ETHYLPARABEN

Ethylparaben (EP), one of the parabens, a ubiquitous food and cosmetic preservatives, has caused widespread concern due to its health risks. Recently, studies have found that parabens exposure during pregnancy is negatively correlated with fetal and early childhood development. However, studies about EP on embryo development are few. In this study, the cardiotoxicity effects of EP concentrations ranging from 0 to 20 mg/L on zebrafish embryo development were explored. Results showed that EP exposure induce abnormal cardiac function and morphology, mainly manifested as pericardial effusion and abnormal heart rate in early-stage development of zebrafish embryos. Through transcriptome sequencing followed by Gene Ontology enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we further confirmed that EP exposure ultimately leads to cardiac morphologic abnormalities via the following three mechanisms: 1. Disruption of the retinoic acid signaling pathway related to original cardiac catheter development; 2. Inhibition of gene expression related to myocardial contraction; 3. Orientation development disturbance of heart tube. Moreover, O-Dianisidine staining, whole-mount in situ hybridization at 30 and 48 hours post fertilization (hpf) and hematoxylin-eosin staining results all confirmed the decreased heart's return blood volume, misoriented heart tubes toward either the right or the middle side, and heart loop defects. For the first time, we explored the mechanism by which EP exposure causes abnormal heart development in zebrafish embryos, laying the foundation for further revealing of the EP toxicity on embryonic development.

Pharmaceuticals and personal care products (PPCPs) have been considered as potential contributors to thyroid nodule (TN) and abnormal thyroid homeostasis, but epidemiological evidence is scarce. A total of 1261 individuals comprised of 367 TN patients and 895 controls were recruited from Sichuan, China. The urinary concentrations of fourteen PPCPs were measured. Five thyroid hormones (THs) in serum were determined as indicators of thyroid homeostasis, including thyroid-stimulating hormone, triiodothyronine (T3), thyroxine (T4), free-T3 and free-T4. Serum levels of thyroglobulin antibody (TGAb) and thyroperoxidase antibody (TPOAb) were quantified to identify individual thyroid antibody (TA) statuses. TN patients exhibited higher propyl-paraben (PrP) (median: 1.30 µg/g Cr) level than controls (0.64 µg/g Cr). PrP were significantly associated with TN risk with ORs of 1.060 (95 % CI: 1.002, 1.122). The relationship of methyl-paraben with TN risk was nonlinear (p = 0.049). PPCP exposure was significant with TN risk only in females and TA positive (TPOAb or TGAb) groups, indicating that PPCP susceptibility to TN differs by sex and TA status. Linear regression models showed ethyl-paraben was significantly negatively associated with T4 (β: -0.005, 95 % CI: -0.011, -0.002) and T3 (β: -0.007, 95 % CI: -0.015, -0.002), and positively associated with TPOAb (β: 0.059, 95 % CI: 0.000, 0.119), suggesting that certain PPCP exposure could affect thyroid homeostasis and autoimmunity. The effects of PPCP exposure on TH and TA levels presented sex-specific. Our findings suggest that PPCP exposure increases TN risk and affects thyroid homeostasis, exhibiting sex and antibody status dependence.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased concomitantly with heightened exposure to environmental chemicals, such as benzophenone-type ultraviolet (BP-type UV) filters and parabens, which are prevalent in personal care products. This study aimed to investigate the potential link between the exposure to these chemicals and the risk of developing NAFLD. We conducted a case-control study involving 228 participants from South China, encompassing individuals diagnosed with NAFLD and healthy controls. Blood samples were collected and analyzed for the presence of 11 parabens and 8 BP-type UV filters. The findings revealed significantly elevated concentrations of several parabens and BP-type UV filters in the blood of patients with NAFLD compared with the healthy cohort. Notably, methylparaben (MeP), ethylparaben (EtP), isopropylparaben (iPrP), butylparaben (BuP), isobutylparaben (iBuP), 3,4-dihydroxybenzoic acid (3,4-DHB), total parabens (Σparabens), BP1, BP3, BP4, and 4-hydroxybenzophenone (4-OH-BP) were identified as significant predictors of NAFLD prevalence. Through multiple regression analyses, the blood levels of iBuP, Σparabens, and BP4 were found to be significantly associated with elevated triglycerides (TG) (β = 0.59 mmol/L, 95% CI = 0.11-1.59), total bilirubin (TBIL) (β = 2.81 μmol/L, 95% CI = 0.46-15.6) or direct bilirubin (DBIL) (β = 1.89 μmol/L, 95% CI = 0.47-10.2), and reduced globulins (GLB) (β = -0.29 g/L, 95% CI = -0.07 to -5.45), respectively, which are indicators of liver damage. Moreover, TBIL and DBIL were found to mediate 26.7% and 24.6% of the increase in NAFLD prevalence associated with Σparabens, respectively. In conclusion, this study offers pioneering insights into human exposure to parabens and BP-type UV filters as well as their hepatotoxic potential.

Parabens, which mainly include methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP), are widely used as cosmetic and food preservatives. Although these chemicals, when used as preservatives, are thought to be safe for humans, many studies have demonstrated that they have estrogenic effects, and can affect the normal development and functions of the reproductive systems in a number of animal species. By treating fruit flies (Drosophila melanogaster) with EP, here we show that lower concentration of EP (0.02%) enhanced fertility while higher concentration of EP (0.10% and 0.20%) shortened the lifespan and reduced the fecundity of fruit flies. When we analyzed the expression levels of the estrogen-related receptor gene (ERR), ecdysone receptor gene (EcR) and Yolk protein receptor gene (YPR) from control and EP-treated fruit flies by using quantitative real-time PCR, we found that the expression levels of all three genes were significantly changed by EP treatment, and that female fruit flies are more sensitive to EP than males. Our data suggests that the estrogenic and the toxic effects of EP to fruit flies may have a molecular basis through the hormonal effect of EP.

Ethylparaben (EtP), a widely used preservative in food and cosmetics, has raised increasing concerns in the field of reproductive toxicology due to its potential adverse effects on human health. In this study, we show that EtP exposure induces developmental arrest at the 2-cell stage in mouse embryos. This arrest coincides with elevated reactive oxygen species levels, mitochondrial dysfunction, DNA damage, and apoptosis. Transcriptomic analysis reveals widespread gene dysregulation following EtP exposure, characterized by the downregulation of maternal-effect genes, cleavage-stage embryo genes, and mitochondria-associated genes. These downregulated genes are primarily involved in transcription activation and apoptosis, while upregulated genes are enriched in DNA damage response pathways. Furthermore, EtP exposure alters histone modifications in embryos, leading to impaired transcriptional activity. We find that melatonin and spermidine partially rescue the developmental arrest by mitigating oxidative stress. Together, our findings demonstrate that EtP exacerbates oxidative stress, disrupts mitochondrial integrity, and damages DNA in mouse embryos, ultimately impairing transcription and developmental progression. Notably, EtP-induced disruption of histone modifications compromises zygotic genome activation, resulting in embryonic arrest. In contrast, melatonin and spermidine alleviate oxidative damage and mitochondrial dysfunction, partially restoring normal embryonic development following EtP exposure.

Parabens, which are chemicals used as preservatives in cosmetic and pharmaceutical products, have been reported to be associated with low sperm quality in animal and human models. Despite the high exposure of men to paraben-containing products in Nigeria, there are no known studies that investigate the association of parabens with sperm quality in the country. To determine the association of urinary levels of metabolites of parabens with sperm count and quality. A multicenter case-control study among fertile and infertile men in five hospitals in southern Nigeria. A total of 136 men diagnosed with male infertility (cases) were compared with 154 controls with normal fertility. Urinary levels of parabens (ethyl-paraben, methylparaben, propylparaben, and butylparaben) were measured using liquid chromatography mass spectrometry, while semen analysis and hormone assays were carried out using World Health Organization standards and radioimmunoassay, respectively. Data were analyzed with non-parametric statistics and non-parametric linear regression. The results showed high levels of parabens in both cases and controls. However, there was no statistically significant difference in urinary levels of ethyl-paraben, methylparaben, propylparaben, and butylparaben between cases and controls. In contrast, propylparaben had a decreasing association with total motility in both groups, but the effect was only statistically significant in the case of male infertility. The results of the regression analysis showed that a unit increase in propylparaben significantly decreased total motility in the cases (infertile men). Similarly, a unit increase in propylparaben decreased morphology significantly in the unadjusted model for infertile men. Only serum testosterone showed an insignificant correlation with urinary parabens. We conclude that urinary parabens are associated with features of poor sperm quality - motility, morphology, and volume. Measures to reduce exposure of men to agents containing parabens in Nigeria may reduce the prevalence of male infertility in the country.

Parabens, preservatives commonly used in personal care products (PCPs), have emerged as environmental contaminants of concern due to their biological activity, water solubility, and pseudo-persistence. This study assessed the occurrence of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) in PCPs available on the Argentine market, as well as their distribution in surface water, suspended particulate matter (SPM), and sediments from La Plata city and the surrounding metropolitan area, Argentina. A total of 183 PCPs were analyzed in sampling campaigns conducted in 2018 and 2022. MeP and PrP were the most frequently detected compounds, with an overall decrease in detection frequency between the two campaigns, suggesting a shift toward "paraben-free" formulations. However, inconsistencies were observed between product labeling and actual paraben content. In environmental matrices, MeP and PrP were consistently detected across all campaigns, primarily in water and SPM, with maximum concentrations of 1519 ng/L and 24,610 ng/g (dry weight), respectively. Detection patterns were spatially and temporally homogeneous, indicating a continuous input from urban sources. Multivariate analysis confirmed the association of MeP and PrP with surface water and SPM and suggested limited retention in sediments. These findings highlight the need for stricter regulatory frameworks, improved labeling transparency, and the implementation of systematic monitoring programs that address both consumer products and their environmental implications. This study provides the first integrated evaluation of parabens in consumer products and urban aquatic environments in Argentina.

Parabens are preservatives that are widely used in cosmetics, pharmaceuticals, and foods, which raise concern due to their potential as endocrine-disrupting chemicals (EDCs). According to PRISMA guidelines, this study analyzes paraben concentrations in foods globally, with no temporal or geographical restrictions. Of the 713 initially identified articles, 75 were included and classified into 14 food groups. In the European Union (EU), the highest levels pertained to methylparaben and were detected in dairy products (302.82 ng g -1 ), vegetables (231.90 ng g -1 ) and eggs (229.90 ng g -1 ), albeit within regulatory safety limits. However, cumulative exposure from multiple contaminated food sources could lead to the acceptable daily intake (ADI) being exceeded. Outside of the EU, especially in China and Saudi Arabia, higher concentrations were reported in processed condiments (methylparaben: 495700.00 ng g -1 ), vegetables (ethylparaben: 312600.00 ng g -1 ) and cookies (methylparaben: 253700.00 ng g -1 ), with levels far exceeding those found in the EU. Stronger worldwide controls are required to reduce paraben exposure through food.

Maternal exposure to endocrine-disrupting chemicals (EDCs), particularly those found in personal care products (PCPs), may affect child development. Socioeconomic inequalities in EDC exposure warrant further investigation. This study assessed the role of income and education in the association between PCP use and exposure to bisphenol A (BPA) and parabens in pregnant women. Associations between PCP use and urinary concentrations of BPA and four parabens in pregnant women from the Taiwan Maternal and Infant Cohort Study were estimated using linear regression, with results expressed as the percentage change in concentrations for each additional PCP use per week. The analysis was stratified by income and education and predicted concentrations, and a 95% confidence interval (CI) was graphed according to the frequency of PCP use. Higher concentrations of methylparaben, ethylparaben, and propylparaben were associated with more frequent use of different PCPs, especially makeup. The above-lowest income group showed positive associations between frequency use of rinse-off PCPs and methylparaben (2.5%, 95%CI = 0.9%, 4.0%), propylparaben (2.8%, 95%CI = 0.3%, 5.3%), and between leave-on PCPs and methylparaben (3.1%, 95%CI = 1.8%, 4.4%), ethylparaben (2.2%, 95%CI = 0.1%, 4.2%), and propylparaben (2.8%, 95%CI = 0.8%, 4.9%). BPA was negatively associated with rinse-off PCPs (-1.2%, 95%CI = -2.3%, -0.2%). A positive association between leave-on PCPs and BPA was suggested in the lowest income group (1.7%, 95%CI = -0.4%, 3.7%). Predicted BPA concentrations were significantly higher in the lowest income group at higher frequencies of PCP use. Stratification by education showed the strongest associations in the postgraduate group for rinse-off PCPs with methylparaben (6.1%, 95%CI = 1.9%, 10.5%) and propylparaben (6.9%, 95%CI = 1.2%, 12.9%), as well as for leave-on PCPs with methylparaben (4.1%, 95%CI = 1.2%, 7.2%). The associations observed between various PCPs and parabens suggest that reducing the use of certain PCPs in pregnant women could help lower paraben exposure. Higher levels of BPA in the lowest income group require further investigation of sources of BPA exposure, especially in disadvantaged populations.

Silicone wristbands are increasingly used as a wearable exposure tool to assess inhalation and dermal exposure to semi-volatile organic chemicals present in indoor environments. However, little research has investigated their utility in detecting exposures specifically related to personal care product (PCP) use. Here, we assessed exposure to methyl-, ethyl-, and propylparabens after applying a lotion containing a known amount of each chemical. A convenience sample of 20 adults wore a wristband and collected all urine excreted for three days over two consecutive weeks, keeping their PCP use consistent. During one of these periods, participants were provided with a lotion containing a known amount of parabens and asked to apply it daily (4.57 g applied over three days, with one pump of lotion each day). Urine and wristband samples were extracted and analyzed for parabens via LC-MS/MS. Parabens present in the lotion were detected in 100 % of wristbands across both study periods, while urinary detection of these paraben ranged from 87 to 100 % across periods. Parabens were measured at higher levels in urine and wristbands collected during the lotion application phase. For every 10 % increase in wristband paraben concentrations, the total paraben mass excreted in urine increased an average of 4 % for methylparaben (95 % CI = 3-5 %, p < 0.0001), 4 % for ethylparaben (95 % CI = 3-5 %, p < 0.0001), and 6 % for propylparaben (95 % CI = 4-7 %, p < 0.0001). This study shows that wristband concentrations reflect differences in use of a PCP containing parabens. Differences in wristband concentrations between study periods were greater than differences in urinary biomarkers of exposure, possibly because wristbands represent total potential exposure from dermal and inhalation routes. As this investigation only required a difference of one pump of lotion applied daily, the sensitivity of wristbands to capture differences in PCP use is promising.

Parabens are widely used as antimicrobials in personal care products and pharmaceuticals. While previous studies demonstrate paraben exposure is ubiquitous, data investigating infants' exposure is limited. We sought to characterize infants' exposure to parabens and identify factors associated with higher levels of exposure. Families enrolled in the CHildren's Immune ResPonse Study between 2016-2018. Parents completed questionnaires, providing information on demographics and lifestyle factors. Urine samples were collected when infants were 1 to 3 months old (n = 71) and 12 months old (n = 29), with 18 infants evaluated at both ages. Parabens were measured in urine samples using liquid chromatography tandem mass spectrometry and served as an indicator of exposure. Methylparaben (MP), ethylparaben (EP), and propylparaben (PP) were detected in >70% of urine samples, and concentrations ranged several orders of magnitude (specific-gravity-corrected medians: MP = 25.4 PP = 3.55; EP = 0.90 ng/mL). Butylparaben was detected less frequently (<50%). Paraben concentrations were lower than those reported for older children and adults; however, we did not find statistically significant differences in paraben concentrations by infant age. Correlations between measurements taken over time were poor, suggesting paraben exposure is variable, and multiple measurements are needed to capture cumulative exposure information. We observed differences in exposure by race/ethnicity and socioeconomic status; non-White infants and infants whose parents completed less education had higher paraben exposure. Recent lotion usage strongly predicted paraben exposure in 1-3-month-olds. For example, infants using lotion in the past seven days had urinary MP concentrations 355% higher than infants without lotion usage (e ß = 4.55, 95% Confidence Interval = 1.68, 12.55, p < 0.001). Together, our results suggest infants are ubiquitously exposed to parabens and personal care product use may be an important source of exposure. To the best of our knowledge, this is the first paper to report paraben levels and evaluate predictors of exposure in infants. This study supports the hypothesis that universal exposure to parabens extends to infants, as indicated by urinary biomarker concentrations. Of the predictors evaluated, lotion use in the last seven days was the strongest predictor of exposure in 1-3-month-olds. Given infant paraben levels are strongly correlated to lotion use, there may be an opportunity for parents to reduce paraben exposure by limiting its application or consulting ingredient labels to ensure no parabens are present.

Hair relaxers have been suggested as a source of exposure to parabens and phthalates. However, dermally absorbed doses of these chemicals resulting from consumer use of hair relaxers have yet to be quantified, and results from epidemiological studies have consistently demonstrated that there is no increased risk for hormone-sensitive, reproductive cancers associated with use of hair relaxers among Black women. Therefore, dermal absorption of parabens and phthalates associated with hair relaxer use for several commercially available hair relaxer kits was modeled using IH SkinPerm™. The chemicals detected in the hair relaxer kits included methylparaben (MP), ethylparaben (EP), butylparaben (BP), diethyl phthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), and the phthalate substitute bis(2-ethylhexyl) adipate (DEHA). The daily absorbed dose ranges (mg/kg/day), standardized over a year of product use, were as follows: 8.64 × 10 -5 -0.00116 MP, 2.30 × 10 -8 -3.07 × 10 -6 EP, 3.24 × 10 -8 -4.33 × 10 -6 BP, 8.65 × 10 -9 -1.15 × 10 -6 DEP, and 8.94 × 10 -7 -0.000119 DEHP for Kit #1; 8.44 × 10 -5 -0.00113 MP and 7.91 × 10 -5 -0.00106 DEP for Kit #2; and 2.49 × 10 -6 -3.33 × 10 -5 MP, 1.52 × 10 -8 -2.03 × 10 -6 EP, 3.29 × 10 -9 -4.39 × 10 -7 DEP, and 3.11 × 10 -6 -4.14 × 10 -5 DEHA for Kit #3. These absorbed doses were well below applicable health-based guidance values, indicating consumer exposure from product use is not expected to pose a health risk. These results provide valuable information for health risk evaluations for hair relaxer use.

Parabens are widely used as preservatives in food, pharmaceuticals, and cosmetics due to their excellent antimicrobial activities, cost-effectiveness, and stability. Previous studies have demonstrated their harmful potential and ubiquity in the environment and human tissues. This study revealed profiles of parabens and their metabolites in urine samples from a general population of different ages in China using non-target screening. Metabolism of parabens in human bodies was further explored through the identified metabolites in combination of molecular networking. A total of 34 paraben compounds were screened in the urine samples. In addition to 3 identified confidence level 1 (CL1) parent parabens, 3 CL2 compounds were also identified, namely 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, and ethylparaben sulfate. Furthermore, 6 CL3 compounds were tentatively identified, five of which were sulfonated and sulfated metabolites of parabens. The remaining 22 were CL4 features without certain chemical structures. Hazardousness assessment suggested toxic potential of the identified metabolites. Distribution of the parabens and metabolites in the urines showed age-dependent differences. Sulfonation and sulfation were potentially significant metabolic pathways of the parabens in human bodies. This study provides a new insight into understanding metabolism of parabens in human bodies and potential risks of human exposure to parabens.

Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) are among the most widely used preservatives in cosmetics, drugs, and foods. These compounds have been associated with toxic effects due to the overuse of products with parabens in their formulation. The toxicity of parabens may be correlated to endocrine disruption, owing to their ability to mimic the actions of estradiol. In this paper, a simple, sustainable, robust, and innovative dispersive liquid-liquid microextraction (DLLME) technique was developed and employed to extract these xenobiotics from body cream samples, aiming to calculate the margin of safety (MoS) to assess the risk of exposure. The validated method presented suitable linearity (r > 0.99), lower limits of detection (ranging from 0.01 to 0.04 % w/w), and satisfactory precision and accuracy (ranging from 4.33 to 10.47, and from -14.25 to 13.85, respectively). Seven of the ten analysed samples presented paraben contents within the acceptable concentration according to European legislation. The MoS value obtained for PrP (37.58) suggested its reduced safety, indicating that PrP may significantly contribute to systemic exposure resulting from the use of personal care products.