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AbstractThe rat S9 microsome fraction is commonly used to assess compound metabolite formation during in vitro genotoxicity assessments. However, methods using S9 have not been standardized for genotoxicity studies, and different experimental methods are used at various facilities. Therefore, this study investigated whether the differences between the two experimental conditions (1) S9 inducers, phenobarbital + beta-naphthoflavones vs. Aroclor 1254 and (2) the plate incubation vs. preincubation method) in the micro-Ames test would affect the results. Nitrosamine and in-house genotoxicity-positive compounds were used with benzopyrene and 2-aminofluorene as positive control compounds. No differences were observed in the genotoxicity results in the groups treated with the positive control. However, the S9 fraction induced by Aroclor 1254 showed higher cytochrome P450 activity than the fraction induced by phenobarbital and beta-naphthoflavone. The incubation method also affected the results; the nitrosamine compounds showed different genotoxicity activity between the plate incorporation method and preincubation method. In-house aminomethyl quinoline compounds also showed different results depending on the S9 type. These results suggest that different inducers and methods induce various metabolic enzyme activities, which may lead to differences in genotoxicity through distinct metabolite production. [ABSTRACT FROM AUTHOR]

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One effective option to minimize N-nitrosodimethylamine (NDMA) in finished drinking water is to identify and control its precursors. However, previous works to identify significant precursors use formation potential (FP) tests using high doses to assure the maximum NDMA formation rather than the NDMA formation in finished waters. In this study, we applied characteristic low treatment doses of ozone (O3)-to-dissolved organic carbon (DOC) of target compounds of 0.8 mg/mg and NH2Cl of 2.5 ± 0.2 mg Cl2/L to evaluate the NDMAFP yields of organic compounds bearing N,N-dimethylamine (DMA) and N,N-dimethylhydrazine (DMH) during preozonation and post-chloramination. The results in pH-buffered Milli-Q water showed a significant decrease from ≤ 52% to non-detectable levels in the O3-NDMAFP yields of O3-reactive precursors (i.e., DMH-like compounds) after preozonation and post-chloramination. Similarly, a significant decrease from 0.5 to 12% to nonquantifiable levels was observed for the NH2Cl-NDMAFP yields of NH2Cl-reactive precursors; however, the NH2Cl-NDMAFP yields of N,N-dimethylbenzylamine (DMBzA)-like compounds only decreased from ~ 110 to ≤ 43%, suggesting that these compounds could contribute to NH2Cl-NDMAFPs even after preozonation. The effect of the matrix in sewage-effluent and lake water samples varied and was specific for precursors; for example, the O3-NDMAFP yield of 1,1,1′,1′-tetramethyl-4,4′-(methylene-di-p-phenylene) disemicarbazide (TMDS), an important O3-reactive NDMA precursor, did not significantly decrease when tested in sewage-effluent samples. Based on the previous occurrence concentration of TMDS in sewage samples, we estimated an NDMAFP of ~ 315 ng/L. This estimate exceeds the guidance concentrations of NDMA (3–100 ng/L), highlighting the importance of TMDS and its related compounds for NDMA formation. [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]

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]

The N-nitrosamine, N-nitrosodimethylamine (NDMA), is an environmental mutagen and rodent carcinogen. Small levels of NDMA have been identified as an impurity in some commonly used drugs, resulting in several product recalls. In this study, NDMA was evaluated in an OECD TG-488 compliant Muta™Mouse gene mutation assay (28-day oral dosing across seven daily doses of 0.02-4 mg/kg/day) using an integrated design that assessed mutation at the transgenic lac Z locus in various tissues and at the endogenous Pig-a gene-locus, along with micronucleus frequencies in peripheral blood. Liver pathology was determined together with NDMA exposure in blood and liver. The additivity of mutation induction was assessed by including two acute single-dose treatment groups (i.e. 5 and 10 mg/kg dose on Day 1), which represented the same total dose as two of the repeat dose treatment groups. NDMA did not induce statistically significant increases in mean lac Z mutant frequency (MF) in bone marrow, spleen, bladder, or stomach, nor in peripheral blood (Pig-a mutation or micronucleus induction) when tested up to 4 mg/kg/day. There were dose-dependent increases in mean lac Z MF in the liver, lung, and kidney following 28-day repeat dosing or in the liver and kidney after a single dose (10 mg/kg). No observed genotoxic effect levels (NOGEL) were determined for the positive repeat dose–response relationships. Mutagenicity did not exhibit simple additivity in the liver since there was a reduction in MF following NDMA repeat dosing compared with acute dosing for the same total dose. Benchmark dose modelling was used to estimate point of departure doses for NDMA mutagenicity in Muta™Mouse and rank order target organ tissue sensitivity (liver > kidney or lung). The BMD50 value for liver was 0.32 mg/kg/day following repeat dosing (confidence interval 0.21–0.46 mg/kg/day). In addition, liver toxicity was observed at doses of ≥ 1.1 mg/kg/day NDMA and correlated with systemic and target organ exposure. The integration of these results and their implications for risk assessment are discussed. [ABSTRACT FROM AUTHOR]

1-amino-4-methyl-piperazine (AMP) is both a starting material for the synthesis of rifampicin (RIF) and a degradation product of RIF hydrolysis. 1-methyl-4-nitroso-piperazine (MNP) is an oxidation product of AMP as well as a potentially genotoxic N-nitrosamine. The EMA and FDA have approved an ad interim limit of 5 ppm for MNP in RIF drug products. As in-house methods for the analysis of MNP in RIF use a wide range of conditions for mobile phases and sample diluents, we decided to investigate whether these conditions affect the formation of MNP and AMP. A UHPLC-MS/MS method was developed to simultaneously quantify AMP and MNP during RIF hydrolysis in buffered aqueous solutions at different pH levels. Analyses were performed in MRM mode; separations were carried out on an InfinityLab Poroshell HPH-C18 (100 mm, 2.1 mm i.d., particle size 1.9 μm). In aqueous RIF solutions, the content of AMP and MNP increases with time; at different pHs, the concentration of AMP increases much faster in acidic than in basic solutions; and the increase in MNP can be reduced by the addition of ascorbic acid. To avoid an overestimation of MNP, water should not be used as a diluent in RIF sample preparations. Methanol is a more suitable diluent than water. A standard addition method has been validated for the quantification of MNP in RIF drug substances. [ABSTRACT FROM AUTHOR]

Context: N-Nitrosamine is one of the highly toxic carcinogenic compounds that are found almost in the entire environment. In the present work, novel penta-silicene (penta-Si) and penta-silicane (penta-HSi) are utilised to sense the N-nitrosamine in the air environment. Initially, structural firmness of penta-Si and penta-HSi is confirmed using cohesive energy. Subsequently, the electronic properties of penta-Si and penta-HSi are discussed with the aid of electronic band structure and projected density of states (PDOS) maps. The calculated band gap of penta-Si and penta-HSi is 0.251 eV and 3.117 eV, correspondingly. Mainly, the adsorption property of N-nitrosamine on the penta-Si and penta-HSi is studied based on adsorption energy, Mulliken population analysis along with relative energy gap changes. The computed adsorption energy range is in physisorption (− 0.101 to − 0.619 eV), which recommends that the proposed penta-Si and penta-HSi can be employed as a promising sensor to detect the N-nitrosamine in the air environment. Methods: The structural, electronic and adsorption behaviour of N-nitrosamine on penta-Si and penta-HSi are studied based on the density functional theory (DFT) approach. The hybrid generalized gradient approximation (GGA) with Becke's three-parameter (B3) + Lee–Yang–Parr (LYP) exchange correlation functional is used to optimise the base material. All calculations in the present work are carried out in Quantum-ATK—Atomistic Simulation Software. [ABSTRACT FROM AUTHOR]

Nano-kaolin-SO3H was prepared and used to synthesis of N-nitrosamines. The products were characterized by their spectral (IR and 1H NMR) data. N-nitrosamines can exist in two mesomeric forms but the reaction is quite regioselective and only one of mesomers is formed as a main product which can exist in two E and Z stereoisomers. In this paper, we have studied the mesomeric effect of N-nitrosamines which explained the diastereotopic nature of corresponding protons in symmetric N-nitrosamines and formation of two isomers in asymmetric N-nitrosamines. [ABSTRACT FROM AUTHOR]

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In this study, the effects of polyphenols extracted from fresh Prunus mume (PMP) on the oxidation and nitrosation in Cantonese sausage were investigated. Different dosages of PMP (0, 0.3, 0.6 and 0.9 g/kg) were added into Cantonese sausages, and the physicochemical properties, lipid and protein oxidation, residual nitrite, and N-nitrosamines (NAs) of the products during processing and storage (room temperature, 21 days) were compared. The results showed that PMP increased hardness, gumminess and chewiness, inhibited the accumulation of NAs, and decreased nitrite residue of sausage. The sausage supplemented with 0.6 g/kg PMP exhibited the lowest oxidation, i.e. had the lowest TBARS value (0.63 mg MDA/kg sausage) and the highest sulfhydryl content (44.10 nmol/mg protein) after 21-day storage. The residual nitrite in sausage supplemented with 0.15 g/kg sodium nitrite decreased from 5.34 mg/kg to 2.82 mg/kg after 0.6 g/kg PMP added. This study can provide a theoretical basis and technical guidance for the application of plant polyphenols in the safety control of cured meat. • Prunus mume polyphenols can improve the texture of Cantonese sausage. • Prunus mume polyphenols inhibit N-nitrosamines accumulation by oxidative inhibition. • Prunus mume polyphenols inhibit nitrosation by promoting nitrite decomposition. [ABSTRACT FROM AUTHOR]

The Ames mutagenicity test is an effective means of screening compounds for their carcinogenic potential. Here, we conducted Ames tests on 15 aryl, benzyl, and aliphatic ring N-nitrosamines. Then, by using two indicators of mutagenicity strength calculated from the Ames test results, namely, maximum specific activity (MSA; number of revertant colonies) and maximum fold increase (MFI; relative ratio of increased colonies), we examined the relationship between Ames mutagenicity strength and Carcinogenic Potency Categorization Approach (CPCA) potency category, which is a structure-activity-relationship-based prediction of the carcinogenic potency of nitrosamines. Eleven of the test compounds were Ames positive and four were negative. Of the 11 positive compounds, three were categorized as strong positive (MSA ≥1000), five as medium positive (100 ≤ MSA <1000), and three as weak positive (MSA <100). The compounds with an aliphatic ring showed a negative relationship between mutagenicity strength (i.e., MSA or MFI) and carcinogenic potential (i.e., CPCA category), whereas, the alpha-methyl aryl N-nitrosamines did not. Overall, MSA and MFI were found to be detailed indicators of the carcinogenic potency of the N-nitrosamines and can potentially be used to support CPCA categorization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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This study investigated the effects of ferulic acid (FA) on the oxidative stability and nitrozation of porcine myofibrillar proteins (MPs) under oxidative stress. The addition of FA significantly (P

The removal of N -nitrosamines from water faces the challenges of their difficult adsorption, and incomplete mineralization of degradation products. Herein, we report a new strategy by in-situ constructing microreactor on carbon cloth arrayed CoNi spinel oxide through membrane encapsulation. The NiCo 2 O 4 -nanoarrays activate peroxonosulfate, generating reactive oxygen species that rapidly degrade N -nitrosamines. The breaking N-N bond of N -nitrosamines provides an effective binding site for adsorbing degradation products (secondary amines). Meanwhile, electrons conducted from secondary amines adsorbed on Ni sites reconstruct the charge of CoNi sites, bolstering the peroxonosulfate activation to further remove N -nitrosamines and secondary amines. Moreover, the microreactive interface formed between membrane substrate and NiCo 2 O 4 -nanoarrays improved the reaction efficiency. It maintains efficient N -nitrosamines removal (96–99%) even in the presence of humic acid. Actual wastewater experiments confirmed its effective control of both N -nitrosamines and N -nitrosodimethylamine formation potential. This study provides a novel approach for eliminating the risk of N-nitrosamines in water. [Display omitted] • Microreactors (UCAM) can degrade N-nitrosamines and adsorb degradation products. • The broken N-N bond in N -nitrosamines and electron transport push removal processes. • The microreactive interfaces in UCAM improve the adsorption and catalysis efficiency. • The kinetic constants of UCAM are 22.2–38.8 times greater than fixed-bed treatment. [ABSTRACT FROM AUTHOR]

Objectives: Recently, N-nitrosamines were unexpectedly detected in valsartan and other generic sartan products. Taking into this account, we developed a sensitive and stable multiple reaction monitoring mode-based “gas chromatography-tandem mass spectrometry (GC-MS/MS)” approach for the quantification of “four N-nitrosamines” in valsartan, especially, N-nitrosodiisopropylamine, N-nitroso ethyl isopropylamine, N-nitrosodiethylamine, and N-nitrosodimethylamine. Materials and Methods: GC and MS conditions were optimized with specificity, sensitivity, linearity, precision, and accuracy of the parameters. The approach was validated as per the “International Council for Harmonization” recommendations. Results: The identification limits and limits of quantification of N-nitrosamines in valsartan varied between 0.02 and 0.03 ppm, and 0.06-0.09 ppm, respectively. The obtained values were satisfactory with limits established by the United States Food and Drug Administration for sensitivity requirements. The regression coefficients greater than 0.999 for four N-nitrosamines in the calibration curve demonstrated the strong linearity of the process. The retrievals of “N-nitrosamines” in valsartan between 91.9-122.7%. For the intra-day and inter-day accuracy studies, the (relative standard deviation) was less than 9.15%. Conclusion: The proposed approach has rapid analysis capability, high precision, accuracy, and good sensitivity, which give a reliable approach for N-nitrosamines quality control in valsartan. [ABSTRACT FROM AUTHOR]

Carcinogenic N-nitrosamines were recently found in the sartan family of drugs and caused many drug recalls. Both of their detection and quantification are therefore important. Methods reported for N-nitrosamine quantitation rely on the use of standards and are just applicable to simple N-nitrosamines. There is an urgent need to quantify N-nitrosamines derived from drugs with a complicated structure that lack standards. To tackle the issue, this study describes a novel absolute quantitation strategy for N-nitrosamines using coulometric mass spectrometry (CMS) without standards. In our approach, N-nitrosamine is first converted into electrochemically active hydrazine via zinc reduction under acidic condition and the resulting hydrazine can then be easily quantified using CMS. To validate our method, six simple N-nitrosamines, N-nitrosodiethylamine (NDEA), N-nitroso-4-phenylpiperidine (NPhPIP), N-nitrosodiphenylamine (NDPhA), N-nitrosodibutylamine (NDBA), N-nitrosodipropylamine (NDPA), and N-nitrosopiperidine (NPIP), were chosen as test samples, and they all were quantified with excellent measurement accuracy (quantitation error ≤1.1%). Taking this one step further, as a demonstration of the method utility, a drug-like N-nitrosamine, (R)-N-(2-(6-chloro-5-methyl-1′-nitroso-2,3-dihydrospiro-[indene-1,4′-piperidin]-3-yl)-propan-2-yl)-acetamide (VII), was also synthesized and successfully quantified using our method at 15 ppb level in a complex formulation matrix, following solvent extraction, N-nitrosamine isolation, and reductive conversion. Because of the feature of requiring no standards, CMS provides a simple and powerful approach for N-nitrosamine absolute quantitation and has great potential for analysis of other drug impurities or metabolites. [ABSTRACT FROM AUTHOR]

N-nitrosamines are a class of carcinogenic chemical compound. Considering the large-scale application of agrochemicals globally, the elimination of N-nitrosamines from pesticides should be a priority for manufacturers and regulators. A set of methods was developed and validated for the determination of the toxicologically relevant N-nitrosamine impurity of ethalfluralin (ethyl-N-(2-methylallyl) N-nitroso amine—EMANA) in 33% w v−1 emulsifiable concentrate (EC) formulations. Solid Phase Extraction (SPE) was compared with the “dilute and shoot” approach. Gas chromatography (GC) was combined with Flame Ionization Detection (FID) and mass spectrometry (MS). For MS, two mass filtering modes (Selective Ion Monitoring—SIM, tandem mass spectrometry—MS/MS) and two ionization modes (Electron Ionization—EI, Positive chemical ionization—PCI) were applied. It was concluded that, in the case of samples with high nitrosamine concentration (>90 μg g−1), the “dilute and shoot” approach can be applied without compromising the quality of the results. SPE, however, is required to attain the LOQ (0.33 μg g−1) with good recovery (97.4–110.67%), linearity (R > 0.99) and precision (%RSD 0.68–1.74). The LOQ supersedes the limit set by EFSA (1 μg g−1) in the Technical Active Substance—TAS. The concentration range of the methods is 0.05–110 μg g−1. The methods were applied for the official surveillance program of the Greek agrochemicals market.

There has been a great focus on halogen-bonding as a unique interaction between electron-deficient halogen atoms with Lewis basic moieties. Although the application of halogen-bonded atoms in organic chemistry has been eagerly researched in these decades, the development of chiral molecules with halogen-bonding functionalities and their utilization in asymmetric catalysis are still in the\ir infancy. We have previously developed chiral halonium salts with amide functionalities, which behaved as excellent catalysts albeit in only two reactions due to the lack of substrate activation abilities. In this manuscript, we have developed chiral halonium salts with an N-nitrosamine moiety and applied them to the Mannich reaction of isatin-derived ketimines with malonic esters. The study focused on our novel bromonium salt catalyst which provided the corresponding products in high yields with up to 80% ee. DFT calculations of the chiral catalyst structure suggested that the high asymmetric induction abilities of this catalyst are due to the Lewis basic role of the N-nitrosamine part. To the best of our knowledge, this is the first catalytic application of N-nitrosamines.

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In the present study, we investigated the genotoxicity of the active products formed from N -nitrosoproline (NPRO) dissolved in oleic acid following ultraviolet A (UVA) irradiation, bypassing the need for metabolic activation. We previously demonstrated the photomutagenicity of NPRO dissolved in a phosphate-buffered solution. It has been suggested that the association of the nitrosamine group with acid ions facilitates rapid photodissociation and photoactivation. We hypothesized that NPRO's inherent carboxyl group may mimic an acid, inducing photodissociation and photomutagenicity, even in a non-aqueous solvent lacking acidic ions. Following UVA irradiation, NPRO dissolved in oleic acid exhibited a dose-dependent mutagenic activity. Similar results were obtained when NPRO was dissolved in linoleic acid and triolein. Nitric oxide formation, which is dependent on NPRO concentration, is accompanied by mutagenic activity. The mutagenicity spectrum obtained in response to NPRO irradiation followed the absorption curve of NPRO dissolved in oleic acid. Irradiated NPRO in oleic acid displayed relative stability, retaining approximately 18, 36, and 63 % of initial mutagenicity after 10 days of storage at 25, 4, and −20 °C, respectively. Thus NPRO stored in a fatty environment undergoes photoactivation upon irradiation, leading to genotoxicity. • UVA-irradiated NPRO dissolved in oleic acid exhibited dose-dependent mutagenic activity. • The action spectrum of mutagenicity in response to NPRO irradiation followed the absorption curve of NPRO in oleic acid. • Irradiated NPRO in oleic acid displayed relative stability, retaining approximately 18 % of initial mutagenicity after 10 days. [ABSTRACT FROM AUTHOR]

N -Nitrosamine impurities, including nitrosamine drug substance-related impurities (NDSRIs), have challenged pharmaceutical industry and regulators alike and affected the global drug supply over the past 5 years. Nitrosamines are a class of known carcinogens, but NDSRIs have posed additional challenges as many lack empirical data to establish acceptable intake (AI) limits. Read-across analysis from surrogates has been used to identify AI limits in some cases; however, this approach is limited by the availability of robustly-tested surrogates matching the structural features of NDSRIs, which usually contain a diverse array of functional groups. Furthermore, the absence of a surrogate has resulted in conservative AI limits in some cases, posing practical challenges for impurity control. Therefore, a new framework for determining recommended AI limits was urgently needed. Here, the Carcinogenic Potency Categorization Approach (CPCA) and its supporting scientific rationale are presented. The CPCA is a rapidly-applied structure-activity relationship-based method that assigns a nitrosamine to 1 of 5 categories, each with a corresponding AI limit, reflecting predicted carcinogenic potency. The CPCA considers the number and distribution of α-hydrogens at the N -nitroso center and other activating and deactivating structural features of a nitrosamine that affect the α-hydroxylation metabolic activation pathway of carcinogenesis. The CPCA has been adopted internationally by several drug regulatory authorities as a simplified approach and a starting point to determine recommended AI limits for nitrosamines without the need for compound-specific empirical data. • Describes the scientific rationale and supporting data for the Carcinogenic Potency Categorization Approach (CPCA). • The CPCA was adopted in international regulatory guidance in 2023. • The CPCA uses structure-activity relationships to determine acceptable intake limits for nitrosamine impurities in pharmaceuticals. • CPCA structural features and weights, mechanisms of reactivity, and predictive performance are presented. • Case studies showing application of the CPCA to nitrosamine impurities are included. • A Java application for fingerprinting CPCA structural features is available as supplemental data. [ABSTRACT FROM AUTHOR]

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Post-combustion CO2 capture using amine solvents is the most feasible method of reducing anthropogenic CO2 emissions, which are the largest contributor to global warming. The formation of carcinogenic N-nitrosamines (i.e. by-products) can hinder the industrial application of this technology. In this study, the effects of direct UV photolysis (N-nitrosamine concentration and amines) and advanced oxidation processes (UV/H2O2 and UV/O3) on the three specific N-nitrosamines that are commonplace in amine-based CO2 capture (i.e. N-nitrosodiethylamine (NDEA), N-nitrosodiethanolamine (NDELA), and N-nitrosomorpholine (NMOR)) were examined. A significant decrease in the photodegradation rate constants was observed for NDEA (1.02 × 100 to 2.94 × 10−1 min−1), NDELA (1.52 × 100 to 3.32 × 10−1 min−1), and NMOR (1.93 × 100 to 2.20 × 10−1 min−1) as their concentrations increased within 1–50 mg/L. This is the first report of a significant increase in the degradation rate constants of N-nitrosamine with an increase in amine concentrations (i.e. monoethanolamine, diethanolamine, and morpholine) within 10–200 mM. The photodegradation rate constants increased as the molar ratio of H2O2 to N-nitrosamine increased to 20, but then decreased at molar ratios beyond this. O3 had a negligible effect on the photodegradation of N-nitrosamines. [ABSTRACT FROM AUTHOR]

N-Nitrosamines, known as drug impurities and suspected carcinogens, have drawn significant public concern. In response to drug regulatory needs, the European Medicines Agency (EMA) has previously proposed a carcinogenic potency categorization approach based on the N-nitrosamine α-hydroxylation hypothesis, i.e., that N-nitrosamine mutagenicity increases with the number of α-hydrogen atoms. However, this structure-activity relationship has not been fully tested in vivo. NEIPA (N-nitrosoethylisopropylamine) and NDIPA (N-nitrosodiisopropylamine) are small N-Nitrosamines with similar structures, differing in that the former compound has an additional α-hydrogen atom. In this study, NEIPA and NEIPA doses, 25–100 mg/kg, were administered orally to C57BL/6 J mice for seven consecutive days, and their mutation and DNA damage effects were compared. Compared with NDIPA, the mutagenicity and DNA damage potencies of NEIPA (which contains one more α-hydrogen) were much greater. These differences may be related to their distinct metabolic pathways and target organs. This case study confirms the role of α-hydroxyl modification in the mutagenicity of nitrosamines, with oxidation at the α-hydrogen being a crucial step in the formation of mutagens from N-Nitrosamines, and can inform mutagenicity risk assessment and the formulation of regulatory standards for N-nitrosamine impurities. • α-hydroxylation hypothesis is a key theory for the carcinogenicity of nitrosamines. • Oxidation at the α-carbon of nitrosamines is crucial in the formation of mutagens. • NEIPA has an extra α-carbon compared with NDIPA. • Mutagenic and DNA injury potencies of NEIPA were much stronger than that of NDIPA. • These shed lights for the formulation of regulatory rule of nitrosamine impurities. [ABSTRACT FROM AUTHOR]

A novel HPLC method with fluorimetric detection was developed for the determination of potentially carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in active pharmaceutical ingredient enalapril maleate. N-nitrosamines were subject to denitrosation followed by derivatisation with dansyl chloride or fluorenylmethoxycarbonyl chloride (Fmoc-Cl). Fmoc-Cl offers much better sensitivity and repeatability than dansyl chloride derivatisation. A satisfactory linearity was obtained for the method, with R2 = 0.9994 for NDMA and 0.9990 for NDEA, and a limit of quantification level of 0.038 μg/g for NDMA and 0.050 μg/g for NDEA. The precision decreased with the concentration to a maximum level of about 10%. The recoveries were in the range of 74.2 ± 4.2% to 101.6 ± 16.1% for NDMA and 90.6 ± 2.9% to 125.4 ± 7.4% for NDEA. Dansyl chloride was found to be an inappropriate derivatisation agent, mainly due to potential contamination with dimethylamine, leading to unrepeatable peaks in the blank solution. Since the method involves the derivatisation of amines liberated from the N-nitrosamines, it was necessary to remove the amines from the test sample. Several critical points in the standard/sample preparation have been mentioned, which affect the reproducibility of the method and are not covered in similar articles.

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Ionic liquids (ILs) are a class of solvents increasingly used as "green chemicals." Widespread applications of ILs have led to concerns about their accidental entry to the environment. ILs have been assessed for some environmental impacts; however, little has been done to characterize their potential impacts on drinking water if ILs accidentally enter surface water. IL cations are often aromatic or alkyl quaternary amines that resemble structures of previously confirmed N -nitrosamine (NA) precursors. Therefore, this study has evaluated two common ILs, 1-ethyl-3-methylimidazolium bromide (EMImBr) and 1-ethyl-1-methylpyrrolidinium bromide (EMPyrBr), for their NA formation potential. Each IL species was reacted with pre-formed monochloramine under various laboratory conditions. The reaction mixtures were extracted using liquid–liquid extraction and analyzed for NAs using high performance liquid chromatography tandem mass spectrometry. At low concentration of IL (250 μmol/L), the yields of NAs (NMEA or NPyr) increased with increasing doses of monochloramine from both IL species. The total NA yield was as high as 2.5 ± 0.3 ng/mg from EMImBr, and as high as 8.6 ± 0.8 ng/mg from EMPyrBr. At high concentration of IL (5 mmol/L), the NA yield reached a maximum at 2.5 mmol/L NH 2 Cl, and then decreased with subsequent increases in the reactant concentrations, demonstrating ILs' solvent effects. This study re-emphasizes the importance of preventing discharge of ILs to water bodies to prevent secondary impacts on drinking water. Unlabelled Image [ABSTRACT FROM AUTHOR]

• A simple and fast derivatization method was used to analysis of four ATDs by GC–MS. • The method also provided excellent sensitivity and selective without side product. • The LOQs of the analytes were significantly lower than actual sample concentration. • The method will provide a new strategy for the detection of ATDs in plasma and urine. A sensitive and selective method was developed for simultaneous determination of four antidepressants (ATDs) in plasma and urine samples by gas chromatography- mass spectrometry (GC–MS) based on an N-nitrosation reaction. In this study, fluoxetine (Flu), nortriptyline (Nor), maprotiline (Map), and paroxetine (Paro) were first derivatized with sodium nitrite to appropriate N-nitrosamines under acidic condition, then the derivatives were easier to detect by GC–MS. The derivatization conditions including the amount of hydrochloric acid, the amount of sodium nitrite, reaction temperature, reaction time and the extraction reagents were optimized. Under the optimal conditions, the limit of detections (LODs) and limit of quantitations (LOQs) were in the range of 0.04–1.38 μg L−1 and 0.14–4.62 μg L−1, respectively. Low, medium, and high concentrations of antidepressants were added in plasma and urine samples, spiked recovery ranged from 85.88%–110.34% for plasma and 80.64%–113.07% for urine, respectively. The derivatization reaction was very quickly, only 5 min was needed for the reaction process, in addition, the proposed method exhibited superior sensitivity and selectivity, it showed sufficient advantages for determination of Flu, Nor, Map, and Paro in plasma and urine of patients. [ABSTRACT FROM AUTHOR]

Abstract A gas chromatography-tandem mass spectrometry coupled to QuEchERS extraction method was developed for the determination of 7 volatile N -nitrosamines (VNAs) in Chinese Sichuan salted vegetables, and the method detection limit (MDL), method quantification limit (MQL), recovery and relative standard deviation (RSD) were determined. Furthermore, the VNA contents of 406 Sichuan salted vegetables were measured and discussed. The MDL of the 7 VNAs ranged from 0.02 to 0.15 ng/g, and their recoveies when spiked with 10 ng/g standards ranged from 91.5 to 106.1%. The within-day RSD and between-day RSD were 2.1–4.6% and 2.4–7.2%, respectively. These results indicate that the method developed was of good accuracy, repeatability and reproducibility. The mean content of total VNAs in the 406 Sichuan salted vegetables was 0.56 ng/g, and more than 95% of them (n = 386) were at low VNA content (<3 ng/g), which suggests good control of VNAs in Sichuan salted vegetables. Preparation method and packaging mode significantly affected the VNA content of Sichuan salted vegetables (P < 0.05), while vegetable type and production region did not (P > 0.05). The VNA with both the highest concentration and the highest occurrence frequency of ≥3 ng/g was N -nitrosopyrrolidine. Highlights • Seven VNAs of 406 Sichuan salted vegetables were determined by QuEChERS- GC-MS/MS. • The developed method presented high sensitivity, precison and accuracy. • Sichuan salted vegetables showed low levels of volatile N -nitrosamines. • Preparation method and packaging mode significantly affected the VNA content. • N -nitrosopyrrolidine was identified as the main VNA in Sichuan salted vegetables. [ABSTRACT FROM AUTHOR]

Highlights • Carbon xerogel electrodes have high adsorption capacity for organic N-nitrosamines. • N-nitrosamines were decomposed in amine-based carbon capture waterwash solutions by an electrochemical process. • Electrochemical reduction of N-nitrosamines with high (>80%) removal efficiency. Abstract N-nitrosamines, as a class of compounds, have been reported to be mutagenic, cytotoxic, genotoxic and carcinogenic. N-nitrosamine formation and emission are a major concern for amine-based CO 2 capture systems. A process using a stationary carbon electrode inside an electrochemical cell was developed and tested in this study to adsorb and decompose two N-nitrosamines, N-nitrosopyrrolidine and N-nitrosodiethylamine, from an aqueous amine solution. The carbon xerogel electrode material has a high N-nitrosamine adsorption capacity and can initiate an electrochemically-mediated reduction of N-nitrosamines to a secondary amine. A greater than 80% reduction of N-nitrosodiethylamine and 90% of N-nitrosopyrrolidine was observed from a simulated amine-based waterwash solution using an applied current up to 300 mA. N-nitrosamine decomposition was effective in solutions with relatively high amine or salt concentrations. [ABSTRACT FROM AUTHOR]

This study investigated N -nitrosomorpholine (NMOR) genotoxicity following UVA irradiation without metabolic activation. Following UVA irradiation, the photo treated NMOR (irradiated NMOR) was directly mutagenic, without UVA or metabolic activation, in the Ames test. The activity was relatively stable, and approximately 79% of the activity remained after 10 days of storage at 37 °C, 4 °C, or −20 °C. Micronuclei (MN) formation was observed in HaCaT cells after treatment with irradiated NMOR without metabolic activation. The action spectrum of MN formation in response to NMOR irradiation followed the NMOR absorption curve. In vivo , MN formation was observed in the peripheral blood reticulocytes of mice injected with irradiated NMOR under the inhibition of cytochrome P450-mediated metabolism of NMOR. Volatile NMOR may attach to environmental materials and be irradiated with environmental UVA light. Photoactivated NMOR-attached air pollutants could float in the air and fall onto the human body, leading to genotoxicity induced by the irradiated NMOR. • In vivo micronuclei formation in peripheral reticulocytes of mice injected with irradiated-N-nitrosomorpholine without CYP metabolism. [ABSTRACT FROM AUTHOR]

The recent discovery of N-nitrosodimethylamine (NDMA), a mutagenic N-nitrosamine, in pharmaceuticals has adversely impacted the global supply of relevant pharmaceutical products. Contamination by N-nitrosamines diverts resources and time from research and development or pharmaceutical production, representing a bottleneck in drug development. Therefore, predicting the risk of N-nitrosamine contamination is an important step in preventing pharmaceutical contamination by DNA-reactive impurities for the production of high-quality pharmaceuticals. In this study, we first predicted the degradation pathways and impurities of model pharmaceuticals, namely gliclazide and indapamide, in silico using an expert-knowledge software. Second, we verified the prediction results with a demonstration test, which confirmed that N-nitrosamines formed from the degradation of gliclazide and indapamide in the presence of hydrogen peroxide, especially under alkaline conditions. Furthermore, the pathways by which degradation products formed were determined using ranitidine, a compound previously demonstrated to generate NDMA. The prediction indicated that a ranitidine-related compound served as a potential source of nitroso groups for NDMA formation. In silico software is expected to be useful for developing methods to assess the risk of N-nitrosamine formation from pharmaceuticals.

Abstract More than 24 N -nitrosamine compounds contribute to the total N -nitrosamine (TNA) burden monitored routinely to assess human exposure to this important group of known and suspected human carcinogens. A literature review (n = 122) identified multiple sources of human exposure to TNAs, including waters (40 ± 10.5 ng/L; average ± standard deviation), food and beverages (6.7 ± 0.8 ng/g), tobacco (16,100 ± 3650 ng/g) and personal care products (1500 ± 750 ng/g). Due to source control interventions, levels of TNAs in beer have dropped by about 96% between 1980 and 1990, whereas N- nitrosamine levels in other known sources have shown little to no change. Maximum daily TNA exposure in the U.S. in units of ng/d is estimated at 25,000 ± 4,950, driven by consumption of tobacco products (22,000 ± 4350), food (1900 ± 380), alcohol (1000 ± 200), and drinking water (120 ± 24). Behavioral choices of individuals in non-occupational settings were calculated to result in a spectrum of exposure values ranging from a lower bound of 1900 ± 380 ng/d to a higher bound of 25,000 ± 4950 ng/d, indicating opportunities for a possible 12-fold reduction in TNA exposure to 8% of the above maximum through deliberate choices in diet and lifestyle. Graphical abstract Image 1 Highlights • N -nitrosamines are found in tobacco, food, water and personal care products. • Exposure estimated at 1900 to 25,000 ng/day/person, excluding personal care. • 6000 ± 2950 cancer cases per 1M persons attributable to N -nitrosamines. • 1,940,000 ± 950,000 lifetime cancer cases in U.S. attributable to N -nitrosamines. • Up to 92% of exposure and cancer cases avoidable through lifestyle choices. [ABSTRACT FROM AUTHOR]

N-nitrosodimethylamine (NDMA) , N-nitroxymethylamine (NMEA), N-nitrosodiethylamine (NDEA) , N-nitrosodipropylamine (NDPA) , N-nitrosopiperidine (NPIP )，N-nitrosopyrrolidine ( NPYR )，N-nitrosomorpholine ( NMOR ) and N- nitrosodibutylamine (NDBA) in dried fish, dried small shrimps and shrimp meat were determined by gas chromatography-tandem mass spectrometry (GC-MS/MS) with alkaii solution treating and active carbon solid phase extraction. 10 g of sample was placed into a 50 mL screw-cap plastic centrifugation tube，and 50 μL of internal standards solution including NDMA-d6,NDPA-d14 and NPYR-d8 with each concentration of 1 mg/L， 1. 0 g of Ba(OH)2 • 8H2O and distilled water with volumn to the 50 mL scale line were added. Then the tube was heated at 80 °C for 1 h in an oven and centrifuged at 10 000 r/min for 10 min. All the supernatant was passed through a Sep-Pak® Plus AC-2 cartridge which had been conditioned with 6 mL of dichloromethane, 6 mL of methanol and 6 mL of water in turns，and the anlytes were eluted with 5 mL of dichloromethane from the cartridges after aspiration to dryness by a vacuum pump. The eluent was concentrated further to 1 mL under nitrogen flow at 40 °C and was then passed through a 0.22 mm pore filter for injection. The chromatographic separation was carried on a DB WAXUI column (30 m X 250 μm X 0. 25 μm) and detected with tandem mass spectrometry at multiple reactions monitoring mode. The calibration curves show good linearity in the range of 1-200 μg/L with the correlation coefficients (R2 ) greater than 0. 998. The limits of detection and quantification are in the ranges of 0. 03-0. 25 μg/kg and 0. 10-0. 85 μg/kg，respectively. The recoveries of N-nitrosamines are 71. 3 %-119. 0 %，except that NDBA is slightly lower at high addition levels， and the relative standard deviations (RSD) is 0. 65%-15. 4%. 23 samples from local supermarket including 8 ready-dried fish，5 fresh dried fish， 4 dried small shrimp and 6 shrimp meat were detected. The results indicate that NDMA is the major N-nitrosamines and is detected in all samples with the highest level among of the analytes，and the other N-nitrosamines are detected in partial samples with relative lower levels even blow the LOQ. The samples with the highest levels of NDMA are dried fishes and the levels of ready-to-eat dried fishes are much higher than that of the fresh dried fishes，the samples with medium and the lowest levels of NDMA are dried small shrimps and shrimp meats， respectively. NDBA should be paid more attention during the relative food safety control. This method is simple，environment-friendly， easy for high-throughput detection and reliable for both qualitative and quantitative analysis. [ABSTRACT FROM AUTHOR]

A simple method was developed for monitoring eight N-nitrosamines ( N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosodipropylamine, N-nitrosomorpholine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitrosodibutylamine) in beef jerkys by gas chromatography-tandem mass spectrometry with one-step treatment coupled to active carbon solid-phase extraction. Sample was first treated with barium hydroxide solution, and then the sample solution is cleaned and concentrated using a Sep-Pak AC-2 cartridge. Chromatographic separation was achieved on a DB-1701 capillary column, and mass spectrometry was performed with electron-impact ionization and multiple reaction monitoring. Good linear ranges were obtained for eight analytes in the range of 1-200 ng mL with the coefficient ( R ) higher than 0.999. Limit of detection and limit of quantitation were in ranges of 0.05-0.10 and 0.10-0.30 ng g, respectively; at 0.3, 3.0, and 10 ng g spiking levels, the recoveries were 70.1-121.5% with the relative standard deviations at 3.4-17.8%. Comparing with the traditional methods, the merits of the new method are simple, relative procedure and environment-friendly, easy to use, and suitable for routine screening or analyzing samples in batch. [ABSTRACT FROM AUTHOR]

N -nitrosamines are a class of carcinogenic chemicals. Despite considerable efforts to reduce their occurrence in drinking water, drugs and animal-derived foods, there have been few reports on the dietary assessment of N -nitrosamines in dried aquatic products, and their potential dietary exposure risk has remained unclear. Therefore, six N -nitrosamines were investigated in dried aquatic products in this study. The target analytes were quantified by LC-MS/MS coupled with the steam distillation. Among six N -nitrosamines, N -nitrosodimethylamine (NDMA) was detected in 77.8% (154/198) of the samples with an average level of 5.84 μg/kg and 28.8% of the tested samples exceeded the limit set in Chinese National Standard for Food Safety 2762–2017. Furthermore, N -nitrosodiethylamine (NDEA) was only detected in four samples and no other classes of N -nitrosamines were detected. Expanding upon this discovery, we further evaluated the carcinogenic risk of NDMA exposure in dried aquatic products via the margin of exposure (MOE) approach. The average intake of NDMA from dried aquatic products ranged from 1.90 to 2.04 ng/kg. bw/day for the male adults and from 3.17 to 4.84 ng/kg. bw/day for the male adolescents. Based on the average exposure of NDMA, the MOE value indicated no potential carcinogenic risks for the adults. However, the MOE value for the adolescents was significantly lower than 10,000, indicating the potential carcinogenic risks. For the 95th percentile highly exposed population, their MOE values were also below 10,000, indicating an associated carcinogenic risk for all age groups. Therefore, there is an urgent need to decrease or even eliminate the contamination of NDMA in dried aquatic products. • Investigate the occurrence of N -nitrosamines in aquatic products on a large scale. • Assess the dietary exposure of N -nitrosodimethylamine. • Report the risk of N -Nitrosodimethylamine based on bench mark dose limit and margin of exposure. [ABSTRACT FROM AUTHOR]

N -Nitrosamines are one of the environmentally significant byproducts from aqueous amine-based post-combustion carbon capture systems (CCS) due to their potential risk to human health. Safely mitigating nitrosamines before they are emitted from these CO 2 capture systems is therefore a key concern before widescale deployment of CCS can be used to address worldwide decarbonization goals. Electrochemical decomposition is one viable route to neutralize these harmful compounds. The circulating emission control waterwash system, commonly installed at the end of the flue gas treatment trains to minimize amine solvent emissions, plays an important role to capture N -nitrosamines and control their emission into the environment. The waterwash solution is the last point where these compounds can be properly neutralized before becoming an environmental hazard. In this study, the decomposition mechanisms of N -nitrosamines in a simulated CCS waterwash with residual alkanolamines was investigated using several laboratory-scale electrolyzers utilizing carbon xerogel (CX) electrodes. H-cell experiments revealed that N -nitrosamines were decomposed through a reduction reaction and are converted into their corresponding secondary amines thereby neutralizing their environmental impact. Batch-cell experiments statistically examined the kinetic models of N -nitrosamine removal by a combined adsorption and decomposition processes. The cathodic reduction of the N -nitrosamines statistically obeyed the first-order reaction model. Finally, a prototype flow-through reactor using an authentic waterwash was used to successfully target and decompose N -nitrosamines to below the detectable level without degrading the amine solvent compounds allowing them to be return to the CCS and lower the system operating costs. The developed electrolyzer was able to efficiently remove greater than 98% of N -nitrosamines from the waterwash solution without producing any additional environmentally harmful compounds and offers an effective and safe route to mitigate these compounds from CO 2 capture systems. [Display omitted] • Investigation of electrochemical decomposition mechanisms for hazardous N -nitrosamines in amine-rich waterwash from CCS. • Low-cost synthesized carbon xerogel electrodes were used for several laboratory-scale electrolyzers. • N -Nitrosamines were decomposed by cathodic reduction without producing any environmentally harmful compounds. • A prototype flow-through reactor was able to remove greater than 98% of N -nitrosamines from authentic waterwash. N -Nitrosamines are an environmentally significant byproducts from CO 2 capture systems but can be safely mitigated by electrochemical decomposition enabling widescale deployment of CO 2 capture systems to reach worldwide decarbonization targets. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Telomeres are critical to maintain the integrity of the chromosomes, and telomere abnormalities are important features of carcinogenesis. Telomere length differs among individuals due to genetic and environmental factors. Aiming to examine the relationship between DNA-damaging agents and average telomere length in peripheral blood, we conducted a cross-sectional study among 157 workers working in the rubber industry in Sweden. METHODS: N-nitrosamines were measured in air by personal sampling on Thermosorb/N tubes and analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS) for 60 individuals. Based on a similar working situation, the exposure was estimated for all workers. Polycyclic aromatic hydrocarbons (PAH) were measured as the metabolite 1-hydroxypyrene (1-HP) in urine by LC. Carbon disulphide (CS2) was measured as the metabolite 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine by LC/MS/MS. Toluidines (orto-, meta-, and para-) were measured in urine by gas chromatography (GC)/MS. The average telomere length in peripheral blood was determined by quantitative polymerase chain reaction (PCR). RESULTS: There was a reduction in telomere length with increasing exposure to N-nitrosamines in air [measured (N=60) N-nitrosamines β-coefficient= -10, (95% confidence interval [95% CI] -17– -1.9) P=0.016; estimated (N=157) N-nitrosamines β-coefficient = -5.3, (95% CI -9.5– -0.97) P=0.016]. Also, there were negative associations between para-toluidine [β-coefficient= -0.031 (95% CI -0.055– -0.0063) P=0.014], as well as age β-coefficient= -0.005 (95% CI -0.007– -0.002) P=0.001] and telomere length. There were no strong associations between other exposures and telomere length nor did smoking modify the effect. CONCLUSION: N-nitrosamines exposure may lead to telomere shortening.

N -nitrosamines are formed during different industrial processes and are of significant concern due to their carcinogenic and mutagenic properties. This study reports concentrations of N -nitrosamines in eight different industrial wastewater treatment plants in Switzerland and the variability of their abundance. Only four N -nitrosamines species, N -nitrosodimethylamine (NDMA), N -nitrosodiethylamine (NDEA), N -nitrosodibutylamine (NDPA) and N -nitrosomorpholine (NMOR) were above the limit of quantification in this campaign. Remarkably high concentrations (i.e. up to 975 μg NDMA/L, 90.7 μg NDEA/L, 1.6 μg NDPA/L and 710 μg NMOR/L) of these N -nitrosamines were detected at seven of eight sites. These concentrations are two to five orders of magnitude higher than those typically detected in municipal wastewater effluents. These results suggest that industrial effluents may be a major source of N -nitrosamines. Although very high concentrations of N -nitrosamine have been detected in industrial discharges, various processes in surface water can partially mitigate their concentrations (e.g. photolysis, biodegradation and volatilization) and hence the risk to human health and aquatic ecosystems. Nevertheless, there is little information on long-term effects on aquatic organisms and therefore the discharge of N -nitrosamines to the environment should be avoided until the impact on ecosystems is assessed. During winter a less efficient mitigation of N -nitrosamines can be expected (lower biological activity, less sunlight) and therefore, emphasis should be put on this season in future risk assessment studies. [Display omitted] • 4 N-nitrosamines out 8 were detected in the effluents of eight industrial sites. • High NDMA concentrations are released by industries (0.2–975 μg/L). • Industrial compared to municipal discharges are more important for N-nitrosamines. [ABSTRACT FROM AUTHOR]

The quantitative analytical methods for seven N-nitrosamines including N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodibutylamine (NDBA), N-nitrosopiperidine (NPIP), N-nitrosopyrrolidine (NPYR), and N-nitrosomorpholine (NMOR) were established for agricultural food matrices. Four food matrices were used for the method development: rice soup as a fatless solid matrix, apple juice as a fatless liquid matrix, corn oil as a fat-rich liquid matrix, and 20 % alcohol as an alcohol matrix. A combination of solid-supported liquid-liquid extraction (SLLE) using Extrelut NT and a solid phase extraction (SPE) using Florisil was employed for fatless matrices. For an alcohol matrix, only SLLE was used without SPE, and liquid-liquid extraction (LLE) was established for a fat-rich matrix. The extract was analyzed by gas chromatography-positive chemical ionization-tandem mass spectrometry (GC-PCI-MS/MS) using ammonia gas as an ion source. Linearity, recovery, repeatability, inter-day precision, reproducibility, and uncertainty were evaluated for method validation using four matrices. Method detection limits for all of the investigated N-nitrosamines were ranged from 0.10 to 0.18 μg/kg for the rice soup, from 0.10 to 0.19 μg/kg for the apple juice, 0.10 μg/kg for the corn oil, and from 0.10 to 0.25 μg/kg for 20 % alcohol, depending on N-nitrosamines. Established methods were applied to determine seven N-nitrosamines in some agricultural food products. [ABSTRACT FROM AUTHOR]