Hazard assessment of nitrosamine and nitramine by-products of amine-based CCS: Alternative approaches

Buist, Harrie; DeVito, Stephen C.; Goldbohm, R.A.; Stierum, Rob; Venhorst, Jennifer; Kroese, E. Dinant

doi:10.1016/j.yrtph.2014.01.017

Cited by 21 publications

(27 citation statements)

References 69 publications

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“…DNA methylating agents such as N -methyl- N -nitrosourea (MNU), N -nitrosodimethylamine (NDMA), and Temozolomide (TMZ) form DNA lesions that are both toxic and mutagenic. One of those lesions is O 6 -methylguanine (m6G), which is potently mutagenic because it predominantly pairs with thymine during replication. , There is much interest in these agents in the fields of environmental and clinical toxicology, because DNA methylating agents are contaminants found in and around toxic waste sites; − they form in preserved foods and beverages; − they form during carbon capture processes; , they are contaminants in cardiovascular and other medications; − and they are present in tobacco smoke and other tobacco products. , Similarly, there is interest in the field of cancer therapy because the lead agent used in treatment of glioblastoma, TMZ, forms m6G as a critical component of its mechanism of action. − …”

Section: Introductionmentioning

confidence: 99%

Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O⁶-Methylguanine Methyltransferase, MGMT

Thongararm

Fedeles

Khumsubdee

et al. 2019

Chem. Res. Toxicol.

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DNA methylating agents are abundant in the environment and are sometimes used in cancer chemotherapy. They react with DNA to form methyl-DNA adducts and byproduct lesions that can be both toxic and mutagenic. Foremost among the mutagenic lesions is O 6 -methylguanine (m6G), which base pairs with thymine during replication to cause GC→AT mutations. The gpt delta C57BL/6J mouse strain of Nohmi et al. (Mol. Mutagen, 1996;28:465-70) reliably produces mutational spectra of many DNA damaging agents. In this work, mouse embryo fibroblasts (MEFs) were made from gpt delta C57BL/6J mice and evaluated as a screening tool to determine the qualitative and quantitative features of mutagenesis by N-methyl-N-nitrosourea (MNU), a direct-acting DNA alkylator that serves as a model for environmental N-nitrosamines, such as Nnitrosodimethylamine and therapeutic agents such as temozolomide. The DNA repair protein MGMT (O 6 -methylguanine DNA methyltransferase) protects against environmental mutagenesis by DNA methylating agents and, by removing m6G, limits the therapeutic potential of temozolomide in cancer therapy. The gpt delta MEFs were treated with MNU to establish dosedependent toxicity. In parallel, MNU mutagenicity was determined in the presence and absence of the MGMT inhibitor AA-CW236 (4-(2-(5-(chloromethyl)-4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)ethyl)-3,5-dimethylisoxazole). With and without the inhibitor, the principal mutagenic event of MNU was GC→AT, but more mutations were observed when the inhibitor was present. Evidence that the mutagenic lesion was m6G was based on mass spectral data collected using O 6 -methyl-d 3 -guanine as an internal standard; m6G levels were higher in AA-CW236 treated MEFs by an amount proportional to the higher mutation

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Section: Introductionmentioning

confidence: 99%

Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O⁶-Methylguanine Methyltransferase, MGMT

Thongararm

Fedeles

Khumsubdee

et al. 2019

Chem. Res. Toxicol.

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“…Until more research on the potential effects of specific components is done, their presence, even in very concentrations, requires monitoring. An example here is nitrosamines, a group of generally carcinogenic compounds . However, few studies are available for the nitrosamines that are typically formed in the CO 2 capture process.…”

Section: Environmental and Health Aspects Of Some Degradation Compoundsmentioning

confidence: 99%

Important Aspects Regarding the Chemical Stability of Aqueous Amine Solvents for CO₂ Capture

Vevelstad

Buvik

Knuutila

et al. 2022

Ind. Eng. Chem. Res.

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The chemical stability of aqueous amines is an essential property to study before new amines are introduced in pilot plants, to reduce risks related to the operation, cost and environment. There are no standard methods for studying degradation and no standardized way of knowing which components to search for. This work will give an overview of the current status of amine degradation research with recommendations for further work within this field. Degradation of aqueous amines in the CO 2 absorption process will always occur, though some amines are more stable than others. Degradation leads to compounds with various functional groups, some of which require monitoring from an environmental or health perspective. Future experimental activity should focus on closing the knowledge gaps. Improved knowledge could help to better predict and monitor degradation, help design better mitigation technologies, and minimize solvent degradation by finetuning the plant operation.

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“…N-Nitrosamine GTIs have been recognized as a kind of potent carcinogens. They showed mutagenic activities in Ames test with Salmonella typhimurium and triggered the carcinogenic effect in rats, mice, hamsters, guinea pigs, and rabbits (Wagner et al 2012;Santos et al 2014;Buist et al 2015;Ravnum et al 2014). Since the valsartan and losartan products produced by several pharmaceutical companies were proven to contain potential contamination with carcinogenic nitrosamine impurities, namely, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitroso-N-methyl-4-aminobutyric acid (NMBA) ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Development of a sensitive and stable GC-MS/MS method for simultaneous determination of four N-nitrosamine genotoxic impurities in sartan substances

Liu¹,

Xie²,

Mai

et al. 2021

J Anal Sci Technol

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Recently, N-nitrosamines have been unexpectedly found in generic sartan products. Herein, we developed a sensitive and stable GC-MS/MS method with multiple reactions monitoring mode for the simultaneous determination of four N-nitrosamines in sartan substances, namely, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, and N-nitrosodiisopropylamine. The conditions of gas chromatography and mass spectrometry were optimized. The method was validated according to the International Council for Harmonization guidelines in terms of sensitivity, linearity, accuracy, precision, specificity, and stability. The limits of detection of N-nitrosamines in sartan substances ranged from 0.002 to 0.150 ppm, and the corresponding limits of quantification were in the range of 0.008-0.500 ppm, which met the sensitivity requirements for the limits set by the Food and Drug Administration of the United States. The internal standard curve of four N-nitrosamines showed good linearity of regression coefficients over 0.99. The recoveries of N-nitrosamines in selected sartan drugs ranged from 87.68 to 123.76%. The intraday and interday relative standard deviation values were less than 9.15%. Therefore, this proposed method exhibited good sensitivity and precision, high accuracy, and fast analysis speed, which provide a reliable method for quality control of N-nitrosamines in sartan products.

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Hazard assessment of nitrosamine and nitramine by-products of amine-based CCS: Alternative approaches

Cited by 21 publications

References 69 publications

Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O⁶-Methylguanine Methyltransferase, MGMT

Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O⁶-Methylguanine Methyltransferase, MGMT

Important Aspects Regarding the Chemical Stability of Aqueous Amine Solvents for CO₂ Capture

Development of a sensitive and stable GC-MS/MS method for simultaneous determination of four N-nitrosamine genotoxic impurities in sartan substances

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Hazard assessment of nitrosamine and nitramine by-products of amine-based CCS: Alternative approaches

Cited by 21 publications

References 69 publications

Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O6-Methylguanine Methyltransferase, MGMT

Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O6-Methylguanine Methyltransferase, MGMT

Important Aspects Regarding the Chemical Stability of Aqueous Amine Solvents for CO2 Capture

Development of a sensitive and stable GC-MS/MS method for simultaneous determination of four N-nitrosamine genotoxic impurities in sartan substances

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Product

Resources

About

Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O⁶-Methylguanine Methyltransferase, MGMT

Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O⁶-Methylguanine Methyltransferase, MGMT

Important Aspects Regarding the Chemical Stability of Aqueous Amine Solvents for CO₂ Capture