Mono-n-hexyl phthalate: exposure estimation and assessment of health risks based on levels found in human urine samples.

Mono-n-hexyl phthalate (MnHexP) is a primary metabolite of di-n-hexyl phthalate (DnHexP) and other mixed side-chain phthalates that was recently detected in urine samples from adults and children in Germany. DnHexP is classified as toxic for reproduction category 1B in Annex VI of Regulation (EC) 1272/2008 and listed in Annex XIV of the European chemical legislation REACH; thereby, its use requires an authorisation. Health-based guidance values for DnHexP are lacking and a full-scale risk assessment has not been carried out under REACH. The detection of MnHexP in urine samples raises questions about the sources of exposure and concerns of consumer safety. Here, we propose the calculation of a provisional oral tolerable daily intake value (TDI) of 63 µg/kg body weight/day for DnHexP and compare it to intake levels corresponding to levels of MnHexP found in urine. The resulting mean intake levels correspond to less than 0.2% of the TDI, and maximum levels to less than 5%. The TDI was derived by means of an approximate probabilistic analysis using the credible interval from benchmark dose modelling of published ex vivo data on reduced foetal testosterone production in rats. Thus, for the dose associated to a 20% reduction in testosterone production, a lower and upper credible interval of 14.9 and 30.0 mg/kg bw/day, respectively, was used. This is considered a conservative approach, since apical developmental endpoints (e.g. changed anogenital distance) were only observed at higher doses. In addition, we modelled various scenarios of the exposure to the precursor substance DnHexP from different consumer products, taking measured contamination levels into account, and estimated systemic exposure doses. Of the modelled scenarios including the application of sunscreen (as a lotion or pump spray), the use of lip balm, and the wearing of plastic sandals, and considering conservative assumptions, the use of DnHexP-contaminated sunscreen was highlighted as a major contributing factor. A hypothetical calculation using conservative assumptions for the latter resulted in a margin of safety in relation to the lower credible interval of 3267 and 1007 for adults and young children, respectively. Most importantly, it was found that only a fraction of the TDI is reached in all studied exposure scenarios. Thus, with regard to the reported DnHexP exposure, a health risk can be considered very unlikely.

Exploring noninvasive matrices for assessing long-term exposure to phthalates: a scoping review.

The phthalic acid esters (PAEs) are one class of the most abundant and frequently studied pseudo-persistent organic pollutants. Noninvasive urine is an effective substrate for evaluating PAE exposure, but repeated sampling is needed to overcome this bias. This adds much work to on-site collection and the cost of detection increases exponentially. Therefore, the aim of this study was to conduct a scope review to describe the detection methods and validity of the use of other noninvasive matrices, such as nails and hair, for assessing long-term exposure to PAEs. The PubMed, Web of Science and China National Knowledge Infrastructure (CNKI), electronic databases were searched from 1 January 2000 to 3 April 2024, and 12 studies were included. Nine and three studies used hair and nails, respectively, as noninvasive matrices for detecting PAE exposure. Five articles compared the results of nail or hair and urine tests for validity of the assessment of PAE exposure. The preprocessing and detection methods for these noninvasive samples are also described. The results of this review suggest that, compared with nails, hair may be more suitable as a noninvasive alternative matrix for assessing long-term exposure to PAEs. However, sample handling procedures such as the extraction and purification of compounds from hair are not uniform in various studies; therefore, further exploration and optimization of this process, and additional research evidence to evaluate its effectiveness, are needed to provide a scientific basis for the promotion and application of hair detection methods for assessing long-term PAE exposure levels.

Protective effect of curcumin against microplastic and nanoplastics toxicity.

Microplastics and nanoplastics (MNPs) are present in urban dust and the aquatic environments of industrialized cities. MNPs in the human body accumulate in the lymphoid follicles, Peyer's patches of the gastrointestinal tract, and pulmonary vascular endothelial cells, which slowly result in toxicity. Since previous studies introduced curcumin as a natural protective agent against environmental toxins, we reviewed preclinical studies that had used curcumin to protect organs or cells from toxicity secondary to exposure to MNPs. It was found that exposure to MNPs resulted in osteolysis, immunotoxicity, thyroid disturbances, nephrotoxicity, neurotoxicity, hepatotoxicity, pulmonary toxicity, gastrointestinal toxicity, cardiovascular toxicity, and especially endocrine, and reproductive toxicity. Nevertheless, except for one study reviewed, curcumin restored all oxidative and histopathological damages induced by MNPs to normal due to curcumin's inherent antioxidant, antiapoptotic, anti-inflammatory, and anti-proliferative properties.

Quercetin antagonizes apoptosis, autophagy and immune dysfunction induced by di(2-ethylhexyl) phthalate via ROS/ASK1/JNK pathway.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that can damage various organizations and physiques through oxidative stress. Quercetin (Que) is a rich polyphenol flavonoid with good anti-inflammatory and antioxidant effects. However, the protection mechanism of Que against DEHP exposure-induced IPEC-J2 cell injury and the implication of autophagy, apoptosis and immunity are still unclear. In this experiment, we looked into the toxicity regime of DEHP exposure on IPEC-J2 cells and the antagonistic function of Que on DEHP. In the experiment, 135 µM DEHP and/or 80 µM Que were used to treat the IPEC-J2 cells for 24 h. Experiments indicated that DEHP exposure can cause increased reactive oxygen species (ROS) levels leading to oxidative stress, decreased CAT, T-AOC and GSH-Px activities, increased MDA and H2O2 accumulation, activated the ASK1/JNK signalling pathway, and further increases in the levels of apoptosis markers Bax, Caspase3, Caspase9, and Cyt-c, while reduced the Bcl-2 expression. DEHP also increased the expression of genes linked to autophagy (ATG5, Beclin1, LC3), while decreasing the expression of P62. Additionally, DEHP exposure led to elevated levels of IL1-ß, IL-6, MCP-1, and TNF expression. When exposed to Que alone, there were no significant changes in cellular oxidative stress level, ASK1/JNK signalling pathway expression level, apoptosis, autophagy and cellular immune function. The combination of DEHP and Que treatment remarkably decreased the proportion of autophagy and apoptosis, and recovered cellular immunity. In summary, Que can attenuate DEHP-induced apoptosis and autophagy in IPEC-J2 cells by regulating the ROS/ASK1/JNK signalling pathway and improving the immune dysfunction of IPEC-J2 cells.

Temporal Trends in Phthalate Metabolite Exposure of Girls in the United States Across Sociodemographic Factors and Intersectional Social Identities: National Health and Nutrition Examination Survey 2001-2018.

BACKGROUND: Exposure to phthalates during the pubertal window impacts chronic disease risk and temporal trends in exposure can inform public health initiatives. OBJECTIVE: Characterize temporal trends in phthalate metabolite exposure for adolescent girls overall and by sociodemographic characteristics. METHODS: We used the cross-sectional data from each cycle of the National Health and Nutrition Examination Survey from years 2001 to 2018. We restricted participants to ages of 8-14 with at least one urinary measurement of the selected 12 phthalate metabolites within the study period (n=2,063). We used multivariable linear regression to assess temporal trends for selected individual phthalate metabolite concentrations (ng/ml) and source groupings of parent metabolites (sum low and high molecular weight phthalates; ∑LMW and ∑HMW) overall and individually by sociodemographic characteristics (race/ethnicity), nativity, socioeconomic status (SES), intersection of race/ethnicity-SES) to assess for modification. RESULTS: Overall ∑HMW and ∑LMW concentrations declined between 2001 and 2018; however, only ∑LMW consistently differed by all sociodemographic characteristics. Trends in ∑LMW concentration were significantly higher across all racial/ethnic groups, ranging from an average of 35% (Other Hispanic) to 65% (Mexican American and non-Hispanic Black) higher than non-Hispanic White (all p-values<0.0001). Compared to non-Hispanic White, we observed an average decrease of 15% in MiBP for non-Hispanic Black (ßSpline=-0.16, p<0.0001) and 28% for Other Hispanic (ßSpline=-0.33, p=0.01) in 2011-2018 vs. 2001-2010. Summary and individual LMW metabolite phthalate concentrations were 11%-49% higher among low vs. high SES girls. LMW metabolites MBP and MiBP were on average 22% and 35% higher; respectively, among foreign born vs. U.S. born. Compared to non-Hispanic Whites, all racial/ethnic groups had statistically significant higher trends in ∑LMW concentration irrespective of SES status. SIGNIFICANCE: Girls identifying with a historically disadvantaged racial/ethnic group have elevated ∑LMW concentrations irrespective of SES class; suggesting the need for interventions to mitigate exposure among the most historically disadvantaged strata.

Comprehensive survey on the use of plastic additives in toy products used in Japan.

BACKGROUND: Plastic additives have adverse effects on human health. Children frequently use toys that contain various substances found in paints, plasticizers, and other materials, which heighten the risk of specific chemical exposure. Infants are particularly prone to chemical exposure through the "mouthing" behavior because of the possibility of placing toys in their mouths. Thus, this vulnerability should be considered during risk assessments of chemical exposure. METHODS: This study performed a comprehensive analysis of the chemical components in various 84 plastic toys including "designated toys" (toys that may be harmful to infant health if in contact with their mouths: Article 78 of the Enforcement Regulations of the Food Sanitation Law by the Minister of Health, Labor and Welfare) such as dolls, balls, blocks, bathing toys, toy vehicles, pacifiers, and household items, purchased in the Japanese market by nontargeted and targeted analysis. RESULTS: Plasticizers, flame retardants, and fragrances were the main compounds in almost all the toy products. The results showed that plastic products made in China tended to contain high levels of phthalate esters. In particular, hazardous plasticizers, such as diisodecyl, di-n-octyl, and diisononyl phthalates were detected above the regulatory limit (0.1%) in used products manufactured before regulations were passed in Japan. Furthermore, we detected alternative plasticizers, such as acetyl tributyl citrate (ATBC; 52%), diisononyl adipate (DINA; 50%), and di(2-ethylhexyl) terephthalate (DEHT; 40%). ATBC was detected at high concentrations in numerous toy products. Thus, infants with free access to indoor plastic toys might be exposed to these chemicals. CONCLUSIONS: This study observed that the chemical profiles of toy products were dependent on the year of manufacture. Furthermore, the detection of currently regulated plasticizers in secondhand products manufactured before regulations were enforced, along with the increasing trend of using alternative substances to regulated phthalate esters in products, suggests the potential exposure of infants to these plasticizers through the use of toys. Therefore, regular fact-finding surveys should continue to be conducted for the risk assessment and safety management of domestic toy products.

[Adsorption and Desorption Behavior of PAEs Plasticizer on PVC and Rubber Particles After Natural Environment Aging].

Microplastics （MPs） coexist with plasticizers in the aqueous environment to form composite pollution, but the adsorption and desorption behaviors of MPs and plasticizers under natural conditions are unknown. Polyvinyl chloride （PVC） and rubber were used as the target MPs to characterize the changes in their morphological features after aging for one anniversary in atmospheric exposure and lake sedimentary burial environments and to investigate the adsorption and desorption behavior of the MPs to the coexisting phthalate esters （PAEs） plasticizer before and after aging. The results showed that the surface of MPs was rougher after exposure to the atmospheric environment and burial in a depositional environment, showing the characteristics of porous polymers. The carbonyl index （CI） of PVC and rubber increased by 62.2% and 321.2%, respectively, in the atmospheric environment and increased by 51.1% and 223.1%, respectively, in the depositional environment. The atmospheric exposure was capable of accelerating the aging process of MPs. PAEs were adsorbed on the surface of MPs through hydrophobic interaction, and the amount of adsorption was significantly and positively correlated with their hydrophobic properties. The adsorption capacity and adsorption rate of PVC on PAEs were inhibited after aging. Aging promoted the adsorption of rubber on strongly hydrophobic PAEs plasticizers and inhibited the adsorption of weakly hydrophobic PAEs. The environmental aging process reduced the desorption of strongly hydrophobic PAEs from rubber, enhanced the reversibility of rubber adsorption of weakly hydrophobic PAEs, and increased the desorption rate of PAEs from PVC.

Biochemical and transcriptomic analyses reveal the toxicological response and potential mechanism of butyl benzyl phthalate in zebrafish gills.

Butyl benzyl phthalate (BBP), a common phthalate plasticizer, is frequently detected in aquatic environments. However, there has been relatively little research on its effects on gill-related responses. This study exposed adult zebrafish to BBP concentrations ranging from 5 to 500 µg/L for 28 days, specifically investigating its toxicity in the gills. Assessment of oxidative stress biomarkers and gene expression related to apoptosis and mitochondria was conducted. Results demonstrated that exposure to 500 µg/L of BBP disrupted the antioxidant defense system, leading to lipid peroxidation and DNA damage. Moreover, the expression level of the caspase-3 gene exhibited an approximate two-fold increase, whereas the expression of 18rs-rrn decreased by 50 % on day 28. Gene Ontology enrichment analysis indicated suppressed expression of antioxidant and metabolic process terms, alongside inhibition of metabolism, immune, and signal transduction-related pathways. This study offers novel insights into the toxic effects and mechanisms of BBP on fish, providing valuable data for assessing environmental risks linked to BBP contamination and advocating for its management in aquatic ecosystems.

Evaluation of the Effects of Di-(2-ethylhexyl) phthalate (DEHP) on Caenorhabditis elegans Survival and Fertility.

Di-2-ethylhexyl (DEHP), which is widely used in industrial products, is produced annually in excess of 2 million tons worldwide. DEHP is an endocrine disruptor and one of the major environmental pollutant chemicals (EDCs) in nature. There is some information about the effects of these products, which provide great advantages in every respect, on human health and the environment. In this study, C. elegans organism was used to evaluate the health and environmental risks of DEHP. The survival and fertility effects of DEHP on the C. elegans organism were examined and the results were evaluated. In the study, it was determined that DEHP not only shortened the survival time of C. elegans but also caused a decrease in fertility. DEHP (0.625 mM and 10 mM) caused a 23.2-30.6% decrease in fertility. Additionally, the LC50 (50% lethal concentration) value of DEHP was found to be 321 µg/mL.

Phthalate migration potential in vacuum-packed fish.

Phthalates or phthalate esters (PAEs) have become a serious concern due to their toxicity and risks of migration from contact materials to food matrices and the environment. The aim of this study is to monitor the possible migration potential of PAEs in pelagic fish stored in vacuum packaging depending on the storage time and to determine the polyethylene polymers. In order to achieve this goal, sea bass (Dicentrarchus labrax) and anchovy fish (Engraulis encrasicolus) were randomly packaged in vacuum bags and then stored for 90 days. Phthalate content was determined by GC/MS technique in the muscle tissue of each fish species at certain periods (0, 30, and 90 days) of storage, and on the first day in the packaging material and fish meat. As a result of the analysis performed in µ-Raman spectroscopy, no microplastics were detected in both fish species' meats. FTIR spectroscopy results of the packaging material determined nylon in the chemical content of the packaging material before processing. It has been determined that the chemical composition of the packaging used in the vacuum packaging process is affected by the temperature, depending on the storage period, and different polymer types are formed in the processed package material. It was determined that the dominant PAE homologues were Di-n-pentyl phthalate (DPENP) in both fish meat and Di-(2-ethylhexyl)-phthalate (DEHP) in the package. However, during storage, Dibutylphthalate (DBP) became dominant in anchovies and DPENP became dominant in sea bass, differing according to fish species and storage time.

In vitro Evaluation of DINCH-Plasticized Blood Bags for Red Blood Cell Storage with CPDA-1 Anticoagulant.

Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in blood bags. Despite its protective effects on red blood cell (RBC) storage, concerns about its reproductive toxicity exist. This study investigated the in vitro quality of RBC concentrates stored in bags using di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) as an alternative plasticizer. Methods: Using a pool-and-split study design, we produced 20 matched homogenous quintets of RBC concentrates in two DINCH bags and three DEHP bags with citrate phosphate dextrose adenine (CPDA-1) anticoagulant. RBC storage quality was assessed weekly for 35 days. Results: On day 35, the median hemolysis levels in the DINCH bags (0.297-0.342%) were marginally higher (p < 0.05) than the DEHP bags (0.204-0.240%). All DINCH bags showed <0.8% hemolysis. RBCs in the DINCH bags showed increased mean corpuscular volume and decreased eosin 5' maleimide binding than in the DEHP bags. Higher pO2 and lower pCO2 levels in the DINCH bags indicated better gas permeability than in DEHP bags. Other metabolic parameters were comparable in both bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Conclusion: The quality of RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for nonleukoreduced RBC storage even without the use of next-generation additive solutions to improve RBC preservation quality.

A plasticizer is a chemical substance added to plastic to increase its flexibility. DEHP is a plasticizer that has been widely used in many products including plastic tubing and bags of medical devices. However, concerns about DEHP-related toxicity have been debated for many years. DEHP has been replaced with other plasticizers in many products, but it is still being used in blood bags due to its protective effect on RBC preservation. DINCH is an alternative plasticizer with a low toxicology profile. This study investigated the quality of RBC concentrates stored in blood bags using DINCH. Twenty sets of five RBC concentrates were produced using two DINCH bags and three DEHP bags with CPDA-1 anticoagulant, and the storage quality was assessed weekly for 35 days. On day 35, the median hemolysis levels in the DINCH bags (0.297­0.342%) were slightly increased than the DEHP bags (0.204­0.240%). However, all DINCH bags showed hemolysis lower than the regulatory limit of 0.8%. DINCH bags exhibited better gas permeability than DEHP bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Most of the other metabolic parameters were comparable in both bags. The quality of nonleukocyte-reduced RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for RBC storage, even without the use of next-generation additive solutions to improve RBC preservation quality.

Urine Phthalate Metabolites are Elevated in Patients with Esophageal Squamous Cell Carcinoma and Associated with Advanced Cancer Stage and Poor Survival.

Background: The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined. Results: The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3-T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥3 µg/L and clinical stage IVB were independent prognostic factors for worse OS. Conclusion: The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.

An insight into carcinogenic activity and molecular mechanisms of Bis(2-ethylhexyl) phthalate.

Di(ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant to which humans are exposed via multiple routes. Human health risk assessments for this substance have recently been updated, focusing on reproductive toxicity, including DEHP, in the list of chemicals classified as carcinogenic, mutagenic, or toxic to reproduction (CMR). Moreover, DEHP has also been defined as probably and possibly carcinogenic to humans based on its carcinogenicity in rodents. However, the mechanism of action of DEHP and its relevance in humans remain unclear. Rodent data suggests that DEHP induces cancer through non-genotoxic mechanisms related to multiple molecular signals, including PPARα activation, perturbation of fatty acid metabolism, induction of cell proliferation, decreased apoptosis, production of reactive oxygen species, and oxidative stress. According to the DEHP toxicological dataset, several in vitro cell transformation assays have been performed using different protocols and cellular models to produce different results. This study aimed to evaluate the carcinogenic potential of DEHP by using the A31-1-1 BALB/c-3T3 cell line in a standard cell transformation assay. Additionally, transcriptomic analysis was performed to explore the molecular responses and identify the affected toxicological pathways. Although DEHP treatment did not induce transformation in BALB/c-3T3 cells, the transcriptomic results revealed significant modulation of several pathways associated with DEHP metabolism, tissue-specific functions related to systemic metabolism, and basal cellular signaling with pleiotropic outcomes. Among these signaling pathways, modulation of cell-regulating signaling pathways, such as Notch, Wnt, and TGF-ß, can be highlighted. More specific modulation of such genes and pathways with double functions in metabolism and neurophysiology underlies the well-known crosstalk that may be crucial for the mechanism of action of DEHP. Our findings offer evidence to support the notion that these models are effective in minimizing the use of animal testing for toxicity assessment.

Determination of dialkyl phthalate esters in indoor air of PVC industry: Risk assessment for human health using Monte-Carlo simulations.

Dialkyl phthalate esters are incorporated to enhance the pliability and prevent brittleness in polyvinyl chloride (PVC) tubing. Exposure to these compounds occurs throughout human lifetimes via ingestion, inhalation, and direct skin contact. A study was conducted to evaluate concentrations of four specific phthalates-dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP)-in the indoor air of both industrial and administrative sectors within the PVC manufacturing facilities. Air sampling was conducted in the spring season at two polyethylene factories in Zahedan Industrial Park (Sistan and Baluchestan Province, Iran). The outcomes demonstrated that mean concentrations of these substances in industrial along with administrative departments 485.7 µg/m3 and 49.83 µg/m3for DMP, 807.38 µg/m3 and 30.17 µg/m3 for DEP, 849.62 µg/m3 and 37.50 µg/m3 for DBP along with 1268.08 µg/m3 and 45.50 µg/m3 for DEHP respectively. The probabilistic lifetime cancer risk (LTCR) of DEHP in the indoor air of Zahedan PVC factories for men and women was determined using the Monte Carlo simulation technique. The computed mean LTCRs of DEHP for men and women in the indoor air of industrial and administrative departments in Zahedan PVC were 1.3 × 10-3, 1.2 × 10-3and 4.7 × 10-5,4.2 × 10-5respectively. Data showed that DEHP was a potential risk to human health.

Smart RNA Sequencing Reveals the Toxicological Effects of Diisobutyl Phthalate (DiBP) in Porcine Oocytes.

Diisobutyl phthalate (DiBP) is commonly used in the plastics industry, and recent studies have shown that environmental exposure and accumulation in the food chain caused inflammation in some organs. However, the underlying mechanisms by which DiBP affects oocyte quality have not yet been fully defined. We used immunostaining and fluorescence to evaluate the effects of DiBP exposure and demonstrated that it impaired the morphology of matured porcine oocytes through generation of cytoplasmic fragmentation, accompanied by the perturbed dynamics of the spindle and actin cytoskeleton, misdistributed endoplasmic reticulum, as well as partial exocytosis of cortical granules and ovastacin. Moreover, analysis of Smart RNA-seq found that DiBP-induced aberrant oocyte maturation could be induced by abnormal mitochondrial function and apoptosis. Importantly, we discovered that supplementation with pyrroloquinoline quinone (PQQ) significantly attenuated the meiotic abnormalities induced by DiBP exposure through the modulation of reactive oxygen species levels. Our findings demonstrated that DiBP exposure adversely affects oocyte meiotic maturation and that PQQ supplementation was an effective strategy to protect oocyte quality against DiBP exposure.

Microbicidal Polymer Nanoparticles Containing Clotrimazole for Treatment of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of Candida albicans was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. In vitro release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of C. albicans growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on C. albicans. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against C. albicans.

Mono-(2-ethylhexyl) phthalate induces trophoblast hypoxia and mitochondrial dysfunction through HIF-1α-miR-210-3p axis in HTR-8/SVneo cell line.

The exposure to the ubiquitous phthalate metabolite mono-(2-ethylhexyl) phthalate (MEHP) is connected to dysregulated trophoblast function and placenta health; however, the underlying mechanisms preluding this scenario remain to be elucidated. In this study, we explored the hypoxemic effects of MEHP on a human placental first-trimester trophoblast cell line (HTR-8/Svneo). MEHP-treated trophoblast cells displayed significantly increased levels of oxidative stress and hypoxia-inducible factor-1 alpha (HIF-1α) attributed by the induction of hypoxia. Further, HIF-1α exhibited higher DNA binding activity and upregulated gene expression of its downstream target vascular endothelial growth factor A (VEGFA). The hypoxia-induced microRNA miR-210-3p was also significantly increased upon MEHP treatment followed by disrupted mitochondrial ATP generation and membrane potential. This was identified to possibly be facilitated by lowered mitochondrial DNA copy number and inhibited expression of electron transport chain subunits, such as mitochondrial complex-IV. These results suggest potential adverse effects of MEHP exposure in a trophoblast cell line mediated by HIF-1α and the epigenetic modulator miR-210-3p. Chronic placental hypoxia and oxidative stress have long been implicated in the pathogenesis of pregnancy complications such as preeclampsia. As we've revealed genetic and epigenetic factors underscoring a potential mechanism induced by MEHP, this brings to light another significant implication of phthalate exposure on maternal and fetal health.

Quantification of additives in beached plastic debris from Aotearoa New Zealand.

Plastics have become an essential part of modern society. Their properties can be easily manipulated by incorporating additives to impart desirable attributes, such as colour, flexibility, or stability. However, many additives are classified as hazardous substances. To better understand the risk of plastic pollution within marine ecosystems, the type and concentration of additives in plastic debris needs to be established. We report the quantification of thirty-one common plastic additives (including plasticisers, antioxidants, and UV stabilisers) in beached plastic debris collected across Aotearoa New Zealand. Additives were isolated from the plastic debris by solvent extraction and quantified using high-resolution liquid chromatography-mass spectrometry. Twenty-five of the target additives were detected across 200 items of debris, with plasticisers detected at the highest frequency (99 % detection frequency). Additives were detected in all samples, with a median of four additives per debris item. A significantly higher number of additives were detected per debris item for polyvinyl chloride (median = 7) than polyethylene or polypropylene (median = 4). The additives bis(2-ethylhexyl) phthalate, diisononyl phthalate, diisodecyl phthalate, and antioxidant 702 were detected at the highest concentrations (up to 196,930 µg/g). The sum concentration of additives per debris item (up to 320,325 µg/g) was significantly higher in polyvinyl chloride plastics (median 94,716 µg/g) compared to other plastic types, primarily due to the presence of phthalate plasticisers. Non-target analysis was consistent with the targeted analysis, indicating a higher number and concentration of additives in polyvinyl chloride debris items compared to all other polymer types. Feature identification indicated the presence of more additives than previously detected in the targeted analysis, including plasticisers (phthalate and non-phthalate), processing aids, and nucleating agents. This study highlights phthalates and polyvinyl chloride as key targets for consideration in ecotoxicology and risk assessments, and the development of policies to reduce the impacts of plastic pollution.

Distribution of microplastics and phthalic acid esters during dry anaerobic digestion of food waste and potential microbial degradation analysis.

Food waste (FW) and its biogas residue were considered as sources of terrestrial microplastics (MPs) and phthalic acid esters (PAEs) contamination. However, there was a lack of research and understanding of the MPs and PAEs pollution problem in FW dry anaerobic digestion process (DADP). The MPs and PAEs in three stages of the DADP with the largest monomer disposal scale in China were identified. At the biogas residue extrusion stage, MPs abundance and PAEs concentration reached the highest values, which were 3.63 ± 0.45 × 103 N·kg-1 and 3.62 ± 0.72 mg·kg-1, respectively. Furthermore, there was a significant positive correlation between MPs and PAEs throughout the process (p < 0.05). Although bacteria and fungi with plastic degradation potential were present in all stages, the contamination problem of MPs and PAEs cannot be completely solved through DADP. This study provides a scientific basis for preventing and controlling the pollution of MPs and PAEs.

Elucidating the mechanisms and mitigation strategies for six-phthalate-induced toxicity in male germ cells.

Phthalate esters (PAEs) are primary plasticizers and endocrine-disrupting chemicals (EDCs) that are extensively used in numerous everyday consumer products. Although the adverse effects of single PAEs have been studied, our understanding of the effect of multiple phthalate exposure on male germ cell vitality remains limited. Therefore, this study aimed to investigate the collective effects of a mixture of PAEs (MP) comprising diethyl-, bis (2-ethylhexyl)-, dibutyl-, diisononyl-, diisobutyl-, and benzyl butyl-phthalates in the proportions of 35, 21, 15, 15, 8, and 5%, respectively, on differentiated male germ cells using GC-1 spermatogonia (spg) cells. As a mixture, MP substantially hindered GC-1 spg cell proliferation at 3.13 µg/mL, with a half-maximal inhibitory concentration of 16.9 µg/mL. Treatment with 25 µg/mL MP significantly induced reactive oxygen species generation and promoted apoptosis. Furthermore, MP activated autophagy and suppressed phosphorylation of phosphoinositide 3-kinase, protein kinase B, and mammalian target of rapamycin (mTOR). The triple inhibitor combination treatment comprising parthenolide, N-acetylcysteine, and 3-methyladenine effectively reversed MP-induced GC-1 spg cell proliferation inhibition, mitigated apoptosis and autophagy, and restored mTOR phosphorylation. This study is the first to elucidate the mechanism underlying MP-induced male germ cell toxicity and the restoration of male germ cell proliferation mediated by chemical inhibitors. Therefore, it provides valuable insights into the existing literature by proposing a combinatorial toxicity mitigation strategy to counteract male germ cell toxicity induced by various EDCs exposure.