial effects of salidroside against butylparaben-induced nephrotoxicity. Our in vitro findings demonstrated oxidative stress and cytotoxicity to HEK293T cells caused by butylparaben. In the zebrafish model, the concentration of butylparaben exposure ranged from 0.5 to 15 µM. An assortment of experimental techniques was employed, including the assessment of kidney tissue morphology using Hematoxylin-Eosin staining, kidney function analysis via fluorescent dextran injection, and gene expression studies related to kidney injury, development, and function. Additionally, butylparaben caused lipid peroxidation in the kidney, thereby damaging glomeruli and renal tubules, which resulted from the downregulation of the PI3K-AKT signaling pathway. Furthermore, salidroside ameliorated butylparaben-induced nephrotoxicity through the PI3K-AKT signaling pathway. This study reveals the seldom-reported kidney toxicity of butylparaben and the protective effect of salidroside against toxicological reactions related to nephrotoxicity. It offers valuable insights into the risks to kidney health posed by environmental toxins.

Detrimental impacts and QSAR baseline toxicity assessment of Japanese medaka embryos exposed to methylparaben and its halogenated byproducts.

Despite the theoretical risk of forming halogenated methylparabens (halo-MePs) during water chlorination in the absence or presence of bromide ions, there remains a lack of in vivo toxicological assessments on vertebrate organisms for halo-MePs. This research addresses these gaps by investigating the lethal (assessed by embryo coagulation) or sub-lethal (assessed by hatching success/heartbeat rate) toxicity and teratogenicity (assessed by deformity rate) of MeP and its mono- and di-halogen derivatives (Cl- or Br-) using Japanese medaka embryos. In assessing selected apical endpoints to discern patterns in physiological or biochemical alterations, heightened toxic impacts were observed for halo-MePs compared to MeP. These include a higher incidence of embryo coagulation (4-36 fold), heartbeat rate decrement (11-36 fold), deformity rate increment (32-223 fold), hatching success decrement (11-59 fold), and an increase in Reactive Oxygen Species (ROS) level (1.2-7.4 fold)/Catalase (CAT) activity (1.7-2.8 fold). Experimentally determined LC50 values are correlated and predicted using a Quantitative Structure Activity Relationship (QSAR) based on the speciation-corrected liposome-water distribution ratio (Dlipw, pH 7.5). The QSAR baseline toxicity aligns well with (sub)lethal toxicity and teratogenicity, as evidenced by toxic ratio (TR) analysis showing TR < 10 for MeP exposure in all cases, while significant specific or reactive toxicity was found for halo-MeP exposure, with TR > 10 observed (excepting three values). Our extensive findings contribute novel insights into the intricate interplay of embryonic toxicity during the early-life-stage of Japanese medaka, with a specific focus on highlighting the potential hazards associated with halo-MePs compared to the parent compound MeP.

Cardiovascular disrupting effects of bisphenols, phthalates, and parabens related to endothelial dysfunction: Review of toxicological and pharmacological mechanisms.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. CVDs are promoted by the accumulation of lipids and immune cells in the endothelial space resulting in endothelial dysfunction. Endothelial cells are important components of the vascular endothelium, that regulate the vascular flow. The imbalance in the production of vasoactive substances results in the loss of vascular homeostasis, leading the endothelial dysfunction. Thus, endothelial dysfunction plays an essential role in the development of atherosclerosis and can be triggered by different cardiovascular risk factors. On the other hand, the 17ß-estradiol (E2) hormone has been related to the regulation of vascular tone through different mechanisms. Several compounds can elicit estrogenic actions similar to those of E2. For these reasons, they have been called endocrine-disrupting compounds (EDCs). This review aims to provide up-to-date information about how different EDCs affect endothelial function and their mechanistic roles in the context of CVDs.

Parabens promotes invasive properties of multiple human cells: A potential cancer-associated adverse outcome pathway.

Parabens are esters of p-hydroxybenzoic acid, which have been used as preservatives and considered safe for nearly a century, until the last two decades when concerns began to be raised about their association with cancers. Knowledge of the mode of action of parabens on the metastatic properties of different cancer cells is still very limited. In the present study, we investigated the effects of methylparaben (MP) and propylparaben (PP) on cell invasion and/or migration in multiple human cancerous and noncancerous cells, including hepatocellular carcinoma cells (HepG2), cervical carcinoma cells (HeLa), breast carcinoma cells (MCF-7), and human placental trophoblasts (HTR-8/SVneo). MP and PP at concentrations in a range of 5-500 µg/L significantly promoted the invasion of four cell lines, with a minimum effective concentration of 5 µg/L. MP and PP up-regulated the expression levels and enzymatic activities of matrix metalloproteinase 2 and 9 (MMP2 and MMP9), as well as altered the expression of the tissue inhibitors of metalloproteinase 1 and 2 (TIMP1 and TIMP2) in four cell lines, suggesting MMPs/TIMPs as potential key events (KEs) for paraben-induced cell invasion. Activation of the p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal protein kinases 1/2 (JNK1/2) signaling pathways was required for MP- and PP-promoted invasion of four cell lines, suggesting MAPK signaling pathways as candidates for KEs in cancer or noncancerous cells response to paraben exposure. This study showed for the first time that the two widely used parabens, MP and PP, promoted invasive capacity of multiple human cells through a common mode of action. This study provides evidence for the establishment of a potential cancer-associated AOP for parabens based on pathway-specific mechanism(s), which contributes towards assessing the health risks of these environmental chemicals.

Estrogenic disruption effects and formation mechanisms of transformation products during photolysis of preservative parabens.

The ubiquitous presence of emerging contaminants (ECs) in the environment and their associated adverse effects has raised concerns about their potential risks. The increased toxicity observed during the environmental transformation of ECs is often linked to the formation of their transformation products (TPs). However, comprehension of their formation mechanisms and contribution to the increased toxicity remains an unresolved challenge. To address this gap, by combining quantum chemical and molecular simulations with photochemical experiments in water, this study investigated the formation of TPs and their molecular interactions related to estrogenic effect using the photochemical degradation of benzylparaben (BZP) preservative as a representative example. A non-targeted analysis was carried out and three previously unknown TPs were identified during the transformation of BZP. Noteworthy, two of these novel TPs, namely oligomers BZP-o-phenol and BZP-m-phenol, exhibited higher estrogenic activities compared to the parent BZP. Their IC50 values of 0.26 and 0.50 µM, respectively, were found to be lower than that of the parent BZP (6.42 µM). The binding free energies (ΔGbind) of BZP-o-phenol and BZP-m-phenol (-29.71 to -23.28 kcal·mol-1) were lower than that of the parent BZP (-20.86 kcal·mol-1), confirming their stronger binding affinities toward the estrogen receptor (ER) α-ligand binding domain. Subsequent analysis unveiled that these hydrophobic residues contributed most favorably to ER binding, with van der Waals interactions playing a significant role. In-depth examination of the formation mechanisms indicated that these toxic TPs primarily originated from the successive cleavage of ester bonds (OCH2C6H5 and COO group), followed by their combination with BZP*. This study provides valuable insight into the mechanisms underlying the formation of toxic TPs and their binding interactions causing the endocrine-disrupting effects. It offers a crucial framework for elucidating the toxicological patterns of ECs with similar structures.

Disruption of gonadotropin hormone biosynthesis by parabens: A potential development and reproduction-associated adverse outcome pathway.

Parabens are widely used as antibacterial preservatives in foods and personal care products. The knowledge about the modes of toxic action of parabens on development and reproduction remain very limited. The present study attempted to establish a development and reproduction-associated adverse outcome pathway (AOP) by evaluating the effects of methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) on the biosynthesis of gonadotropins, which are key hormones for development and reproduction. MP and BP significantly upregulated the mRNA and protein levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in pituitary gonadotropic cells in a concentration-dependent manner. Activation of gonadotropin-releasing hormone receptor (GnRHR) was required for gonadotropin biosynthesis induced by BP, but not MP. Molecular docking data further demonstrated the higher binding efficiency of BP to human GnRHR than that of MP, suggesting GnRHR as a potential molecular initiative event (MIE) for BP-induced gonadotropin production. L-type voltage-gated calcium channels (VGCCs) were found to be another candidate for MIE in gonadotropic cells response to both MP and BP exposure. The calcium-dependent activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2 was subsequently required for MP- and BP-induced activation of GnRHR and L-type VGCCs pathways. In summary, MP and BP promoted gonadotropin biosynthesis through their interactions with cellular macromolecules GnRHR, L-type VGCCs, and subsequent key event ERK1/2. This is the first study to report the direct interference of parabens with gonadotropin biosynthesis and establish a potential AOP based on pathway-specific mechanism, which contributes to the effective screening of environmental chemicals with developmental and reproductive health risks.

High-dose exposure to butylparaben impairs thyroid ultrastructure and function in rats.

Parabens (PBs) are a class of preservatives commonly used in cosmetics and pharmaceuticals. Studies have shown that these compounds may act as endocrine disruptors, affecting thyroxine levels in humans. PBs with longer chain substituents, such as butylparaben (BuP), are less prone to complete biotransformation and are therefore more likely to accumulate in the body. In this study, the effect of high-dose exposure to BuP on thyroid microstructure, ultrastructure, and function was investigated in rats. 50 mg/kg bw per day of BuP was injected subcutaneously into the neck of rats for 4 weeks. Rat thyroid weight, microstructure, and ultrastructure were determined, and the levels of thyroid sodium/iodide symporter (NIS), serum thyroid hormones, and thyroid autoantibodies were measured. The human thyroid cell line was used to study the mechanism of BuP on thyroid epithelial cells. The weight of the thyroid gland of BuP-exposed rats was increased, the structure of the thyroid follicles was irregular and damaged, the mitochondria and rough endoplasmic reticulum were swollen and damaged, and the microvilli at the tip of the epithelium were reduced and disappeared. Serum total T3, total T4, free T3, and free T4 were decreased in BuP-exposed rats, and TSH, peroxidase antibody, and thyroglobulin antibody were increased. In vitro, BuP decreased the level of NIS in thyroid epithelial cells, inhibited proliferation and viability, and induced apoptosis in a dose-dependent manner. This study demonstrated that high-dose exposure to BuP induced structural, ultrastructural, and functional impairment to the thyroid gland of rats, which may be one of the factors leading to hypothyroidism.

Chronic exposure to parabens promotes non-alcoholic fatty liver disease in association with the changes of the gut microbiota and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD via gut microbiota-dependent AA metabolism. These results highlight the need for reducing oral exposure to synthetic preservatives to improve metabolic disturbance under HFD conditions.

Into the toxicity potential of an array of parabens by biomimetic liquid chromatography, cell viability assessments and in silico predictions.

Five parabens (PBs) i.e., Methylparaben (MP), Ethylparaben (EP), Isopropylparaben (iPrP), Isobutylparaben (iBuP), Benzylparaben (BzP), and their parent compound i.e., para-hydroxy Benzoic Acid (pHBA), were studied both in vitro and in silico. Specifically, we determined their retention on several both protein- (Human Serum Albumin and α1-acidic glycoprotein) and (phospho) lipid- (immobilized artificial membrane (IAM)) based biomimetic stationary phases to evaluate their penetration potential through the biomembranes and their possible distribution in the body. The IAM phases were based either on phosphatidylcholine (PC) analogues i.e., PC.MG and PC.DD2 or on sphingomyelin (SPH). We also assessed their viability effect on breast cancer cells (MCF-7) via MTT assay subjecting the cells to five different PB concentrations i.e., 100 µM, 10 µM, 1 µM, 0.1 µM and 0.01 µM. Finally, their pharmacokinetics and toxicity were assessed by the ADMET Predictor™ software. Isopropylparaben was found to be more active than 17ß estradiol (E2) employed as positive control, on the screened cell line inducing cell proliferation up to 150 % more of untreated cells. Other analogues showed only a slight/moderate cell proliferation activity, with parabens having longer/branched side chain showing, on average, a higher proliferation rate. Significant linear direct relationships (for PC.DD2 r2 = 0.89, q2 = 0.86, for SPH r2 = 0.89, q2 = 0.85, for both P value < 0.05) were observed between the difference in proliferative effect between the readout and the control at 0.01 µM concentration and the retention on the IAM phases measured at pH 5.0 for all compounds but pHBA, which is the only analyte of the dataset supporting a carboxylic acid moiety. IAM affinity data measured at pH 7.0 were found to be related to the effective human jejunal permeability as predicted by the software ADMET® Predictor, which is relevant when PBs are added to pharmaceutical and food commodities.

Exposure to biocides and its association with atopic dermatitis among children and adolescents: A population-based cross-sectional study in South Korea.

BACKGROUND: Biocides have emerged as a contributor to the rising cases of atopic dermatitis among children and adolescents. Previous animal studies suggested that phenols, parabens, and pyrethroid insecticides present in these products might play a role in atopic dermatitis. However, there's limited epidemiological evidence confirming the individual or combined effects of exposure to these chemicals on atopic dermatitis in young populations. This study aimed to investigate the association between phenol, paraben, and pyrethroid metabolite levels in urine and atopic dermatitis among Korean children and adolescents METHODS: We analyzed 556 preschool children (3-5 years), 701 schoolchildren (6-11 years), and 731 adolescents (12-17 years) enrolled in the 4th Korean National Environmental Health Survey (KoNEHS) (2018-2020). We used logistic regression and Bayesian kernel machine regression to evaluate the association between atopic dermatitis and individual or mixed exposure to urinary triclosan (TCS), parabens (methylparaben, ethylparaben, propylparaben, and butylparaben), and 3-phenoxybenzoic acid (3-PBA) levels. RESULTS: Urinary TCS levels were positively associated with atopic dermatitis in schoolchildren. When stratified by sex, male schoolchildren exhibited an increasing prevalence of atopic dermatitis as their urinary TCS and 3-PBA levels increased. The combined effect of biocide mixtures on atopic dermatitis was also significantly increased in male schoolchildren, with TCS as the main contributor. CONCLUSIONS: These study findings suggest that biocides at levels found in Korean children and adolescents affect atopic dermatitis.

Grouping of esters of 4-hydroxybenzoic acid for hazard assessment.

Hazardous properties of a large number of esters of 4-hydroxybenzoic acid (parabens) have been proposed by ECHA to be assessed as a group. We recommend to restrict the grouping approach to short chain esters, i.e. methyl, ethyl, propyl and butyl paraben which are very similar in chemical structures, physicochemical properties, toxicokinetics, and hazardous properties. While these parabens show a weak estrogenicity in some in vitro or in vivo screening assays, they do not induce estrogen-receptor-mediated adverse effects in intact animals. Therefore, there is no support regarding classification and labeling of endocrine disruption or reproductive toxicity of these parabens.

Repeated measurements and mixture effects of urinary bisphenols, parabens, polycyclic aromatic hydrocarbons, and other chemicals on biomarkers of oxidative stress in pre- and postpartum women.

The association between oxidative stress and exposure to bisphenols, parabens, phenols, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOCs) has been investigated by many in vitro and in vivo studies. However, most of these findings are based on cross-sectional studies, as a result of which the combined effects of these compounds have been rarely analyzed. In this study, our objective was to assess urinary bisphenols, parabens, PAHs, and VOCs, in relation to oxidative stress during pre-and postpartum periods, analyze the association between these chemicals and oxidative stress via repeated measurements using a linear mixed model (LMM), and evaluate the combined effects exerted by these chemicals on oxidative stress using Bayesian Kernel Machine Regression (BKMR). A total 529 urine samples were collected from 242 pregnant women during the 1st and 2nd trimesters, as well as postpartum follow-ups. Three bisphenols, four parabens, benzopheone-3 (BP-3), triclosan (TCS), four PAHs, two VOCs, and 3- phenoxy-benzoic acid (3-PBA) were analyzed. We also measured 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA), which serve as oxidative stress biomarkers in maternal urine samples. During this period, 8-OHdG decreased steadily, whereas MDA increased during pregnancy and decreased after childbirth. LMM indicated that Bisphenol A, Prophyl-paraben, BP-3, and 1-hydroxypyrene (1-OHP) showed a significant association with increased MDA levels. The BKMR models revealed that the mixture effect exerted by these 16 chemicals had changed MDA levels, which indicate oxidative stress, and that both Butyl Paraben (BP) and 1-hydroxypyrene (1-OHP) had contributed to such oxidative stress. Mixtures of each subgroup (bisphenols, parabens, and PAHs) were associated with increased MDA levels. These findings suggest that exposure to some phenols and PAHs during pre- and post-partum stages may cause oxidative stress, and that exposure to these chemicals should be minimized during this period.

Embryonic and larval exposure to propylparaben induces developmental and long-term neurotoxicity in zebrafish model.

Parabens are preservatives found in cosmetics, processed foods, and medications. The harmful repercussions on the central nervous system by one of the most common parabens, propylparaben (PrP), are yet unknown, especially during development. In this study, the neurodevelopmental effects of PrP and long-term neurotoxicity were investigated in the zebrafish model, using an integrated approach. Zebrafish embryos were exposed to two different concentrations of PrP (10 and 1000 µg/L), then larvae were examined for their behavioral phenotypes (open-field behavior, startle response, and circadian rhythmicity) and relevant brain markers (cyp19a1b, pax6a, shank3a, and gad1b). Long-term behavioral and cognitive impacts on sociability, cerebral functional asymmetry and thigmotaxis were also examined on juveniles at 30 dpf and 60 dpf. Moreover, proteomics and gene expression analysis were assessed in brains of 60 dpf zebrafish. Interestingly, thigmotaxis was decreased by the high dose in larvae and increased by the low dose in juveniles. The expression of shank3a and gad1b genes was repressed by both PrP concentrations pointing to possible effects of PrP on neurodevelopment and synaptogenesis. Proteomics analysis evidenced alterations related to brain development and lipid metabolism. Overall, the results demonstrated that early-life exposure to PrP promotes developmental and persistent neurobehavioral alterations in the zebrafish model, affecting genes and protein levels possibly associated with brain diseases.

Toxicity of benzyl paraben on aquatic as well as terrestrial life.

Parabens are derivatives of alkyl esters of p-hydroxybenzoic acid and come in different classes. These compounds are primarily used as antimicrobial preservative agents in many commercial products, including cosmetics and pharmaceuticals. Accordingly, Benzyl paraben (BeP) is known to be a potential endocrine disruptor. The aim of this study was to determine the toxicity of benzyl paraben (BeP) on aquatic and terrestrial organisms, specifically Scenedesmus sp., Moina macrocopa, and Eisenia fetida. All the organisms were treated with different concentrations of BeP (0.025 mg/L and 1000 mg/L), and LC25, LC50, and LC90 values were used to measure the toxicity levels. Results showed the LC values of BeP for M. macrocopa (3.3 mg/L, 4.7 mg/L, 7.3 mg/L) and E. fetida (173.2 mg/L, 479.8 mg/L, 1062 mg/L), respectively. Toxicity tests on green algae (Scenedesmus sp.) were conducted, the green algae were subjected to various BeP concentration. At 50 mg/L of BeP, cell viability was reduced to 56.2% and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay indicated 35.4% viable cells. The chlorophyll value and the biochemical parameters of the algal cells were corroborative with the cell viability test. Lethal indices (LC50) for M. macrocopa and E. fetida were evaluated for their toxicity on biochemical properties and were found to be catalase (0.111 mg/L, 0.5 mg/L), lipid peroxidation (0.072 mg/L, 0.056 mg/L), and total protein (0.309 mg/L, 0.314 mg/L), respectively. Overall, this study demonstrated the toxic impact of BeP on non-target aquatic as well as terrestrial species.

Cardio- and neuro-toxic effects of four parabens on Daphnia magna.

Parabens can potentially disrupt the hormonal regulation of energy metabolism, leading to issues related to obesity, metabolic health, and the cardiovascular and nervous systems. However, the health effects of parabens have yielded conflicting research results. The impact of these substances on aquatic organisms, specifically their neuro- and cardio-toxic effects, has been insufficiently investigated. Hence, the primary goal of our research was to investigate and comprehensively assess the neuro- and cardio-toxic effects of four distinct parabens using the Daphnia magna model. After 48 h of exposure to various concentrations (0.1, 1, and 10 mg/L) of four parabens (methyl-, ethyl-, propyl-, and butyl-paraben), along with a solvent control, we conducted a series of physiological tests, behavioral observations, and gene transcription analyses, focusing on cardiomyopathy, serotonin, glutamate, dopamine, GABA, acetylcholine receptors, and ion flux. From a physiological perspective, the heart rate and thoracic limb activity of the exposed daphnids showed substantial time- and dose-dependent inhibitions. Notably, among the parabens tested, butylparaben exhibited the most potent inhibition, with significant alterations in cardiomyopathy-related gene transcription. In the context of neurotoxicity, all the parabens had a significant impact on gene expression, with methylparaben having the most pronounced effect. Additionally, significant changes were observed in parameters such as distance moved, the distance between individuals, and the extent of body contact among the daphnids. In summary, our findings indicate that each paraben has the capacity to induce neurobehavioral and cardiotoxic disorders in Daphnia magna. The effects of butylparaben on the cardiovascular and nervous systems were found to be the most pronounced. These discoveries showed the potential ecological implications of paraben exposure in aquatic ecosystems, particularly regarding the predator avoidance abilities of Daphnia magna.

Ethylparaben Toxicity on Cladocerans Daphnia Similis and Ceriodaphnia Silvestrii and Species Sensitivity Analysis.

Parabens, a group of preservatives with a wide industrial range, threaten human and aquatic biota health due to their toxicity and endocrine disruption potential. As conventional wastewater treatment may not be enough to keep natural environments safe, toxicity studies are useful tools for supporting ecological risk assessments. Here, we focused on assessing ethylparaben's, one of the most common kinds of paraben, toxicity in the cladocerans Daphnia similis and Ceriodaphnia silvestrii. The EC50 sensitivity for D. similis and C. silvestrii was 24 (21-28) mg L- 1 and 25 (19-33) mg L- 1, respectively. Inhibition of reproduction and late development of females were observed in C. silvestrii exposed to 8 mg L- 1. Furthermore, species sensitivity distribution was used to assess ecological risk, and ethylparaben demonstrated low potential risk for aquatic biota.

Butylparaben promotes phosphatidylserine exposure and procoagulant activity of human red blood cells via increase of intracellular calcium levels.

Parabens are widely used as preservatives, added to products commonly used by humans, and to which individuals are exposed orally or dermally. Once absorbed into the body, parabens move into the bloodstream and travel through the systemic circulation. We investigated the potential impact of parabens on the enhanced generation of thrombin by red blood cells (RBCs), which are the principal cellular components of blood. We tested the effects of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and p-hydroxybenzoic acid on freshly isolated human RBCs. BuP and simultaneous exposure to BuP and PrP significantly increased phosphatidylserine (PS) externalization to the outer membranes of RBCs. PS externalization by BuP was found to be mediated by increasing intracellular Ca2+ levels in RBCs. The morphological changes in BuP-treated RBCs were observed under an electron microscope. The BuP-exposed RBCs showed increased thrombin generation and adhesion to endothelial cells. Additionally, the externalization of PS exposure and thrombin generation in BuP-treated RBCs were more susceptible to high shear stress, which mimics blood turbulence under pathological conditions. Collectively, we observed that BuP induced morphological and functional changes in RBCs, especially under high shear stress, suggesting that BuP may contribute to the thrombotic risk via procoagulant activity in RBCs.

Environmental Endocrinology: Parabens Hazardous Effects on Hypothalamic-Pituitary-Thyroid Axis.

Parabens are classified as endocrine-disrupting chemicals (EDCs) capable of interfering with the normal functioning of the thyroid, affecting the proper regulation of the biosynthesis of thyroid hormones (THs), which is controlled by the hypothalamic-pituitary-thyroid axis (HPT). Given the crucial role of these hormones in health and the growing evidence of diseases related to thyroid dysfunction, this review looks at the effects of paraben exposure on the thyroid. In this study, we considered research carried out in vitro and in vivo and epidemiological studies published between 1951 and 2023, which demonstrated an association between exposure to parabens and dysfunctions of the HPT axis. In humans, exposure to parabens increases thyroid-stimulating hormone (TSH) levels, while exposure decreases TSH levels in rodents. The effects on THs levels are also poorly described, as well as peripheral metabolism. Regardless, recent studies have shown different actions between different subtypes of parabens on the HPT axis, which allows us to speculate that the mechanism of action of these parabens is different. Furthermore, studies of exposure to parabens are more evident in women than in men. Therefore, future studies are needed to clarify the effects of exposure to parabens and their mechanisms of action on this axis.