Association of Di(2-ethylhexyl) Terephthalate and Its Metabolites with Nonalcoholic Fatty Liver Disease: An Epidemiology and Toxicology Study.

As an alternative plasticizer to conventional phthalates, di(2-ethylhexyl) terephthalate (DEHTP) has attracted considerable concerns, given its widespread detection in the environment and humans. However, the potential toxicity, especially liver toxicity, posed by DEHTP remains unclear. In this study, based on the 2017-2018 National Health and Nutrition Examination Survey, two metabolites of DEHTP, i.e., mono(2-ethyl-5-hydroxyhexyl) terephthalate (MEHHTP) and mono(2-ethyl-5-carboxypentyl) terephthalate (MECPTP), were found to be present in the urine samples of nearly all representative U.S. adults. Moreover, a positive linear correlation was observed between the concentrations of the two metabolites and the risk of nonalcoholic fatty liver disease (NAFLD) in the population. Results of weighted quantile sum and Bayesian kernel machine regression indicated that MEHHTP contributed a greater weight to the risk of NAFLD in comparison with 12 conventional phthalate metabolites. In vitro experiments with hepatocyte HepG2 revealed that MEHHTP exposure could increase lipogenic gene programs, thereby promoting a dose-dependent hepatic lipid accumulation. Activation of liver X receptor α may be an important regulator of MEHHTP-induced hepatic lipid disorders. These findings provide new insights into the liver lipid metabolism toxicity potential of DEHTP exposure in the population.

Effect of Oligomer Addition on Tube Dilation in Polymer Nanocomposite Melts.

This study investigates the effect of adding oligomers on the rheological properties of polymer nanocomposite melts with the goal of enhancing the processability of nanocomposites. The scaling analysis of plateau modulus (GN ) is used in understanding the complex mechanical behavior of entangled poly(methyl acrylate) (PMA) melts upon oligomer addition. Increasing the oligomer amount led to a decrease in GN and an apparent degree of entanglement (Z) in the neat polymer melt. The particle dispersion states at two particle loadings with oligomer addition are examined in transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS). The dilution exponent is found unchanged at 7 and 17 vol% particle loadings for the well-dispersed PMA-SiO2 nanocomposites compared to the neat PMA solution. These findings suggest that attractive particles with strong interfacial layers do not influence the tube dilution scaling of the polymer with the oligomer. To the contrary, composites with weak polymer-particle interfaces demonstrate phase separation of particles when oligomers are introduced and its exponent for tube dilution scaling reaches 4 at a particle loading of 17 vol%, potentially indicating that network-forming clusters influence chain entanglements in this scenario.

Biochemical responses and antioxidant defense mechanisms in Channa Striatus exposed to Bisphenol S.

Bisphenol S (BPS), a BPA analog and a safer alternative, is utilized in a diverse range of industrial applications, such as making polycarbonate plastics, epoxy resins, thermal receipt papers, and currency bills. Recently, the increased use of BPS in containers and packages for daily life has been interrogated due to its identical chemical structure and probable endocrine-disrupting actions as BPA has. The present study aimed to evaluate the alterations in biochemical indices and antioxidant enzymes as certain indicators of the endocrine-disrupting effect of BPS in Channa striatus, a freshwater fish. BPS-exposed fish species were subjected to three sub-lethal concentrations of BPS (1, 4, and 12 ppm) and observed after an interval of 7 and 21 days. Exposure to BPS caused a reduction in the level of protein in muscle, gonads and the liver due to an impairment of protein synthesis. Levels of cholesterol in the muscle, gonads, and liver of BPS-exposed fish were found to be decreased after treatment, indicating either an inhibition of cholesterol biosynthesis in the liver or reduced absorption of dietary cholesterol. The levels of antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase showed remarkable increases, while the activity of glutathione S-transferase decreased considerably, indicating the antioxidant defense mechanism to counteract the oxidative stress induced by BPS. Moreover, a significant increase was noted in the level of lipid peroxidation products, like malondialdehyde and conjugate diene, which represent biomarkers of oxidative stress. The histoarchitecture changes were also observed in the liver, muscle and gonads of BPS-treated fish species. The present study showed that sub-lethal exposure to BPS significantly influenced the activities of these enzymes and peroxidation byproducts. From this study, it is concluded that BPS-caused toxic effects in fish species lead to an imbalance in the antioxidant defense system. It is clearly indicated that BPS toxicity could lead to susceptible oxidative stress in various tissues and could damage vital organs.

Metabolomics in human SGBS cells as new approach method for studying adipogenic effects: Analysis of the effects of DINCH and MINCH on central carbon metabolism.

Growing evidence suggests that exposure to certain metabolism-disrupting chemicals (MDCs), such as the phthalate plasticizer DEHP, might promote obesity in humans, contributing to the spread of this global health problem. Due to the restriction on the use of phthalates, there has been a shift to safer declared substitutes, including the plasticizer diisononyl-cyclohexane-1,2-dicarboxylate (DINCH). Notwithstanding, recent studies suggest that the primary metabolite monoisononyl-cyclohexane-1,2-dicarboxylic acid ester (MINCH), induces differentiation of human adipocytes and affects enzyme levels of key metabolic pathways. Given the lack of methods for assessing metabolism-disrupting effects of chemicals on adipose tissue, we used metabolomics to analyze human SGSB cells exposed to DINCH or MINCH. Concentration analysis of DINCH and MINCH revealed that uptake of MINCH in preadipocytes was associated with increased lipid accumulation during adipogenesis. Although we also observed intracellular uptake for DINCH, the solubility of DINCH in cell culture medium was limited, hampering the analysis of possible effects in the µM concentration range. Metabolomics revealed that MINCH induces lipid accumulation similar to peroxisome proliferator-activated receptor gamma (PPARG)-agonist rosiglitazone through upregulation of the pyruvate cycle, which was recently identified as a key driver of de novo lipogenesis. Analysis of the metabolome in the presence of the PPARG-inhibitor GW9662 indicated that the effect of MINCH on metabolism was mediated at least partly by a PPARG-independent mechanism. However, all effects of MINCH were only observed at high concentrations of 10 µM, which are three orders of magnitudes higher than the current concentrations of plasticizers in human serum. Overall, the assessment of the effects of DINCH and MINCH on SGBS cells by metabolomics revealed no adipogenic potential at physiologically relevant concentrations. This finding aligns with previous in vivo studies and supports the potential of our method as a New Approach Method (NAM) for the assessment of adipogenic effects of environmental chemicals.

Silicone wristbands reveal ubiquitous human exposure to ortho-phthalates and non-ortho-phthalate plasticizers in Southern California.

In the United States and abroad, ortho-phthalates and non-ortho-phthalate plasticizers continue to be used within a diverse array of consumer products. Prior California-specific biomonitoring programs for ortho-phthalates have focused on rural, agricultural communities and, to our knowledge, these programs have not measured the potential for exposure to non-ortho-phthalate plasticizers. Therefore, the potential for human exposure to ortho-phthalates and non-ortho-phthalate plasticizers have not been adequately addressed in regions of California that have higher population density. Since there are numerous sources of ortho-phthalates and non-ortho-phthalate plasticizers in population-dense, urban regions, the objective of this study was to leverage silicone wristbands to quantify aggregate ortho-phthalate and non-ortho-phthalate plasticizer exposure over a 5-day period across two different cohorts (2019 and 2020) of undergraduate students at the University of California, Riverside (UCR) that commute from all over Southern California. Based on 5 d of aggregate exposure across two different cohorts, total ortho-phthalate plus non-ortho-phthalate plasticizer concentrations ranged, on average, from ∼100,000-1,000,000 ng/g. Based on the distribution of individual ortho-phthalate and non-ortho-phthalate plasticizer concentrations, the concentrations of di-isononyl phthalate (DiNP, a high molecular weight ortho-phthalate), di (2-ethylhexyl) phthalate (DEHP, a high molecular weight ortho-phthalate), and di-2-ethylhexyl terephthalate (DEHT, a non-ortho-phthalate plasticizer) detected within wristbands were higher than the remaining seven ortho-phthalates and non-ortho-phthalate plasticizers measured, accounting for approximately 94-97% of the total mass depending on the cohort. Overall, our findings raise concerns about chronic DiNP, DEHP, and DEHT exposure in urban, population-dense regions throughout California.

A novel and efficient strategy for the biodegradation of di(2-ethylhexyl) phthalate by Fusarium culmorum.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is used worldwide and raises concerns because of its prevalence in the environment and potential toxicity. Herein, the capability of Fusarium culmorum to degrade a high concentration (3 g/L) of DEHP as the sole carbon and energy source in solid-state fermentation (SSF) was studied. Cultures grown on glucose were used as controls. The biodegradation of DEHP by F. culmorum reached 96.9% within 312 h. This fungus produced a 3-fold higher esterase activity in DEHP-supplemented cultures than in control cultures (1288.9 and 443.2 U/L, respectively). In DEHP-supplemented cultures, nine bands with esterase activity (24.6, 31.2, 34.2, 39.5, 42.8, 62.1, 74.5, 134.5, and 214.5 kDa) were observed by zymography, which were different from those in control cultures and from those previously reported for cultures grown in submerged fermentation. This is the first study to report the DEHP biodegradation pathway by a microorganism grown in SSF. The study findings uncovered a novel biodegradation strategy by which high concentrations of DEHP could be biodegraded using two alternative pathways simultaneously. F. culmorum has an outstanding capability to efficiently degrade DEHP by inducing esterase production, representing an ecologically promising alternative for the development of environmental biotechnologies, which might help mitigate the negative impacts of environmental contamination by this phthalate. KEY POINTS: • F. culmorum has potential to tolerate and remove di(2-ethylhexyl) phthalate (DEHP) • Solid-state fermentation is an efficient system for DEHP degradation by F. culmorum • High concentrations of DEHP induce high levels of esterase production by F. culmorum.

Two-year carcinogenicity study of a novel plasticizer, bis(2-ethylhexyl) cyclohexane-1,4-dicarboxylate (Eco-DEHCH), by oral diet in Han Wistar rats.

Plasticizers are necessary for the usability of various products, including food contact materials. Exposure to plasticizers is most commonly made through the oral route. Several plasticizers have been reported to have adverse effects on humans and the environment. Thus, the present study aimed to determine the long-term toxicity and carcinogenicity of a novel plasticizer called bis(2-ethylhexyl) cyclohexane-1,4-dicarboxylate (Eco-DEHCH), which is an ecofriendly and biologically less harmful replacer. Groups of 50 male and 50 female Han Wistar rats were fed Eco-DEHCH at daily doses of 1,600, 5,000, or 16,000 ppm in their diet for at least 104 weeks. The rats were regularly monitored for mortality, clinical signs, body weight, food consumption, food efficiency, and perceivable mass. All animals were subjected to complete necropsy and histopathological examination. The results indicate that the rats well tolerated chronic exposure to Eco-DEHCH at highest daily doses of 16,000 ppm, with was equivalent to 805.1 mg/kg/day in males and 1060.6 mg/kg/day in females and did not show signs of toxicity or carcinogenicity. In conclusion, Eco-DEHCH could be a safe and promising alternative plasticizer.

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.

Ionic Liquids as Designed, Multi-Functional Plasticizers for Biodegradable Polymeric Materials: A Mini-Review.

Measures to endorse the adoption of eco-friendly biodegradable plastics as a response to the scale of plastic pollution has created a demand for innovative products from materials from Nature. Ionic liquids (ILs) have the ability to disrupt the hydrogen bonding network of biopolymers, increase the mobility of biopolymer chains, reduce friction, and produce materials with various morphologies and mechanical properties. Due to these qualities, ILs are considered ideal for plasticizing biopolymers, enabling them to meet a wide range of specifications for biopolymeric materials. This mini-review discusses the effect of different IL-plasticizers on the processing, tensile strength, and elasticity of materials made from various biopolymers (e.g., starch, chitosan, alginate, cellulose), and specifically covers IL-plasticized packaging materials and materials for biomedical and electrochemical applications. Furthermore, challenges (cost, scale, and eco-friendliness) and future research directions in IL-based plasticizers for biopolymers are discussed.

Optimizing the Ion Conductivity and Mechanical Stability of Polymer Electrolyte Membranes Designed for Use in Lithium Ion Batteries: Combining Imidazolium-Containing Poly(ionic liquids) and Poly(propylene carbonate).

State-of-the-art Li batteries suffer from serious safety hazards caused by the reactivity of lithium and the flammable nature of liquid electrolytes. This work develops highly efficient solid-state electrolytes consisting of imidazolium-containing polyionic liquids (PILs) and lithium bis(trifluoromethane sulfonyl)imide (LiTFSI). By employing PIL/LiTFSI electrolyte membranes blended with poly(propylene carbonate) (PPC), we addressed the problem of combining ionic conductivity and mechanical properties in one material. It was found that PPC acts as a mechanically reinforcing component that does not reduce but even enhances the ionic conductivity. While pure PILs are liquids, the tricomponent PPC/PIL/LiTFSI blends are rubber-like materials with a Young's modulus in the range of 100 MPa. The high mechanical strength of the material enables fabrication of mechanically robust free-standing membranes. The tricomponent PPC/PIL/LiTFSI membranes have an ionic conductivity of 10-6 S·cm-1 at room temperature, exhibiting conductivity that is two orders of magnitude greater than bicomponent PPC/LiTFSI membranes. At 60 °C, the conductivity of PPC/PIL/LiTFSI membranes increases to 10-5 S·cm-1 and further increases to 10-3 S·cm-1 in the presence of plasticizers. Cyclic voltammetry measurements reveal good electrochemical stability of the tricomponent PIL/PPC/LiTFSI membrane that potentially ranges from 0 to 4.5 V vs. Li/Li+. The mechanically reinforced membranes developed in this work are promising electrolytes for potential applications in solid-state batteries.

Biodegradable Hydrogenated Dimer Acid-Based Plasticizers for PLA with Excellent Plasticization, Thermal Stability and Gas Resistance.

The use of vegetable oil-dervied plasticizers to enhance the flexibility of polylactic acid (PLA) has received much attention due to their renewability, inexpensiveness and biodegradation. However, the double bonds in vegetable oil-based plasticizers limit their compatibility with PLA, resulting in PLA-derived products with reduced flexibility. Herein, we examined soybean oil-derived hydrogenated dimer acid-based polyethylene glycol methyl ether esters (HDA-2n, 2n = 2, 4, 6 or 8, referring to the ethoxy units) developed via the direct esterification of saturated hydrogenated dimer acid and polyethylene glycol monomethyl ethers. The resulting HDA-2n was first used as a plasticizer for PLA, and the effects of the ethoxy units in HDA-2n on the overall performance of the plasticized PLA were systematically investigated. The results showed that, compared with PLA blended with dioctyl terephthalate (DOTP), the PLA plasticized by HDA-8 with the maximum number of ethoxy units (PLA/HDA-8) exhibited better low-temperature resistance (40.1 °C vs. 15.3 °C), thermal stability (246.8 °C vs. 327.6 °C) and gas barrier properties. Additionally, the biodegradation results showed that HDA-8 could be biodegraded by directly burying it in soil. All results suggest that HDA-8 could be used as green alternative to the traditional petroleum-based plasticizer DOTP, which is applied in the PLA industry.

[Rapid determination of polycyclic aromatic hydrocarbons and phthalates in tap water by SBSE combined with GC-MS].

OBJECTIVE: To develop a method which is used for rapid determination of 16 kinds of polycyclic aromatic hydrocarbons(PAHs) and 16 kinds of phthalates(PAEs) in tap water by stirring rod adsorption extraction(SBSE) combined with gas chromatography-mass spectrometry(GC-MS). METHODS: The twister mixing rod coated with polydimethylsiloxane(PDMS) and ethylene glycol-polydimethylsiloxane(EG-silicone) was used to enrich analyte from 50 mL tap water. The twister mixing rod coated with EG-silicone was directly placed into the sample bottle containing 50 mL of tap water, while fixing the PDMS stir bar on the inner wall of the sample bottle and immersing it in the liquid. Add 5%(W/V) sodium chloride to the sample bottle, followed by adding 5% methanol. Stir at room temperature for 2 hours for extraction. Next, remove the mixing stick and dry its surface. The pre-prepared SBSE was analyzed by TD-GC/MS, with the optimized thermal desorption conditions: desorption temperature 275 ℃, desorption time 15 min, cryofocusing temperature-40 ℃. RESULTS: Regression equations revealed acceptable linearity(correlation coefficients >0.986) across the working-standard range from 200-2000 ng/L for the 32 analytes. The limits of detection(LODs)were further evaluated were from 1.13-121 ng/L. With the optimized pretreatment method, the spiked recoveries of tap samples(200 and 2000 ng/L)were in the range of 62.5%-98.4% with the relative standard deviations(RSDs) of 3.5%-25.3%. CONCLUSION: The established method can realize the rapid detection of high throughput in the laboratory, it is simple, convenient to operate, and the extraction and analysis time is short.

Natural resin as a biosource and bio-based plasticizer for edible resin/ethylcellulose composite film preparation.

Nowadays, finding natural and inexpensive resources that can be easily used to make food films has been considered. Despite the widespread use of synthetic resins, natural resins are rarely used. Opopanax resin (OR) was used in this study as a new biosource to prepare the hydrophobic edible film. Ethylcellulose (EC) was blended well with the resin, allowing the formation of a composite film. Film preparation was possible using different amounts of OR and EC. It was interesting that OR had a plasticizing effect on EC film. While using up to 33% w/w glycerol could not produce an elastic EC film, using only 8.5% w/w OR produced a stiff and flexible EC film with lower water sensitivity. Fourier transform infrared (FTIR) spectroscopy analysis showed that the strength of C-O-C and CH bonds in OR + EC film was higher than in EC film. Despite the higher water sensitivity of OR-based composite films than EC-based composite films, they had lower water vapor permeability (WVP) and higher contact angle due to their smoother and more homogeneous film structures with lower porosity, confirmed by scanning electron microscopy (SEM) images. The mechanical properties showed that the film with the highest resin content had the lowest tensile strength (~ 0.4 MPa) and the higher elongation at break (~ 67%) and, therefore, the highest flexibility. The use of natural resins as a biosource is a promising approach in food packaging to prepare hydrophobic films with desirable mechanical properties.

Plant betalains-mixed active/intelligent films for meat freshness monitoring: A review of the fabrication parameters.

The plant pigments called betalains are nutritionally safe polar compounds. They are subdivided into betaxanthins (having orange to yellow hues) and betacyanins (purple to red violet hues). Betacyanins change color with a change in pH, particularly in the range 6-8 and 9-11. Perishable foods like fish, chicken, beef, pork, and others tend to release total volatile base-nitrogen (TVB-N) during storage or deterioration, which leads to a change in the pH of pH-sensitive materials in the vicinity. pH-sensitive pigment-incorporated polymeric films with inherent active properties (or active/intelligent films) are increasingly being studied as an alternative to synthetic pH indicators to detect the accumulation of TVB-N by changing its color to indicate the stage of perishable food spoilage. There are many methods of developing such films under different conditions using different bio-based biodegradable polymer(s) and biocompatible plasticizer combinations. Among the reported methods, solution casting method has been the preferred one in most studies covered in this review. This method can be carried out under mild conditions. As such, betacyanins-incorporated polymeric films essentially require mild processing conditions because of their heat sensitivity, which will invariably affect the performance in food freshness monitoring. In this review, film fabrication parameters like temperature and duration of dissolution of polymers, plasticizer concentration, pH of the film-forming solution, film drying, and conditioning/aging, have been critically appraised based on the available literature. The lack of studies on the safety of active/intelligent films has been systematically highlighted in this review to focus future studies on this area.

Low doses of acetyl trihexyl citrate plasticizer promote adipogenesis in hepatocytes and mice.

Accumulating epidemiological evidence underscores the association between pervasive environmental factors and an increased risk of metabolic diseases. Environmental chemicals, recognized disruptors of endocrine and metabolic processes, may contribute to the global prevalence of metabolic disorders, including obesity. Acetyl tributyl citrate (ATHC), categorized as a citric acid ester plasticizer, serves as a substitute for di-(2-ethylhexyl) phthalate (DEHP) in various everyday products. Despite its widespread use and the increasing risk of exposure in humans and animals due to its high leakage rates, information regarding the safety of exposure to environmentally relevant doses of ATHC remains limited. This study aimed to investigate the potential impact of ATHC exposure on metabolic homeostasis. Both in vivo and in vitro exposure models were used to characterize the effects induced by ATHC exposure. C57BL/6 J male mice were subjected to a diet containing ATHC for 12 weeks, and metabolism-related parameters were monitored and analyzed throughout and after the exposure period. Results indicated that sub-chronic dietary exposure to ATHC induced an increase in body fat percentage, elevated serum lipid levels, and increased lipid content in the liver tissue of mice. Furthermore, the effect of ATHC exposure on murine hepatocytes were examined and results indicated that ATHC significantly augmented lipid levels in AML12 hepatocytes, disrupting energy homeostasis and altering the expression of genes associated with fatty acid synthesis, uptake, oxidation, and secretion pathways. Conclusively, both in vivo and in vitro results suggest that exposure to low levels of ATHC may be linked to an elevated risk of obesity and fatty liver in mice. The potential implications of ATHC on human health warrant comprehensive evaluation in future studies.

Diethyl phthalate and dibutyl phthalate disrupt sirtuins expression in the HepG2 cells.

Background: Phthalates are additives used as plasticizers among other uses, classified as endocrine disruptors and may contribute to some metabolic disorders. The aim of this work was to determine the effect of the exposure of diethyl phthalate (DEP) and dibutyl phthalate (DBP) on cell viability and reactive oxygen species (ROS) production, as well as the regulation of sirloins in HepG2 cells. Methods: HepG2 cells were exposed to DEP or DBP at 0.1, 1, 10 and 100 µg/mL, and after 48 or 72 h the gene and protein expression of sirtuins was quantified by qRT-PCR and Western-Blot, respectively. Results: Results showed that even at a low concentration of 0.1 µg/mL DEP affected the expression of Sirt3 and Sirt4, whereas DBP at 0.1 µg/mL affected Sirt3 and Sirt5 gene expression. Protein analysis showed a reduction in Sirt1 levels at a DEP concentration of 1 µg/mL and higher, while DBP at higher dose (100 µg/mL) decreased Sirt3 protein levels. Cell viability decreased by 20% only at higher dose (100 µg/mL) and ROS production increased at 10 and 100 µg/mL for both phthalates. Conclusion: These findings indicate that exposure to low concentrations (0.1 µg/mL) of DEP or DBP can negatively influence the expression of some sirtuins.

Plasticization mechanism of biobased plasticizers comprising polyethylene glycol diglycidyl ether-butyl citrate with both long and short chains on poly(lactic acid).

Polylactic acid (PLA), a biodegradable polymer with low flexibility, is commonly plasticized with small molecules like tributyl citrate (TBC) for film production. However, these plasticizers, which lack chemical bonds or strong intermolecular interactions with the matrix, tend to migrate to the film surface over time. Their inclusion often compromises material strength for flexibility, increasing elongation at break but reducing tensile strength. In this research, by combining citric acid with n-butanol (B) and poly(ethylene glycol) diglycidyl ether (E), we synthesized three plasticizers, namely TE3, TE2B1, and TE1B2, to enhance the flexibility of PLA. TE2B1 and TE1B2 are equipped with butyl ester groups that offer effective plasticizing effects. Additionally, the incorporation of long-chain alkyl featuring epoxy groups can boost the interaction with PLA. The results showed that the epoxy groups of the long-chain alkyl plasticizers can improve the elongation at break without compromising tensile strength significantly. The migration of plasticizer from PLA matrix can be reduced by strong interactions like chemical bonds, entanglements, and hydrogen bonding with PLA. TE1B2 demonstrated the best plasticizing effect. Adding 15 portions of TE1B2 and TBC separately increased PLA's elongation at break to 304 % and 242 %, with tensile strengths of 36.1 MPa and 22.3 MPa, respectively.

Plasticizer-gelatin mixed solutions as skin protection materials with flexible-film-forming capability.

To demonstrate the feasibility of plasticizer-gelatin solutions as novel skin protection materials from a physical aspect, we evaluated the rheological properties of the solutions and the mechanical properties and textures of their dried sheets and films. Three types of sugars and polyols were employed as organic plasticizers and mixed with gelatin in solutions at plasticizer/gelatin weight ratios of 0.13-1.67. The plasticizers minimally affected the viscosities and gelation temperatures of the gelatin solutions, but they remarkably softened dried gelatin sheets, except for propylene glycol. Glycerol exhibited the best plasticizing effects, but the sheets obtained using glycerol showed tacky textures. Preliminary investigations on the film-forming properties of the solutions on the human skin showed that the fructose-gelatin solution at a weight ratio of 1.0 formed a flexible thin film with a texture and mechanical properties similar to those of a commercially available polyurethane-based flexible film dressing. In terms of physical properties, we conclude that the fructose-gelatin solution has potential as a skin protection material that transforms from a solution to a film on the skin.

Phthalate and gallstones: the mediation of insulin.

Background: Exposure to a mixture of environmental chemicals may cause gallstone, but the evidence remains equivocal. The current study aims to investigate the association between phthalate metabolites and gallstones, and to explore their mediators. Methods: Data from the National Health and Nutrition Examination Survey 2017-2018 on U.S. adults (≥20 years) were analyzed to explore the association between phthalate metabolites and gallstones by employed survey-weighted logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses examined the role of oxidative stress markers, inflammatory markers, metabolic syndrome, body composition, diabetes, and insulin. Results: The current study included 1,384 participants, representing 200.6 million U.S. adults. Our results indicated a significant association between phthalate metabolites, particularly high molecular weight metabolites such as Di(2-ethylhexyl) phthalate (DEHP) and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), and gallstones. Furthermore, mediation analyses indicated that phthalate metabolites may play a role in the development of gallstones by influencing insulin secretion. Subgroup analyses did not reveal significant interaction. Conclusion: The association between exposure to phthalates and the occurrence of gallstones, potentially mediated by hyperinsulinemia from a nationally representative epidemiological perspective. These insights contribute to a better understanding of the potential health implications of plasticizers, emphasizing the need for proactive management measures.

Enhanced biodegradation of microplastic and phthalic acid ester plasticizer: The role of gut microorganisms in black soldier fly larvae.

Hermetia illucens larvae are recognized for their ability to mitigate or eliminate contaminants by biodegradation. However, the biodegradation characteristics of microplastics and phthalic acid esters plasticizers, as well as the role of larval gut microorganisms, have remained largely unrevealed. Here, the degradation kinetics of plasticizers, and biodegradation characteristics of microplastics were examined. The role of larval gut microorganisms was investigated. For larval development, microplastics slowed larval growth significantly (P < 0.01), but the effect of plasticizer was not significant. The degradation kinetics of plasticizers were enhanced, resulting in an 8.11 to 20.41-fold decrease in degradation half-life and a 3.34 to 3.82-fold increase in final degradation efficiencies, compared to degradation without larval participation. The depolymerization and biodeterioration of microplastics were conspicuously evident, primarily through a weight loss of 17.63 %-25.52 %, variation of chemical composition and structure, bio-oxidation and bioerosion of microplastic surface. The synergistic effect driven by larval gut microorganisms, each with various functions, facilitated the biodegradation. Specifically, Ignatzschineria, Paenalcaligenes, Moheibacter, Morganella, Dysgonomonas, Stenotrophomonas, Bacteroides, Sphingobacterium, etc., appeared to be the key contributors, owing to their xenobiotic biodegradation and metabolism functions. These findings offered a new perspective on the potential for microplastics and plasticizers biodegradation, assisted by larval gut microbiota.