N-Nitrosodimethylamine investigations in Muta™Mouse define point-of-departure values and demonstrate less-than-additive somatic mutant frequency accumulations.

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 lacZ 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 lacZ 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 lacZ 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.

Determining recommended acceptable intake limits for N-nitrosamine impurities in pharmaceuticals: Development and application of the Carcinogenic Potency Categorization Approach (CPCA).

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.

In Silico Prediction of N-Nitrosamine Formation Pathways of Pharmaceutical Products.

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.

Intake of tobacco nitrosamines of smokers in various provinces of China and their cancer risk: A meta-analysis.

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.

Chiral Bromonium Salt (Hypervalent Bromine(III)) with N-Nitrosamine as a Halogen-Bonding Bifunctional Catalyst.

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.

Determination of Genotoxic Impurity N-Nitroso-N-methyl-4-aminobutyric Acid in Four Sartan Substances through Using Liquid Chromatography-Tandem Mass Spectrometry.

N-nitroso-N-methyl-4-aminobutyric acid (NMBA) is the third N-nitrosamine impurity found in sartans. Herein, a sensitive and stable LC-MS/MS method with multiple reactions monitoring mode has been developed for the quantitative determination of NMBA in four sartan substances. The effective separation of NMBA and sartan substances was achieved on a C18 column under gradient elution conditions. The mass spectrometry method of the atmospheric pressure chemical ionization source and internal standard method was selected as the quantitative analysis method of NMBA. Then, this proposed LC-MS/MS analysis method was validated in terms of specificity, sensitivity, linearity, accuracy, precision and stability. Good linearity with correlation coefficient over 0.99 was obtained at the NMBA concentration of 3-45 ng/mL, and the limit of quantification was 3 ng/mL. Additionally, the recoveries of NMBA in four sartan substances ranged from 89.9% to 115.7%. The intra-day and inter-day relative standard deviation values were less than 5.0%. In conclusion, this developed determination method for NMBA through liquid chromatography-tandem mass spectrometry showed the characteristics of good sensitivity, high accuracy and precision, which will be of great help for the quantitative analysis of NMBA in sartan products.

Utilisation of parametric methods to improve percentile-based estimates for the carcinogenic potency of nitrosamines.

N-Nitrosamines have recently been the subject of intense regulatory scrutiny, including the setting of low exposure limits (18 ng/day) (European Medicines Agency (EMA), 2020). This paper evaluates different methodologies to determine statistically robust bounds on the carcinogenic potency of chemical classes, using historic TD50 data (Peto et al., 1984; Thresher et al., 2019) and exemplified for N-nitrosamines. Initially, the distribution of TD50 values (TD50s) for N-nitrosamines of known potency was characterised. From this, it is possible to compare parametric and non-parametric methods to obtain percentiles of interest from the distribution of TD50s, which are shown to be robust to uncertainty in the initial TD50 estimates. These methods may then be applied to different chemical subclasses. The values obtained may be of use in refining acceptable intakes for N-nitrosamines and their subclasses.

Use of less-than-lifetime (LTL) durational limits for nitrosamines: Case study of N-Nitrosodiethylamine (NDEA).

The ICH M7(R1) guideline describes a framework to assess the carcinogenic risk of mutagenic and carcinogenic pharmaceutical impurities following less-than-lifetime (LTL) exposures. This LTL framework is important as many pharmaceuticals are not administered for a patient's lifetime and as clinical trials typically involve LTL exposures. While there has been regulatory caution about applying LTL concepts to cohort of concern (COC) impurities such as N-nitrosamines, ICH M7 does not preclude this and indeed literature data suggests that the LTL framework will be protective of patient safety for N-nitrosamines. The goal was to investigate if applying the LTL framework in ICH M7 would control exposure to an acceptable excess cancer risk in humans. Using N-nitrosodiethylamine as a case study, empirical data correlating exposure duration (as a percentage of lifespan) and cancer incidence in rodent bioassays indicate that the LTL acceptable intake (AI) as derived using the ICH M7 framework would not exceed a negligible additional risk of cancer. Therefore, controlling N-nitrosamines to an LTL AI based on the ICH M7 framework is thus demonstrated to be protective for potential carcinogenic risk to patients over the exposure durations typical of clinical trials and many prescribed medicines.

N-Nitrosamine formation from chloramination of two common ionic liquids.

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 ±â€¯0.3 ng/mg from EMImBr, and as high as 8.6 ±â€¯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 NH2Cl, 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.

Impact of tobacco-specific nitrosamine-derived DNA adducts on the efficiency and fidelity of DNA replication in human cells.

The tobacco-derived nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are known human carcinogens. Following metabolic activation, NNK and NNN can induce a number of DNA lesions, including several 4-(3-pyridyl)-4-oxobut-1-yl (POB) adducts. However, it remains unclear to what extent these lesions affect the efficiency and accuracy of DNA replication and how their replicative bypass is influenced by translesion synthesis (TLS) DNA polymerases. In this study, we investigated the effects of three stable POB DNA adducts (O2-POB-dT, O4-POB-dT, and O6-POB-dG) on the efficiency and fidelity of DNA replication in HEK293T human cells. We found that, when situated in a double-stranded plasmid, O2-POB-dT and O4-POB-dT moderately blocked DNA replication and induced exclusively T→A (∼14.9%) and T→C (∼35.2%) mutations, respectively. On the other hand, O6-POB-dG slightly impeded DNA replication, and this lesion elicited primarily the G→A transition (∼75%) together with a low frequency of the G→T transversion (∼3%). By conducting replication studies in isogenic cells in which specific TLS DNA polymerases (Pols) were deleted by CRISPR-Cas9 genome editing, we observed that multiple TLS Pols, especially Pol η and Pol ζ, are involved in bypassing these lesions. Our findings reveal the cytotoxic and mutagenic properties of specific POB DNA adducts and unravel the roles of several TLS polymerases in the replicative bypass of these adducts in human cells. Together, these results provide important new knowledge about the biological consequences of POB adducts.

Simultaneous removal of ammonia and N-nitrosamine precursors from high ammonia water by zeolite and powdered activated carbon.

When adding sufficient chlorine to achieve breakpoint chlorination to source water containing high concentration of ammonia during drinking water treatment, high concentrations of disinfection by-products (DBPs) may form. If N-nitrosamine precursors are present, highly toxic N-nitrosamines, primarily N-nitrosodimethylamine (NDMA), may also form. Removing their precursors before disinfection should be a more effective way to minimize these DBPs formation. In this study, zeolites and activated carbon were examined for ammonia and N-nitrosamine precursor removal when incorporated into drinking water treatment processes. The test results indicate that Mordenite zeolite can remove ammonia and five of seven N-nitrosamine precursors efficiently by single step adsorption test. The practical applicability was evaluated by simulation of typical drinking water treatment processes using six-gang stirring system. The Mordenite zeolite was applied at the steps of lime softening, alum coagulation, and alum coagulation with powdered activated carbon (PAC) sorption. While the lime softening process resulted in poor zeolite performance, alum coagulation did not impact ammonia and N-nitrosamine precursor removal. During alum coagulation, more than 67% ammonia and 70%-100% N-nitrosamine precursors were removed by Mordenite zeolite (except 3-(dimethylaminomethyl)indole (DMAI) and 4-dimethylaminoantipyrine (DMAP)). PAC effectively removed DMAI and DMAP when added during alum coagulation. A combination of the zeolite and PAC selected efficiently removed ammonia and all tested seven N-nitrosamine precursors (dimethylamine (DMA), ethylmethylamine (EMA), diethylamine (DEA), dipropylamine (DPA), trimethylamine (TMA), DMAP, and DMAI) during the alum coagulation process.

Capability of cation exchange technology to remove proven N-nitrosodimethylamine precursors.

N-nitrosodimethylamine (NDMA) precursors consist of a positively charged dimethylamine group and a non-polar moiety, which inspired us to develop a targeted cation exchange technology to remove NDMA precursors. In this study, we tested the removal of two representative NDMA precursors, dimethylamine (DMA) and ranitidine (RNTD), by strong acidic cation exchange resin. The results showed that pH greatly affected the exchange efficiency, with high removal (DMA>78% and RNTD>94%) observed at pHMg2+>RNTD+>K+>DMA+>NH4+>Na+. The partition coefficient of DMA+ to Na+ was 1.41±0.26, while that of RNTD+ to Na+ was 12.1±1.9. The pseudo second-order equation fitted the cation exchange kinetics well. Bivalent inorganic cations such as Ca2+ were found to have a notable effect on NA precursor removal in softening column test. Besides DMA and RNTD, cation exchange process also worked well for removing other 7 model NDMA precursors. Overall, NDMA precursor removal can be an added benefit of making use of cation exchange water softening processes.

Genotoxicity and the stability of N-nitrosomorpholine activity following UVA irradiation.

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.

N-Nitrosodimethylamine formation from anthropogenic nitrogenous compounds during preozonation and post-chloramination with characteristic low treatment dose.

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.

Genotoxicity assessments of N-nitrosoethylisopropylamine (NEIPA) and N-nitrosodiisopropylamine (NDIPA) in the C57BL/6J mouse.

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.

Transnitrosation of alicyclic N-nitrosamines containing a sulfur atom.

Aromatic and aliphatic nitrosamines are known to transfer a nitrosonium ion to another amine. The transnitrosation of alicyclic N-nitroso compounds generates S-nitrosothiols, which are potential nitric oxide donors in vivo. In this study, certain alicyclic N-nitroso compounds based on non-mutagenic N-nitrosoproline or N-nitrosothioproline were synthesised, and the formation of S-nitrosoglutathione (GSNO) was quantified under acidic conditions. We then investigated the effect of a sulfur atom as the substituent and as a ring component on the GSNO formation. In the presence of thiourea under acidic conditions, GSNO was formed from N-nitrosoproline and glutathione, and an N-nitroso compound containing a sulfur atom and glutathione produced GSNO without thiourea. The quantity of GSNO derived from the reaction of the N-nitrosamines containing a sulfur atom and glutathione was higher than that from the N-nitrosoproline and glutathione plus thiourea. Among the analogues that contained a sulfur atom either in the ring or as a substituent, the thiazolidines produced a slightly higher quantity of GSNO than the analogue with a thioamide group. A compound containing sulfur atoms both in the ring and as a substituent exhibited the highest activity for GSNO formation among the alicyclic N-nitrosamines tested. The results indicate that the intramolecular sulfur atom plays an important role in the transnitrosation via alicyclic N-nitroso compounds to form GSNO.

N-Nitrosamine sensing properties of novel penta-silicane nanosheets-a first-principles outlook.

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.

Targeted electrochemical reduction of carcinogenic N-nitrosamines from emission control systems within CO2 capture plants.

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 CO2 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 CO2 capture systems.

A survey of industrial N-nitrosamine discharges in Switzerland.

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.

Seasonal variability, predictive modeling and health risks of N-nitrosamines in drinking water of Shanghai.

The prevalence of carcinogenic N-nitrosamines in drinking water is of significant concern. In the present study, eight N-nitrosamines from three representative drinking water treatment plants (DWTPs) in Shanghai, China were monitored for an entire year to evaluate their seasonal variability, probabilistic cancer risk and the resulting disease burden. The possibility of employing routinely monitored water quality parameters as predictors of N-nitrosamines was also examined. The results showed that the Taipu River-fed reservoir suffered more serious N-nitrosamine contamination than the Yangtze River-fed reservoirs. Winter witnessed higher levels of N-nitrosamines in both source and finished water. N-nitrosamine concentrations increased from source water to finished water in autumn or winter, but no spatial variations were observed in summer. The total lifetime cancer risk (LCR) posed by N-nitrosamines in finished water was within the acceptable range (1.00 × 10-6 to 1.00 × 10-4), with N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) being the main contributors. Winter and autumn were found to have higher total LCR values. The average individual disability-adjusted life years (DALYs) lost was 4.43 × 10-6 per person-year (ppy), exceeding the reference risk level (1.00 × 10-6 ppy). Liver cancer accounted for 97.1 % of the total disease burden, while bladder and esophagus cancers made a little contribution (2.9 %). A multiple regression model was developed to estimate the total N-nitrosamines in finished water as a function of water quality parameters, and the R2 value was 0.735. This study not only provides fundamental data for public health policy development, but also reveals the necessity to incorporate a seasonal control strategy in DWTPs to minimize the associated health risks induced by N-nitrosamines.