Explore the vast range of titles available.

The formation of carbonyls and epoxides in e-cigarette (EC) aerosol is possible due to heating of the liquid constituents. However, high background levels of these compounds have inhibited a clear assessment of exposure during use of ECs. An EC containing an e-liquid replaced with 10% of 13C-labeled propylene glycol and glycerol was used in a controlled use clinical study with 20 EC users. In addition, five smokers smoked cigarettes spiked with the described e-liquid. Seven carbonyls (formaldehyde, acetaldehyde, acrolein, acetone, crotonaldehyde, methacrolein, propionaldehyde) were measured in the aerosol and the mainstream smoke. Corresponding biomarkers of exposure were determined in the user’s urine samples. 13C-labeled formaldehyde, acetaldehyde and acrolein were found in EC aerosol, while all seven labeled carbonyls were detected in smoke. The labeled biomarkers of exposure to formaldehyde (13C-thiazolidine carboxylic acid and 13C-N-(1,3-thiazolidine-4-carbonyl)glycine), acrolein (13C3-3-hydroxypropylmercapturic acid) and glycidol (13C3-dihydroxypropylmercapturic acid) were present in the urine of vapers indicating an EC use-specific exposure to these toxicants. However, other sources than vaping contribute to a much higher extent by several orders of magnitude to the overall exposure of these toxicants. Comparing data for the native (unlabeled) and the labeled (exposure-specific) biomarkers revealed vaping as a minor source of user’s exposure to these toxicants while other carbonyls and epoxides were not detectable in the EC aerosol.

Bisphenol A diglycidyl ether (BADGE) and its related derivatives (BADGEs for short) are reactive epoxides condensed from bisphenol A (BPA) and epichlorohydrin. Nowadays, they are heavily used as additives in the production process of food and beverage contacting materials. However, BADGEs are considered as emerging organic pollutants due to their high toxicity including cytotoxicity, mutagenicity, and genotoxicity. In this work, an online analytical method integrated column-switching technique with supercritical fluid chromatography (SFC) was proposed for the simultaneous determination of bisphenol A diglycidyl ether and its derivatives. In this process, a homemade column was utilized in the first dimension of the column-switching SFC system to preconcentrate the analytes as well as eliminate interferences online. Under the optimal conditions, the obtained calibration curves for BADGEs showed good linearity ranging from 0.02 μg/mL to 10.00 μg/mL, while the values of LOD and LOQ were in the range of 0.0024–0.0035 μg/mL and 0.0080–0.0116 μg/mL, respectively. The optimized method exhibited a good recovery ranging from 85.6% to 105.5% with relative standard deviations less than 11.8%. The developed method provides an eco-friendly and effective way for the rapid and automated analysis of BADGEs at trace levels in canned beverages and can be applied to the high-throughput analysis of other similar matrices.

Background Although manufacturers of 1,4‐butanediol diglycidyl ether (BDDE)‐cross‐linked hyaluronic acid (HA) fillers assert effective removal of unreacted BDDE, the hydrolyzed derivative 3,3′‐(butane‐1,4‐diyl)bis(oxy)bis(propane‐1,2‐diol) (BDPE) is routinely monitored, despite possessing structural features associated with sensitization potential. Aims To quantify free BDPE content across commercially available HA dermal fillers and assess potential safety implications. Materials/Methods A validated liquid chromatography–tandem mass spectrometry method was developed to quantify BDPE levels in 38 commercial HA filler products from seven major manufacturers. In silico prediction models were used to evaluate the skin sensitization and irritation potential of BDPE. Results BDDE levels were non‐detectable in all analyzed products. By contrast, free BDPE content varied markedly, with over 1000‐fold differences observed between products, indicating substantial variability in purification efficiency across manufacturing processes. Considerable variability was also identified among Food and Drug Administration–approved products, with some containing BDPE concentrations exceeding 100 ppm. Conversely, several products exhibited low BDPE levels ranging from 0.1 to 2.5 ppm, further highlighting inconsistencies in manufacturing control. Conclusions Industry claims regarding complete cross‐linker removal may fail to account for the persistence of BDPE species. The substantial inter‐product variability observed in this study suggests inadequate process control among manufacturers. Given the structural similarity of BDPE to known sensitizers and the direct dermal injection route that circumvents the skin barrier, free BDPE should be designated a critical quality attribute with defined acceptance limits. These findings suggest that BDPE can be reduced to concentrations below 2.5 ppm, supporting the need for stricter manufacturing standards.

The co-occurrence of pesticides in aquatic ecosystems highlights the need for studies investigating their potential toxicity as mixtures to the aquatic biota. Well-designed studies are essential to assess the presence and toxicity of relevant pesticide mixtures, particularly those such as the chloroacetamide herbicide metolachlor (MET), the triazole fungicide epoxiconazole (EP) and the diamide anthranilic insecticide chlorantraniliprole (CAP), which have not been previously tested, and whose co-occurrence is possible in waters close to cultivated areas. A solid phase extraction ultra-performance liquid chromatography-tandem quadrupole mass spectrometry method was developed to quantify equivalent toxicity concentrations for CAP, EP, and MET in artificial freshwater during acute toxicity tests. Compounds were separated within 1.30 min, showing linearity over the calibration ranges of 2–150 µgL −1 for CAP and 50–3000 µgL −1 for EP and MET. Detection and quantification limits were (µgL −1 ): 0.001 and 0.0037 MET; 0.000038 and 0.00013 EP; and 0.002 and 0.007 CAP, respectively. Precision and accuracy met intra-assay validation requirements. Recoveries were tested at low and high concentration levels and were between 77% and 120%. Additionally, matrix effect showed different behavior among compounds. In an acute toxicity test proposed, MET and EP remained stable (24 h), while CAP decayed 27% ± 4% in the same period. The method proved effective despite different concentrations in toxicity testing design.

Vicinal diols are important signaling metabolites of various inflammatory diseases, and some of them are potential biomarkers for some diseases. Utilizing the rapid reaction between diol and 6-bromo-3-pyridinylboronic acid (BPBA), a selective and sensitive approach was established to profile these vicinal diols using liquid chromatography-post column derivatization coupled with double precursor ion scan-mass spectrometry (LC-PCD-DPIS-MS). After derivatization, all BPBA-vicinal-diol esters gave a pair of characteristic isotope ions resulting from 79Br and 81Br. The unique isotope pattern generated two characteristic fragment ions of m/z 200 and 202. Compared to a traditional offline derivatization technique, the new LC-PCD-DPIS-MS method retained the capacity of LC separation. In addition, it is more sensitive and selective than a full scan MS method. As an application, an in vitro study of the metabolism of epoxy fatty acids by human soluble epoxide hydrolase was tested. These vicinal-diol metabolites of individual regioisomers from different types of polyunsaturated fatty acids were easily identified. The limit of detection (LOD) reached as low as 25 nM. The newly developed LC-PCD-DPIS-MS method shows significant advantages in improving the selectivity and therefore can be employed as a powerful tool for profiling vicinal-diol compounds from biological matrices.

Methyleugenol is a substituted alkenylbenzene found in several herbs and spices. It is classified by the European Union’s Scientific Committee on Food as a genotoxic carcinogen. We addressed the biological mechanism of the genotoxic properties of methyleugenol and its oxidative metabolites. Methyleugenol and the oxidative metabolites significantly enhanced the DNA damage in human colon carcinoma cells (HT29). Methyleugenol did not affect the protein status of γH2AX, a biomarker of DNA double-strand breaks, whereas its metabolites methyleugenol-2′,3′-epoxide and 3′-oxomethylisoeugenol significantly increased the cellular phosphorylated H2AX level. Both of these metabolites also showed a significant induction of micronuclei in HT29 cells. Furthermore, we investigated whether topoisomerase interaction contribute to the observed effect on DNA integrity. Methyleugenol-2′,3′-epoxide and 3′-oxomethylisoeugenol inhibited the activity of recombinant topoisomerase I. In HT29 cells, neither methyleugenol nor the metabolites affected the level of topoisomerase protein bound to DNA, excluding a topoisomerase poisoning mode of action. In addition, 3′-oxomethylisoeugenol potently diminished the level of camptothecin-stabilized topoisomerase I/DNA intermediates and camptothecin-induced DNA strand breaks. In conclusion, it could be suggested that 3′-oxomethylisoeugenol may also interact with classical or food-borne topoisomerase I poisons, diminishing their poisoning effectiveness.

Context: Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in China clinics. Objective: This study investigated the effects of triptolide on the pharmacokinetics of amlodipine in male Sprague-Dawley rats. Materials and methods: The pharmacokinetics of amlodipine (1 mg/kg) with or without triptolide pre-treatment (2 mg/kg/day for seven days) were investigated using a sensitive and reliable LC-MS/MS method. Additionally, the inhibitory effects of triptolide on the metabolic stability of amlodipine were investigated using rat liver microsome incubation systems. Results: The results indicated that when the rats were pre-treated with triptolide, the C max of amlodipine increased from 13.78 ± 3.57 to 19.96 ± 4.56 ng/mL (p < 0.05), the T max increased from 4.04 ± 1.15 to 5.89 ± 1.64 h (p < 0.05), and the AUC 0- t increased by approximately 104% (p < 0.05), which suggested that the pharmacokinetic behaviour of amlodipine was affected after oral co-administration of triptolide. Additionally, the metabolic half-life was prolonged from 22.5 ± 4.26 to 36.8 ± 6.37 min (p < 0.05) with the pre-treatment of triptolide. Conclusions: In conclusion, these results indicated that triptolide could affect the pharmacokinetics of amlodipine, possibly by inhibiting the metabolism of amlodipine in rat liver when they are co-administered.

Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette smoke, and forest fires is of great concern because of its potent carcinogenicity. The adverse health effects of BD are mediated by its epoxide metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA to form promutagenic nucleobase adducts. Because of their direct role in cancer, BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the present work, a mass spectrometry-based methodology was developed for accurate, sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are selectively released from DNA backbone by neutral thermal hydrolysis, followed by ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI + -HRMS 3 analysis on an Orbitrap Velos mass spectrometer. Following method validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells treated with micromolar concentrations of EB and in liver tissues of rats exposed to sub-ppm concentrations of BD (0.5–1.5 ppm). EB-GII concentrations increased linearly from 1.15 ± 0.23 to 10.11 ± 0.45 adducts per 10 6 nucleotides in HT1080 cells treated with 0.5–10 μM DEB. EB-GII concentrations in DNA of laboratory rats exposed to 0.5, 1.0, and 1.5 ppm BD were 0.17 ± 0.05, 0.33 ± 0.08, and 0.50 ± 0.04 adducts per 10 6 nucleotides, respectively. We also used the new method to determine the in vivo half-life of EB-GII adducts in rat liver DNA (2.20 ± 0.12 d) and to detect EB-GII in human blood DNA. To our knowledge, this is the first application of nanoLC/ESI + -HRMS 3 Orbitrap methodology to quantitative analysis of DNA adducts in vivo. Figure a ᅟ

In intensive agriculture areas the use of pesticides can alter soil properties and microbial community structure with the risk of reducing soil quality. In this study the fatty acid methyl esters (FAMEs) evolution has been studied in a factorial lab experiment combining five substrates (a soil, two aged composts and their mixtures) treated with a co-application of three pesticides (azoxystrobin, chlorotoluron and epoxiconazole), with two extraction methods, and two incubation times (0 and 58 days). FAMEs extraction followed the microbial identification system (MIDI) and ester-linked method (EL). The pesticides showed high persistence, as revealed by half-life (t1/2) values ranging from 168 to 298 days, which confirms their recalcitrance to degradation. However, t1/2 values were affected by substrate and compost age down to 8 days for chlorotoluron in S and up to 453 days for epoxiconazole in 12M. Fifty-six FAMEs were detected. Analysis of variance (ANOVA) showed that the EL method detected a higher number of FAMEs and unique FAMEs than the MIDI one, whereas principal component analysis (PCA) highlighted that the monosaturated 18:1ω9c and cyclopropane 19:0ω10c/19ω6 were the most significant FAMEs grouping by extraction method. The cyclopropyl to monoenoic acids ratio evidenced higher stress conditions when pesticides were applied to compost and compost+soil than solely soil, as well as with final time. Overall, FAMEs profiles showed the importance of the extraction method for both substrate and incubation time, the t1/2 values highlighted the effectiveness of solely soil and the less mature compost in reducing the persistence of pesticides.

In soil, the determination of total concentration using an exhaustive extraction method has little relevance to evaluate the exposure of an organism to a chemical, because of sorption processes. This study aims to propose a mild extraction method to evaluate the bioavailability of the fungicide epoxiconazole to the earthworm Aporrectodea icterica. Experiments were conducted in soils presenting various textures and organic carbon contents, spiked with formulated epoxiconazole 7 to 56 days prior to their extraction. In parallel, the epoxiconazole concentration was determined in exposed earthworms and the fungicide’s effects were evaluated by measuring weight gain, enzymatic activities and total protein contents. Among the various mild chemical solvents tested to evaluate the environmental availability of the fungicide, the 50 mM hydroxypropyl-β-cyclodextrin solution allowed to extract around 30 % of epoxiconazole. This percentage corresponded to the ratio determined in exposed A. icterica under similar soil conditions. Furthermore, this mild method was demonstrated to be sensitive to soil sorption capacities and to ageing. The mild extraction method was then applied to explore the relationship between total and (bio)available concentrations in soil and in A. icterica, over 7- or 28-day exposure time. This demonstrated the proportionality between epoxiconazole concentration in earthworm and available in soil (up to 96 %, with regression coefficient R ² = 0.98). Sublethal effects on earthworm remained not significant.