Occurrence and Environmental Risk Assessment of Contaminants of Emerging Concern in Brazilian Surface Waters.

We investigated the occurrence and the environmental risk of eight contaminants of emerging concern (CECs; acetaminophen, naproxen, diclofenac, methylparaben, 17ß-estradiol, sulfathiazole, sulfadimethoxine, and sulfamethazine) in three Brazilian water bodies, namely, the Monjolinho River Basin (São Paulo State), the Mogi Guaçu River (São Paulo State), and the Itapecuru River (Maranhão State) in three sampling campaigns. The CECs were only quantified in surface water samples collected at the Monjolinho River Basin. Acetaminophen, naproxen, and methylparaben were detected in the range of <200 to 575.9 ng L-1, <200 to 224.7 ng L-1, and <200 to 303.6 ng L-1, respectively. The detection frequencies of the three measured compounds were between 33% and 67%. The highest concentrations of CECs were associated with intense urbanization and untreated sewage discharge. Furthermore, CEC concentrations were significantly correlated with total organic carbon, electrical conductivity, and dissolved oxygen levels, suggesting that domestic pollution from urban areas is an important source in the distribution of CECs in the Monjolinho River Basin. The environmental risk assessment indicated a high risk for acetaminophen (risk quotient [RQ] values between 2.1 and 5.8), a medium risk for naproxen (RQs between 0.6 and 0.7), and a low risk for methylparaben (RQs < 0.1) to the freshwater biota of the Monjolinho River Basin. Our findings show potential threats of CECs in Brazilian water bodies, especially in vulnerable areas, and reinforce the need for improvements in environmental regulations to include monitoring and control of these compounds in aquatic systems. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.

A validated stability­indicating reversed­phase­UPLC method for simultaneous estimation of promethazine hydrochloride, methylparaben, propylparaben and sodium benzoate assay of cough suppressant and antihistamine liquid oral dosage forms.

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.

Environmental pollution of paraben needs attention: A study of methylparaben and butylparaben co-exposure trigger neurobehavioral toxicity in zebrafish.

Parabens (PBs) are commonly utilized as preservatives in various commodities. Of all the PBs, methylparaben (MeP) and butylparaben (BuP) are usually found together at similar levels in the aqueous environment. Although a few studies have demonstrated that PBs are neurotoxic when present alone, the neurobehavioral toxic effects and mechanisms of coexisting MeP and BuP at environmental levels has not been determined. Neurobehavior is a sensitive indicator for identifying neurotoxicity of environmental pollutants. Therefore, adult female zebrafish (Danio rerio) were chronic co-exposure of MeP and BuP at environmental levels (5, 50, and 500 ng/L) for 60 d to investigate the effects on neurobehavior, histopathology, oxidative stress, mitochondrial function, neurotransmitters and gene expression. The results demonstrated that chronic co-exposure of MeP and BuP interfered with several behaviors (learning-memory, anxiety, fear, aggressive and shoaling behavior) in addition to known mechanisms of producing oxidative stress and disrupting energy. More intriguingly, chronic co-exposure of MeP and BuP caused retinal vacuolization and apoptosis in the optic tectum zone. It even has further effects on the phototransduction pathway, impairing optesthesia and leading to neurotransmitters dysregulation. These are critical underlying mechanisms resulting in neurobehavioral abnormalities. This study confirms that the pollution of multiple PBs by chronic co-exposure in aquatic environments can result neurobehavioral toxicity. It also suggests that the prolonged effects of PBs on aquatic ecosystems and health require close attention.

In vitro exposure of porcine spermatozoa to methylparaben, and propylparaben, alone or in combination adversely affects sperm quality.

Parabens (PBs) are widely used in the cosmetic, pharmaceutical, and food industries as preservatives of products. Because of its great use, humans and other organisms are highly exposed daily. However, little is known about the effect of PBs on male infertility. Therefore, the aim of the present study was to evaluate the effect of methylparaben (MePB) and propylparaben (PrPB), alone or in combination, on the physiological characteristics of pig in vitro exposed sperm to different concentrations (0, 200, 500, and 700 µM) for viability, motility, and acrosome integrity evaluation and (0, 200, 500, 700, 1000, and 2000 µM) for DNA fragmentation index evaluation, after 4 h of exposure. The results showed that sperm viability decreased after exposure to MePB from the concentration of 500 µM. In the PrPB and mixture groups, viability decreased at all concentrations except for the control. The decrease in viability of sperm exposed to PrPB was greater than that of the mixture and MePB groups. Sperm motility decreased in all the experimental groups exposed to PBs, at all concentrations, except for the control group. Acrosome integrity was not decreased in the MePB group; however, in the PrPB group, it decreased at a concentration of 200 µM and in the mixture at 500 µM. All groups exhibited DNA damage at different concentrations, except for the control group. Additionally, the effect of PBs on sperm quality was concentration-dependent. The results demonstrated that MePB and PrPB alone or in combination can have adverse effects on sperm quality parameters. MePB had lower toxicity than did both PrPB and the mixture. The mixture did not have an additive effect on any of the parameters evaluated. This could partially explain the link between PB exposure and infertility.

Simultaneous and sensitive detection of methylparaben and its metabolites by using molecularly imprinted solid-phase microextraction fiber array technique.

BACKGROUND: Methylparaben (MP), a commonly used antibacterial preservative, is widely used in personal care products, foods, and pharmaceuticals. MP and its metabolites are easy to enter the water environment, and their exposure and accumulation have negative effects on the ecological environment and human health, and have endocrine disrupting activity and potential physiological toxicity. It is still the primary issue of environmental analysis and ecological risk assessment to develop simple and reliable methods for simultaneous sensitive detection of these compounds in environmental water. RESULTS: In this paper, a flexible molecularly imprinted fiber array strategy is proposed for simultaneous enrichment and detection of trace MP and its four main metabolites. The experimental results showed that the three-fiber imprinted fiber array constructed by MP imprinted fiber had the best effect on the simultaneous enrichment of these five target analytes. The enrichment capacity of the imprinted fiber array was 214-456 times, 314-1201 times and 38-685 times that of commercial PA, PDMS and PDMS/DVB fiber arrays, respectively. The limit of detection (LOD) of this method was 0.033 µg L-1. The spiked recovery rate was 86.78-113.96 %, and RSD was less than 9.17 %. In addition, this molecularly imprinted SPME fiber array has good stability, long service life and can be used repeatedly at least 100 times. SIGNIFICANCE: This molecularly imprinted fiber array strategy can flexibly assemble different molecularly imprinted SPME fibers together, effectively improve the enrichment ability and detection sensitivity, and achieve simultaneous selective enrichment and detection of several analytes. This is an easy, efficient and reliable method for monitoring several trace analytes simultaneously in intricate environmental matrices.

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

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

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

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

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

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

An integrated transcriptome-microbiome host relationship associated with paraben toxicity in the brackish water flea Diaphanosoma celebensis.

Parabens, a group of alkyl esters of p-hydroxybenzoic acid, have been found in aquatic systems in particular, leading to concerns about their potential impact on ecosystems. This study investigated the effects of three commonly used parabens, methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP), on the brackish water flea Diaphanosoma celebensis. The results showed that PrP had the most adverse impact on survival rates, followed by EtP and MeP, while MeP and EtP induced significant adverse effects on reproductive performance. A transcriptome analysis revealed significant differential gene expression patterns in response to paraben exposure, with MeP associated with the most significant effects. MeP and EtP exposure produced greater disruption in the microbiota of D. celebensis than did PrP compared with control groups, and we identified eight key microbiota, including Ruegeria and Roseovarius. Correlation analysis between transcriptome and microbiome data revealed key interactions between specific microbiota and host gene expression. Certain microbial taxa were associated with specific genes (e.g. cuticle related genes) and toxicological pathways, shedding light on the complex molecular response and in vivo toxicity effects of parabens. These findings contribute to a deeper understanding of the molecular mechanisms underlying paraben toxicity and highlight the importance of considering the ecological impact of chemical contaminants in aquatic ecosystems.

Evaluating the efficacy of recyclable nanostructured adsorbents for rapid removal of methylparaben from aqueous solutions.

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.

Waste coconut shell-derived carbon monolith as an efficient binder-free cathode for electrochemical advanced oxidation treatment of endocrine-disrupting compounds.

Discharge of endocrine-disrupting compounds such as methylparaben (MePa) into natural water bodies deteriorates the aquatic ecosystem. In this regard, electrochemical oxidation (EO) and electro-Fenton (EF) processes are acknowledged as effective methods to eliminate biorecalcitrant compounds from different wastewater matrices. In these systems, the H2O2-producing ability of carbon-based cathodes is put to advantage for producing homogenous hydroxyl radicals by simulating Fenton's reaction, which dramatically augments the contaminant removal efficiency. However, commercial carbon based cathodes are not economically affordable, especially for voluminous treatment. Hence in the present work, waste-derived carbonised coconut shell (CCS) monolith was employed as a cathode in EO and EF treatment of MePa. Almost the entire MePa with initial concentration of 10 mg/L was removed in 60 min by EO and 45 min by EF process at neutral pH, applied current density of 7.5 mA/cm2, NaCl concentration of 1.0 g/L and 10 mg/L of Fe2O3 dosing. The MePa removal efficiency of the CCS cathode-fitted system after 60 min was better than the commercial graphite plate and Ti-based mixed metal oxide employing system due to higher H2O2 electrosynthesis (H2O2 = 9.0 ± 0.6 mg/L after 60 min). Moreover, the same setup was used for treating 10 mg/L of MePa-spiked real sewage and demonstrated MePa and total organic carbon removal efficiency of 80.16 ± 2.31% and 37.42 ± 3.50%, respectively, in 45 min. Further, the CCS-mediated EF treatment achieved >90% removal of MePa for eight continuous batch cycles and recorded a current density drop of just 0.23% per cycle. The degradation pathway and toxicity assessment of the intermediates using the Ecological Structure Activity Relationships (ECOSAR) tool supported the eco-friendliness of the current treatment scheme.

Association between urinary methylparaben level and bone mineral density in children and adolescents aged 8-19 years.

Previous epidemiological study has explored a positive association between methylparaben (Mep) and bone mineral density (BMD) in adults. Evidence linking Mep and BMD in children and adolescents is very limited. This study examined the association between Mep and BMD in children and adolescents aged 8-19 years. In this cross-sectional study, 1830 children and adolescents aged 8-19 years from NHANES 2011-2016 were analyzed. Mep was ln-transformed for analysis of the skewed distribution. Multiple linear regression analyses were performed to evaluate Mep's association with BMD (containing total BMD, trunk bone BMD, pelvis BMD, lumbar spine BMD, and thoracic spine BMD). Moreover, a generalized additive model (GAM) and a fitted smoothing curve (penalized spline method) were conducted to explore the exact shape of curve between them. In the fully adjusted model, ln-transformed Mep and BMD showed an independent and positive association (total BMD (ß = 0.003, 95% CI (0.001, 0.005), P = 0.01), trunk bone BMD (ß = 0.002, 95% CI (0.000, 0.005), P = 0.04), pelvis BMD (ß = 0.004, 95% CI (0.001, 0.008), P = 0.02), lumbar spine BMD (ß = 0.005, 95% CI (0.001, 0.008), P = 0.01), thoracic spine BMD (ß = 0.003, 95% CI (0.001, 0.005), P = 0.02)) and a linear association. Subgroup analysis showed positive association between ln-transformed Mep and BMD. Furthermore, the positive association was significant in females and children aged 12-19 years (P for trend < 0.05). This study is the first study to find evidence demonstrating that exposure to Mep may be positively associated with BMD in children and adolescents aged 8-19 years. Validation of our findings will need further research.

Nickel-iron-driven heterogenous bio-electro-fenton process for the degradation of methylparaben.

Discharge of emerging contaminants such as parabens in natural water bodies is a grievous concern. Among parabens, methylparaben (MP) is most prevalent due to its extensive usage in personal care and food products and has been purported to trigger hormonal-related diseases. In this regard, the bio-electro-Fenton (BEF) process garners attention for remediating refractory compounds because of its ability to generate in situ hydroxyl radicals (•OH) utilising the energy harvested from electroactive microorganisms. In the present investigation, a Ni-Fe-driven heterogenous BEF system (BEF-MFC) was used to degrade MP from different matrices. At neutral catholyte pH, 99.54 ± 0.22% of MP was removed from an initial concentration of 10 mg/L in 240 min of retention time with an estimated treatment cost of about 1.01 $/m3. The removal rate ameliorated when the catholyte pH was dropped to 3.0 and by imposing an external voltage of 0.5 V, requiring just 120 min to achieve comparable MP removal efficiencies. However, catalyst leaching was higher at acidic pH (leaching of Fe ions = 0.44 mg/L and Ni ions = 0.06 mg/L) and applying external voltage increased the treatment cost slightly to 1.08 $/m3. Further, treatment of 10 mg/L MP-spiked real wastewater at pH of 7.0 with the BEF-MFC attained 85.70 ± 3.30% and 56.50 ± 1.70% reduction in MP and total organic carbon, respectively, in 240 min. In addition, a maximum power density of 205.90 ± 2.27 mW/cm2 was harvested in the BEF-MFC; thus, portraying the dual benefit of Ni-Fe heterogeneous catalyst. Even though, Ni-Fe performed reasonably well as Fenton-cum-cathode catalyst, future endeavours should be poised to fine-tune catalysts to accelerate H2O2 and •OH generation, which will reinforce the scalability of this system.

Hybrid porous material supported in a cellulose acetate polymeric membrane for the direct immersion thin-film microextraction of parabens in water.

A simple and sensitive direct immersion thin-film microextraction (DI-TFME) method based on MIL-101(Cr) modified with carbon nanofibers supported in cellulose acetate (CA-MIL-101(Cr)@CNFs) polymeric membrane was developed for the extraction and preconcentration of parabens in environmental water samples. A high-performance liquid chromatography-diode array detector (HPLC-DAD) was used for the determination and quantification of methylparaben (MP) and propylparaben (PP). The factors affecting the DI-TFME performance were investigated using central composite design (CCD). The linearity of the DI-TFME/HPLC-DAD method obtained under optimal conditions was 0.04-0.04-500 µg/L with a correlation coefficient (R2) greater than 0.99, respectively. The limits of detection (LOD) and quantification (LOQ) for methylparaben were 11 ng/L and 37 ng/L; for propylparaben, they were 13 ng/L and 43 ng/L, respectively. The enrichment factors were 93.7 and 123 for methylparaben and propylparaben. The intraday (repeatability) and interday (reproducibility) precisions expressed as relative standard deviations (%RSD) were less than 5%. Furthermore, the DI-TFME/HPLC-DAD method was validated using real water samples spiked with known concentrations of the analytes. The recoveries ranged from 91.5 to 99.8%, and intraday and interday trueness values were less than ±15%. The DI-TFME/HPLC-DAD approach was effectively used for the preconcentration and quantification of parabens in river water and wastewater samples.

Different isoforms of parabens into marine environment: Biological effects on the bacterium Aliivibrio fischeri and the marine mussel Mytilus galloprovincialis.

Different isoforms of alkyl esters of p-Hydroxybenzoic acid, also known as parabens, are of great concern due to their widespread presence into the aquatic environment, their high concentrations in wastewater discharges, as well as their ability to induce adverse effects on aquatic organisms. Considering the imperative need for assessing their fate and risk to aquatic environment, the present study investigated the biological effects of two isoforms of parabens, methyl- (MeP) and propyl- (PrP), on the bacterium Aliivibrio fischeri (using the Bioluminescence Inhibition/Microtox® bioassay) and the mussel Mytilus galloprovincialis (in terms of mussel mortality, cellular, oxidative and genotoxic stress indices). The assessment of MeP and PrP behavior into aquatic media (artificial sea water/ASW and 2 % NaCl), primarily performed by UHPLC-UV-MS analysis, showed only a slight hydrolysis of PrP to 4-Hydrobenzoic acid (4-HBA). Furthermore, exposure of both species to different concentrations of each paraben revealed differences among their toxic potential, as well as their ability to cause cellular, oxidative and genotoxic effects on hemocytes of challenged mussels. Interestingly, the Microtox® bioassay showed that PrP mediated toxicity in A. fischeri were more pronounced than MeP, as revealed by the estimated toxic endpoints (in terms of concentration that promote 50 % of bioluminescence inhibition, EC50). Similarly, in challenged mussels, a significant disturbance of mussel hemocytes' lysosomal membrane integrity, as well as enhanced levels of superoxides, nitric oxides, lipid peroxidation byproducts, and micronuclei formation were observed. These findings are of great interest, since MeP and PrP differential toxic potential, as well their ability to induce pre-pathological alterations in marine species, like mussels, give new evidence for their risk to aquatic biota.

Exposure to methylparaben at environmentally realistic concentrations significantly impairs neuronal health in adult zebrafish.

Methylparaben (MeP) is an emerging aquatic pollutant that is found to impact neural functions. However, it still lacks a comprehensive understanding about its neurotoxicology. The present study exposed adult zebrafish to environmentally realistic concentrations (0, 1, 3, and 10 µg/L) of MeP for 28 days, with objectives to elucidate the neurotoxic effects and mechanisms. Proteomic profiling found that MeP pollutant induced distinct mechanism of neurotoxicity as a function of sex. MeP pollutant appeared to preferentially target the neurotransmission cascade via synapse junctions. In male brain, glutamatergic neural signaling was enhanced by 10 µg/L of MeP in characteristics of higher glutamate neurotransmitter content (by 61.9%) and up-regulated glutamate receptor expression by 2.6-fold relative to the control. In MeP-exposed female brain, biomarker proteins of synapse formation and regeneration had significantly lower abundance, accounting for the blockage of synaptic neurotransmission. Furthermore, under the stress of MeP pollutant, both male and female zebrafish initiated a negative feedback mechanism along stress neuroendocrine axis by down-regulating the transcriptions of corticotropin-releasing hormone and its binding protein, which subsequently decreased blood cortisol concentrations. MeP subchronic exposure also disturbed innate immune function. In particular, significant increases in lipopolysaccharide (LPS) content by 15.6% were caused by MeP exposure in male brain, thereby inducing the synthesis of pro-inflammatory cytokines. In contrast, female brain was able to adaptively up-regulate the protein expression of blood brain barrier to inhibit the infiltration of LPS endotoxin into brain. Overall, the present findings pinpoint the potent neurotoxicity of MeP pollutant even at environmentally realistic concentrations.

Polymorphism of Carbamazepine Pharmaceutical Cocrystal: Structural Analysis and Solubility Performance.

Polymorphism is a common phenomenon among single- and multicomponent molecular crystals that has a significant impact on the contemporary drug development process. A new polymorphic form of the drug carbamazepine (CBZ) cocrystal with methylparaben (MePRB) in a 1:1 molar ratio as well as the drug's channel-like cocrystal containing highly disordered coformer molecules have been obtained and characterized in this work using various analytical methods, including thermal analysis, Raman spectroscopy, and single-crystal and high-resolution synchrotron powder X-ray diffraction. Structural analysis of the solid forms revealed a close resemblance between novel form II and previously reported form I of the [CBZ + MePRB] (1:1) cocrystal in terms of hydrogen bond networks and overall packing arrangements. The channel-like cocrystal was found to belong to a distinct family of isostructural CBZ cocrystals with coformers of similar size and shape. Form I and form II of the 1:1 cocrystal appeared to be related by a monotropic relationship, with form II being proven to be the thermodynamically more stable phase. The dissolution performance of both polymorphs in aqueous media was significantly enhanced when compared with parent CBZ. However, considering the superior thermodynamic stability and consistent dissolution profile, the discovered form II of the [CBZ + MePRB] (1:1) cocrystal seems a more promising and reliable solid form for further pharmaceutical development.

Association of parabens and bisphenols with lung function in children aged 5-12 years from Shanghai, China.

Epidemiological studies have reported potential effects of individual paraben or bisphenol exposure on lung function, but few studies have estimated their joint effects. We conducted a cross sectional survey to investigate the associations of parabens and bisphenols exposure with lung function in 205 children aged 5-12 years from Shanghai, China. Urinary concentrations of six parabens [methyl-, ethyl-, propyl-, butyl-, benzyl-, and heptyl-paraben (MeP, EtP, PrP, BuP, BzP, and HeP)] and seven bisphenols [bisphenol A (BPA), bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol B (BPB), bisphenol P (BPP), bisphenol S (BPS), and bisphenol Z (BPZ)] were assessed by the high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Lung function, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%), was further measured. Linear regression, bayesian kernel machine regression (BKMR), and weighted quantile sum regression (WQS) evaluated the individual and joint relationships of the parabens and bisphenols with the lung function parameters. Further, the analysis was stratified by child sex. Parabens (MeP, EtP, PrP, and BuP) and bisphenols (BPA, BPAP, BPB, and BPS) with detection rates >75% were included for analyses. In linear regressions, parabens (MeP, PrP, and BuP) were generally negatively associated with FEV1, FVC, PEF, and FEF25-75%, but no associations for bisphenols were found. The association of parabens with lung function was more pronounced in girls. The aforementioned negative associations between parabens and lung function were confirmed by both the BKMR and WQS, with MeP being considered most heavily weighing chemical. Our findings suggested that exposure to parabens, either individuals or as a mixture, were associated with decreased lung function in children aged 5-12 years, and these associations were stronger among girls. Considering the cross-sectional study design, large longitudinal studies are warranted to confirm our findings.

Simultaneous determination of dehydroacetic acid, benzoic acid, sorbic acid, methylparaben and ethylparaben in foods by high-performance liquid chromatography.

In this study, an analytical method was established and validated to determine the preservatives such as dehydroacetic acid, benzoic acid, sorbic acid, methylparaben and ethylparaben. The level of preservatives was measured by solvent extraction method adding purification process with carrez reagent and by high-performance liquid chromatography (HPLC). The developed analytical method was successfully applied to determine the concentration of preservatives in various food samples including jam, cheese and soy sauce, displaying high accuracy (recoveries between 87.8% and 110%) and precision (%RSD less than 5.92% and 7.72% for intra-day and inter-day, respectively). To verify the applicability of the improved test method, selected 13 food items and collected 521 samples were monitored. As a result, all the cases met the Korea standard guidelines. Consequently, this study is expected to contribute to the safety management of preservatives for domestic distribution and imported food.

Associations between urinary parabens and lung cancer.

Parabens are a family of endocrine-disrupting chemicals. Environmental estrogens may play a vital role in the development of lung cancer. To date, the association between parabens and lung cancer is unknown. Based on the 189 cases and 198 controls recruited between 2018 and 2021 in Quzhou, China, we measured 5 urinary parabens concentrations and examined the association between urinary concentrations of parabens and lung cancer risk. Cases showed significantly higher median concentrations of methyl-paraben (MeP) (2.1 versus 1.8 ng/mL), ethyl-paraben (0.98 versus 0.66 ng/mL), propyl-paraben (PrP) (2.2 versus 1.4 ng/mL), and butyl-paraben (0.33 versus 0.16 ng/mL) than controls. The detection rates of benzyl-paraben were only 8 and 6% in the control and case groups, respectively. Therefore, the compound was not considered in the further analysis. The significant correlation between urinary concentrations of PrP and the risk of lung cancer (odds ratio (OR)adjusted = 2.22, 95% confidence interval (CI): 1.76, 2.75; Ptrend < 0.001) was identified in the adjusted model. In the stratification analysis, we found that urinary concentrations of MeP were significantly associated with lung cancer risk (OR = 1.16, 95% CI: 1.01, 1.27 for the highest quartile group). Besides, comparing the second, third, and fourth quartile groups with the lowest group of PrP, we also observed urinary PrP concentrations associated with lung cancer risk, with the adjusted OR of 1.52 (95% CI: 1.29, 1.65, Ptrend = 0.007), 1.39 (95% CI: 1.15, 1.60, Ptrend = 0.010), and 1.85 (95% CI: 1.53, 2.30, Ptrend = 0.001), respectively. MeP and PrP exposure, reflected in urinary concentrations of parabens, may be positively associated with the risk of lung cancer in adults.