METHYLPARABEN

Preservatives are primarily used for their antimicrobial properties and form an important component of food, cosmetic, and drug formulations. The efficacy of preservatives depends on various factors, which include the bacterial membrane composition and the interaction between components of a specific formulation. Molecules such as phenoxyethanol (POE), caprylylglycol (CPG), and methylparaben (MEP) are widely used as preservatives in the food and cosmetic industries; however, a molecular understanding of their interactions with surfactants and the kinetics of membrane partitioning remains unexplored. In this study, coarse-grained molecular dynamics simulations were carried out to evaluate and quantify the kinetics of membrane partitioning for preservatives and surfactants in the Escherichia coli inner phospholipid membrane. We propose a mass-transfer-based model to determine membrane partitioning kinetics. Faster kinetics were observed for first-order partitioning of POE and MEP (τ ∼ 0.01 μs) when compared with zeroth-order kinetics (τ ∼ 0.1 μs) for CPG. In contrast, surfactants such as sodium laureth sulfate (SLES) and cocamidopropyl betaine (CAPB) follow zeroth-order membrane partitioning kinetics with significantly higher time constants (1.5-10 μs). Interestingly, zeroth-order kinetics occurred when micellar aggregates were present, and the rate-controlling step was the slow rate of release of single molecules from the aggregate, in comparison to faster membrane uptake kinetics. Using a sequential micellar breakup model with single surfactant release dynamics, we analytically recover this unique zeroth-order membrane partitioning kinetics. In preservative-surfactant mixtures, the kinetics of preservative partitioning were found to decrease by a factor of 2-10. Significantly, the equilibrium membrane saturation coefficients for both preservatives and surfactant remained invariant in the mixtures due to the wide separation of partitioning time scales for the surfactants and preservatives. The kinetic models developed in this study can be used to quantify membrane partitioning of preservatives and understand the influence of surfactants in specific formulations.

Methylparaben and propylparaben are widely used as preservatives in consumer products, including cosmetics, personal care items, and pharmaceuticals. Concerns have been raised regarding their potential for systemic absorption and estrogenic activity, which may contribute to endocrine disruption. This review evaluates current evidence on dermal absorption, metabolism, and systemic distribution of methylparaben and propylparaben, emphasizing factors influencing their bioavailability. Additionally, the estrogenic potential of these compounds in experimental studies is examined, assessing receptor binding affinity and biological effects. Overall, while parabens exhibit weak estrogenic activity compared to endogenous hormones, repeated exposure and cumulative effects warrant further investigation. The toxicokinetic data combined with estrogenic activity assessments provide critical insight into the risk of endocrine disruption associated with paraben exposure. This assessment provides an understanding of methylparaben and propylparaben safety, supporting informed regulatory decisions and consumer awareness.

Alzheimer's disease (AD) was a progressive neurodegenerative disorder characterised by an insidious onset and gradual cognitive decline. It remained a significant global health challenge. Methylparaben (MEP), a preservative commonly used in cosmetics and food processing, had been associated with the development and progression of AD. First, we acquired the initial three-dimensional (3D) structure of MEP from PubChem (CID: 7456), followed by structural optimization via energy minimization using Chem3D software to complete its 3D structural characterisation. This was followed by systematic target prediction across the SwissTargetPrediction, SEA, GeneCards and OMIM databases. We then constructed protein-protein interaction (PPI) networks using STRING and visualised them in Cytoscape to identify core targets. Molecular docking simulations using CB-Dock2 elucidated the binding affinities between MEP and the key proteins. Experimental validation combined Gene Expression Omnibus (GEO) database analysis with quantitative reverse transcription polymerase chain reaction (qRT-PCR) to quantify transcriptional changes in SK-N-SH neural cells. A total of 153 potential targets associated with MEP and AD were identified. Ten core targets were determined through screening using the STRING platform and Cytoscape software, including HIF1A, IGF1R, PDGFRB, PTK2, VCAM1, CXCL12, ERBB2, ESR1, JAK2 and BCL2L1. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the core MEP targets in AD primarily concentrate on the following key signalling pathways: Neuroactive ligand-receptor interactions, EGFR tyrosine kinase inhibitor resistance, HIF-1 signalling pathway and gamma-aminobutyric acid (GABA) synapse. Molecular docking simulations using CB-Dock2 confirmed a high binding affinity between MEP and these core targets. To investigate the mechanism of action of MEP, we validated the findings using clinical datasets and the human neuroblastoma cell line SK-N-SH. Upregulation of ten transcriptional expressions was observed, suggesting that MEP might influence cognitive function in patients with AD. This study elucidated the potential molecular mechanisms of MEP in the progression of Alzheimer's disease-related tau pathology, offering new insights for the prevention and intervention of degenerative diseases that might be triggered by excessive exposure to MEP environments.

Methylparaben is a commonly used preservative in the cosmetics, pharmaceutical, and food industries, valued for its antibacterial and antifungal effects. Numerous in vitro and in vivo studies have investigated its adverse effects on sperm count, testosterone levels, and reproductive organ weight. Baicalin, which comes from the dried roots of the plant Scutellaria baicalensis Georgi, is a natural compound that may have various health benefits, such as reducing fibrosis, itching, bacteria, oxidative stress, inflammation, and cancer. This study investigated the effect of baicalin on the changes in male reproductive hormones and enzyme activity brought about by methylparaben. A total of forty-five adult male Wistar rats were randomly allocated into nine distinct groups, each comprising five rats. Over a period of 28 days, these subjects were administered treatments via gastric gavage, which included distilled water, peanut oil, methylparaben, or differing doses of baicalin, either in isolation or in conjunction with methylparaben. Post-treatment, blood samples were obtained under terminal anesthesia for the purpose of serum analysis. Assays for hormonal levels (FSH, LH, testosterone) and enzymatic activity (17β-HSD3) were performed utilising ELISA and spectrophotometric techniques in accordance with established protocols. Rats treated with methylparaben (Group 3) had much lower levels of FSH, LH, testosterone, and 17β-HSD compared to the other groups, and baicalin was able to reduce these effects in a dose-dependent manner. Higher baicalin doses restored hormone and enzyme levels to near-control values levels indicating its protective benefits. The results indicate that baicalin could mitigate the reproductive toxicity induced by methylparaben, owing to its antioxidant and regulatory characteristics, highlighting its potential as a protective agent against endocrine-disrupting chemicals.

Psoriasis is a chronic inflammatory skin disease with limited safe and effective treatments. Methylparaben, a widely used preservative in cosmetics, pharmaceuticals, and food, is an emerging environmental pollutant linked to immune-related skin disorders, but its role and mechanism in psoriasis remain unclear. This study explored its potential mechanism using network toxicology, molecular docking, molecular dynamics simulation, and eight machine learning algorithms. Methylparaben targets were retrieved from GeneCards and TCMSP, and psoriasis-related targets from CTD and GeneCards. Overlapping targets were screened with Venny 2.1.0. A PPI network was constructed via STRING, and core targets identified using Cytoscape 3.10.2. GO and KEGG enrichment analyses were performed on DAVID. Molecular docking evaluated the binding affinity of methylparaben with key targets. A total of 138 compound-related and 5,592 psoriasis-related targets were identified. Core targets such as INS, HIF1A, and PPARG are involved in regulating immune-inflammatory responses, keratinocyte proliferation and differentiation, and oxidative stress. GO analysis revealed enrichment in xenobiotic metabolism, lipopolysaccharide response, and metal ion binding. KEGG analysis highlighted pathways related to cancer, chemical carcinogenesis from reactive oxygen species, and drug metabolism via cytochrome P450 enzymes. Molecular docking showed stable binding of methylparaben to INS (-4.5 kcal/mol), HIF1A (-5.9 kcal/mol), and PPARG (-5.5 kcal/mol), primarily through hydrogen bonds and hydrophobic interactions. Methylparaben may exert its effects on psoriasis via multi-target and multi-pathway mechanisms, influencing inflammation, oxidative stress, and cellular regulation. These findings provide valuable insight into its toxicological mechanism and potential therapeutic application.

The objective of the current investigation was to develop a novel clobetasol propionate (CP) emulgel to enhance the efficacy and minimize side effects during topical application. Preparation of CP loaded emulsion was carried out by the hot emulsification method. The emulsion consisted of combinations of surfactants (Span 20/Tween 20), cosolvent (polyethylene glycol 400), preservatives (methylparaben, propylparaben), with liquid paraffin as the oil phase. The selected emulsion (batch CP7) has nano-size (387.6 ± 58.49 nm), narrow and uniform particle size distribution (PDI, 0.221), spherical morphology and negative zeta potential (-36.4 ± 5.66 mV). The CP7 emulsion was further converted to emulgel by incorporating it in carbopol 934 (2% w/w). The rheology and mechanical characterization of the prepared emulgel indicate appropriate viscosity (~ 300,000 cP), enough spreadability (4.47 ± 0.40 cm), mild hardness (27 g), reasonable adhesiveness (0.6 mJ), and good bioadhesive strength (11.07 ± 1.14 g/cm²), which is ideal for topical use. The CP release from emulgel and hydrogel was found distinct with the emulgel formulation showing significantly ( p  < 0.0001) slower and delayed drug release. Results of the anti-inflammatory study demonstrated greater inhibition (94.60% at 600 µg/mL) by CP emulgel, compared to other tested groups. The skin irritation potential by the HET-CAM method showed lower irritation score (~ 2.18, p  < 0.001) by the fabricated CP emulgel, which could be attributed to the encapsulation of CP within the emulsion. Overall, the developed CP emulgel demonstrated favorable characteristics for effective CP delivery, making it a promising option for the topical treatment of inflammatory skin disorders. The online version contains supplementary material available at 10.1007/s13205-026-04856-2.

Parabens are endocrine-disrupting chemicals that are widely used as preservatives in the form of methyl (MP)-, ethyl-, propyl-, and butyl-paraben in cosmetics, personal care products, food, and pharmaceuticals. This study analyzed the presence of four parabens in 268 human milk samples and 189 placental samples collected from pregnant women in Taiwan and calculated the estimated daily intake (EDI) of total parabens among breastfed infants at one and three months of age. Parabens were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry. We also explored the dietary and PCP factors associated with parabens exposure. Monte Carlo simulation was employed to characterize uncertainty in the EDI calculation. Our findings indicate that MP was the most frequently detected paraben in placental, first- and third-month milk, with detection frequencies of 57%, 80%, and 45%, respectively. The Σparabens concentration ranged from below the limit of detection (LOD) to 8.2 ng/g in placenta, < LOD to 35.8 ng/g in first-month milk, and < LOD to 21.6 ng/g in third-month milk. Furthermore, the 95th percentile EDI of MP was higher in third-month milk (617 ng/kg-day) compared to first-month milk (118 ng/kg-day), yet remained several orders of magnitude below the EFSA-established acceptable daily intake of 10 mg/kg-day. This biomonitoring study highlights the widespread, low-level exposure of infants to parabens, especially MP, through both prenatal and postnatal pathways. These findings reinforce the need for continued surveillance of parabens exposure during the critical developmental period. This study is among the first large-scale biomonitoring studies to measure parabens in placenta and human milk samples from an Asian population. Methylparaben emerged as the most commonly detected parabens in both placenta and breast milk, indicating both prenatal and postnatal exposure for infants. Although the estimated daily intake levels were well below the safety thresholds, the detection of parabens in the early developmental period raises concern for potential long-term health effects. By integrating biomonitoring data with maternal dietary habits and personal care product use, this work highlights the need for continuous monitoring and regulatory measures of early-life parabens exposure.

Many chemicals used in personal care products (PCPs) have suspected health effects. Thus, PCP use may be an important modifiable source of chemical exposures. We conducted a five-day intervention during which women (N = 103, ages 18-30) in Grenoble, France, were asked to refrain from using their usual PCPs and were provided with alternative products free from the chemicals of interest. These included eleven phenols, sixteen phthalates, and two glycol ethers. Participants collected a sample of each urinary event for 24-hour periods before and on the last day of the intervention, from which chemical metabolites were assessed. Mixed regression models compared concentrations during the pre-intervention and intervention phases. A Health Impact Assessment (HIA) evaluated intervention's impacts on child health, if applied to French pregnant women. A daily median of 12 PCPs were used pre-intervention and 7 in the intervention phase. Compared to the pre-intervention phase, medians of phenoxyacetic acid (-64% [-72; -54]), bisphenol A (-39% [-53; -20]), methylparaben (-30% [-44; -13]), and monoethyl phthalate (-22% [-33; -7.8]) decreased during the intervention phase, while propylparaben was less often detected. The HIA suggested that the bisphenol A pregnancy concentration reduction could prevent 4.0% of asthma (95% CI: 0.4%, 10.2%) and 4.4% (95% CI: 0.4%, 10.8%) of wheezing cases and avoid a 0.44 (95% CI: 1.31, -0.42) IQ point loss in offsprings. PCPs are a modifiable source of harmful chemicals such as bisphenol A and parabens, and reducing/replacing PCPs lowered urinary concentrations of harmful chemicals in just five days. The HIA conducted for bisphenol A suggested that such reductions may have substantial health benefits. While average decreases in urinary concentrations were substantial, several chemicals remained detected after the intervention phase. Individual changes in PCPs use can decrease exposure to these chemicals, but regulatory actions would probably be more efficient and fairer.

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.

Parabens are extensively used preservatives with endocrine disrupting effects and neurotoxicity. Their restricted usage may drive the development of alternatives for producing preservative-free products. Nevertheless, the prevalence and health risks of paraben analogues remain poorly understood. Herein, we screened potential paraben analogues using high-resolution mass spectrometry and assessed their prevalence in personal care products (PCPs) and population exposure trends. We first identified p-hydroxyacetophenone (PhAc), a structural analogue of parabens, in children's urine based on the common fragmentation characteristics of parabens. Quantitative analysis revealed that the average content of PhAc in PCPs was 2-38 times higher than that of typical parabens. Furthermore, the longitudinal biomonitoring study conducted from 2016 to 2023 revealed that the geometric mean levels of PhAc in the urine of children aged 5-13 years in South China increase from 35.20 μg/L to 102.68 μg/L, which is 1-3 orders of magnitude greater than parabens. Nevertheless, PhAc is not a permitted preservative in PCPs and its health risk is unclear. To investigate the potential neurotoxicity of extensively present PhAc, neuronal cells were exposed to different concentrations of PhAc and typical parabens for 24 h, respectively. The results indicated that PhAc exhibited greater potential neurotoxicity than methylparaben, the most widely used paraben. Even exposure to doses comparable to urinary PhAc concentrations (100 nM-1 μM) could significantly disrupt metabolism homeostasis, damage cell membranes and morphology, and increase apoptosis rate in neuronal cells. Therefore, PhAc, a new paraben analogue with wider product applications, higher human exposure, and greater potential neurotoxicity, may pose considerable ecological and human health risks.

Parabens (PBs), extensively used as preservatives in food, cosmetics, and pharmaceuticals, are increasingly detected across diverse environmental matrices. Nevertheless, their presence and potential impacts on marine apex predators remain poorly understood. Here, hepatic tissues from 87 Indo-Pacific humpback dolphins collected from the northern South China Sea (NSCS) during 2004-2021 were analyzed for four PBs and five paraben metabolites (m-PBs) to investigate their bioaccumulation characters and potential health risks. Five target compounds were detected, with their total concentrations (4840 ± 4120 ng/g ww) comparable to those of persistent organic pollutants previously detected in this species. All five PBs/m-PBs demonstrated transplacental transfer potential, with OH-MEP showing the highest transfer efficiency (45.78 %). Risk assessment revealed that hepatic methylparaben concentrations in over 45 % of the non-calf dolphins exceeded the estimated hepatic toxicity thresholds. Furthermore, the observed increasing time trends of methylparaben levels suggest that the NSCS humpback dolphin populations may suffer long-lasting high risks in the future. These findings provide the initial evidence of the PB/m-PB occurrence and associated health risks in the NSCS dolphins and underscore the urgency of mitigating paraben contamination in South China.