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AbstractDetailed analysis of dietary nitrosamine exposure for the U.S. population has been limited, yet it is critical for evaluating the amount of nitrosamines in the American diet. The dietary exposures to N-nitrosamines from consumption of food and beverages were estimated for the U.S. population aged 2 years and older and children aged 2 to 5 years using 2-day food consumption data from the publicly available, combined 2015–2018 National Health and Nutrition Examination Survey (NHANES) and data on residual volatile N-nitrosamine levels in food available from our recent comprehensive literature review. The estimated eaters-only mean dietary exposure to N-nitrosamines ranged from 0.1 µg/person/day for U.S. children aged 2–5 years to 0.2 µg/person/day for the U.S. population aged 2 years and older. For the U.S. population aged 2 years and older, over 40% of the daily dietary exposure to N-nitrosamines resulted from the consumption of processed cured meats. [ABSTRACT FROM AUTHOR]

A batch electrocoagulation (EC) process using aluminum electrodes was optimized for the removal of natural organic matter (NOM) and subsequent reduction in total trihalomethane (TTHM) formation potential from synthetic (SynW) and river water (RW) samples. Optimum operating conditions were found to be 45 min of electrolysis time, an initial NOM concentration of 10 mg/L , and an applied voltage of 15 V. Initial NOM concentrations tested were 3, 5, 10, 15, 20, 30, 40, and 50 mg/L and treatment efficiency increased with increasing initial concentration. The kinetic study demonstrated that NOM removal followed second-order kinetics. NOM removal resulted in the reduction of trihalomethanes (THMs) formation in treated water. THM concentrations were measured in untreated and EC-treated water. Bromodichloromethane had the highest removal (92.4%) compared to trichloromethane (89.5%) after 10 min. The TTHM concentration after a 10–30 min treatment was below the US Environmental Protection Agency (USEPA) maximum contaminant level of 80 μg/L. After 60 min, the TTHM concentration in the RW samples was reduced by 77.5%, which was considerably less than the reduction in the SynW samples (89.7%) within 10 min. The lower THMFP removal from RW may be due to interference from natural or anthropogenic constituents. The total amount of sludge generated in experiments was compared with the estimate derived using Faraday's equation. A current efficiency of 1.4 was obtained, indicating super-faradaic behavior of the EC process at the optimum operating conditions. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to characterize the generated sludge and entrapment of NOM in aluminum hydroxide [ Al(OH)3 ] flocs as the most likely removal mechanism. At optimum operating conditions, the energy consumption was 2.391 kWh/m2. Thus, EC is an effective method for reducing NOM and THMFP from RW samples. [ABSTRACT FROM AUTHOR]

N-nitrosodimethylamine (NDMA) is a potentially carcinogenic byproduct of disinfecting drinking water. NDMA has been classified as a Group B2 carcinogen by the U.S. Environmental Protection Agency (EPA). The pathway of NDMA formation during chlorination has been proposed; however, it is still necessary to identify the most influential factor in this process. The objective of this study was to compare the factors and conditions that lead to the formation of NDMA from dimethylamine (DMA) to identify the primary factors responsible for the occurrence of this compound in drinking water. The study examined the formation of NDMA in chlorinated water under seven different conditions, considering three factors (NO2−, NO3−, and NH3). All factors were maintained at their actual concentrations in tap or surface water. The highest levels of NDMA were observed at pH 6 when NO3− and NH3 were present, with concentrations of 22.7 ng/L and 9.79 ng/L, respectively. At pH 6, NDMA levels were observed to be 22 times higher than at pH 8. Chlorine alone was not sufficient to convert DMA to NDMA within a short period of time, specifically at least 5 h, in the absence of other factors. The concentration of NDMA increased to 41.6 ng/L in the presence of NH3. After 16 h, the presence of NO3− led to a gradual increase in NDMA levels to 19.0 ng/L. However, no further increase was observed at this point. The findings suggest that NO3− and NH3 are important factors of NDMA in chlorinated drinking water. Although previous mechanisms have not given much attention to these factors, they are expected to play a significant role in the formation of nitrosamines in both natural water and drinking water. Controlling the factors or pH appeared to be crucial for managing NDMA formation, and further research on reducing N-nitrosamines is necessary. [ABSTRACT FROM AUTHOR]

This article discusses strategies to improve the functional value of meat and meat products. It highlights the nutritional value of meat, including its high protein content and essential amino acids. The article also explores the impact of factors such as fatty acid composition, trace elements, and heat treatment on the healthfulness and nutritional quality of meat. Several studies are mentioned that investigate methods to enhance the composition and quality of meat products, such as using bioactive components and functional additives. The article concludes by emphasizing the importance of bioactive compounds in promoting optimal growth and development and potentially preventing certain diseases. However, it also acknowledges the potential negative effects of improper heat treatment on meat, which can lead to the formation of harmful compounds. [Extracted from the article]

N-nitrosamines and nitrosamine drug substance related impurities (NDSRIs) became a critical topic for the development and safety of small molecule medicines following the withdrawal of various pharmaceutical products from the market. To assess the mutagenic and carcinogenic potential of different N-nitrosamines lacking robust carcinogenicity data, several approaches are in use including the published carcinogenic potency categorization approach (CPCA), the Enhanced Ames Test (EAT), in vivo mutagenicity studies as well as read-across to analogue molecules with robust carcinogenicity data. We employ quantum chemical calculations as a pivotal tool providing insights into the likelihood of reactive ion formation and subsequent DNA alkylation for a selection of molecules including e.g., carcinogenic N-nitrosopiperazine (NPZ), N-nitrosopiperidine (NPIP), together with N-nitrosodimethylamine (NDMA) as well as non-carcinogenic N-nitrosomethyl-tert-butylamine (NTBA) and bis (butan-2-yl) (nitros)amine (BBNA). In addition, a series of nitrosomethylaminopyridines is compared side-by-side. We draw comparisons between calculated reaction profiles for structures representing motifs common to NDSRIs and those of confirmed carcinogenic and noncarcinogenic molecules with in vivo data from cancer bioassays. Furthermore, our approach enables insights into reactivity and relative stability of intermediate species that can be formed upon activation of several nitrosamines. Most notably, we reveal consistent differences between the free energy profiles of carcinogenic and non-carcinogenic molecules. For the former, the intermediate diazonium ions mostly react, kinetically controlled, to the more stable DNA adducts and less to the water adducts via transition-states of similar heights. Non-carcinogenic molecules yield stable carbocations as intermediates that, thermodynamically controlled, more likely form the statistically preferred water adducts. In conclusion, our data confirm that quantum chemical calculations can contribute to a weight of evidence approach for the risk assessment of nitrosamines. [ABSTRACT FROM AUTHOR]

Background Results Conclusions Nitrite salts are frequently utilized as meat additives to improve the quality and safety of processed meat products. However, these salts are associated with the formation of carcinogenic nitrosamines. Given its potential regulating effect on the formation of intermediate molecules, such as nitric oxide, it is hypothesized that carnosine, a meat constituent possessing antioxidant activity and other multiple health benefits, could dampen the formation of nitrosamines. The current study therefore assessed the effect of carnosine on nitrosamine formation in both a monophasic aqueous system and a biphasic water–lipid system simulating a gastric environment.In the monophasic system, relatively high levels of carnosine were required to significantly reduce the formation of different species of nitrosamine compared with the control (no carnosine). While higher levels of some nitrosamines were generated in both phases of the biphasic system, low carnosine concentrations significantly suppressed nitrosamine formation in the aqueous phase, while in the lipid phase, intermediate levels of carnosine were required. At higher carnosine levels, further reduction in nitrosamines was observed in the lipid phase.This study demonstrates the capacity of carnosine to reduce nitrosamine formation in aqueous and lipid environments and suggests the potential of dietary carnosine to lower the risks associated with the consumption of processed meat products. © 2024 His Majesty the King in Right of Canada and The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. Reproduced with the permission of the Minister of Agriculture and Agri‐Food Canada. [ABSTRACT FROM AUTHOR]

N-Nitrosamines represent a class of bifunctional nitrogen-radical precursors, but their application potential remains largely unexplored. This study reports the highly atom-economical production of diverse α-oximino sulfonamides via direct photo-mediated radical relay oximinosulfonamidation of activated or unactivated alkenes with N-nitrosamines triggered by organic sulfide. N-Nitrosamines worked as bifunctional reagents in this transformation, simultaneously generating aminyl radicals and NO radicals. The organic sulfide was designed to act as a radical decaging agent as well as a source of sulfonyl. Its strong radical capturing ability and affinity for alkenes enable the rapid capturing of the aminyl radicals, thereby inhibiting the rapid recombination of radical pairs in the solvent cage. The synthesized oxime units could also be easily converted into other functional groups, leading to selective downstream transformations. The mild photodegradation reaction of harmful N-nitrosoamines showed high functional group tolerance and compatibility, facilitating the late-stage functionalization of natural products and drug molecules, expanding the biologically relevant chemical space. [ABSTRACT FROM AUTHOR]

• First estimation of nitrosamine intake via tobacco by smokers in 30 provinces, China. • First estimation of cancer risk (CR) of nitrosamines in tobacco to smokers in China. • CRs of NNK and NDMA are comparable in tobacco smoke (1.99 × 10−4 vs. 1.66 × 10 -4). • CR by nitrosamine intake: tobacco (3.80 × 10−4) > food (1.74 × 10−4) > water (1.38 × 10−5). • Tobacco smoking brings 202% extra cancer risk of nitrosamines to Chinese smokers. Nitrosamines are a class of carcinogens which have been detected widely in food, water, some pharmaceuticals as well as tobacco. The objectives of this paper include reviewing the basic information on tobacco consumption and nitrosamine contents, and assessing the health risks of tobacco nitrosamines exposure to Chinese smokers. We searched the publications in English from "Web of Science" and those in Chinese from the "China National Knowledge Infrastructure" in 2022 and collected 151 literatures with valid information. The content of main nitrosamines in tobacco, including 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), N -nitrosonornicotine (NNN), N -nitrosoanatabine (NAT), N -nitrosoanabasine (NAB), total tobacco-specific nitrosamines (TSNA), and N -nitrosodimethylamine (NDMA) were summarized. The information of daily tobacco consumption of smokers in 30 provinces of China was also collected. Then, the intakes of NNN, NNK, NAT, NAB, TSNAs, and NDMA via tobacco smoke were estimated as 1534 ng/day, 591 ng/day, 685 ng/day, 81 ng/day, 2543 ng/day, and 484 ng/day by adult smokers in 30 provinces, respectively. The cancer risk (CR) values for NNN and NNK inhalation intake were further calculated as 1.44 × 10−5 and 1.95 × 10−4. The CR value for NDMA intake via tobacco smoke (inhalation: 1.66 × 10−4) indicates that NDMA is similarly dangerous in tobacco smoke when compared with the TSNAs. In China, the CR values caused by average nitrosamines intake via various exposures and their order can be estimated as the following: smoke (3.75 × 10−4) > food (1.74 × 10−4) > drinking water (1.38 × 10−5). Smokers in China averagely suffer 200% of extra cancer risk caused by nitrosamines in tobacco when compared with non-smokers. [Display omitted] [ABSTRACT FROM AUTHOR]

This article explores the incorporation of fluorine atoms into organic compounds and its potential impact on their chemical and biological properties. Specifically, it focuses on the gem-difluoromethylene functionality as a bioisostere of the methylene group, which has applications in drug discovery. The article presents a detailed synthetic method for introducing the gem-difluoromethylene group using a building block approach. The method involves the preparation of sulfonate esters from sulfonyl chlorides and bromodifluoroethanol, followed by a photochemical Smiles rearrangement to generate the desired compound. Additionally, the article describes a synthesis method for gem-difluorinated thiophene, a compound that can be used as a building block in medicinal chemistry. The synthesis involves a multicomponent cyclization and oxidative chlorination reaction, followed by a radical Smiles rearrangement mediated by visible light. The authors provide supporting information and acknowledge the assistance of others in the analysis. [Extracted from the article]

This study was designed to study dual risk of MWFs and vibration according to exposure simulation of selected industry. Air samples of two types MWFs were evaluated according to NIOSH 5026. Vibration acceleration exposure was assessed based on the ISO 8041:2005 standard. Cell treatment of both MWF air samples and vibration as the same as dual exposure to MWF airborne and vibration was assessed. There is a potency of nitrosamine formation in airborne samples of ethylamine containing MWF, while heterocyclic including bore is found in airborne bore containing MWF. DNA breaks caused by boron-containing MWF were higher than nitrosamine air samples. Oxidative stress production and chronic inflammation were highlighted in the response to cell treatments. The risk of cell toxicity in machining workers was evaluated at a level lower than the occupational exposure limit for MWFs and vibration. [ABSTRACT FROM AUTHOR]

Tobacco carcinogens metabolism-related genes (TCMGs) could generate reactive metabolites of tobacco carcinogens, which subsequently contributed to multiple diseases. However, the association between genetic variants in TCMGs and bladder cancer susceptibility remains unclear. In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese population [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.72–0.97, P = 1.86 × 10–2]. Notably, AKR1C2 rs7087341 showed an interaction effect with cigarette smoking on bladder cancer risk (Pinteraction = 5.04 × 10–3), with smokers carrying the T allele increasing the risk up to an OR of 3.96 (Ptrend < 0.001). Genetically, rs7087341 showed an allele-specific transcriptional regulation as located at DNA-sensitive regions of AKR1C2 highlighted by histone markers. Mechanistically, rs7087341 A allele decreased AKR1C2 expression, which was highly expressed in bladder tumors that enhanced metabolism of tobacco carcinogens, and thereby increased DNA adducts and reactive oxygen species formation during bladder tumorigenesis. These findings provided new insights into the genetic mechanisms underlying bladder cancer. [ABSTRACT FROM AUTHOR]

The rapid expansion of urban areas and the increasing demand for water resources necessitate substantial investments in technologies that enable the reuse of municipal wastewater for various purposes. Nonetheless, numerous challenges remain, particularly regarding disinfection by-products (DBPs), especially carcinogenic compounds such as N-nitrosamines (NTRs). To tackle the ongoing issues associated with reverse osmosis (RO) membranes, this study investigated the rejection of NTRs across a range of commercially available RO membranes. In addition, the research aimed to improve rejection rates by integrating molecular plugs into the nanopores of the polyamide (PA) layer. Hexylamine (HEX) and hexamethylenediamine (HDMA), both linear chain amines, have proven to be effective as molecular plugs for enhancing the removal of NTRs. Given the environmental and human health concerns associated with linear amines, the study also aimed to assess the feasibility of diamine molecules as potential alternatives. The application of molecular plugs led to changes in pore size distribution (PSD) and effective pore number, resulting in a decrease in membrane permeability (from 5 to 33%), while maintaining levels suitable for RO processes. HEX and HDMA exhibited a positive effect on NTR rejection with ACM1, ACM5 and BW30LE membranes. In particular, NDMA rejection, the smallest molecule of the tested NTRs, with ACM1 was improved by 65.5% and 70.6% after treatment with HEX and HDMA, respectively. [ABSTRACT FROM AUTHOR]

Sensors play a critical role in the detection and monitoring of various substances present in our environment, providing us with valuable information about the world around us. Within the field of sensor development, one area that holds particular importance is the detection of small molecules. Small molecules encompass a wide range of organic or inorganic compounds with low molecular weight, typically below 900 Daltons including gases, volatile organic compounds, solvents, pesticides, drugs, biomarkers, toxins, and pollutants. The accurate and efficient detection of these small molecules has attracted significant interest from the scientific community due to its relevance in diverse fields such as environmental pollutants monitoring, medical diagnostics, industrial optimization, healthcare remedies, food safety, ecosystems, and aquatic and terrestrial life preservation. To meet the demand for precise and efficient monitoring of small molecules, this summary aims to provide an overview of recent advancements in sensing and quantification strategies for various organic small molecules including Hydrazine, Glucose, Morpholine, Ethanol amine, Nitrosamine, Oxygen, Nitro-aromatics, Phospholipids, Carbohydrates, Antibiotics, Pesticides, Drugs, Adenosine Triphosphate, Aromatic Amine, Glutathione, Hydrogen Peroxide, Acetone, Methyl Parathion, and Thiophenol. The focus is on understanding the receptor sensing mechanism, along with the electrical, optical, and electrochemical response. Additionally, the variations in UV–visible spectral properties of the ligands upon treatment with the receptor, fluorescence and absorption titration analysis for limit of detection (LOD) determination, and bioimaging analysis are discussed wherever applicable. It is anticipated that the information gathered from this literature survey will be helpful for the perusal of innovation regarding sensing strategies. [ABSTRACT FROM AUTHOR]

The objective of this research was to investigate the impact of inoculating autochthonous starter cultures on the alterations in microorganisms, biogenic amines, nitrite, and N-nitrosamines in Chinese traditional fermented fish products (CTFPs) during in vitro human digestion. The results revealed that gastric digestion significantly (p < 0.05) inhibited the proliferation of lactic acid bacteria, yeast, Staphylococcus, and Enterobacteriaceae, whereas various microorganisms proliferated extensively during small intestine digestion. Meanwhile, small intestine digestion could significantly increase (p < 0.05) levels of putrescine, cadaverine, and tyramine. The reduced content observed in inoculated fermentation groups suggests that starter cultures may have the ability to deplete biogenic amines in this digestion stage. Gastric digestion significantly (p < 0.05) inhibited nitrite accumulation in all CTFPs samples. Conversely, the nitrite content increased significantly (p < 0.05) in all groups during subsequent small intestine digestion. However, the rise in the inoculated fermentation groups was smaller than that observed in the spontaneous fermentation group, indicating a potentially positive role of inoculated fermentation in inhibiting nitrite accumulation during this phase. Additionally, gastric digestion significantly (p < 0.05) elevated the levels of N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine in CTFPs. Inoculation with L. plantarum 120, S. cerevisiae 2018, and mixed starter cultures (L. plantarum 120, S. cerevisiae 2018, and S. xylosus 135 [1:1:1]) effectively increased the degree of depletion of NDMA during this digestion process. [ABSTRACT FROM AUTHOR]

Nitrosamine compounds pose a significant concern as potential carcinogens, prompting heightened scrutiny from regulatory bodies, particularly regarding their presence in pharmaceuticals. The detection of unacceptable levels of N‐nitrosodiethylamine (NDMA) in ranitidine has led to widespread recalls, driving interest in alternative medications such as nizatidine, which shares a similar pharmacological class and is used to treat various gastrointestinal conditions. Despite fewer reports on NDMA levels in nizatidine, its structural similarity to ranitidine, characterized by a tertiary amine, underscores the potential for NDMA formation. Addressing the analytical challenges associated with nitrosamine detection, this study focuses on developing and validating an ultra‐high pressure liquid chromatography triple quadrupole mass spectrometry (UHPLC–MS/MS) method for quantifying NDMA in both nizatidine active pharmaceutical ingredients and tablet formulations. Method validation adheres to International Council for Harmonisation recommendations, with a demonstrated linear range of 0.25–100 ng/mL for NDMA, exhibiting excellent linearity (regression coefficient >0.999) and efficient recovery rates ranging from 95.98% to 109.57%. The method shows high sensitivity, with limits of detection and quantification of 0.25 and 0.5 ng/mL, respectively. The developed UHPLC–MS/MS method offers a simple, precise, accurate, and selective approach for monitoring NDMA levels in nizatidine formulations available in Australia, promising enhanced sensitivity and specificity with limits of quantification in the ppb and sub‐ppb ranges. [ABSTRACT FROM AUTHOR]

In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and tanshinone IIA, arachidonic acid, and quercetin, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of PLAU and IGFBP3. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression via regulating the expression of PLAU and IGFBP3. [ABSTRACT FROM AUTHOR]

The world is committed to reducing CO2 emissions, and research on CO2 capture and effective utilization is being actively studied. Among the methods in development, direct air capture (DAC) is classified as a negative emission technology and has attracted significant study. The current problem with CO2 capture technologies for decarbonization is their cost due to the high separation energy required to release CO2. We have developed a new light-swing method that can potentially utilize a natural source of energy, i.e., sunlight, as an alternative to temperature- and pressure-swing methods. Herein, we report photoirradiation-based CO2 capture based on photoisomerization of azobenzene-amine and guanidine derivatives. The visible light-swing CO2 absorption and release system using azobenzene-guanidine has shown potential in DAC systems owing to its reusability. A plausible mechanism for CO2 release under light irradiation involves photoisomerization from trans- to cis-azobenzene in which steric repulsion with other molecules is the driving force, and CO2 is released due to the functional disruption of intermolecular interactions. This concept demonstrates the potential of using various photokinetic molecules as a driving force for light-swing CO2 capture. [ABSTRACT FROM AUTHOR]

Background: Digital dermatitis (DD) is a contagious bovine foot disease causing reduced animal welfare and negative economic consequences for the farmer. Treponema spp. are the most important causative agents. Studies indicate that trimming equipment can transfer DD-associated treponemes between cows. The aim of this observational study in 22 DD-positive Norwegian dairy herds was to investigate the risk of transferring Treponema spp. with trimming equipment and chutes after claw trimming, and after washing and disinfection. Swabs from the trimming equipment and chutes were collected from nine different locations, at five different time points. Bacterial DNA was extracted from 647 swabs and analysed by qPCR for Treponema spp. In addition, 172 swabs taken immediately after trimming, were analysed by a multiplex qPCR targeting T. phagedenis, T. pedis and T. medium/vincentii. Biopsy sampling from DD lesions was performed on cows in the same herds during trimming. Altogether 109 biopsies were analysed by FISH for confirmation of the DD diagnosis and identification of Treponema phylotypes (PTs). Results: High numbers of Treponema spp. were detected from all nine locations on the trimming equipment and chutes immediately after trimming, and T. phagedenis was detected on two or more locations in all but two herds, 1 and 19. There was a decline in the amount of Treponema spp. after washing and disinfection. The belly belt, the cuff, and the footrest on the chute had the highest proportion of positive samples after disinfection. The belly belt had the highest copy numbers of all nine locations (median = 7.9, max = 545.1). No Treponema spp. was detected on the hoof knives after disinfection. Treponema phagedenis, T. pedis, and Treponema phylotype 3 (T. refringens) were detected by FISH analysis of the biopsies. Treponema phagedenis was detected in biopsies from all herds except 1 and 19. Conclusion: This study shows that DD-associated Treponema spp. were present on the trimming equipment and chutes after trimming cows in DD-positive herds. Washing and disinfection reduced the load of Treponema spp. However, large differences in Treponema spp. between different locations were documented. High copy numbers on the grinder and the chute after disinfection, indicates that sufficient cleaning and disinfection of these locations is difficult, and that passive transfer of DD-associated treponemes (viable or not) is possible. [ABSTRACT FROM AUTHOR]

Electronic cigarettes (e-cigarettes), as alternative nicotine delivery methods, has rapidly increased among youth and adults in recent years. However, cardiovascular safety is an important consideration regarding e-cigarettes usage. e-cigarette emissions, including nicotine, propylene glycol, flavorings, nitrosamine, and metals, might have adverse effects on cardiovascular health. A large body of epidemiological evidence has indicated that e-cigarettes are considered an independent risk factor for increased rates of cardiovascular disease occurrence and death. The incidence and mortality of various types of cardiovascular disease, such as cardiac arrhythmia, hypertension, acute coronary syndromes, and heart failure, have a modest growth in vapers (users of e-cigarettes). Although the underlying biological mechanisms have not been fully understood, studies have validated that oxidative stress, inflammation, endothelial dysfunction, atherosclerosis, hemodynamic effects, and platelet function play important roles in which e-cigarettes work in the human body. This minireview consolidates and discusses the epidemiological and biological links between e-cigarettes and various types of cardiovascular disease. [ABSTRACT FROM AUTHOR]

The potential for drug substances and drug products to contain low levels of N -nitrosamines is of continued interest to the pharmaceutical industry and regulatory authorities. Acid-promoted nitrosation mechanisms in solution have been investigated widely in the literature and are supported by kinetic modelling studies. Carbonyl compounds, particularly formaldehyde, which may be present as impurities in excipients and drug product packaging components or introduced during drug substance manufacturing processes are also known to catalyze nitrosation, but their impact on the risk of N -nitrosamine formation has not been systematically investigated to date. In this study, we experimentally investigated the multivariate impact of formaldehyde, nitrite and pH on N -nitrosation in aqueous solution using dibutylamine as a model amine. We augmented a published kinetic model by adding formaldehyde-catalyzed nitrosation reactions. We validated the new kinetic model vs. the experimental data and then used the model to systematically investigate the impact of formaldehyde levels on N -nitrosamine formation. Simulations of aqueous solution systems show that at low formaldehyde levels the formaldehyde-catalyzed mechanisms are insignificant in comparison to other routes. However, formaldehyde-catalyzed mechanisms can become more significant at neutral and high pH under higher formaldehyde levels. Model-based sensitivity analysis demonstrated that under high nitrite levels and low formaldehyde levels (where the rate of formaldehyde-catalyzed nitrosation is low compared to the acid-promoted pathways) the model can be used with kinetic parameters for model amines in the literature without performing additional experiments to fit amine-specific parameters. For other combinations of reaction parameters containing formaldehyde, the formaldehyde-catalyzed kinetics are non-negligible, and thus it is advised that, under such conditions, additional experiments should be conducted to reliably use the model. [Display omitted] • Automated experimental investigation of formaldehyde-catalyzed N -nitrosation of dibutylamine in the presence of nitrite in aqueous solution. • An augmented kinetic model for the solution phase N -nitrosation of dialkyl amines including formaldehyde-catalyzed reactions is presented. • Simulations show that acid-promoted nitrosation mechanisms have significantly greater impact on nitrosamine formation than formaldehyde-catalyzed mechanisms at low formaldehyde concentrations. • Formaldehyde-catalyzed mechanisms become more significant at neutral to high pH in the presence of high levels of formaldehyde, e.g., during certain synthetic or workup steps. • Global sensitivity analysis shows that experimental data should be generated for an amine without available kinetic parameters required to use the model. [ABSTRACT FROM AUTHOR]

The detection of nitrosamine impurities, particularly small dialkyl types, which are frequently known to be potent mutagenic carcinogens, in some Sartan group active pharmaceutical ingredients (APIs) and finished drug products caused global regulatory organizations to have concerns. Accordingly, Registration Holders/Applicants, API manufacturers, and their raw material suppliers are required to check the presence of nitrosamines in their products and carry out risk assessments using the quality risk management principles specified in the ICH Q9 guide. In this context, a new LC-MS/MS method has been developed and validated for the simultaneous determination of NDMA, NDEA, NMBA, NDIPA, NEIPA, NDBA, and MeNP nitrosamine compounds in API and finished products as well as in primary packaging materials, one of the risk sources. This validated method was applied to check the nitrosamine content may occur from canister, blister, printed aluminum foil, nasal spray, and eye drop packaging materials as part of the Extractables & Leachables studies arising from interactions between the product and the primary packaging. For the determination and quality control of nitrosamines in sartan group pharmaceutical products and packaging materials, the developed LC-MS/MS analytical method offers highly reliable, fast, high accuracy, good sensitivity and simultaneous detection even at low concentrations. • A new LC-MS/MS method was developed and validated for the detection of nitrosamine impurities in different combined finished products containing sartan group and alu-foil packaging. • Different packaging components were studied within the scope of the Extractables&Leachables study to evaluate the possibility of leaching not only from tablet blisters but also from different pharmaceutical packaging components and ink printed labels. • Validation parameters and acceptance criteria were determined in accordance with USP 〈736〉 mass spectrometry monograph and ICH Q2 (R2) guide. • Packaging components (such as canister, blister, printed aluminum foil, nasal spray, and eye drop packaging materials) were checked in accordance with risk assessment studies carried out in line with the ICH Q9 guide. [ABSTRACT FROM AUTHOR]

Dietary exposure to N-nitrosamines has recently been assessed by the European Food Safety Authority (EFSA) to result in margins of exposure that are conceived to indicate concern with respect to human health risk. However, evidence from more than half a century of international research shows that N-nitroso compounds (NOC) can also be formed endogenously. In this commentary of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG), the complex metabolic and physiological biokinetics network of nitrate, nitrite and reactive nitrogen species is discussed with emphasis on its influence on endogenous NOC formation. Pioneering approaches to monitor endogenous NOC have been based on steady-state levels of N-nitrosodimethylamine (NDMA) in human blood and on DNA adduct levels in blood cells. Further NOC have not been considered yet to a comparable extent, although their generation from endogenous or exogenous precursors is to be expected. The evidence available to date indicates that endogenous NDMA exposure could exceed dietary exposure by about 2–3 orders of magnitude. These findings require consolidation by refined toxicokinetics and DNA adduct monitoring data to achieve a credible and comprehensive human health risk assessment. [ABSTRACT FROM AUTHOR]

We aimed to examine the potential protective effects of Iraqi H. tiliaceus L. chloroform leaves extract on DEN-induced HCC in male Wistar Albino rats. Rats were assigned to four groups, six in each group. Group I: rats were administered a daily oral dose of 1 mL/kg/day of distilled water. Group II: rats were intraperitoneally injected with 70 mg/kg DEN once per week for 10 consecutive weeks. Group III: rats received 250 mg/kg of chloroform leaves extract. Groups IV: the rats were administered 500 mg/kg of chloroform leaves extract, along with their food, for five days per week over 20 weeks, with a subsequent dose of DEN once per week for 10 consecutive weeks. The results indicate that the extract demonstrated a significant reduction (p<0.05) in oxidative stress, pro-inflammatory mediators, and HCC parameters, the extract also had a beneficial effect on liver function tests, and there was a significant elevation (p<0.05) of antioxidant parameters in a dose-dependent manner. This study supports the protective properties of the chloroform extract of Iraqi H. tiliaceus L. leaves in HCC. [ABSTRACT FROM AUTHOR]

Tobacco-specific nitrosamines (TSNAs) are a group of toxic substances specific to tobacco. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. We aimed to examine the association between urinary tobacco-specific NNAL and HPV infection among American women. We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014 to collect details on their urinary NNAL, HPV infection status, and other essential variables. The association between dietary urinary NNAL and HPV infection status was analyzed by using a weighted multivariate logistic regression model, and stratified subgroup analysis. In total, 5197 participants aged 18–59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 22.0% and 19.1%, respectively. The highest quartile of NNAL(Q4) was more positively associated with low-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 1.83 (1.35,2.50), p<0.001). the highest quartile of NNAL(Q4) was more positively associated with high-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 2.20 (1.57,3.08), p < 0.001). In subgroup analyses, the positive correlation between urinary NNAL levels and low-risk HPV infection status was inconsistent in marital status and BMI (interaction p < 0.05). The positive association of urinary NNAL levels with high-risk HPV infection status was inconsistent in smoking and BMI. (interaction p < 0.05). Tobacco-specific NNAL levels positively correlate with high- and low-risk HPV. Future well-designed longitudinal studies are still needed to validate the effect of tobacco exposure on HPV infection by NNAL. [ABSTRACT FROM AUTHOR]

Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in the increased release of chloramine disinfectants into surface water, significantly promoting the formation of nitrosamine disinfection by-products (DBPs) in drinking water. Unfortunately, these nitrosamine DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating disinfectants remain in global practice. The current review provides valuable insights into the occurrence, identification, contamination status, exposure limits, and toxicity of the new unregulated disinfection by-products (nitrosamine DBPs) in drinking water. As a result, concentrations of nitrosamine DBPs far exceed allowable limits in drinking water, and prolonged exposure has the potential to cause metabolic disorders, a critical step in tumor initiation and progression. Importantly, based on recent research, we have concluded the role of nitrosamines DBPs in different metabolic pathways. Remarkably, nitrosamine DBPs can induce chronic inflammation and initiate tumors by activating sphingolipid and polyunsaturated fatty acid metabolism. Regarding amino acid and nucleotide metabolism, nitrosamine DBPs can inhibit tryptophan metabolism and de novo nucleotide synthesis. Moreover, inhibition of de novo nucleotide synthesis fails to repair DNA damage induced by nitrosamines. Additionally, the accumulation of lactate induced by nitrosamine DBPs may act as a pivotal signaling molecule in communication within the tumor microenvironment. However, with the advancement of tumor metabolomics, understanding the role of nitrosamine DBPs in causing cancer by inducing metabolic abnormalities significantly lags behind, and specific mechanisms of toxic effects are not clearly defined. Urgently, further studies exploring this promising area are needed. [ABSTRACT FROM AUTHOR]

Concern over safe drinking water has increased. In this study, aluminum oxide was coated with carbon nanotubes by chemical vapor deposition using ethanol or methanol as precursors to remove N-nitrosamines, 2-methylisoborneol (MIB) and geosmin from water. Seven types of N-nitrosamines were investigated. The differences in the surface of the carbon nanotubes were attributed to the carbon precursors ethanol and methanol. Despite the high concentration of analytes, the adsorption capacity of both carbon nanotubes (CNTs) was around 19 mg/mg for MIB and geosmin. Against approximately 0.9 ng/mg for activated carbon. For N-nitrosamines, the adsorption capacity of CNTs reached 50 ng/mg for NDBA, N-nitrosamines with the highest molecular weight, while activated carbon had values below 6.0 ng/mg. The results showed π-π interactions play a dominant role in the adsorption of MIB and geosmin under the investigated conditions. On the other hand, for N-nitrosamines, both dipole-dipole and π-π interactions come into play, with the latter becoming more prominent as the molecular weight of N-nitrosamines increases. The removal efficiencies of CNT-coated aluminum oxide reached 84,0%. The analytes with longer carbon chains were removed more efficiently and CNT-coated aluminum oxide grown from ethanol or methanol had no statistical difference between the removal efficiencies of all evaluated analytes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Heterocyclic amines (HAs) and N‐nitrosamines (NAs) are formed easily during the thermal processing of food, and epidemiological studies have demonstrated that consuming HAs and NAs increases the risk of cancer. However, there are few studies on the application of back propagation artificial neural network (BP‐ANN) models to simultaneously predict the content of HAs and NAs in sausages. This study aimed to investigate the effects of cooking time and temperature, smoking time and temperature, and fat‐to‐lean ratio on the formation of HAs and NAs in smoked sausages, and to predict their total content based on the BP‐ANN model. RESULTS: With an increase in processing time, processing temperature and fat ratio, the content of HAs and NAs in smoked sausages increased significantly, while the content of HA precursors and nitrite residues decreased significantly. The optimal network topology of the BP‐ANN model was 5–11–2, the correlation coefficient values for training, validation, testing and all datasets were 0.99228, 0.99785, 0.99520 and 0.99369, respectively, and the mean squared error value of the best validation performance was 0.11326. The bias factor and the accuracy factor were within acceptable limits, and the predicted values approximated the true values, indicating that the model has good predictive performance. CONCLUSION: The contents of HAs and NAs in smoked sausages were significantly influenced by the cooking conditions, smoking conditions and fat ratio. The BP‐ANN model has high application value in predicting the contents of HAs and NAs in sausages, which provides a theoretical basis for the suppression of carcinogen formation. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The hepatoprotective effect of synthesized 3-(3,5-bis (trifluoromethyl) phenyl)-5-methyl-1-((1- methyl-1H-pyrrol-2-yl) methyl)-2-thioxoimidazolidin-4-one (3FL-M) was evaluated against diethyl nitrosamineinduced liver injury (DEN). Wistar rats were divided into 3 groups as: placebo (received 10% tween 80%), hepatotoxic control (injected with 200 mg/kg of DEN) and treatment (injected 200 mg/kg of DEN and received 50 mg/kg oral feeding of the synthesized 3FL-M). Half the number of the rats were sacrificed on 2nd week of the experiment, whereas the other half were sacrificed after 6 weeks. Blood was collected to run liver biochemical analysis, and to evaluate pro-inflammatory cytokines tumor necrosis factor-alpha TNF-α and interleukine6 IL-6. Liver sections were used to detect nuclear protein ki-67 and hepatocyte specific antibody HSA. 3FL-M was subjected to molecular docking calculations based on binding affinities towards TNF-α and IL-6. DEN-treated rats showed elevation in the liver serum enzymes as well as pro-inflammatory cytokines with clear destruction of the hepatic architecture, in contrast 3FL-M treated rats showed normalized liver enzymes and cytokines levels with resolution of the hepatocytes. Molecular modelling revealed that 3FL-M exhibited the significant affinities toward the binding pocket of the TNF-α and IL-6, however, further studies is recommended for developing it as a chemotherapeutic drug-like molecule. [ABSTRACT FROM AUTHOR]

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p <.05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice. [ABSTRACT FROM AUTHOR]

N‐Nitrosamines acting as contaminants in our environment is a topic of increasing concern. Detection methods are required, necessitating analytical standards. Herein, we discuss some conventional methodologies to prepare N‐nitrosamines and compare them with unconventional pathways towards their synthesis. These methods are often more environmentally benign and safer. [ABSTRACT FROM AUTHOR]

A reversed‐phase ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method is presented for the quantification of the mutagenic impurity 7‐nitroso‐3‐(trifluoromethyl)‐5,6,7,8‐tetrahydro‐[1,2,4]triazolo[4,3‐a]pyrazine found in three sitagliptin drug substances (sitagliptin base [SG], sitagliptin hydrochloride monohydrate [SG HCl{H}] salt, and sitagliptin phosphate monohydrate [SG P{H}] salt). A simple and highly sensitive method was developed for SG, SG HCl(H) salt, and SG P(H) salt. Sample preparation was adapted to each product considering solubility, sensitivity, and accuracy issues. Chromatographic separation was achieved using an Acquity HSS T3 column (3.0 × 100 mm, 1.8 μm) and a mobile phase consisting of formic acid 0.1% in water combined with methanol. Detection and quantification of the impurity were carried out using triple quadrupole mass spectrometry detection with electrospray ionization in the multiple reaction monitoring mode. The limit of detection and limit of quantification was found to be 0.1–0.3 and 10 ppb, respectively. The accuracy and precision of the method were satisfactorily determined with recovery values between 74.1% and 119.4%. Linearity is demonstrated in the range of 10 and 2000 ppb with regression coefficients (R) within the range of 0.9918–0.9972. The method is currently used for the analysis of the mutagenic impurity in the three‐drug substances in the Moehs Group. [ABSTRACT FROM AUTHOR]

N-nitrosamine pollutants are probable carcinogens. Regulatory agencies declared their presence in the drugs unsafe for human consumption and demanded their recall. Using ultra-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (UPLC-APCI-MS/MS) in tablet dosage form based on International Conference on Harmonization (ICH) tripartite guideline criteria, we aim to develop and test a new approach for identifying and validating nitrosamine-contaminants, N -nitrosodimethylamine (NDMA) and N -nitrosodiethylamine (NDEA) in irbesartan, olmesartan and metformin. The column was Phenomenex Luna-C18, 100 × 3.0 mm and 3.0 μm. A mobile gradient phase of formic acid in either water or methanol separated the impurities. NDMA and NDEA had retention times of 0.85 and 2.55 min, respectively. The detector's linearity was established at concentrations ranging from 0.6 to 100 ng/mL. R2 for NDMA and NDEA were 0.9996 and 0.9998, respectively, with a linear response function established at 0.6–100 ng/mL. Limit of detection and limit of quantification for NDMA and NDEA were 0.35, 0.29 and 0.55, 0.37 ng/mL, respectively. On average, recovery rates for NDMA and NDEA ranged from 96.0 to 98.4 and 96.2 to 98.0%, respectively. The relative standard deviation for NDMA and NDEA was 3.46 and 2.69, respectively. According to the ICH guidelines, the developed method was quick, sensitive and valid. The pharmaceutical formulations of irbesartan, olmesartan and metformin may be regularly examined using the approach provided here. [ABSTRACT FROM AUTHOR]

Inorganic nitrate provided by either nitrate salts or food supplements may improve cardiometabolic health. However, current methods to assess dietary nitrate, nitrite and nitrosamine consumption are inadequate. The purpose of this study was to develop a reference database to estimate the levels of nitrate, nitrite and nitrosamines in the global food supply. A systematic literature search was undertaken; of the 5,747 articles screened, 448 met the inclusion criteria. The final database included data for 1,980 food and beverages from 65 different countries. There were 5,105 unique records for nitrate, 2,707 for nitrite, and 954 for nitrosamine. For ease of use, data were sorted into 12 categories; regarding nitrate and nitrite concentrations in food and beverages, 'vegetables and herbs' were most reported in the literature (n = 3,268 and n = 1,200, respectively). For nitrosamines, 'protein foods of animal origin' were most reported (n = 398 records). This database will allow researchers and practitioners to confidently estimate dietary intake of nitrate, nitrite and nitrosamines. When paired with health data, our database can be used to investigate associations between nitrate intake and health outcomes, and/or exercise performance and could support the development of key dietary nitrate intake guidelines. [ABSTRACT FROM AUTHOR]

The robust control of genotoxic N -nitrosamine (NA) impurities is an important safety consideration for the pharmaceutical industry, especially considering recent drug product withdrawals. NAs belong to the 'cohort of concern' list of genotoxic impurities (ICH M7) because of the mutagenic and carcinogenic potency of this chemical class. In addition, regulatory concerns exist regarding the capacity of the Ames test to predict the carcinogenic potential of NAs because of historically discordant results. The reasons postulated to explain these discordant data generally point to aspects of Ames test study design. These include vehicle solvent choice, liver S9 species, bacterial strain, compound concentration, and use of pre-incubation versus plate incorporation methods. Many of these concerns have their roots in historical data generated prior to the harmonization of Ames test guidelines. Therefore, we investigated various Ames test assay parameters and used qualitative analysis and quantitative benchmark dose modelling to identify which combinations provided the most sensitive conditions in terms of mutagenic potency. Two alkyl-nitrosamines, N -nitrosodimethylamine (NDMA) and N -nitrosodiethylamine (NDEA) were studied. NDMA and NDEA mutagenicity was readily detected in the Ames test and key assay parameters were identified that contributed to assay sensitivity rankings. The pre-incubation method (30-min incubation), appropriate vehicle (water or methanol), and hamster-induced liver S9, alongside Salmonella typhimurium strains TA100 and TA1535 and Escherichia coli strain WP2uvrA(pKM101) provide the most sensitive combination of assay parameters in terms of NDMA and NDEA mutagenic potency in the Ames test. Using these parameters and further quantitative benchmark dose modelling, we show that N -nitrosomethylethylamine (NMEA) is positive in Ames test and therefore should no longer be considered a historically discordant NA. The results presented herein define a sensitive Ames test design that can be deployed for the assessment of NAs to support robust impurity qualifications. [ABSTRACT FROM AUTHOR]

Nitrite, nitrate, and their salts are added to processed meat products to improve color, flavor, and shelf life and to lower the microbial burden. N-Nitrosamine compounds are formed when nitrosing agents (such as secondary nitrosamines) in meat products interact with nitrites and nitrates that have been added to the meat. With the consumption of such meat products, nitrosation reactions occur in the human body and N-nitrosamine formation occurs in the gastrointestinal tract. Despite the benefits nitrites and nitrates have on food, their tendency to create nitrosamines and an increase in the body's nitrous amine load presents health risks. The inclusion of nitrosamine compounds in possible and probable carcinogen classes according to the International Agency for Research on Cancer requires a re-examination of the literature review on processed meat products. This article evaluates the connections between various cancer types and nitrosamines found in processed meat products. [ABSTRACT FROM AUTHOR]

Rationale: Enasidenib (EDB) is an orally active selective mutant isocitrate dehydrogenase‐2 enzyme inhibitor approved by the U.S. Food and Drug Administration to treat acute myeloid leukemia. It lacks a reported forced degradation study and a stability‐indicating assay method (SIAM). This study addresses this gap by establishing a degradation profile in accordance with the International Council for Harmonisation Q1A and Q1B (R2) guidelines and developing a validated SIAM for EDB. Methods: EDB was exposed to forced degradation under various conditions (hydrolytic, photolytic, oxidative, and thermal stress). Degradation samples were analyzed using high‐performance liquid chromatography on an Agilent ZORBAX Eclipse Plus C18 column with a mobile phase consisting of 0.1% formic acid in Milli‐Q water and acetonitrile at a flow rate of 1 mL/min and detection at 270 nm. Liquid chromatography‐quadrupole time‐of‐flight‐high‐resolution mass spectrometry (LC/Q‐TOF HRMS) was used for the identification and characterization of degradation products. Nitrosamine risk assessment was conducted using a modified nitrosation assay procedure (NAP) test due to the presence of a secondary amine group in the drug, which is liable to forming nitrosamine drug substance–related impurities (NDSRI). Results: The drug exhibited significant degradation under acidic, basic, photolytic, and oxidative conditions in the solution state. A total of nine degradation products (DP) were formed (DP‐I, DP‐III, and DP‐IV: acidic conditions; DP‐I and DP‐III: basic conditions; DP‐II, DP‐V, DP‐VI, and DP‐VII: oxidative stress; and DP‐VII, DP‐VIII, and DP‐IX: photolytic conditions), which were separated and identified using reversed‐phase high‐performance liquid chromatography and characterized using liquid chromatography–tandem mass spectrometry. The mechanism behind the formation of EDB degradation products has been discussed, and this study was the first to develop a degradation pathway for EDB. In addition, the possibilities of NDSRI formation for EDB were studied using a modified NAP test, which can contribute to the risk assessment of the drug. Conclusions: Forced degradation studies were conducted by establishing a SIAM for EDB. All the degradation products were characterized by mass spectral data obtained using LC/Q‐TOF‐HRMS. [ABSTRACT FROM AUTHOR]

Background Studying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer. Methods The Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma. Results Among individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N' -Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users. Conclusion These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications. [ABSTRACT FROM AUTHOR]

Introduction Smoking exposes people to high levels of Tobacco-Specific Nitrosamines (TSNAs), which include potent carcinogens. We systematically reviewed TSNA exposure between people smoking, vaping, and doing neither. Aims and Methods Databases were searched between August 2017–March 2022, using vaping-related terms. Peer-reviewed articles reporting TSNA metabolites (NNAL, NNN, NAB, and NAT) levels in bio-samples among adults exclusively vaping, exclusively smoking, or doing neither were included. Where possible, meta-analyses were conducted. Results Of 12 781 identified studies, 22 were included. TSNA levels fell substantially when people who smoke switched to vaping in longitudinal studies and were lower among people who vaped compared to smoked in cross-sectional studies. Levels of TSNAs were similar when comparing people who switched from smoking to vaping, to those who switched to no use of nicotine products, in longitudinal studies. Levels were higher among people who vaped compared to people who neither vaped nor smoked in cross-sectional studies. When comparing people who vaped to smoked: pooled urinary NNAL was 79% lower across three randomized controlled trials and 96% lower across three cross-sectional studies; pooled NAB was 87% lower and NAT 94% lower in two cross-sectional studies. When comparing people who neither vaped nor smoked to people who vaped, pooled urinary NNAL was 80%, NAB 26%, and NAT 27% lower in two cross-sectional studies. Other longitudinal data, and NNN levels could not be pooled. Conclusions Exposure to all TSNAs was lower among people who vaped compared to people who smoked. Levels were higher among people who vaped compared to people who neither vaped nor smoked. Implications As well as TSNAs, there are many other toxicant exposures from smoking and vaping that can increase the risk of disease. However, it is likely that the reduced exposure to TSNAs from vaping relative to smoking reduces the risk to health of those who use vaping products to quit smoking. Future high-quality research, with robust definitions of exclusive vaping and smoking, and accounting for TSNAs half-lives, is needed to fully assess exposure to TSNAs among people who vape. [ABSTRACT FROM AUTHOR]

Heated Tobacco Products (HTPs) purport to reduce exposure to tobacco-related toxicants compared to combustible cigarettes. This cross-sectional study examined the content of nicotine, two humectants (propylene glycol (PG) and vegetable glycerin (VG)), and four tobacco-specific nitrosamines (TSNAs: NNN, NNK, NAT, and NAB) in the tobacco filler of a popular HTP brand (IQOS). Non-menthol and menthol IQOS sticks were purchased from nine countries between 2017 and 2020 and were classified into two versions ("Bold" and "Light") using Philip Morris's flavor descriptors. The average nicotine concentration was 4.7 ± 0.5 mg/stick, and the highest nicotine concentration was found in products from Japan (5.1 ± 0.2 mg/stick). VG was the dominant humectant found in all sticks, with an average concentration of (31.5 ± 2.3 mg/stick). NNN, NNK, and NAT were substantially higher in the "Bold" sticks than the "Light" sticks. Significant differences between countries for TSNAs were also observed: the NAT and NAB contents were the highest in the "Light" products from Canada (192.5 ± 24.1 and 22.9 ± 1.0 ng/stick, respectively); the NNK concentration was the highest in the "Bold" products from Poland (64.8 ± 7.9 ng/stick); and the highest NNN concentrations were observed in the "Bold" products from South Africa (488.9 ± 26.7 ng/stick). As NNN and NNK are known human carcinogens, and as humectants like PG and VG can degrade into toxic carbonyl compounds upon heating, monitoring the concentration of these chemicals in HTPs is important for protecting users' health and ensuring compliance with regulations. [ABSTRACT FROM AUTHOR]

Nitroso derivatives with unique characteristics have been extensively studied in various fields, including biology and clinical research. Although there has been substantial investigation of "nitrosable" components in many drugs and commonly consumed nutrients, there is still a need for a higher awareness about their formation and characterization. This study demonstrates how these derivatives can be produced through a mechanochemical procedure under solid‐state conditions. The results include synthesizing previously unknown compounds with potential biological and pharmaceutical applications, such as a nitrosamine derived from a Diclofenac‐like structure. [ABSTRACT FROM AUTHOR]

A sensitive and robust method for determination and quantification of potential genotoxic impurities in sartans has been developed. These impurities need to be controlled at trace levels during quantification in drug substances and drug products for safe consumption. Recent regulatory requirements also suggested the need to have highly sensitive analytical method for trace level quantification of nitrosamine impurities. In this paper, we have described a simple, rapid and sensitive liquid chromatography-mass spectrometry method for six potential genotoxic nitrosamine impurities: N-Nitroso dimethyl amine (NDMA), N-Nitroso diethyl amine (NDEA), N-Nitroso Ethyl Iso propylamine (NIPEA), N-Nitroso-Nmethyl-4-aminobutyric acid (NMBA) N-Nitroso diisopropylamino (NDIPA) and N-Nitroso dibutyl amine (NDBA) in Azilsartan (AZL), Valsartan (VAL), Telmisartan (TEL), Olmesartan (OLM), Losartan (LOS) and Irbesartan (IRB) with a limit of quantification of less than 0.003 ppm. Chromatographic separation is achieved using Poroshell HPH- C18, 150 × 4.6 mm, 2.7 μm column with 0.1% formic acid in water as mobile phase A and 0.1% formic acid in methanol as mobile phase B at a flow rate of 0.5 mL/min using gradient mode of elution at a total run time of 20 min. Six nitrosamine impurities are ionized and quantified in positive mode of atmospheric pressure chemical ionization using multiple reaction monitoring. As per ICH guidelines, method validation is performed and evaluated the limit of quantification and detection and found to give good S/N ratios with good linearity range of 0.003–0.045 ppm with regression coefficient > 0.999 for all the six nitrosamine impurities. Method recoveries are also established using three-step sample preparation and are found to be satisfactory within 80–120%. The single method can be used routinely applied for the detection of nitrosamines in AZL, VAL, TEL, OLM, LOS and IRB. [ABSTRACT FROM AUTHOR]

Tobacco product use is a risk factor in the development of oral cancer, although epidemiology studies show this risk is far less with smokeless tobacco product use than cigarette smoking. While smokeless tobacco contains harmful and potentially harmful constituents (HPHCs), the oral permeation of HPHCs in oral tobacco products is not completely understood. To improve the understanding, three different extract concentrations of the CORESTA reference products (CRP) for snus (CRP1.1) and moist snuff (CRP2.1) were applied to cellular tissue derived from two donors of EpiOral™ model, a 3D human buccal model, and permeation of nicotine and tobacco-specific nitrosamines (TSNAs) were measured over two hours. Permeation of 0.15% caffeine in complete artificial saliva and cell viability were also measured. Results showed that a consistent and concentration dependent cumulative permeation of nicotine and TSNAs was observed with high percent recovery in all conditions. A high degree of sensitivity was seen for all analytes, with minimal cytotoxicity for both CRPs. The data presented here show the EpiOral™ model is fit-for-purpose to evaluate the permeation of nicotine and TSNAs in nicotine-containing snus and moist snuff oral tobacco. • Fit-for-purpose 3D buccal in vitro model for smokeless tobacco product permeation. • Permeation of TSNAs and nicotine measured simultaneously over 2 h. • High degree of sensitivity for TSNAs and nicotine was observed in this model. [ABSTRACT FROM AUTHOR]

Chemical modification of cellulose is challenging due to its low reactivity and poor solubility. Halogenation followed by displacement reactions has been demonstrated to be a valuable strategy for appending new functionalities to the anhydroglucose rings of cellulose and cellulose derivatives. In this paper, we report a simple and efficient pathway to modify the inexpensive, commercial cellulose ether, hydroxyethyl cellulose (HEC). First, methanesulfonyl chloride (MsCl) in N, N-dimethyl formamide (DMF) can selectively chlorinate the terminal primary hydroxyl groups from hydroxyethyl cellulose (HEC), thereby affording high terminal chloride content. Then, the resulting chlorinated HEC undergoes displacement reactions with various nucleophiles including azide (NaN3), amine (1-methylimidazole), and thiols (3-mercaptopropionic acid and 2-mercaptoethanol). All products were characterized by NMR and FT-IR spectroscopic methods. Exploiting this strategy, we prepared a library of HEC derivatives, including cationic and anionic derivatives, which are of great interest in various applications including as surfactants, in gas separation membranes, and as crystallization inhibitors in amorphous solid dispersions for oral drug bioavailability enhancement. [ABSTRACT FROM AUTHOR]

In this study, a device that can automatically disinfect door handles and prevent contact infection was designed. This device will spray alcohol onto door handles –6 s after the user leaves, as detected by infrared sensing. We used observation and design thinking methods to carry out needs analysis, prototype design, experimental testing, and effect evaluation. The experimental results showed that this delayed spraying method can effectively reduce the amount of bacteria and dirt on door handles and also increase the user’s sense of hygiene and safety. Moreover, this method can contribute to epidemic prevention without spraying alcohol directly onto the human body. [ABSTRACT FROM AUTHOR]