Human dietary exposure to bisphenol-diglycidyl ethers in China: Comprehensive assessment through a total diet study.

Despite the widespread use of bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE) in various consumer products as protective plasticizer, studies on human dietary exposure to these compounds are scare. In this study, nine bisphenol diglycidyl ethers (BDGEs) including BADGE, BFDGE, and seven of their derivatives were determined in the Chinese adult population based on composite dietary samples collected from the sixth (2016-2019) China total diet study (TDS). Contamination level of nine BDGEs was determined in 288 composite dietary samples from 24 provinces in China. BADGE·2H2O and BADGE are the most frequently detected and BADGE·2H2O presented the highest mean concentration (2.402 µg/kg). The most contaminated food composite is meats, with a mean ∑9BDGEs of 8.203 µg/kg, followed by aquatic products (4.255 µg/kg), eggs (4.045 µg/kg), and dairy products (3.256 µg/kg). The estimated daily intake (EDI) of ∑9BDGEs based on the mean and 95th percentile concentrations are 121.27 ng/kg bw/day and 249.71 ng/kg bw/day. Meats, eggs, and aquatic products are the main source of dietary exposure. Notably, beverages and water, alcohols were the main contributors of dietary exposure to BADGE and BADGE·2H2O, followed by animal-derived foods. Dietary exposure assessment demonstrated that human dietary BDGEs do not pose risks to general population based on the mean and 95th percentile hazard index with < 1. This is the first comprehensive national dietary exposure assessment of BDGEs in Chinese general population.

Safety assessment of a newly synthesized copolymer for micellar delivery of hydrophobic caffeic acid phenethyl ester.

Caffeic acid phenethyl ester (CAPE), a major pharmacologically active component of poplar type propolis, is known for its proapoptotic, anti-inflammatory, antioxidant, antiviral, and enzyme inhibiting activities. The aim of this study was to perform an in vitro and in vivo safety assessment of a micellar system based on a newly synthesized copolymer, consisting of polyglycidol and poly(allyl glycidyl ether) (C12-PAGE-PG) as a drug delivery platform for CAPE. The in vitro studies on HepG2 and L929 cells by MTT and LDH assays after treatment with the empty and CAPE-loaded micelles showed no cytotoxic effects of the empty micelles and retained cytotoxic activity of CAPE loaded in the micelles. No hemolysis or stimulation of mouse lymphocytes or macrophages was observed in vitro. In vivo hematological, biochemical, and histological assays on rats, treated with the empty (2580 and 5160 µg/kg) or CAPE-loaded (375 and 750 µg CAPE/kg) micelles did not reveal pathological changes of any of the parameters assayed after 14-days' treatment. In conclusion, initial toxicological data characterize C12-PAGE-PG as a non-toxic and promising copolymer for development of micellar drug delivery systems, particularly for a hydrophobic active substance as CAPE.

Stereoselective total synthesis of Patulolide C.

Stereoselective total synthesis of Patulolide C has been accomplished from easily available and inexpensive (S)-chiral epoxide. The key steps involved in the concise synthesis of Patulolide C utilizes ring opening of chiral epoxide, cleavage of 1,2-diol, deprotection of benzyl ether of hydroxyl acid and Yamaguchi macrolactonisation dilution conditions as key steps. The advantage of this method include inexpensive starting material, mild reaction conditions and high purity of products.

Identification of the fungicide epoxiconazole by virtual screening and biological assessment as inhibitor of human 11ß-hydroxylase and aldosterone synthase.

Humans are constantly exposed to a multitude of environmental chemicals that may disturb endocrine functions. It is crucial to identify such chemicals and uncover their mode-of-action to avoid adverse health effects. 11ß-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) catalyze the formation of cortisol and aldosterone, respectively, in the adrenal cortex. Disruption of their synthesis by exogenous chemicals can contribute to cardio-metabolic diseases, chronic kidney disease, osteoporosis, and immune-related disorders. This study applied in silico screening and in vitro evaluation for the discovery of xenobiotics inhibiting CYP11B1 and CYP11B2. Several databases comprising environmentally relevant pollutants, chemicals in body care products, food additives and drugs were virtually screened using CYP11B1 and CYP11B2 pharmacophore models. A first round of biological testing used hamster cells overexpressing human CYP11B1 or CYP11B2 to analyze 25 selected virtual hits. Three compounds inhibited CYP11B1 and CYP11B2 with IC50 values below 3 µM. The most potent inhibitor was epoxiconazole (IC50 value of 623 nM for CYP11B1 and 113 nM for CYP11B2, respectively); flurprimidol and ancymidol were moderate inhibitors. In a second round, these three compounds were tested in human adrenal H295R cells endogenously expressing CYP11B1 and CYP11B2, confirming the potent inhibition by epoxiconazole and the more moderate effects by flurprimidol and ancymidol. Thus, the in silico screening, prioritization of chemicals for initial biological tests and use of H295R cells to provide initial mechanistic information is a promising strategy to identify potential endocrine disruptors inhibiting corticosteroid synthesis. A critical assessment of human exposure levels and in vivo evaluation of potential corticosteroid disrupting effects by epoxiconazole is required.

Cationic starch: Safe and economic harvesting flocculant for microalgal biomass and inhibiting E. coli growth.

Cationized starch-based flocculation processes are the subject of increasing attention because of their non-toxicity, biodegradability and relatively low price synthesized. The study aimed to evaluate the flocculability of different cationic starches using different concentrations of glycidyltrimethylammonium chloride (GTAC) with different degree of substitution (DS) ranged from 0.13 to 0.57. Cationized starch were characterized using Fourier Transform Infrared (FTIR), scanning electron microscopy (SEM) and toxicity checked using experimental animal procedure. They were used in comparison with aluminum sulphate for harvesting microalgal biomass collected from high rate algal pond (HRAP) at Zenin wastewater treatment plant (WWTP), Giza, Egypt. Jar test showed that gradual increase of aluminum sulphate doses (50-400 mg/L) has reduced algal suspension consequently turbidity with accompanied pH decrease from 8.6 to 6.6. Cationic starch with low DS has shown efficiency as flocculants by reducing turbidity of algal suspension from 110 to ≈2 NTU by gradual increase from 10 to 60 mg/L without change in pH value. Fecal coliforms and E. coli were inhibited from 9.6 × 102 and 8.4 × 10 CFU/ml to non-detectable count. Cationic starch with high DS (0.57) has the least effect of algae harvesting and turbidity reduction that 40 NTU after increase the dose to 60 mg/L. Results showed that 10 mg of cationic starch (DS = 0.13) has achieved the same flocculation efficiency of 100 mg of aluminum sulphate. In conclusion, further investigation is required to increase the degree of substitution of cationic starch, consequently the flocculation efficiency might be improved.

Synthesis of Five and Six-Membered Heterocycles Using Activated Nitriles for Industrial Applications.

The aim of this study is a synthesis of new bioactive heterocyclic compounds incorporated fatty chain for use in different industrial applications. Cyanoacetamide derivative (2) was successfully transferred into five and six membered heterocyclic derivatives by the reaction with various chemical reagents. Addition number of moles of propylene oxide to these compounds gave nonionic surface-active agents having a good solubility, biodegradability and hence lowers the toxicity to human beings and becomes environmentally friendly. The antimicrobial and surface activities were investigated that showed the most of them have pronounced activity, which makes them suitable for diverse applications like the manufacturing of drugs, pesticides, emulsifiers, cosmetics, etc.

Thermoseparating aqueous two-phase systems: Recent trends and mechanisms.

Having the benefits of being environmentally friendly, providing a mild environment for bioseparation, and scalability, aqueous two-phase systems (ATPSs) have increasingly caught the attention of industry and researchers for their application in the isolation and recovery of bioproducts. The limitations of conventional ATPSs give rise to the development of temperature-induced ATPSs that have distinctive thermoseparating properties and easy recyclability. This review starts with a brief introduction to thermoseparating ATPSs, including its history, unique characteristics and advantages, and lastly, key factors that influence partitioning. The underlying mechanism of temperature-induced ATPSs is covered together with a summary of recent applications. Thermoseparating ATPSs have been proven as a solution to the demand for economically favorable and environmentally friendly industrial-scale bioextraction and purification techniques.

Stereoselective synthesis of epoxyisoprostanes: an organocatalytic and "pot-economy" approach.

An efficient and direct synthetic route to epoxyisoprostane EC methyl ester has been accomplished in 8 steps (10% overall yield) from readily available starting materials using a series of asymmetric organocatalytic reactions and one-pot operations.

Release of bisphenols from can coatings into canned beer in China market.

BACKGROUND: The aim of this research was to understand the migration of bisphenols from can coatings into foods in the Chinese market. RESULTS: The migration of bisphenols was studied in commercial cans from the Chinese market filled with four types of food simulant (FS), which were heated at 121 °C for 30 min and stored at 40 °C for 30 days. Only bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE) were found in the can coatings, and SimC (10% (v/v) ethanol/water) was the most suitable FS for their release. The levels of these bisphenols in 24 kinds of canned beer from Chinese markets were also investigated. The average concentrations of BPA and BADGE were 2.85 ± 0.79 and 0.38 ± 0.19 µg · L⁻¹ respectively, which were both lower than the EU limits, and their respective daily intakes were estimated at 0.015 and 0.0020 µg · kg⁻¹ body weight · day⁻¹. Besides, increasing storage temperature and time accelerated the release of bisphenols into FSs. CONCLUSION: The present results provide some guidance to reduce the migration of bisphenols during the transport and storage of canned foods.

Total synthesis of 6-deoxypladienolide D and Assessment of Splicing Inhibitory Activity in a Mutant SF3B1 cancer cell line.

A total synthesis of the natural product 6-deoxypladienolide D (1) has been achieved. Two noteworthy attributes of the synthesis are (1) a late-stage allylic oxidation which proceeds with full chemo-, regio-, and diastereoselectivity and (2) the development of a scalable and cost-effective synthetic route to support drug discovery efforts. 6-Deoxypladienolide D (1) demonstrates potent growth inhibition in a mutant SF3B1 cancer cell line, high binding affinity to the SF3b complex, and inhibition of pre-mRNA splicing.

Prevalence of visual impairment in El Salvador: inequalities in educational level and occupational status / Prevalencia de deficiencia visual en El Salvador: desigualdades según el nivel educativo y la situación laboral

OBJECTIVE: To examine the prevalence of blindness, visual impairment, and related eye diseases and conditions among adults in El Salvador, and to explore socioeconomic inequalities in their prevalence by education level and occupational status, stratified by sex. METHODS: Based upon the Rapid Assessment of Avoidable Blindness (RAAB) methodology, this nationwide sample comprised 3 800 participants (3 399 examined) ≥ 50 years old from 76 randomly selected clusters of 50 persons each. The prevalence of blindness, visual impairment and related eye diseases and conditions, including uncorrected refractive error (URE), was calculated for categories of education level and occupational status. Multiple logistic regression models were fitted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and stratified by sex. RESULTS: Age-adjusted prevalence was 2.4% (95% CI: 2.2-2.6) for blindness (men: 2.8% (95% CI: 2.5-3.1); women: 2.2% (95% CI: 1.9-2.5)) and 11.8% (95% CI: 11.6-12.0) for moderate visual impairment (men: 10.8% (95% CI: 10.5-11.1); women: 12.6% (95% CI: 12.4-12.8)). The proportion of visual impairment due to cataract was 43.8% in men and 33.5% in women. Inverse gradients of socioeconomic inequalities were observed in the prevalence of visual impairment. For example, the age-adjusted OR (AOR) was 3.4 (95% CI: 2.0-6.4) for visual impairment and 4.3 (95% CI: 2.1-10.4) for related URE in illiterate women compared to those with secondary education, and 1.9 (95% CI: 1.1-3.1) in cataract in unemployed men. CONCLUSIONS: Blindness and visual impairment prevalence is high in the El Salvador adult population. The main associated conditions are cataract and URE, two treatable conditions. As socioeconomic and gender inequalities in ocular health may herald discrimination and important barriers to accessing affordable, good-quality, and timely health care services, prioritization of public eye health care and disability policies should be put in place, particularly among women, the unemployed, and uneducated people.

OBJETIVO: Analizar la prevalencia de la ceguera, la deficiencia visual, y las enfermedades y afecciones oculares relacionadas en adultos de El Salvador, y explorar las desigualdades socioeconómicas en cuanto a su prevalencia según el nivel educativo y la situación laboral, estratificados por sexos. MÉTODOS: Se adoptó el método de Evaluación Rápida de la Ceguera Evitable, y se escogió una muestra a escala nacional de 3 800 participantes (de ellos se examinaron 3 399) de 50 años de edad o mayores, pertenecientes a 76 agrupamientos seleccionados aleatoriamente y constituidos por 50 personas cada uno. Se calculó la prevalencia de la ceguera, la deficiencia visual y las enfermedades y afecciones oculares relacionadas, incluido el error de refracción no corregido, según las diferentes categorías de nivel educativo y situación laboral. Se emplearon modelos de regresión logística múltiple para calcular las razones de posibilidades (OR) y los intervalos de confianza (IC) de 95%, y se estratificaron por sexos. RESULTADOS: La prevalencia ajustada por edad fue de 2,4% (IC de 95%: 2,2-2,6) para la ceguera (hombres: 2,8% [IC de 95%: 2,5-3,1]; mujeres: 2,2% [IC de 95%: 1,9-2,5]) y de 11,8% (IC de 95%: 11,6-12,0) para la deficiencia visual moderada (hombres: 10,8% [IC de 95%: 10,5-11,1]; mujeres: 12,6% [IC de 95%: 12,4-12,8]). La proporción de deficiencias visuales debidas a catarata fue de 43,8% en los hombres y de 33,5% en las mujeres. En la prevalencia de la deficiencia visual se observaron gradientes inversos de desigualdades socioeconómicas. Por ejemplo, la OR ajustada por edad fue de 3,4 (IC de 95%: 2,0-6,4) para la deficiencia visual y de 4,3 (IC de 95%: 2,1-10,4) para el error de refracción no corregido relacionado en las mujeres analfabetas, en comparación con las que tenían un nivel de educación secundaria, y fue de 1,9 (IC de 95%: 1,1-3,1) para la catarata en los hombres desempleados. CONCLUSIONES: La prevalencia de ceguera y deficiencia visual es alta en la población adulta de El Salvador. Las principales afecciones asociadas son la catarata y el error de refracción no corregido, ambas tratables. Puesto que las desigualdades socioeconómicas y de género en materia de salud ocular pueden ser indicativas de discriminación y de la existencia de barreras importantes para obtener acceso a servicios de atención de salud asequibles, de buena calidad y oportunos, es preciso dar prioridad a la atención oftalmológica pública y a las políticas dirigidas a corregir la discapacidad, en particular en las mujeres y en las personas desempleadas y sin formación.

Synthesis with perfect atom economy: generation of furan derivatives by 1,3-dipolar cycloaddition of acetylenedicarboxylates at cyclooctynes.

Cyclooctyne and cycloocten-5-yne undergo, at room temperature, a 1,3-dipolar cycloaddition with dialkyl acetylenedicarboxylates 1a,b to generate furan-derived short-lived intermediates 2, which can be trapped by two additional equivalents of 1a,b or alternatively by methanol, phenol, water or aldehydes to yield polycyclic products 3b-d, orthoesters 4a-c, ketones 5 or epoxides 6a,b, respectively. Treatment of bis(trimethylsilyl) acetylenedicarboxylate (1c) with cyclooctyne leads to the ketone 7 via retro-Brook rearrangement of the dipolar intermediate 2c. In all cases, the products are formed with perfect atom economy.

Occurrence of 3-MCPD and glycidyl esters in edible oils in the United States.

Fatty acid esters of 3-monochloropropanediol (3-MCPD) and glycidol are processing contaminants found in a wide range of edible oils. While both 3 MCPD and glycidol have toxicological properties that at present has concerns for food safety, the published occurrence data are limited. Occurrence information is presented for the concentrations of 3-MCPD and glycidyl esters in 116 retail and/or industrial edible oils and fats using LC-MS/MS analysis of intact esters. The concentrations for bound 3-MCPD ranged from below the limit of quantitation (

High throughput microfluidic rapid and low cost prototyping packaging methods.

In this work, 3 different packaging and assembly techniques are presented. They can be classified into two categories: one-time use and reusable packaging techniques. The one-time use packaging technique employs UV-based and temperature curing epoxies to connect microtubes to access holes, wire-bonding for integrated circuit connections, and silver epoxy for electrical connections. This method is based on a robust assembly technique that can support relatively high pressure close to 1 psi and does not need any support to strengthen the microfluidic architecture. Reusable packaging techniques consist of PDMS-based microtube interconnectors and anisotropic adhesive films for electrical connections. These devices are more sensitive and fragile. Consequently, Plexiglas support is added to the microfluidic structure to improve the electrical contact when anisotropic adhesive films are used, and also to strengthen the microfluidic architecture. In addition, a micromanipulator is needed to maintain tubes while using a thin PDMS layer to connect them to the access holes. Different PDMS layer thicknesses, ranging from 0.45-3 mm, are tested to compare the best adherence versus injection rates. Applied injection rates are varied from 50-300 µl/hr for 0.45-3 mm PDMS layers, respectively. These techniques are mainly applicable for low-pressure applications. However, they can be extended for high-pressure ones through plasma-oxygen process to permanently seal the PDMS to glass substrates. The main advantage of this technique, besides the fact that it is reusable, consists of keeping the device observable when the microchannel length is very short (in the range of 3 mm or lower).

Merging sustainability with organocatalysis in the formation of organic carbonates by using CO(2) as a feedstock.

The use of phenolic compounds as organocatalysts is discussed in the context of the atom-efficient cycloaddition of carbon dioxide to epoxides, forming useful cyclic organic carbonate products. The presence and cooperative nature of adjacent phenolic groups in the catalyst structure results in significantly enhanced catalytic efficiencies, allowing these CO(2) fixation reactions to operate efficiently under virtually ambient conditions. The cooperative effect has also been studied by computational methods. Furthermore, when the cycloaddition reactions are carried out on a larger scale and under solvent-free conditions, further enhancements in activity are observed, combined with the advantageous requirement of reduced loadings of the binary organocatalyst system. The reported system is among one of the mildest and most effective metal-free catalysts for this conversion and contributes to a much more sustainable development of organic carbonate production; this feature has not been the main focus of previous contributions in this area.

Transfer of the epoxidation of soybean oil from batch to flow chemistry guided by cost and environmental issues.

The simple transfer of established chemical production processes from batch to flow chemistry does not automatically result in more sustainable ones. Detailed process understanding and the motivation to scrutinize known process conditions are necessary factors for success. Although the focus is usually "only" on intensifying transport phenomena to operate under intrinsic kinetics, there is also a large intensification potential in chemistry under harsh conditions and in the specific design of flow processes. Such an understanding and proposed processes are required at an early stage of process design because decisions on the best-suited tools and parameters required to convert green engineering concepts into practice-typically with little chance of substantial changes later-are made during this period. Herein, we present a holistic and interdisciplinary process design approach that combines the concept of novel process windows with process modeling, simulation, and simplified cost and lifecycle assessment for the deliberate development of a cost-competitive and environmentally sustainable alternative to an existing production process for epoxidized soybean oil.

Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food.

Fatty acid esters of 3-chloropropane-1,2-diol (3-MCPD) and glycidol are a newly identified class of food process contaminants. They are widespread in refined vegetable oils and fats and have been detected in vegetable fat-containing products, including infant formulas. There are no toxicological data available yet on the 3-MCPD and glycidol esters, and the primary toxicological concern is based on the potential release of 3-MCPD or glycidol from the parent esters by lipase-catalyzed hydrolysis in the gastrointestinal tract. Although 3-MCPD is assessed as a nongenotoxic carcinogen with a tolerable daily intake (TDI) of 2 µg/kg body weight (bw), glycidol is a known genotoxic carcinogen, which induces tumors in numerous organs of rodents. The initial exposure estimates, conducted by Federal Institute for Risk Assessment (BfR) under the assumption that 100% of the 3-MPCD and glycidol are released from their esters, revealed especially that infants being fed commercial infant formula could ingest harmful amounts of 3-MCPD and glycidol. However, the real oral bioavailability may be lower. As this gives rise for toxicological concern, the currently available toxicological data of 3-MCPD and glycidol and their esters are summarized in this review and discussed with regard to data gaps and further research needs.

Practical and highly selective sulfur ylide mediated asymmetric epoxidations and aziridinations using an inexpensive, readily available chiral sulfide. Applications to the synthesis of quinine and quinidine.

Heating one of the most abundant naturally occurring inorganic chemicals (elemental sulfur) with one of the most readily available homochiral molecules (limonene) gives a one-step synthesis of a chiral sulfide which exhibits outstanding selectivities in sulfur ylide mediated asymmetric epoxidations and aziridinations. In particular reactions of benzyl and allylic sulfonium salts with both aromatic and aliphatic aldehydes gave epoxides with perfect enantioselectivities and the highest diastereoselectivities reported to date. In addition reactions with imines gave aziridines again with the highest enantioselectivities and diastereoselectivities reported to date. The reactions are scaleable, and the sulfide can be reisolated in high yield. The epoxidation has been used as the key step in a convergent and stereoselective synthesis of each of the diastereoisomers of the cinchona alkaloids, quinine and quinidine.