Food processing contaminants: Dietary exposure to 3-MCPD and glycidol and associated burden of disease for Italian consumers.

In this study we assessed Italian consumers' dietary exposure to 3-MCPD and glycidol followed by risk characterization, potential cancer risk and the associated burden of disease. Consumption data was retrieved from the most recent Italian Food Consumption Survey (2017-2020), while contamination data was obtained from the European Food Safety Authority. The level of risk due to exposure to 3-MCPD was negligible, below the tolerable daily intake (TDI), except for high consumption of infant formulas. For infants, the intake level was higher than the TDI (139-141% of TDI), indicating a potential health risk. Exposure to glycidol indicated a health concern for infants, toddlers, other children, and adolescents consuming infant formulas, plain cakes, chocolate spreads, processed cereals, biscuits, rusks, and cookies (margin of exposure (MOE) < 25,000). The risk of cancer due to exposure to glycidol was estimated and the overall health impact was quantified in Disability-Adjusted Life Years (DALYs). The risk of cancer due to chronic dietary exposure to glycidol was estimated at 0.08-0.52 cancer cases/year/100,000 individuals depending on the life stage and dietary habits in Italy. The burden of disease quantified in DALYs varied from 0.7 to 5.37 DALYs/year/100,000 individuals. It is crucial to continuously gather consumption and occurrence data for glycidol over time to track patterns, assess potential health risks, identify exposure sources, and develop effective countermeasures, as long-term exposure to chemical contaminants can lead to an increased risk for human health. This data is critical for protecting public health and reducing the likelihood of cancer and other health issues related to glycidol exposure.

Associations of 3-monochloropropane-1,2-diol and glycidol with prevalence of metabolic syndrome: Findings from Lanxi Nutrition and Safety Study.

In this study, we investigated the association of 2,3-dihydroxypropyl mercapturic acid (DHPMA), a urinary biomarker of environmental and dietary exposure to 3-monochloropropane-1,2-diol and glycidol, with prevalent MetS in a Chinese middle-aged and elderly population. The urinary DHPMA concentrations were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analysis and further calibrated by the urinary creatinine content. MetS cases were defined by the Adult Treatment Panel III criteria for Asian-Americans of National Cholesterol Education Program (NCEP/ATPIII). Multivariate-adjusted modified Poisson regression models were used to analyze the associations between the urinary DHPMA concentrations and MetS prevalence. Of the 1613 participants aged 45-75 years, we documented 552 (34.2%) MetS cases. After adjustment for potential risk factors, the relative risks (95% confidence intervals) of MetS prevalence across the increasing quartiles of DHPMA concentrations were 1.14 (0.93-1.39), 1.29 (1.06-1.56), and 1.50 (1.25-1.80), respectively, compared with the lowest quartile. We also observed strong positive association between urinary DHPMA concentrations and hypertriglyceridemia prevalence (P < 0.001 for trend). These positive associations remained unchanged in the subgroups stratified by general demographic, dietary and behavioral risk factors. These results suggested that urinary DHPMA was associated with higher prevalence of MetS among Chinese elderly people.

Identification of gene targets of developmental neurotoxicity focusing on DNA hypermethylation involved in irreversible disruption of hippocampal neurogenesis in rats.

We have previously found that maternal exposure to 6-propyl-2-thiouracil (PTU), valproic acid (VPA), or glycidol (GLY) has a sustained or late effect on hippocampal neurogenesis at the adult stage in rat offspring. Herein, we searched for genes with hypermethylated promoter region and downregulated transcript level to reveal irreversible markers of developmental neurotoxicity. The hippocampal dentate gyrus of male rat offspring exposed maternally to PTU, VPA, or GLY was subjected to Methyl-Seq and RNA-Seq analyses on postnatal day (PND) 21. Among the genes identified, 170 were selected for further validation analysis of gene expression on PND 21 and PND 77 by real-time reverse transcription-PCR. PTU and GLY downregulated many genes on PND 21, reflecting diverse effects on neurogenesis. Furthermore, genes showing sustained downregulation were found after PTU or VPA exposure, reflecting a sustained or late effect on neurogenesis by these compounds. In contrast, such genes were not observed with GLY, probably because of the reversible nature of the effects. Among the genes showing sustained downregulation, Creb, Arc, and Hes5 were concurrently downregulated by PTU, suggesting an association with neuronal mismigration, suppressed synaptic plasticity, and reduction in neural stem and progenitor cells. Epha7 and Pvalb were also concurrently downregulated by PTU, suggesting an association with the reduction in late-stage progenitor cells. VPA induced sustained downregulation of Vgf and Dpysl4, which may be related to the aberrations in synaptic plasticity. The genes showing sustained downregulation may be irreversible markers of developmental neurotoxicity.

Production, safety, health effects and applications of diacylglycerol functional oil in food systems: a review.

Diacylglycerol (DAG) is a world leading anti-obesity functional cooking oil synthesized via structural modification of conventional fats and oils. DAG exits in three stereoisomers namely sn-1,2-DAG, sn-1,3-DAG, and sn-2,3-DAG. DAG particularly sn-1,3-DAG demonstrated to have the potential in suppressing body fat accumulation and lowering postprandial serum triacylglycerol, cholesterol and glucose level. DAG also showed to improve bone health. This is attributed to DAG structure itself that caused it to absorb and digest via different metabolic pathway than conventional fats and oils. With its purported health benefits, many studies attempt to enzymatically or chemically synthesis DAG through various routes. DAG has also received wide attention as low calorie fat substitute and has been incorporated into various food matrixes. Despite being claimed as healthy cooking oil the safety of DAG still remained uncertain. DAG was banned from sale as it was found to contain probable carcinogen glycidol fatty acid esters. The article aims to provide a comprehensive and latest review of DAG emphasizing on its structure and properties, safety and regulation, process developments, metabolism and beneficial health attributes as well as its applications in the food industry.

[Alkaline transesterification CG-MS/MS method of monochlorpropanediol and glycidyl esters' determination in some edible fats, oils and fat blends on Russian market].

Monochlorpropanediol fatty acid esters (MCPDE) and glycidyl fatty acid esters (GE) are mainly considered to be processing contaminants and their concentration can rise during high temperature refining and deodorization of edible oils. Free forms formed during digestive hydrolysis of esters such as 3-monochloropropane-1,2-diol (3-MCPD), 2-MCPD and glycidol can provoke a negative effect on human health. Therefore the quantitative determination of MCPDE and GE in edible oils, fats and fat blends is needed. The aim - this manuscript deals with MCPDE and GE concentration measured as free 3-MCPD, 2-MCPD and glycidol in different edible oils, fats and fat blends of Russian market. Material and methods. 55 edible oil and fat samples sold on Russian market including refined and non-refined oils and fat blends such as spreads, dairy fat replacers, and margarines have been analyzed. Slow alkaline transesterification method with GC-MS/MS was used. Results. According to the data obtained, the highest concentrations of the contaminants were detected in fat blends: <0.10-5.03 mg/kg for 3-MCPD, <0.10-2.50 mg/kg for 2-MCPD and 0.1 5-11.17 mg/kg for glycidol. In palm oils and its fractions concentration of 3-MCPD was <0.10-6.61 mg/kg, 2-MCPD - <0.10-2.69 mg/kg and glycidol - <0.10-6.29 mg/kg. The content of glycidol in sunflower oils fluctuated in the range <0.10-1.19 mg/kg, 3-MCPD was <0.10-2.47 mg/kg, and 2-MCPD <0.10-0.67 mg/kg. Non-refined edible oils and olive oils had no or little MCPDE or GE. Conclusion. In this work we indicate high importance of monitoring MCPDE and GE in edible oils and fats both as ready-to-eat products and as ingredients prior to the Russian market release. There is strong need in mitigation of these process contaminants during fat blends manufacturing.

The hemoglobin adduct N-(2,3-dihydroxypropyl)-valine as biomarker of dietary exposure to glycidyl esters: a controlled exposure study in humans.

Fatty acid esters of glycidol (glycidyl esters) are heat-induced food contaminants predominantly formed during industrial deodorization of vegetable oils and fats. After consumption, the esters are digested in the gastrointestinal tract, leading to a systemic exposure to the reactive epoxide glycidol. The compound is carcinogenic, genotoxic and teratogenic in rodents, and rated as probably carcinogenic to humans (IARC group 2A). Assessment of exposure from occurrence and consumption data is difficult, as lots of different foods containing refined oils and fats may contribute to human exposure. Therefore, assessment of the internal exposure using the hemoglobin adduct of glycidol, N-(2,3-dihydroxypropyl)-valine (2,3-diHOPr-Val), may be promising, but a proof-of-principle study is needed to interpret adduct levels with respect to the underlying external exposure. A controlled exposure study was conducted with 11 healthy participants consuming a daily portion of about 36 g commercially available palm fat with a relatively high content of ester-bound glycidol (8.7 mg glycidol/kg) over 4 weeks (total amount 1 kg fat, individual doses between 2.7 and 5.2 µg/kg body weight per day). Frequent blood sampling was performed to monitor the 2,3-diHOPr-Val adduct levels during formation and the following removal over 15 weeks, using a modified Edman degradation and ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results demonstrated for the first time that the relatively high exposure during the intervention period was reflected in corresponding distinct increases of 2,3-diHOPr-Val levels in all participants, following the expected slope for hemoglobin adduct formation and removal over time. The mean adduct level increased from 4.0 to 12.2 pmol 2,3-diHOPr-Val/g hemoglobin. By using a nonlinear mixed model, values for the adduct level/dose ratio (k, mean 0.082 pmol 2,3-diHOPr-Val/g hemoglobin per µg glycidol/kg body weight) and the adduct lifetime (τ, mean 104 days, likely the lifetime of the erythrocytes) were determined. Interindividual variability was generally low. 2,3-DiHOPr-Val was therefore proven to be a biomarker of the external dietary exposure to fatty acid esters of glycidol. From the background adduct levels observed in our study, a mean external glycidol exposure of 0.94 µg/kg body weight was estimated. This value is considerably higher than current estimates for adults using occurrence and consumption data of food. Possible reasons for this discrepancy are discussed (other oral or inhalational glycidol sources, endogenous formation, exposure to other chemicals also forming the adduct 2,3-diHOPr-Val). Further research is necessary to clarify the issue.

Optimization of the Synthesis of Glycerol Derived Monoethers from Glycidol by Means of Heterogeneous Acid Catalysis.

We present an efficient and green methodology for the synthesis of glycerol monoethers, starting from glycidol and different alcohols, by means of heterogeneous acid catalysis. A scope of Brønsted and Lewis acid catalysts were applied to the benchmark reaction of glycidol and methanol. The selected catalysts were cationic exchangers, such as Nafion NR50, Dowex 50WX2, Amberlyst 15 and K10-Montmorillonite, both in their protonic form and exchanged with Al(III), Zn(II) and Fe(III). Thus, total conversions were reached in short times by using 1 and 5% mol catalyst loading and room temperature, without the need for excess glycidol or the presence of a solvent. Finally, these conditions and the best catalysts were successfully applied to the reaction of glycidol with several alcohols such as butanol or isopropanol.

DNA methylation analysis in rat kidney epithelial cells exposed to 3-MCPD and glycidol.

3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been regarded as a rat carcinogen, which is known to induce Leydig-cell and mammary gland tumors in males, as well as kidney tumors in both genders. 3-MCPD is highly suspected to be a non-genotoxic carcinogen. 2,3-Epoxy-1-propanol (glycidol) can be formed via dehalogenation from 3-MCPD. We aimed to investigate the cytotoxic effects of 3-MCPD and glycidol, then to demonstrate the possible epigenetic mechanisms with global and gene-specific DNA methylation in rat kidney epithelial cells (NRK-52E). IC50 value of 3-MCPD was determined as 48 mM and 41.39 mM, whereas IC50 value of glycidol was 1.67 mM and 1.13 mM by MTT and NRU test, respectively. Decreased global DNA methylation at the concentrations of 100 µM and 1000 µM for 3-MCPD and 100 µM and 500 µM for glycidol were observed after 48 h exposure by using 5-methylcytosine (5-mC) ELISA kit. Methylation changes were detected in promoter regions of c-myc and Rassf1a in 3-MCPD and glycidol treated NRK-52E cells by using methylation-specific PCR (MSP), whereas changes on gene expression of c-myc and Rassf1a were observed by using real-time PCR. However, e-cadherin, p16, VHL and p15 genes were unmethylated in their CpG promoter regions in response to treatment with 3-MCPD and glycidol. Alterations in DNA methylation might be key events in the toxicity of 3-MCPD and glycidol.

Orally administered glycidol and its fatty acid esters as well as 3-MCPD fatty acid esters are metabolized to 3-MCPD in the F344 rat.

IARC has classified glycidol and 3-monochloropropane-1,2-diol (3-MCPD) as group 2A and 2B, respectively. Their esters are generated in foodstuffs during processing and there are concerns that they may be hydrolyzed to the carcinogenic forms in vivo. Thus, we conducted two studies. In the first, we administered glycidol and 3-MCPD and associated esters (glycidol oleate: GO, glycidol linoleate: GL, 3-MCPD dipalmitate: CDP, 3-MCPD monopalmitate: CMP, 3-MCPD dioleate: CDO) to male F344 rats by single oral gavage. After 30 min, 3-MCPD was detected in serum from all groups. Glycidol was detected in serum from the rats given glycidol or GL and CDP and CDO in serum from rats given these compounds. In the second, we examined if metabolism occurs on simple reaction with rat intestinal contents (gastric, duodenal and cecal contents) from male F344 gpt delta rats. Newly produced 3-MCPD was detected in all gut contents incubated with the three 3-MCPD fatty acid esters and in gastric and duodenal contents incubated with glycidol and in duodenal and cecal contents incubated with GO. Although our observation was performed at 1 time point, the results showed that not only 3-MCPD esters but also glycidol and glycidol esters are metabolized into 3-MCPD in the rat.

Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose.

Hemoglobin adducts have been used as biomarkers of exposure to reactive chemicals. Glycidol, an animal carcinogen, has been reported to form N-(2,3-dihydroxy-propyl)valine adducts to hemoglobin (diHOPrVal). To support the use of these adducts as markers of glycidol exposure, we investigated the kinetics of diHOPrVal formation and its elimination in vitro and in vivo. Five groups of rats were orally administered a single dose of glycidol ranging from 0 to 75mg/kg bw, and diHOPrVal levels were measured 24h after administration. A dose-dependent increase in diHOPrVal levels was observed with high linearity (R(2)=0.943). Blood sampling at different time points (1, 10, 20, or 40days) from four groups administered glycidol at 12mg/kg bw suggested a linear decrease in diHOPrVal levels compatible with the normal turnover of rat erythrocytes (life span, 61days), with the calculated first-order elimination rate constant (kel) indicating that the diHOPrVal adduct was chemically stable. Then, we measured the second-order rate constant (kval) for the reaction of glycidol with N-terminal valine in rat and human hemoglobin in in vitro experiments with whole blood. The kval was 6.7±1.1 and 5.6±1.3 (pmol/g globin per µMh) in rat and human blood, respectively, indicating no species differences. In vivo doses estimated from kval and diHOPrVal levels were in agreement with the area under the (concentration-time) curve values determined in our earlier toxicokinetic study in rats. Our results indicate that diHOPrVal is a useful biomarker for quantification of glycidol exposure and for risk assessment.

Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol.

We previously found that the 28-day oral toxicity study of glycidol at 200mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc(+) neurons at 1000ppm and Fos(+) neurons at ≥300ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure.

Gene expression profile of brain regions reflecting aberrations in nervous system development targeting the process of neurite extension of rat offspring exposed developmentally to glycidol.

We previously found that exposure to glycidol at 1000 ppm in drinking water caused axonopathy in maternal rats and aberrations in late-stage hippocampal neurogenesis, targeting the process of neurite extension in offspring. To identify the profile of developmental neurotoxicity of glycidol, pregnant Sprague-Dawley rats were given drinking water containing glycidol from gestational day 6 until weaning on day 21 after delivery, and offspring at 0, 300 and 1000 ppm were subjected to region-specific global gene expression profiling. Four brain regions were selected to represent both cerebral and cerebellar tissues, i.e., the cingulate cortex, corpus callosum, hippocampal dentate gyrus and cerebellar vermis. Downregulated genes in the dentate gyrus were related to axonogenesis (Nfasc), myelination (Mal, Mrf and Ugt8), and cell proliferation (Aurkb and Ndc80) at ≥ 300 ppm, and upregulated genes were related to neural development (Frzb and Fzd6) at 1000 ppm. Upregulation was observed for genes related to myelination (Kl, Igf2 and Igfbp2) in the corpus callosum and axonogenesis and neuritogenesis (Efnb3, Tnc and Cd44) in the cingulate cortex, whereas downregulation was observed for genes related to synaptic transmission (Thbs2 and Ccl2) in the cerebellar vermis; all of these changes were mostly observed at 1000 ppm. Altered gene expression of Cntn3, which functions on neurite outgrowth-promotion, was observed in all four brain regions at 1000 ppm. Gene expression profiles suggest that developmental exposure to glycidol affected plasticity of neuronal networks in the broad brain areas, and dentate gyrus neurogenesis may be the sensitive target of this type of toxicity.

Beyond the Charge: Interplay of Nanogels' Functional Group and Zeta-Potential for Antifungal Drug Delivery to Human Pathogenic Fungus Aspergillus Fumigatus.

The ubiquitous mold Aspergillus fumigatus (A. fumigatus) is one of the main fungal pathogens causing invasive infections in immunocompromised humans. Conventional antifungal agents exhibit limited efficacy and often cause severe side effects. Nanoparticle-based antifungal delivery provides a promising alternative, which can increase local drug concentration; while, mitigating toxicity, thereby enhancing treatment efficacy. Previous research underscores the potential of poly(glycidol)-based nanogels (NG) with negative surface charge as carriers for delivering antifungals to A. fumigatus hyphae. In this study, NG is tailored with 2-carboxyethyl acrylate (CEA) or with phosphoric acid 2-hydroxyethyl acrylate (PHA). It is discovered that quenching with PHA clearly improves the adhesion of NG to hyphal surface and the internalization of NG into the hyphae under protein-rich conditions, surpassing the outcomes of non-quenched and CEA-quenched NG. This enhancement cannot be solely attributed to an increase in negative surface charge but appears to be contingent on the functional group of the quencher. Further, it is demonstrated that itraconazole-loaded, PHA-functionalized nanogels (NGxPHA-ITZ) show lower MIC in vitro and superior therapeutic effect in vivo against A. fumigatus compared to pure itraconazole. This confirms NGxPHA as a promising antifungal delivery system.

A comparison of the exposure system of glycidol-related chemicals on the formation of glycidol-hemoglobin adducts.

Glycidol fatty acid esters that are present in foods are degraded in vivo to the animal carcinogen glycidol, which binds to the N-terminal valine of hemoglobin (Hb) to form N-(2,3-dihydroxypropyl)valine (diHOPrVal) adducts. The existence of other chemicals that are converted to glycidol is unknown. To determine the effect of different exposure conditions on the formation of diHOPrVal adducts, several glycidol-related chemicals (3-monochloropropane-1,2-diol; 3-MCPD, epichlorohydrin, glyceraldehyde, acrylic acid, and 1,2-propanediol) were evaluated using in vitro and in vivo (single/repeated dose) methods. In vitro, the reaction of 3-MCPD or epichlorohydrin with human Hb produced 17% and 0.7% of diHOPrVal, as compared to equimolar glycidol, respectively. Following a single administration of glycidol-related compounds to ICR mice, diHOPrVal formation was observed only in the epichlorohydrin-treated group after day 5 of exposure. After 14 days of repeated dosing, the amounts of diHOPrVal produced by epichlorohydrin and 3-MCPD in vivo were <1% of diHOPrVal produced by an equal molar concentration of glycidol. Furthermore, glyceraldehyde group produced 0.2% of diHOPrVal at the same molar concentration of glycidol equivalents, in which diHOPrVal formation could not be confirmed by the in vitro assay. The results indicate the usefulness of diHOPrVal as an exposure marker for glycidol; however, the contribution of its formation in vivo by exposure to various chemicals will be necessary to validate and interpret the results.

Novel approach for enhancing skin allograft survival by bioadhesive nanoparticles loaded with rapamycin.

Skin graft rejection is a significant challenge in skin allografts for skin defects, particularly in extensive burn injury patients when autografts are insufficient. Enhancing the survival duration of allogeneic skin grafts can improve the success rate of subsequent autologous skin grafting, thereby promoting the therapeutic efficacy for wound healing. Rapamycin (Rapa), a potent immunosuppressant with favorable efficacy in organ transplantation, is limited by its systemic administration-associated toxicity and side effects. Therefore, addressing the short survival time of allogeneic skin grafts and minimizing the toxicity related to systemic application of immunosuppressive agents is an urgent requirement. Here, we present a topical formulation based on bioadhesive poly (lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with surface-modified encapsulation of Rapamycin (Rapa/BNPs), applied for local immunosuppression in a murine model of allogeneic skin grafts. Our Rapa/BNPs significantly prolong nanoparticle retention, reduce infiltration of T lymphocytes and macrophages, decrease the level of pro-inflammatory cytokines and ultimately extend skin allograft survival with little systemic toxicity compared to free Rapa or Rapamycin-loaded non-bioadhesive nanoparticles (Rapa/NNPs) administration. In conclusion, Rapa/BNPs effectively deliver local immunosuppression and demonstrate potential for enhancing skin allograft survival while minimizing localized inflammation, thus potentially increasing patient survival rates for various types of skin defects.

Preparation and Boron Removal Performance of Glycidol Modified PANI Nanorods: An Optimization Study Based on Response Surface Methodology.

Boron removal from aqueous solutions has attracted increasing attention, offering benefits for animal and plant health as well as profound significance for exploiting Salt Lake boron resources. In this work, we synthesized novel glycidol-functionalized and hydrophilic polyaniline (PANI) nanorod adsorbents, which were prepared to separate boron compounds from boric acid aqueous solutions. The as-prepared adsorbents were significantly different from the traditional polymers' grafting reaction because they had a higher functional yield and more active position for adsorption. The maximum adsorption capacity (0.2210 mmoL∙g-1) and optimal adsorption conditions (boric acid concentration of 1307 mg/L, pH = 9.82, time of 10 h) were obtained with single-factor experimentation and the response surface method (RSM). In addition, adsorption kinetics studies showed that the adsorption reaction belonged to the pseudo-first-order kinetic model, and diffusion was the key limiting factor; therefore, the adsorption equilibrium time is more than 10 h. Finally, the related possible adsorption mechanism was investigated based on the species and the diffusion of boron in the aqueous phase.

Potential Role of Lipase Activity on the Internal Exposure Assessment of Glycidol Released from Its Fatty Acid Esters.

Glycidyl fatty acid esters (GEs) can be found in food, and they can be converted into genotoxic animal carcinogen glycidol in vivo by the action of lipase. This study examined whether human ingestion of charbroiled pork containing high levels of GEs (300 µg/day) increased glycidol-hemoglobin adduct (diHOPrVal), a marker of internal exposure to glycidol using LC-MS/MS. Contrary to expectation, the diHOPrVal value before ingesting charbroiled pork was 3.11 ± 1.10 pmol/g globin, which slightly decreased to 2.48 ± 0.47 pmol/g globin after 5 days of consumption. The decrease in lipase activity caused by the continuous consumption of lipid-rich foods such as meat in humans might decrease internal exposure to glycidol released from its esters. Thus, lipase activity was measured in C57/BL6J mice fed a high-fat diet (HFD) for 8 weeks, and diHOPrVal formation was measured after the administration of glycidyl oleate. Lipase activity was significantly lower in the HFD group than in the normal diet group. The amount of diHOPrVal was reduced in the HFD group. Therefore, the lipase activity was reduced by HFD, thereby decreasing the degradation of glycidol from glycidyl oleate. These results indicate that changes in lipase activity depending on the amount of lipids in the diet may affect the assessment of GEs exposure, and monitoring the lipase activity would provide a comprehensive understanding of exposure assessment.

Determination of chemical constituent yields in e-cigarette aerosol using partial and whole pod collections, a comparative analysis.

Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often consist of data from the first 50-100 puffs. However, it is not clear whether these discrete puff blocks are representative of constituent yields over the life of a pod. We aimed to assess the effect of differing aerosol collection strategies on reported yields for select chemical constituents in the aerosol of closed pod-based ENDS products. Constituents analyzed were chosen to reflect important classes of compounds from the Final Premarket Tobacco Product Application Guidance. Yields were normalized to total device mass loss (DML). Collection strategies that consisted of partial pod collection were valid for determining yields of constituents whose DML normalized yields were consistent for the duration of pod life. These included primary aerosol constituents, such as propylene glycol, glycerol, and nicotine, and whole pod yields could be determined from initial puff blocks. However, changes were observed in the yields of some metals, some carbonyl compounds, and glycidol over pod life in a chemical constituent and product dependent manner. These results suggest that collection strategies consisting of initial puff block collections require validation per chemical constituent/product and are not appropriate for chemical constituents with variable yields over pod life. Whole pod collection increased sensitivity and accuracy in determining metal, carbonyl, and glycidol yields compared to puff block-based collection methodologies for all products tested.

An Approach to Flavor Chemical Thermal Degradation Analysis.

Toxicological evaluations of flavor chemicals for use in inhalation products that utilize heat for aerosol generation are complicated because of the potential effect heat may have on the flavor chemical. The objective was to develop a thermal degradation technique to screen flavor chemicals as part of a toxicological testing program for their potential use in ENDS formulations. Based upon published data for acetaldehyde, acrolein, and glycidol from ENDS products (common thermal degradants of propylene glycol and glycerin), the pyrolizer temperature was adjusted until a similar ratio of acetaldehyde, acrolein, and glycidol was obtained from a 60/40 ratio (v/v) of glycerin/propylene glycol via GC/MS analysis. For each of 90 flavor chemicals, quantitative measurements of acetaldehyde, acrolein, and glycidol, in addition to semiquantitative non-targeted analysis tentatively identifying chemicals from thermal degradation, were obtained. Twenty flavor chemicals transferred at greater than 99% intact, another 26 transferred at greater than 95% intact, and another 15 flavor chemicals transferred at greater than 90% intact. Most flavor chemicals resulted in fewer than 10-12 tentatively identified thermal degradants. The practical approach to the thermal degradation of flavor chemicals provided useful information as part of the toxicological evaluation of flavor chemicals for potential use in ENDS formulations.

Apigenin and its octoic acid diester attenuated glycidol-induced autophagic-dependent apoptosis via inhibiting the ERK/JNK/p38 signaling pathways in human umbilical vein endothelial cells (HUVECs).

Glycidol is a well-known food contaminant mainly formed in refined edible oils and various thermally processed foods. Here, we studied the toxicity effects and related mechanism of glycidol on Human umbilical vein endothelial cells (HUVECs). Glycidol was found to induce Gap period 2 (G2)/Mitosis (M) phase cell cycle arrest, apoptosis, and autophagy in HUVECs. Inhibition of autophagy by 3-methyladenine (3-MA) attenuated glycidol-induced cell death, suggesting that glycidol-induced apoptosis was autophagy-dependent. Moreover, glycidol treatment induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38. Inhibition of ERK, JNK, and p38 phosphorylation by the inhibitors U0126, SP600125, and SB203580 attenuated glycidol-induced autophagy and prevented glycidol-mediated reduction in cell viability, demonstrating that glycidol inhibited HUVECs growth by inducing autophagic-dependent apoptosis through activation of the ERK, JNK and p38 signaling pathways. In addition, apigenin (API) and its octoic acid diester apigenin-7 (API-C8), 4'-O-dioctanoate were found to significantly attenuate glycidol-induced cell growth inhibition by inhibiting the above signaling pathways. Collectively, glycidol induces autophagic-dependent apoptosis via activating the ERK/JNK/p38 signaling pathways in HUVECs and API-C8 could attenuate the toxicity effects.