Methylparaben Research Articles

Track of methylparaben in the bulk phase and on the extracellular matrix of dual-species biofilms: Biodegradation and bioaccumulation

Methylparaben (MP) is a preservative considered an environmental contaminant of emerging concern due to its persistence in water sources, including drinking water (DW). This study assesses the interaction between MP and dual-species biofilms of Acinetobacter calcoaceticus and Stenotrophomonas maltophilia. These biofilms were grown under realism-based conditions in a multiple-cylinder biofilm reactor on polypropylene (PPL) surfaces, for 7 days, and then exposed to MP at 0.5 mg/L for three consecutive days. S. maltophilia predominantly succeeds within these biofilms compared to A. calcoaceticus. Exposure to MP resulted in a 4-fold increase in the number of culturable cells and a 1.4-fold rise in polysaccharide content, suggesting that bacterial cells may utilize MP as a carbon source to enhance biofilm fitness. MP was found to adsorb to PPL with biofilms following a pseudo-second-order kinetic model. Circa 37 % of MP adsorbed to PPL after 3 days of exposure. Besides that, MP was biodegraded by biofilms following an apparent first-order kinetic model. Part (25 %) of the MP was biodegraded whereas only 0.02 % bioaccumulated on the biofilm matrix. Biodegradation was related to esterase and lipase activity. The results provide new insights into the interaction between MP with biofilms and materials used in DW industries.

Salvianolic acids modulate lifespan and gut microbiota composition in amyloid-β-expressing Drosophila melanogaster.

Alzheimer's disease (AD), a form of neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ), hyperphosphorylated Tau, and neuroinflammation. The increasing population affected by AD urges for the development of effective treatments. The correlation between AD and gut microbiome remains underexplored, potentially providing a better understanding of the disease. Salvianolic acid A (Sal A) and salvianolic acid B (Sal B) are the active components extracted from Salvia miltiorrhiza (Danshen), and their antioxidant, anti-inflammation and Aβ inhibition activities were shown previously. In this study, these compounds were used to investigate their effects on Aβ toxicity, using Drosophila melanogaster expressing human Aβ42 as the model organism, by examining their lifespan and changes in gut bacterial communities. The study used two batches of flies, reared on food with or without methylparaben (MP) supplementation to evaluate the influence of MP on this animal model during pharmacological studies. MP is a common antimicrobial agent used in flies' food. The treatment of Sal A prolonged the lifespan of Aβ-expressing flies reared on MP-supplemented food significantly (P < 0.001), but not those without MP. The lifespan of Sal B-treated flies did not show a significant difference compared to untreated flies for both groups reared on food with and without MP. Sal A-treated flies in the presence of MP exhibited a lower abundance of Corynebacterium and Enterococcus than the untreated flies, while Lactiplantibacillus was the most dominant taxa. Urea cycle was predicted to be predominant in this group compared to the untreated group. The control group, Aβ-expressing flies treated with Sal A and Sal B on MP-supplemented food had improved lifespan compared to their respective groups reared on food without MP, while untreated Aβ-expressing flies was the exception. The gut microbiota composition of flies reared on MP-supplemented food was also significantly different from those without MP (P < 0.001).

Acute toxicity assessment and QSAR modeling of zebrafish embryos exposed to methyl paraben and its halogenated byproducts

Halogenated methyl parabens are formed readily during water chlorination, with or without bromide ion presence. However, research gaps persist in in vivo toxicological assessments of vertebrates exposed to halo-MePs. To address this gap, this study evaluated acute toxicities at 24−96 h-post-fertilization in zebrafish embryos exposed to methyl paraben and its mono- or di-halogenated derivatives, using various apical endpoints. Significant enhanced toxic effects were confirmed for halo-MePs compared to MeP on embryo coagulation (3–19 fold), heartbeat rate decrement (11–80 fold), deformity rate increment (9–68 fold), and hatching failure (4–33 fold), with parentheses indicating the determined toxic potency ratios. Moreover, halo-MePs showed a significantly higher increase in biochemical levels of reactive oxygen species, catalase, superoxide dismutase, and malondialdehyde, while acetylcholinesterase activity was inhibited compared to NT and MeP. The experimental toxic potencies (log(1/EC50 or LC50)) were compared with the predicted ones (log(1/EC50 or LC50, baseline)) using the baseline toxicity Quantitative Structure-Activity Relationship previously established for zebrafish embryos. Halo-MePs were specific (or reactive) toxicants based on their toxic ratios of more than 10 for apical endpoints including heartbeat rate, deformity rate, and hatching rate, while MeP acted as a baseline toxicant. Overall, this study presents the comprehensive toxicological assessment of halo-MePs in zebrafish embryos, contributing to an essential in vivo toxicity database for halogenated phenolic contaminants in aquatic ecosystems.

Analysis of molecular interactions of an aqueous benzoates with glycolic and lactic acid: spectroscopic, acoustic, and volumetric approach

Volumetric as well as Acoustic properties for the ternary liquid combination (water + sodium methyl p-hydroxybenzoate + glycolic acid/lactic acid) are evaluated at several temperatures using a Densimeter (DSA 5000 M) over the range of concentrations (0.000, 0.015, 0.025, 0.035) mol.kg−1. Several thermo-acoustical properties were computed utilizing the experimental data. These values were then used to derive several parameters, including the apparent molar volume( V∅ ); partial molar volume (V∅0); apparent molar isentropic compression (K∅,S); transfer properties(Δ V∅0, Δ K∅,s0 ); partial molar isentropic compression (K∅,s0); apparent molar expansibility ( E∅0 ) as well as its first derivative ( ∂Eϕ0/∂T ) P; and coefficient of thermal expansivity( αp ). The obtained results are explained by analyzing the several interactions that take place inside the liquid system by implementing the theory of co-sphere overlap. Utilizing these thermodynamical parameters, the interaction coefficients are computed to evaluate the ternary mixture corresponding to the interactions between solutes and solvents. FTIR spectrum analysis revealed the presence of H-bonds along with the other molecular interactions in the analyzed systems, as shown by the shifting of the O-H stretching band.

Covalent organic framework composite hydrogel sorbent beads for vortex-assisted dispersive miniaturized solid phase extraction of parabens and synthetic phenolic antioxidants in foodstuffs

A covalent organic framework composite hydrogel sorbent beads was fabricated for the vortex-assisted dispersive miniaturized-solid phase extraction and determination of parabens and synthetic phenolic antioxidants from food matrices. The covalent organic framework was entrapped into alginate hydrogel beads. This composite sorbent effectively adsorbs analytes through hydrophobic, π-π and hydrogen bonding interactions. Under optimal extraction conditions, the developed method demonstrated good linearity from 1.00 to 100 µg kg−1 for methyl paraben and 2.00 to 100 µg kg−1 for tertiary butylhydroquinone, propyl paraben, butyl paraben and butylated hydroxyanisole. Limits of detection ranged from 0.25 to 0.50 µg kg−1. The developed sorbent was applied to the extraction of parabens and synthetic phenolic antioxidants from tomato paste, mayonnaise, infant milk powder and coffee creamer samples. The analytes were separated and quantified by high-performance liquid chromatography, achieving recoveries ranging from 89 to 98 % with RSDs lower than 7 %. The vortex-assisted extraction approach was efficient, and the fabricated sorbent could be reused for up to eight cycles. The greenness of the methodology was also evaluated.

A systematic review of the toxic potential of parabens in fish.

Parabens are the most prevalent ingredients in cosmetics and personal care products (PCPs). They are colorless and tasteless and exhibit good stability when combined with other components. Because of these unique physicochemical properties, they are extensively used as antimicrobial and antifungal agents. Their release into the aquatic ecosystem poses potential threats to aquatic organisms, including fish. We conducted an electronic search in PubMed (http://www.ncbi.nlm.nih.gov/pubmed) using the search term parabens and fish and sorted 93 articles consisting of methyl paraben (MTP), ethyl paraben (ETP), propyl paraben (PPP), butyl paraben (BTP), and benzyl paraben (BNP) in several fish species. Furthermore, we confined our search to six fish species (common carp, Cyprinus carpio; fathead minnows, Pimephales promelas; Japanese medaka, Oryzias latipes; rainbow trout, Oncorhynchus mykiss; Nile tilapia, Oreochromis niloticus; and zebrafish, Danio rerio) and four common parabens (MTP, ETP, PPP, and BTP) and sorted 48 articles for review. Our search indicates that among all six fish, zebrafish was the most studied fish and the MTP was the most tested paraben in fish. Moreover, depending on the alkyl chain length and linearity, long-chained parabens were more toxic than the parabens with short chains. Parabens can be considered endocrine disruptors (EDs), targeting estrogen-androgen-thyroid-steroidogenesis (EATS) pathways, blocking the development and growth of gametes, and causing intergenerational toxicity to impact the viability of offspring/larvae. Paraben exposure can also induce behavioral changes and nervous system disorders in fish. Although the USEPA and EU limit the use of parabens in cosmetics and pharmaceuticals, their prolonged persistence in the environment may pose an additional health risk to humans.

Enhancing Sensitivity in the Hyphenation of High-Performance Liquid Chromatography to Benchtop Nuclear Magnetic Resonance Spectroscopy at Isocratic and Onflow Conditions.

The onflow hyphenation of high-performance liquid chromatography (HPLC) in adsorption mode with a benchtop 1H nuclear magnetic resonance (NMR) spectrometer is described for the first time. Protonated solvents and isocratic conditions are used. The sensitivity was increased by choosing suitable NMR acquisition parameter as well as optimizing injection parameters and postacquisition data processing methods. With optimized conditions, the limit of detection (LOD) and the limit of quantification (LOQ) were LOD = 0.010 g L-1 and LOQ = 0.031 g L-1 for the methoxy 1H of methyl paraben at 4.07 ppm, LOD = 0.038 g L-1 and LOQ = 0.134 g L-1 for the aromatic 1H of pentyl paraben between 7.00 and 8.50 ppm. These are expressed in injection concentration and are comparable to existing HPLC hyphenation with high-field NMR spectrometers. The analysis of a 2 g L-1 paraben mixture, far below the legal limits for usage in cosmetics, illustrates the applicability of the method. Taking advantage of the spectral resolution, chromatographically overlapping peaks are resolved using analyte-specific NMR elution traces. A methodology is detailed to facilitate the transfer of the optimized method to other (analyte) systems.

Toxic Beauty: Parabens and benzophenone-type UV Filters linked to increased non-alcoholic fatty liver disease risk

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.

Evolution of microbial community and resistance genes in denitrification system under single and combined exposure to benzethonium chloride and methylparaben

Benzethonium chloride (BZC) and methylparaben (MeP) are commonly added into cosmetics as preservatives, which are frequently detected in wastewater treatment plants. Different response patterns of denitrification system were proposed under single and combined exposure to BZC and MeP (0, 0.5, 5 mg/L) by evaluating system performance, functional genes, extracellular polymeric substance (EPS), cytotoxicity, microbial community structure and resistance genes (RGs). The inhibition effect of BZC on denitrification system was stronger than MeP, and the co-exposure of BZC and MeP showed synergistic effect, enhancing the inhibition effect of BZC single exposure. BZC and/or MeP could promote the diffusion of RGs in sludge, including intracellular RGs (si-RGs) and extracellular RGs (se-RGs). Moreover, the single exposure of BZC and co-exposure of BZC and MeP increased the dissemination risks of RGs in water (w-RGs). IntI1 and tnpA-04, mobile genetic elements (MGEs), correlated positively with diverse RGs from different fractions. Notably, the spread of RGs through horizontal gene transfer mediated by MGEs and the flow of si-RGs into extracellular and water were observed in this study.

Exposure and potential risks of thirteen endocrine- disrupting chemicals in pharmaceuticals and personal care products for breastfed infants in China

Ingestion of breast milk represents the primary exposure pathway for endocrine-disrupting chemicals (EDCs) in newborns. To elucidate the associated risks, it is essential to quantify EDC levels in both breast milk and infant urine. This study measured the concentrations of 13 EDCs, including parabens (methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), iso-propyl paraben, butyl paraben, and iso-butyl paraben), bisphenols (bisphenol A (BPA), bisphenol F, bisphenol S, bisphenol AF, and bisphenol Z), triclosan (TCS), and triclocarban, in breast milk and infant urine to assess their potential health effects and endocrine disruption risks. In total, 1 014 breast milk samples were collected from 20 cities across China, along with 144 breast milk samples and 134 urine samples from a mother-infant cohort in Hangzhou. The EDCs were detected using ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry. Endocrine-disrupting potency was evaluated using a predictive method based on EDC affinity for 15 hormone receptor proteins. The toxicological priority index (ToxPi), incorporating population exposure data, was employed to assess health risks associated with exposure to multiple EDCs. Among the 13 EDCs, MP, EP, PP, BPA, and TCS were detected in over 50 % of breast milk samples, with the highest median concentrations observed for MP (0.37 ng/mL), EP (0.29 ng/mL), and BPA (0.17 ng/mL). Across the 20 cities, 0 %–40 % of infants had a hazard index (HI) exceeding 1. Based on affinity prediction analysis and estimated exposure, cumulative endocrine disruption risk intensity was ranked as MP > TCS > BPA > EP > PP. This research highlights the extensive exposure of Chinese infants to EDCs, offering a detailed analysis of their varying endocrine disruption potencies and underscoring the significant health risks associated with EDCs in breast milk.

Evaluation of dermal exposure to phthalates and parabens resulting from the use of hair relaxers

ABSTRACT 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.

Abstract C113: Parabens promote cell growth in cancer cell lines associated with health disparities

Abstract Parabens are endocrine-disrupting chemicals used as preservatives to extend the shelf life of consumables, pharmaceuticals, and personal care products. Daily use of products containing parabens results in continuous exposure that can negatively impact health. It is known that parabens cause breast cancer cells to grow and express genes linked to cancer and hormone action. Our lab previously showed that parabens increase viability of and regulate estrogen-responsive gene expression in diverse luminal A breast cancer cell lines. In addition, greater effects were seen in a luminal A cell line of West African ancestry compared to one of European ancestry, suggesting that exposure to parabens in personal care products may contribute to breast cancer disparities. Therefore, the purpose of this study was to investigate whether parabens increase cell viability across a variety of cancer cell types, particularly those associated with cancer disparities. To do so, we utilized the National Cancer Institute-60 (NCI-60) Human Tumor Cell Lines screen that includes leukemia, non-small cell lung (NSCL), colon, central nervous system (CNS), melanoma, ovarian, renal, prostate, and breast cancer cell lines, plus a custom panel of pancreatic cancer cell lines. Of these, ovarian, NSCL, prostate, colon, renal, CNS, and pancreatic cancers have known disparities. We treated these cancer cell lines with biologically relevant doses of butylparaben (BP), methylparaben (MP), or propylparaben (PP) (doses ranging from 0.0012 µM – 20 µM) for 72 hours and measured cell viability. Treatment with dimethylsulfoxide or 10 nM estradiol served as negative and positive controls, respectively. In general, we observed a paraben-specific and cell-line specific effect on cell viability. MP exhibited the greatest effect with increased cell viability in 42% of the cell lines, followed by PP (38%), and BP (32%). MP and PP are among the most common parabens found in personal care products and differences in urinary levels based on race/ethnicity (e.g. higher levels in non-Hispanic Blacks/Mexican Americans compared to non-Hispanic Whites) have been reported. Breast, ovarian, and NSCL had the most cell lines (67-83%) that exhibited increased cell viability with any paraben treatment. Increased cell viability was also observed in several leukemia, colon, pancreatic, CNS, and melanoma cell lines (33-50%). Only one renal, and no prostate, cell line exhibited increased cell viability. These data suggest that paraben-mediated protumorigenic effects may promote cancer disparities beyond breast cancer. Studies are currently underway to determine the mechanisms underlying this link. One caveat of this study is that most of the cell lines in this readily available screen are of European ancestry, highlighting a need to develop more genetically diverse in vitro models for understanding the mechanistic link between paraben exposures and cancer risk/outcomes in the context of disparities. Approaching this challenge from an endocrinology and genetic ancestry perspective may help narrow the disparity gap. Citation Format: Jazma L. Tapia, Jillian C. McDonough, Loretta Erhunmwunsee, Lindsey S. Trevino. Parabens promote cell growth in cancer cell lines associated with health disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C113.

Paraben preservatives exhibit inhibition on human and rat steroid 5α-reductase 1: A comprehensive 3D-QSAR and computational analysis

Parabens are preservatives used in personal care products, cosmetics, and pharmaceuticals. Steroid 5α-reductase 1 (SRD5A1) catalyzes the conversion of testosterone to dihydrotestosterone and is present in the brain, contributing to neurosteroid production. This study aimed to assess the effects of nine paraben preservatives on SRD5A1 in human SF126 glioblastoma cell and rat brain microsomes, particularly focusing on dihydrotestosterone production in SF126 cells. The results showed that methyl, ethyl, propyl, butyl, hexyl, heptyl, nonyl, phenyl, and benzyl paraben inhibited human SRD5A1, with nonylparaben having the strongest effect (7.59 μM). Additionally, kinetic analysis indicated that parabens acted as mixed/noncompetitive inhibitors, leading to a significant decrease in dihydrotestosterone production in SF126 cells. While rat SRD5A1 exhibited lower sensitivity to parabens, docking analysis revealed that parabens bind to the NADPH-binding site of both human and rat SRD5A1. In conclusion, these results highlight the inhibitory effects of paraben preservatives on SRD5A1 and elucidate their binding mechanisms, underscoring their role in hormone production.

Innovative UPLC technique for concurrent quantification of etofenamate and benzyl nicotinate in the presence of methylparaben and benzyl alcohol in their topical cream: Greens, white, and Six Sigma methodologies.

The efficacious treatment of muscle and joint pain relies heavily on etofenamate (ETO) and benzyl nicotinate (BN), which possess robust anti-inflammatory and pain-relieving properties when paired with methylparaben (MP) or benzyl alcohol (BA). In this study, we have established and validated innovative RP-UPLC methods for assessing ETO and BN in the presence of MP or BA in their dosage forms, employing eight green tools to evaluate their eco-friendliness and effectiveness. Reversed phase-ultra-performance liquid chromatography (RP-UPLC) technique employs a flow rate of 0.3mL/min on Waters Acquity UPLC BEH Column (C18, 1.7μm, 100 mm × 2.1mm), detection at 254 nm using a photo diode array (PDA) detector and mobile phase of 0.05 M KH2PO4 buffer, acetonitrile, and methanol (50:15:35, v/v/v) adjusted pH6.0 with 0.2% triethylamine. For ETO, BN, MP, and BA, the calibration curves were linear and ranged from 0.005 to 1.0, from 0.001 to 0.2, from 0.002 to 0.08, and from 0.0001 to 0.1mg/mL, respectively. The correlation value was 0.9999, and the accuracy findings ranged from 98.81% to 100.56%. Consequently, the methodology has been successfully implemented in assay testing for the pharmaceuticals in the presence of the MP or BA, demonstrating the high selectivity of these approaches. The present study presents the Blue Applicability Grade Index (BAGI), an innovative approach that complements green metrics in practical white analytical chemistry. According to the International Council for Harmonisation (ICH) criteria, the procedures were effectively validated.

Methylparaben changes the community composition, structure, and assembly processes of free-living bacteria, phytoplankton, and zooplankton

Parabens are common contaminants in river and lake environments. However, few studies have been conducted to determine the effects of parabens on bacteria, phytoplankton, and zooplankton communities in aquatic environments. In this study, the effect of methylparaben (MP) on the diversity and community structure of the aquatic plankton microbiome was investigated by incubating a microcosm with MP at 0.1, 1, 10, and 100 μg/L for 7 days. The results of the Simpson index showed that MP treatment altered the α-diversity of free-living bacteria (FL), phytoplankton, and zooplankton but had no significant effect on the α-diversity of particle-attached bacteria (PA). Further, the relative abundances of the sensitive bacteria Chitinophaga and Vibrionimonas declined after MP addition. Moreover, the relative abundances of Desmodesmus sp. HSJ717 and Scenedesmus armatus, of the phylum Chlorophyta, were significantly lower in the MP treatment group than in the control group. In addition, the relative abundance of Stoeckeria sp. SSMS0806, of the Dinophyta phylum, was higher than that in the control group. MP addition also increased the relative abundance of Arthropoda but decreased the relative abundance of Rotifera and Ciliophora. The β-diversity analysis showed that FL and phytoplankton communities were clustered separately after treatment with different MP concentrations. MP addition changed community assembly mechanisms in the microcosm, including increasing the stochastic processes for FL and the deterministic processes for PA and phytoplankton. Structural equation modeling analysis showed a significant negative relationship between bacteria richness and phytoplankton richness, and a significant positive relationship between phytoplankton (richness and community composition) and zooplankton. Overall, this study emphasizes that MP, at environmental concentrations, can change the diversity and structure of plankton microbial communities, which might have a negative effect on ecological systems.

The use of an RP-HPLC-UV method for the analysis of oxcarbazepine in the presence of its preservatives; stability studies and application to human plasma samples

AbstractA simple, sensitive, selective, accurate and precise method was developed and fully validated for determination of oxcarbazepine (OXC) in presence of their preservatives and determination of oxcarbazepine (OXC) in human plasma. A reversed phase liquid chromatography (RP-HPLC) with UV detection techniques were applied for separation and quantification of studied drug OXC. Successful separation of the drug from methyl paraben (M.P.), propyl paraben (P.P.) and potassium sorbate (P.ST.) was achieved on a Kromasil C18 column (5 μm particle size, pore size 300 Å, l × I.D. 250 × 4.6 mm). The mobile phase that contain aqueous 0.05M potassium dihydrogen phosphate buffer (pH 7): acetonitrile, (50: 50, %v/v). The method was linear over concentration ranges 5.0–50 μg mL−1 for OXC. Bioanalytical validation of the developed method was carried out according to US-FDA guidelines and revealed a good linear relations over a range of (5.0–50), (0.5–10), (0.05–0.15), and (1.0–10) μg mL−1 for OXC, M.P, P.P, and P.ST, respectively, with a correlation coefficient (R2) of more than 0.999. Limit of detection (LOD) were 1.15, 0.03, 0.01 and 0.04 μg mL−1 for OXC, M.P, P.P, and P.ST, respectively, Intra and inter-day precisions, calculated as percentage relative standard deviation (% RSD), were lower than 2.0%. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies through the analysis of plasma samples taken from blood bank.

Determination of ten bisphenols and five parabens in urine by solid supported liquid-liquid extraction and liquid chromatography-tandem mass spectrometry

Bisphenols (BPs) and parabens (PBs) are of great concern for environmental pollution and human health because of their endocrine-disrupting effects and potential health hazards. Urinary biomonitoring of BPs and PBs can provide basic data for human internal exposure evaluation, which is a prerequisite for accurately assessing their health risks. In this study, we developed a new pretreatment procedure based on solid supported liquid-liquid extraction (SLE) for the simultaneous separation of ten BPs and five PBs in human urine, followed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. In the instrumental analysis, the HPLC conditions and MS/MS parameters were comprehensively optimized. Accurate qualitative and quantitative determination of ten BPs and five PBs was achieved by introducing a ternary gradient elution system of water, methanol, and acetonitrile for LC separation. During sample pretreatment, the extraction solvent and elution volume were optimized. Specifically, urine samples were held at room temperature and centrifuged at 3000 r/min for 10 min. The supernatant (2 mL) was then transferred to a glass tube, and the pH was adjusted to 5.0 using HCl (0.5 mL; 0.1 mol/L) and NaAc-HAc buffer (1.5 mL). Thereafter, β-glucuronidase-arylsulfatase (20 μL) and surrogate standard solutions (10 ng;13C12-BPS,13C12-BPAF,13C6-MeP, and 13C6-BuP) were added, and the mixture was incubated in a shaker bath in the dark at 37 ℃ for 16 h. After incubation, the hydrolyzed sample (4 mL) was loaded onto an SLE cartridge and equilibrated for a minimum of 5 min to ensure the solution was completely absorbed by the packing material. Subsequently, the target chemicals were eluted with a mixed ethyl acetate/n-hexane solution (3∶7, v/v; 15 mL). Separation of the targets was performed on a ZORBAX SB-C18 reversed-phase column (250 mm×4.6 mm, 5 μm) using an acetonitrile-methanol-water system as the mobile phase. The method was verified by spiking mixed urine samples at three levels (1, 5, and 50 μg/L), with the recoveries ranging from 84.3% to 119.8%. Except for bisphenols (BPS), whose matrix effect was calculated as -21.8%, the matrix effects of other analytes were lower than 20%, indicating low matrix interference. The linear ranges of the analytes varied from 0.1-500 μg/L to 1-500 μg/L, with correlation coefficients higher than 0.995. The method limits of quantification for target chemicals ranged from 0.03 to 0.30 μg/L, and the relative standard deviations of intra- and inter-day experiments were 1.4%-8.4% and 5.7%-14.6%, respectively, suggesting high stability and reproducibility. The method was successfully applied to the determination of ten BPs and five PBs in 10 urine samples from a general population. The concentrations of target chemicals in the human urine samples varied. Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and bisphenol A (BPA) were detected in all samples, with median mass concentrations of 1.10, 0.60, 0.21, and 0.55 μg/L, respectively. The detection rates of the other chemicals were less than 50%, which may be related to the production and use of specific chemicals, their bioavailability, and biological metabolism in humans.

Urinary biomarkers of environmental exposures and asthma morbidity in a school inner city asthma study

BackgroundThe burden of pediatric asthma and other allergic diseases is not evenly distributed among United States populations. ObjectiveTo determine whether urinary biomarkers are associated with asthma morbidity, and if associations vary by child race, ethnicity and sex. MethodsThis study includes n = 152 children with physician-diagnosed asthma who participated in the School Inner-City Asthma Intervention Study (SICAS-2). Metabolites of phenol, paraben, polycyclic aromatic hydrocarbons, and phthalate analytes were analyzed from urine samples collected at baseline. Asthma symptom days over the past 2 weeks were dichotomized to no asthma symptom days or any asthma symptom days. Cross-sectional regression models were adjusted for age, sex, number of colds, household income, prescription control, race and ethnicity, body mass index (BMI) percentile, and smoke exposure. Weighted quantile sum regression was used to analyze each chemical class and a total mixture effect, controlling for the same covariates. Analyses were conducted with the assistance of the National Institute of Environmental Health Sciences Children's Health Exposure Analysis Resource (CHEAR). ResultsParticipants were mostly Hispanic/Latino and low income with an average age of 7.83 years and the average maximum asthma symptom days over the past two weeks of 2.13 (standard deviation: 3.56). The maximum concentrations indicate extreme values for several chemicals, including bisphenol-3, 2,5-dichlorophenol, propyl and methyl parabens, triclosan, methyl paraben and cotinine. We found a significant interaction effect and differing contributions of analytes for children with allergen sensitivity versus those that did not. For stratified analyses assessing effect modification by child race and ethnicity, weighted quantile sum interaction models showed reduced odds of asthma symptoms to a greater magnitude in children of other races and ethnicities compared to Black, Non-Hispanic children. ConclusionsPreliminary analyses of the association between environmental chemical exposure and asthma symptoms among inner-city children revealed an inverse association, which may be due to personal care and medication use and can be understood further in future analyses. Beneficial effects were detected for most of the chemicals.

Flame retardancy and smoke suppression properties of bio-based chitosan polyelectrolyte flame retardant containing P and N in epoxy resin

This study reports the successful synthesis of flame-retardant and smoke-suppressing epoxy resin (EP) via bio-based polyelectrolyte flame retardants. Herein, a novel polyelectrolyte flame retardant was prepared from chitosan (CS) and hexa-(4-carboxyl-phenoxy)-cyclotriphosphazene (HCPCP) by acid-base neutralization reaction, which the HCPCP was synthesized with hexachlorocyclotriphosphazene (HCCP) and methyl p-hydroxybenzoate (MP) by nucleophilic substitution reaction. The combined effect of the addition on the flame retardant, smoke suppression and mechanical properties of EP samples were systematically investigated. The presence of this bio-based polyelectrolyte provided excellent smoke suppression and flame-retardant properties of the prepared EP. Among them, the peak heat release rate (PHRR), peak smoke production rate (PSPR) and total smoke production (TSP) of EP/9wt%3CS-HCPCP composite (the ratio of CS to HCPCP was 3: 7, and the dosage was 9 wt%) were reduced by 45.42 %, 41.66 % and 22.56 %, respectively. In addition, the EP/CS-HCPCP composites showed a 207.80 % enhancement in char residue compared to pure EP. These results suggest a green and cost-effective strategy for the production of flame-retardant, drip-proof and smoke-suppressed EP composites.

Co-exposure to parabens, bisphenol A, and triclosan and the associations with dyslipidemia in Chinese older adults: The mediation effect of oxidative stress

Dyslipidemia is a prevalent metabolic disorder in older adults and has negative effects on cardiovascular health. However, the combined effect of paraben, bisphenol A (BPA), and triclosan (TCS) exposure on dyslipidemia and the underlying mechanisms remain unclear. This cross-sectional study recruited 486 individuals ≥60 years in Shenzhen, China. Morning spot urine samples were collected and analyzed for four parabens, BPA, TCS, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), a typical biomarker for oxidative stress, using mass spectrometry. Blood samples were tested for lipid levels using an automated biochemical analyzer. Quantile-based g-computation (QGC) was used to assess the combined effects of exposures on dyslipidemia. Mediation analysis was applied to investigate the mediating role of 8-OHdG between exposure and dyslipidemia. QGC showed that co-exposure to parabens, BPA, and TCS was positively linked with hypercholesterolemia (OR: 1.17, 95%CI: 1.10–1.24, P < 0.001) and hyper-LDL-cholesterolemia (OR: 1.35, 95%CI: 1.05–1.75, P = 0.019). Methylparaben (MeP), n-propyl paraben (PrP), and butylparaben (BtP) were the major contributors. 8-OHdG mediated 6.5% and 13.0% of the overall effect of the examined chemicals on hypercholesterolemia and hyper-LDL-cholesterolemia, respectively (all P < 0.05). Our study indicated that co-exposure to parabens, BPA, and TCS is associated with dyslipidemia and oxidative stress partially mediate the association. Future research is needed to explore additional mechanisms underlying these relationships.