Critical review of major sources of human exposure to N-nitrosamines

Gushgari, Adam J.; Halden, Rolf U.

doi:10.1016/j.chemosphere.2018.07.098

Cited by 111 publications

(60 citation statements)

References 101 publications

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“…NDMA and other nitrosamines are common contaminants in low amounts in foods, beverages, cosmetics, water, tobacco products, and consumer goods (1)(2)(3)(4). In 2018, observations of NDMA and NDEA in angiotensin receptor blocker drugs (ARBs) led to recalls of batches of products which had unacceptable amounts of nitrosamines (5,6).…”

Section: Introductionmentioning

confidence: 99%

A Cautionary Tale: Quantitative LC-HRMS Analytical Procedures for the Analysis of N-Nitrosodimethylamine in Metformin

Yang

Marzan

et al. 2020

AAPS J

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A private testing laboratory reported in a Citizen Petition (CP) to FDA that 16 of 38 metformin drug products they tested had N-nitrosodimethyl amine (NDMA) amounts above the allowable intake (AI) of 96 ng/day. Because the FDA had been monitoring drugs for nitrosamines, orthogonal analytical procedures had been developed, validated and applied to detect the following nitrosamines in metformin drug products (if present): (i) NDMA (with a dedicated method) or (ii) NDMA (with a second confirmatory method), Nnitroso-diethylamine (NDEA), N-ethyl-N-nitroso-2-propanamine (NEIPA), N-nitrosodiisopropylamine (NDIPA), N-nitroso-din -propylamine (NDPA), N-nitrosomethylphenylamine (NMPA), N-nitroso-din -butylamine (NDBA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA). In contrast to the private laboratory results, FDA testing on the same set of 38 samples with orthogonal procedures observed amounts over the AI in only 8 of the 38 products and generally observed lower values than reported by the private testing laboratory. As described here, the investigation into the cause of the discrepancy revealed that N,N-dimethylformamide (DMF) can interfere with NDMA measurements. The data showed that the use of sufficient mass accuracy in the data acquisition and appropriate mass tolerance setting in the data processing to assure the selectivity of mass spectrometry measurements of NDMA in the presence of co-eluting DMF was necessary to prevent overestimation of the level of NDMA in metformin drug products. Overall, care should be taken to assure the necessary specificity in analytical procedures for adequate assessment of the nitrosamine level in drug products that also contain DMF or other potential interfering substances.

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Section: Introductionmentioning

confidence: 99%

A Cautionary Tale: Quantitative LC-HRMS Analytical Procedures for the Analysis of N-Nitrosodimethylamine in Metformin

Yang

Marzan

et al. 2020

AAPS J

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“…Contamination can come from food, water sources and wells near the industrial plants or drainage. The main health risk of nitrates comes from their conversion to nitrosamines that belong reportedly to carcinogenic substances acting on nucleic acids causes tumours (Lin, 1990;Gushgari and Halden, 2018). However, despite many epidemiological and experimental studies, there are no direct correlations between cancer development and nitrates and nitrites intake (Knight et al, 1990;Eichholzer and Gutzwiller, 1998).…”

Section: Importance and Risks Of Nitrates And Nitrites To Human Healthmentioning

confidence: 99%

Relationship of nitrates and nitrites in the water environment with humans and their activity

Balejčíková¹,

Tall²,

Kandra³

et al. 2020

ahs

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Nitrates and nitrites in water pose a health and environmental hazards, in particular when exceeding limits defined in the European Union, i.e. max. 50 mg l-1 of nitrates. It is not recommended to exceed the limit of 10 mg l-1 of nitrates for infants and children. The maximum concentration of nitrites is 0.5 mg l-1 for adults and infants less than 0.1 mg l-1. Our work offers a review of the water quality concerning the relationship between nitrates/nitrites and humans. Basic properties and forms of nitrates, their use for human activities, importance and risks to human health and possibilities of their physicochemical determination are summarized. Our study demonstrates also the novel approaches to the nitrates decontamination in a water environment using various nanomaterials. We aimed at a collection of records from the monitoring of nitrates in selected areas in Slovakia to show good quality of water in various water sources, which over time improves due to the increasingly low fertilization intensity and thus of agriculture production, which is gradually being replaced by imports.

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“…(NDMA) is an organic compound found at low levels in numerous processed items of human consumption, including cured and grilled meats (that contain sodium nitrite as a preservative), bacon, fish, dairy products, cheese, vegetables like lettuce and spinach,pepper, fruits, beer, whisky, tobacco smoke and even in some cleansers, toiletry, rubber and cosmetic products. 4 NDMA arises by the combination of nitrous acid and dimethyl amine derived from the degradation of protein from the food in the lower gut. NDMA is a known common environmental contaminant and everyone is exposed to some level of NDMA through air, soil and water.…”

Section: N-nitrosodimethylaminementioning

confidence: 99%

Metformin and nitrosamine impurities

Kumar

Deepa

2020

Int J Res Med Sci

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Metformin is considered as gold standard anti-diabetic drug and is the preferred initial pharmacologic agent for most of the patients with type 2 diabetes mellitus. Metformin is cheap, widely available and safe, backed by pharmaco-epidemiological evidence of more than 60 years regular use in clinical practice. Due to its durable efficacy, once initiated, metformin will be continued as long as it is tolerated and not contraindicated. It has got additional benefits on cholesterol, liver, cardio vascular system and cancer. Recent evidence and recall of metformin extended release formulation due to detection of excess amount of cancer-causing nitrosamine impurities has created concern among health care providers and patients. Adherence to regulatory guidelines and use of approved technologies in manufacturing and quality control may help in solving the issue.

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Critical review of major sources of human exposure to N-nitrosamines

Cited by 111 publications

References 101 publications

A Cautionary Tale: Quantitative LC-HRMS Analytical Procedures for the Analysis of N-Nitrosodimethylamine in Metformin

A Cautionary Tale: Quantitative LC-HRMS Analytical Procedures for the Analysis of N-Nitrosodimethylamine in Metformin

Relationship of nitrates and nitrites in the water environment with humans and their activity

Metformin and nitrosamine impurities

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