ABSTRACT
Plants and microbes share common metabolic pathways for producing a range of bioproducts that are potentially foundational to the future bioeconomy. However, in planta accumulation and microbial production of bioproducts have never been systematically compared on an economic basis to identify optimal routes of production. A detailed technoeconomic analysis of four exemplar compounds (4-hydroxybenzoic acid [4-HBA], catechol, muconic acid, and 2-pyrone-4,6-dicarboxylic acid [PDC]) is conducted with the highest reported yields and accumulation rates to identify economically advantaged platforms and breakeven targets for plants and microbes. The results indicate that in planta mass accumulation ranging from 0.1 to 0.3 dry weight % (dwt%) can achieve costs comparable to microbial routes operating at 40 to 55% of maximum theoretical yields. These yields and accumulation rates are sufficient to be cost competitive if the products are sold at market prices consistent with specialty chemicals ($20 to $50/kg). Prices consistent with commodity chemicals will require an order-of-magnitude-greater accumulation rate for plants and/or yields nearing theoretical maxima for microbial production platforms. This comparative analysis revealed that the demonstrated accumulation rates of 4-HBA (3.2 dwt%) and PDC (3.0 dwt%) in engineered plants vastly outperform microbial routes, even if microbial platforms were to reach theoretical maximum yields. Their recovery and sale as part of a lignocellulosic biorefinery could enable biofuel prices to be competitive with petroleum. Muconic acid and catechol, in contrast, are currently more attractive when produced microbially using a sugar feedstock. Ultimately, both platforms can play an important role in replacing fossil-derived products.
Subject(s)
Bacteria , Biological Products , Biotechnology , Metabolic Networks and Pathways , Plants , Yeasts , Bacteria/genetics , Bacteria/metabolism , Biological Products/metabolism , Biotechnology/economics , Biotechnology/trends , Catechols/metabolism , Parabens/metabolism , Plants/genetics , Plants/metabolism , Pyrones/metabolism , Sorbic Acid/analogs & derivatives , Sorbic Acid/metabolism , Yeasts/genetics , Yeasts/metabolismABSTRACT
The cytochrome P450 monooxygenases (CYPs) are a class of heme-thiolate enzymes that insert oxygen into unactivated C-H bonds. These enzymes can be converted into peroxygenases via protein engineering, which enables their activity to occur using hydrogen peroxide (H2 O2 ) without the requirement for additional nicotinamide co-factors or partner proteins. Here, we demonstrate that soaking crystals of an engineered P450 peroxygenase with H2 O2 enables the enzymatic reaction to occur within the crystal. Crystals of the designed P450 peroxygenase, the T252E mutant of CYP199A4, in complex with 4-methoxybenzoic acid were soaked with different concentrations of H2 O2 for varying times to initiate the in crystallo O-demethylation reaction. Crystal structures of T252E-CYP199A4 showed a distinct loss of electron density that was consistent with the O-demethylated metabolite, 4-hydroxybenzoic acid. A new X-ray crystal structure of this enzyme with the 4-hydroxybenzoic acid product was obtained to enable comparison alongside the existing substrate-bound structure. The visualisation of enzymatic catalysis in action is challenging in structural biology and the ability to initiate the reactions of P450 enzymes, in crystallo by simply soaking crystals with H2 O2 will enable new structural biology methods and techniques to be applied to study their mechanism of action.
Subject(s)
Cytochrome P-450 Enzyme System , Mixed Function Oxygenases , Parabens , Cytochrome P-450 Enzyme System/metabolism , CatalysisABSTRACT
To improve the titre of lignin-derived pyridine-dicarboxylic acid (PDCA) products in engineered Rhodococcus jostii RHA1 strains, plasmid-based overexpression of seven endogenous and exogenous lignin-degrading genes was tested. Overexpression of endogenous multi-copper oxidases mcoA, mcoB, and mcoC was found to enhance 2,4-PDCA production by 2.5-, 1.4-, and 3.5-fold, respectively, while overexpression of dye-decolorizing peroxidase dypB was found to enhance titre by 1.4-fold, and overexpression of Streptomyces viridosporus laccase enhanced titre by 1.3-fold. The genomic context of the R. jostii mcoA gene suggests involvement in 4-hydroxybenzoate utilization, which was consistent with enhanced whole cell biotransformation of 4-hydroxybenzoate by R. jostii pTipQC2-mcoA. These data support the role of multi-copper oxidases in bacterial lignin degradation, and provide an opportunity to enhance titres of lignin-derived bioproducts.
Subject(s)
Lignin , Parabens , Rhodococcus , Lignin/metabolism , Peroxidases/metabolism , Rhodococcus/genetics , Rhodococcus/metabolism , Pyridines/metabolismABSTRACT
BACKGROUND: In 2021, French public authorities initiated the fourth National Environmental Health Plan to prevent environment-related health risks. This plan primarily focuses on the sensitization of health professionals and health care institutions. Endocrine disruptors (EDs) are environmental factors associated with several adverse health effects, such as reproductive disorders, obesity, and cancer. This study aimed to conduct an awareness campaign among professionals at a general hospital center on the risks related to EDs. METHODS: Hospital professionals were directly involved in this study, and urine and hair samples were collected to determine bisphenol and paraben exposure levels. Analyses were performed using validated liquid chromatography-tandem mass spectrometry methods, enabling the simultaneous determination of bisphenols and parabens. A questionnaire on lifestyle habits was distributed to assess its relationship with the exposure profiles. Nineteen professionals were recruited for the study. RESULTS: Bisphenol A was detected in 95% of the urine samples, and the chlorinated derivatives of bisphenol A were between 16% and 63%. parabens showed detection frequencies between 37% and 100%, and methylparaben was quantified at an average concentration of 0.45 ± 0.46 ng/mL. In hair samples, bisphenols A, F, and S were detected at 95%-100%, chlorinated derivatives of bisphenol A were detected at 37%-68%, and parabens were detected at 100%. CONCLUSIONS: This awareness campaign may encourage health care institutions to adopt a policy of reducing endocrine disruptor exposure among their patients and professionals, who could be educated regarding the risks associated with EDs. Conducting a multicenter study to refine the results herein and establish a dynamic to prevent endocrine disruptor and environmental risks in health care systems would be valuable.
Subject(s)
Endocrine Disruptors , Humans , Endocrine Disruptors/analysis , Hair/chemistry , Hospitals , Parabens/analysis , Tandem Mass Spectrometry/methodsABSTRACT
Many contaminants of emerging concern (CECs) have reactive functional groups and may readily undergo biotransformations, such as methylation and demethylation. These transformations have been reported to occur during human metabolism and wastewater treatment, leading to the propagation of CECs. When treated wastewater and biosolids are used in agriculture, CECs and their transformation products (TPs) are introduced into soil-plant systems. However, little is known about whether transformation cycles, such as methylation and demethylation, take place in higher plants and hence affect the fate of CECs in terrestrial ecosystems. In this study, we explored the interconversion between four common CECs (acetaminophen, diazepam, methylparaben, and naproxen) and their methylated or demethylated TPs in Arabidopsis thaliana cells and whole wheat seedlings. The methylation-demethylation cycle occurred in both plant models with demethylation generally taking place at a greater degree than methylation. The transformation rate of demethylation or methylation was dependent on the bond strength of R-CH3, with demethylation of methylparaben or methylation of acetaminophen being more pronounced. Although not explored in this study, these interconversions may exert influences on the behavior and biological activity of CECs, particularly in terrestrial ecosystems. The study findings demonstrated the prevalence of transformation cycles between CECs and their methylated or demethylated TPs in higher plants, contributing to a more complete understanding of risks of CECs in the human-wastewater-soil-plant continuum.
Subject(s)
Parabens , Wastewater , Water Pollutants, Chemical , Humans , Water Pollutants, Chemical/analysis , Acetaminophen , Ecosystem , Soil , Methylation , Demethylation , Environmental MonitoringABSTRACT
Personal care products (PCPs) are sources of exposure to endocrine-disrupting chemicals (EDCs) among women, and socioeconomic status (SES) may influence these exposures. Black women have inequitable exposure to EDCs from PCP use, but no study has investigated how exposure to EDCs through PCPs may vary by SES, independent of race. Using data from the Study of Environment, Lifestyle, and Fibroids, a cohort of reproductive-aged Black women (n = 751), we quantified associations between PCPs and urinary biomarker concentrations of EDC mixtures (i.e., phthalates, phenols, parabens) within SES groups, defined using k-modes clustering based on education, income, marital status, and employment. Information about PCP use and SES was collected through questionnaires and interviews. We used principal component analysis to characterize the EDC mixture profiles. Stratified linear regression models were fit to assess associations between PCP use and EDC mixture profiles, quantified as mean differences in PC scores, by SES group. Associations between PCP use and EDC mixture profiles varied by SES group; e.g., vaginal powder use was associated with a mixture of phenols among lower SES women, whereas this association was null for higher SES women. Findings suggest that SES influences PCP EDC exposure in Black women, which has implications for public health interventions.
Subject(s)
Cosmetics , Endocrine Disruptors , Environmental Pollutants , Phthalic Acids , Humans , Female , Adult , Surveys and Questionnaires , Reproduction , Phenols , Parabens/analysis , Environmental Pollutants/analysisABSTRACT
Bisphenols, parabens, and triclosan (TCS) are common endocrine disrupters used in various consumer products. These chemicals have been shown to cross the placental barrier and affect intrauterine development of fetuses. In this study, we quantified serum levels of six bisphenols, five parabens, and TCS in 483 pregnant women from southern China. Quantile-based g-computation showed that combined exposure to bisphenols, parabens, and TCS was significantly (p < 0.05) and negatively associated with birth weight (ß = -39.9, 95% CI: -73.8, -6.1), birth length (ß = -0.19, 95% CI: -0.34, -0.04), head circumference (ß = -0.13, 95% CI: -0.24, -0.02), and thoracic circumference (ß = -0.16, 95% CI: -0.29, -0.04). An inverse correlation was also identified between mixture exposure and gestational age (ß = -0.12, 95% CI: -0.24, -0.01). Bisphenol A (BPA), bisphenol Z (BPZ), bisphenol AP (BPAP), propylparaben (PrP), and TCS served as the dominant contributors to the overall effect. In subgroup analyses, male newborns were more susceptible to mixture exposure than females, whereas the exposure-outcome link was prominent among pregnant women in the first and second trimesters. More evidence is warranted to elucidate the impacts of exposure to mixtures on birth outcomes, as well as the underlying mechanisms.
Subject(s)
Birth Weight , Gestational Age , Parabens , Phenols , Triclosan , Humans , Female , Pregnancy , Birth Weight/drug effects , Adult , Male , Infant, Newborn , Maternal Exposure , Endocrine Disruptors , Benzhydryl Compounds , China , Pregnancy TrimestersABSTRACT
BACKGROUND: From menarche until menopause, the average menstruator will use over 11 000 tampons or sanitary pads. Vaginal and vulvar tissue is highly permeable, and chemicals are absorbed without undergoing first-pass metabolism. OBJECTIVES: To conduct a review of the literature to determine exposure to environmental chemicals in menstrual products. SEARCH STRATEGY: This review identified 15 papers over the past 10 years. SELECTION CRITERIA: Papers that measured chemicals in menstrual products and that measured human biomarkers of chemical exposure were included. Papers had to also be available in English. DATA COLLECTION AND ANALYSIS: Reviewers assessed the articles and data provided. Multiple chemical groups were found. MAIN RESULTS: Phthalates, volatile organic compounds, parabens, environmental phenols, fragrance chemicals, dioxins and dioxin-like compounds were detected in menstrual products. Research gaps were identified, including the lack of studies on newer products such as menstrual underwear and cups/discs. In addition to measuring chemicals in these products, future research should focus on clarifying the exposure per menstrual cycle to these chemicals to understand how menorrhagia and cycle length influence exposure from menstrual products. CONCLUSION: Menstrual products contained measurable levels of a range of endocrine disrupting chemicals including phthalates, phenols and parabens. This reflects a potentially important route of exposure to chemicals that can impact women's reproductive health.
Subject(s)
Menstrual Hygiene Products , Phthalic Acids , Humans , Female , Menstrual Hygiene Products/adverse effects , Parabens/adverse effects , Reproduction , PhenolsABSTRACT
Butylparaben (BP), a common chemical preservative in cosmetic and pharmaceutical products, has been known to induce oxidative stress and disrupt endocrine function in humans. In contrast, morin, a flavonoid derived from the Moraceae family, exhibits diverse pharmacological properties, including anti-inflammatory and antioxidant. Despite this, the protective role of morin against oxidative stress-induced damage in pancreatic islets remains unclear. Therefore, in this study, we aimed to investigate the potential protective mechanism of morin against oxidative stress-induced damage caused by BP in zebrafish larvae. To achieve this, we exposed the zebrafish larvae to butylparaben (2.5 mg/L) for 5 days, leading to increased oxidative stress and apoptosis in ß-cells. However, our compelling findings revealed that pretreatment with various concentrations of morin effectively reduced mortality and mitigated apoptosis and lipid peroxidation in ß-cells induced by BP exposure. In addition, zebrafish larvae exposed to BP for 5 days exhibited evident ß-cell damage. However, the pretreatment with morin showed promising effects by promoting ß-cell proliferation and lowering glucose levels. Furthermore, gene expression studies indicated that morin pretreatment normalized PEPCK expression while increasing insulin expression in BP-exposed larvae. In conclusion, our findings highlight the potential of morin as a protective agent against BP-induced ß-cell damage in zebrafish larvae. The observed improvements in oxidative stress, apoptosis, and gene expression patterns support the notion that morin could be further explored as a therapeutic candidate to counteract the detrimental effects of BP exposure on pancreatic ß-cells.
Subject(s)
Flavones , Insulin , Parabens , Zebrafish , Animals , Humans , Larva , Antioxidants/pharmacology , Oxidative Stress , Flavonoids/pharmacology , Flavonoids/therapeutic useABSTRACT
The present study involved monitoring the distribution of two widely consumed parabens (methyl paraben (MeP) and butyl paraben (BuP)) and their transformation products in indoor dust from different categories of settlement (urban, semi-urban, rural, and tribal homes). The results revealed a prevalent occurrence of parabens in all the settlement categories. A non-normal distribution pattern for MeP and BuP levels across the sampling sites was noted. While comparing the residence time of parabens in dust samples, it was found that the half-lives of the analytes were greater in the dust from urban (MeP t1/2: 47.510 h; BuP t1/2: 22.354 h) and rural (MeP t1/2: 27.725 h and BuP t1/2: 31.500 h) areas. The presence of paraben metabolites, such as hydroxy methylparaben (OH-MeP), para hydroxy benzoic acid (p-HBA), and benzoic acid (BA) in dust samples supports their transformation within indoor spaces. The average daily intake of parabens through dust ingestion and dermal absorption by children was higher than adults. BuP was the prime contributor (>85%) to the total estradiol equivalency quotient (tEEQ) in all the settlement categories.
Subject(s)
Dust , Parabens , Adult , Child , Humans , Parabens/analysis , Benzoic Acid , Environmental Exposure/analysisABSTRACT
In this study, UiO-67 (Zr)/g-C3N4 composites (U67N) were synthesized at wt.% ratios of 05:95, 15:85, and 30:70 using the solvothermal method at 80 °C for 24 h followed by calcination at 350 °C. The composites were characterized using UV-Vis diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy-energy-dispersive X-ray spectroscopy, transmission electron microscopy, and nitrogen physisorption analysis. In addition, thermal stability analysis of UiO-67 was conducted using thermogravimetric analysis. The photocatalytic performance of the composites was assessed during the degradation and mineralization of a mixture of methylparaben (MeP) and propylparaben (PrP) under simulated sunlight. The adsorption process of U67N 15:85 was characterized through kinetic studies and adsorption capacity experiments, which were modeled using pseudo-first-order and pseudo-second-order kinetics and Langmuir and Freundlich isotherms, respectively. The influence of pH levels 3, 5, and 7 on the photocatalytic degradation of the mixture was investigated, revealing enhanced degradation and mineralization at pH 3. The U67N composite exhibited dual capability in removing contaminants through adsorption and photocatalytic processes. Among the prepared composites, U67N 15:85 demonstrated the highest photocatalytic activity, achieving removal efficiencies of 96.8% for MeP, 92.5% for PrP, and 45.7% for total organic carbon in 300 kJ/m2 accumulated energy (3 h of reaction time). The detoxification of the effluent was confirmed through acute toxicity evaluation using the Vibrio fischeri method. The oxidation mechanism of the heterojunction formed between UiO-67 (Zr) and g-C3N4 was proposed based on PL analysis, photoelectrochemistry studies (including photocurrent response, Nyquist, and Mott-Schottky analyses), and scavenger assays.
Subject(s)
Parabens , Water Pollutants, Chemical , Parabens/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Metal-Organic Frameworks/chemistry , Catalysis , KineticsABSTRACT
In this study, we evaluate the efficiency of two novel nanostructured adsorbents - chitosan-graphitic carbon nitride@magnetite (CS-g-CN@Fe3O4) and graphitic carbon nitride@copper/zinc nanocomposite (g-CN@Cu/Zn NC) - for the rapid removal of methylparaben (MPB) from water. Our characterization methods, aimed at understanding the adsorbents' structures and surface areas, informed our systematic examination of influential parameters including sonication time, adsorbent dosage, initial MPB concentration, and temperature. We applied advanced modeling techniques, such as response surface methodology (RSM), generalized regression neural network (GRNN), and radial basis function neural network (RBFNN), to evaluate the adsorption process. The adsorbents proved highly effective, achieving maximum adsorption capacities of 255 mg g-1 for CS-g-CN@Fe3O4 and 218 mg g-1 for g-CN@Cu/Zn NC. Through genetic algorithm (GA) optimization, we identified the optimal conditions for the highest MPB removal efficiency: a sonication period of 12.00 min and an adsorbent dose of 0.010 g for CS-g-CN@Fe3O4 NC, with an MPB concentration of 17.20 mg L-1 at 42.85 °C; and a sonication time of 10.25 min and a 0.011 g dose for g-CN@Cu/Zn NC, with an MPB concentration of 13.45 mg L-1 at 36.50 °C. The predictive accuracy of the RBFNN and GRNN models was confirmed to be satisfactory. Our findings demonstrate the significant capabilities of these synthesized adsorbents in effectively removing MPB from water, paving the way for optimized applications in water purification.
Subject(s)
Graphite , Nitrogen Compounds , Parabens , Water Pollutants, Chemical , Water Purification , Copper/chemistry , Temperature , Water/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Kinetics , Hydrogen-Ion Concentration , Water Purification/methodsABSTRACT
The presence of butylparaben (BP), a prevalent pharmaceutical and personal care product, in surface waters has raised concerns regarding its impact on aquatic ecosystems. Despite its frequent detection, the toxicity of BP to the cyanobacterium Microcystis aeruginosa remains poorly understood. This study investigates the influence of BP on the growth and physiological responses of M. aeruginosa. Results indicate that low concentrations of BP (below 2.5 mg/L) have negligible effects on M. aeruginosa growth, whereas higher concentrations (5 mg/L and 10 mg/L) lead to significant growth inhibition. This inhibition is attributed to the severe disruption of photosynthesis, evidenced by decreased Fv/Fm values and chlorophyll a content. BP exposure also triggers the production of reactive oxygen species (ROS), resulting in elevated activity of antioxidant enzymes. Excessive ROS generation stimulates the production of microcystin-LR (MC-LR). Furthermore, lipid peroxidation and cell membrane damage indicate that high BP concentrations cause cell membrane rupture, facilitating the release of MC-LR into the environment. Transcriptome analysis reveals that BP disrupts energy metabolic processes, particularly affecting genes associated with photosynthesis, carbon fixation, electron transport, glycolysis, and the tricarboxylic acid cycle. These findings underscore the profound physiological impact of BP on M. aeruginosa and highlight its role in stimulating the production and release of MC-LR, thereby amplifying environmental risks in aquatic systems.
Subject(s)
Microcystis , Microcystis/drug effects , Microcystis/growth & development , Microcystis/metabolism , Microcystins/biosynthesis , Biomass , Cell Membrane/drug effects , Cell Membrane/metabolism , Marine Toxins/biosynthesis , Parabens/pharmacology , Antioxidants/metabolismABSTRACT
BACKGROUND: A growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD). METHODS: A total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group. RESULTS: A phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium. CONCLUSIONS: Early childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Diethylhexyl Phthalate , Environmental Pollutants , Pesticides , Phthalic Acids , Trace Elements , Child , Humans , Child, Preschool , Attention Deficit Disorder with Hyperactivity/chemically induced , Attention Deficit Disorder with Hyperactivity/epidemiology , Autism Spectrum Disorder/chemically induced , Autism Spectrum Disorder/epidemiology , Parabens/analysis , Phenols/urine , Case-Control Studies , Phthalic Acids/urine , Organophosphates/adverse effects , Pesticides/adverse effects , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Environmental Pollutants/urineABSTRACT
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.
Subject(s)
Esters , Parabens , Animals , Parabens/toxicity , Parabens/chemistry , Esters/toxicity , Endocrine System , Receptors, EstrogenABSTRACT
Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances. Among these parabens, particular concerns have been raised regarding the potential adverse effects of iso-butylparaben (IBP). Studies have specifically highlighted its potential for inducing hormonal disruption, significant ocular damage, and allergic skin reactions. This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague-Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50 mg/kg/day for 13 weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including mortality rates, clinical signs, body weights, food and water consumption, ophthalmological findings, urinalysis, hematological and clinical biochemistry tests, organ weights, necropsy and histopathological findings, estrus cycle regularity, semen quality, and toxicokinetic behavior. The findings revealed that IBP induced local irritation at the injection site in males at doses ≥ 10 mg/kg/day and in females at 50 mg/kg/day; however, systemic toxicity was not observed. Consequently, the no-observed-adverse-effect level (NOAEL) for IBP was determined to be 50 mg/kg/day in rats of both sexes, indicating no impact on the endocrine system. The toxicokinetics of IBP exhibited dose-dependent systemic exposure, reaching a maximum dose of 50 mg/kg/day, and repeated administration over 13 weeks showed no signs of accumulation.
Subject(s)
Endocrine Disruptors , Estrous Cycle , Parabens , Rats, Sprague-Dawley , Toxicokinetics , Animals , Parabens/toxicity , Parabens/pharmacokinetics , Parabens/administration & dosage , Male , Female , Estrous Cycle/drug effects , Endocrine Disruptors/toxicity , Endocrine Disruptors/pharmacokinetics , Dose-Response Relationship, Drug , Rats , No-Observed-Adverse-Effect Level , Preservatives, Pharmaceutical/toxicity , Preservatives, Pharmaceutical/pharmacokinetics , Preservatives, Pharmaceutical/administration & dosage , Injections, SubcutaneousABSTRACT
Pathogenic bacteria in drinking-water pose a health risk to consumers, as they compromise the quality of portable water. Chemical disinfection of water containing dissolved organic matter (DOM) causes harmful disinfection by-products. In this work, 4-hydroxybenzoic acid (4-HBA) blended polyethersulfone membranes were fabricated and characterised using microscopic and spectroscopic techniques. The membranes were evaluated for the removal of bacteria and DOM from synthetic and environmental water. Permeate flux increased from 287.30 to 374.60 l m-2 h-1 at 3 bars when 4-HBA increased from 0 to 1.5 wt.%, suggesting that 4-HBA influenced the membrane's affinity for water. Furthermore, 4-HBA demonstrated antimicrobial properties by inhibiting bacterial growth. The membrane with 1 wt.% 4-HBA recorded 99.4 and 100% bacteria removal in synthetic and environmental water, respectively. Additionally, DOM removal of 55-73% was achieved. A flux recovery ratio (FRR) of 94.6% was obtained when a mixture of bacteria and humic acid was filtered, implying better fouling layer reversibility during cleaning. Furthermore, 100% FRR was achieved when a multimedia granular filtration step was installed prior to membrane filtration. The results illustrated that the membranes had a high permeate flux with low irreversible fouling. This indicated the potential of the membranes in treating complex feed streams using simple cleaning protocols.
Subject(s)
Bacteria , Biofilms , Biofouling , Fresh Water , Membranes, Artificial , Water Purification , Biofilms/drug effects , Biofilms/growth & development , Biofouling/prevention & control , Water Purification/methods , Fresh Water/microbiology , Bacteria/drug effects , Humic Substances/analysis , Filtration/methods , Parabens/chemistry , Sulfones/chemistry , Polymers/chemistryABSTRACT
BACKGROUND: Our study aimed to investigate the impact of urinary concentrations of personal care products (PCPs)-related phenols (PNs) and parabens (PBs), including Triclosan (TCS), Bisphenol A (BPA), Benzophenone-3 (BP-3), Butylparaben (BPB), Ethylparaben (EPB), Methylparaben (MPB), and Propylparaben (PPB), on urinary incontinence (UI) occurrence. METHOD: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2007 to 2016. Regression analysis was employed to investigate the relationship between exposure to PCPs-related substances, various levels of exposure, and UI within both the general population and the female demographic. Additionally, the Bayesian Kernel Machine Regression (BKMR) model was used to assess the effects of mixtures on UI. RESULTS: Our analysis comprised 7,690 participants who self-reported their diagnosis. Among them, 12.80% experienced stress urinary incontinence (SUI), 11.80% reported urge urinary incontinence (UUI), and 10.22% exhibited mixed urinary incontinence (MUI). In our fully adjusted multivariable models, BP-3 exposure exhibited a positive association with SUI (OR 1.07, 95% CI 1.02-1.14, p = 0.045). BPA exposure correlated with an increased risk of UUI (OR 1.21, 95% CI 1.01-1.44, p = 0.046) and MUI (OR 1.26, 95% CI 1.02-1.54, p = 0.029). TCS exposure displayed a negative correlation with the incidence of MUI (OR 0.87, 95% CI 0.79-0.97, p = 0.009). No significant links were observed between parabens and urinary incontinence. Notably, among the female population, our investigation revealed that BPA exposure heightened the risk of MUI (OR 1.28, 95% CI 1.01-1.63, p = 0.043). Participants in the highest tertile of BP-3 exposure demonstrated elevated likelihoods of SUI and MUI compared to those in the lowest tertile. In the BKMR analysis, negative trends were observed between the mixture and the risks of UUI and MUI when the mixture ranged from the 25th to the 40th and 35th to the 40th percentiles or above, respectively. Additionally, a positive trend was identified between the mixture and MUI when it was in the 40th to 55th percentile. CONCLUSION: In conclusion, our findings suggest that exposure to BPA, TCS, and BP-3 may contribute to the development of urinary incontinence.
Subject(s)
Urinary Incontinence, Stress , Urinary Incontinence , Humans , Female , Nutrition Surveys , Parabens/adverse effects , Parabens/analysis , Cross-Sectional Studies , Bayes Theorem , Urinary Incontinence/chemically induced , Urinary Incontinence/epidemiology , Urinary Incontinence, Stress/epidemiology , Urinary Incontinence, Stress/etiologyABSTRACT
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.
Subject(s)
Cosmetics , Parabens , Parabens/analysis , Parabens/toxicity , Risk Assessment , Preservatives, Pharmaceutical/analysis , Liquid Phase Microextraction/methods , Humans , Reproducibility of Results , Limit of Detection , Endocrine Disruptors/analysisABSTRACT
A quick, simple, sensitive, efficient and stability-indicating reverse-phase ultraperformance liquid chromatographic method for the estimation of propylparaben, methylparaben and sodium benzoate in a pharmaceutical liquid oral formulation was developed. A Waters Acquity UPLC BEH C18, 50 × 2.1 mm, 1.7 µm i.d. column was used to perform chromatographic separation with a 0.1% perchloric acid mobile phase used as solvent A and a mixture of 0.1 % perchloric acid and methanol in the ratio 20:80 (v/v), respectively, as solvent B. The experiments were carried out at a flow rate of 0.4 ml/min and the detection wavelength was 240 nm. The compartment temperature of the column was set at 40°C and the injection volume was set at 2 µl. The main aim of the research was to develop a single UPLC assay method for promethazine (active ingredient) and preservatives in the oral solution of promethazine HCl and dextromethorphan HBr that contains promethazine (active ingredient) and methylparaben, propylparaben and sodium benzoate (preservatives). An assay of dextromethorphan HBr was developed and validated by another HPLC method. The drug and preservatives were eluted at retention times of 19.3 min for promethazine HCl, 9.3 min for methylparaben, 18.9 min for propylparaben and 8.9 min for sodium benzoate. Validation of the developed method was carried out as stated by the International Conference on Harmonization guidelines ICH Q2B and under USP<1225>. The analytical parameters verified specificity/selectivity, linearity, accuracy, ruggedness and robustness. The linearity ranges of promethazine HCL, methylparaben, propylparaben and sodium benzoate were 10-100, 10-80, 1.0-8.0 and 10-80 µg/ml, respectively, with a correlation coefficient of active ingredients and preservatives of 1.00. Percentage recoveries of promethazine, propylparaben, methylparaben, and sodium benzoate were 100.0-100.2, 99.0-100.3, 99.5-98.0 and 99.0-100.0%. The validated analytical method proves that the method is specific, precise, linear, accurate, sensitive, rugged and stable, indicating the quantification of the active ingredient and all preservatives in liquid oral formulations.