Comparison of N-nitrosamine formation mechanisms in vacuum and modified atmosphere packaged sausages using mathematical modelling

A gas-liquid chromatographic method for quantitative determination of six volatile N-nitrosamines in human postmortem organs (brain, liver, kidneys, and pancreas) is described. This method, which is highly sensitive and selective, makes use of two different detectors, i.e., the electron capture detector (ECD) and the thermal energy analyzer (TEA). The mean absolute percentage recoveries of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosodipropylamine (NDPA, N-nitrosodibutylamine (NDBA), N-nitrosopiperidine (NPIP), and N-nitrosopyrrolidine (NPY) were 54.7, 80.0, 79.6, 72.5, 75.5, and 79.6, respectively. N-Nitrosamines in the organ extracts were converted to their corresponding N-nitramine analogs by pertrifluoroacetic acid oxidation. These derivatives were purified by adsorption chromatography on basic alumina and then analyzed by ECD. N-Nitrosamines were analyzed without derivatization in the organ extracts with the TEA detector. The described method did not cause artifactual formation of N-nitrosomethyl-N-butylamine (NMBA) when methyl-N-butylamine was used as an internal marker of nitrosation. NDMA was found in all the organs examined, whereas NDPA was only detected in the liver of one in four subjects. NDMA was found in all brain samples, indicating that it crosses the blood-brain barrier.

Characteristics and health risk assessment of volatile N-nitrosamines in the plasma of adults in Guangdong Province, China

Metabolic activation of N -alkylnitrosamines in genetically engineered Salmonella typhimurium expressing CYP2E1 or CYP2A6 together with human NADPH-cytochrome P450 reductase

Metabolic activation of N-alkylnitrosamines in genetically engineered Salmonella typhimurium expressing CYP2E1 or CYP2A6 together with human NADPH-cytochrome P450 reductase

We conducted a probabilistic risk assessment for seven nitrosamines (i.e., N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodibuthylmine (NDBA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine (NPIP), N-nitrosomorpholone (NMOR) and N-nitrosomethylethylamine (NMEA)) to assess the cancer risk posed by dietary intake of nitrosamines for Korean people. The estimated cancer risks were the highest in the order of NDMA, NDEA, NDBA, NPYR, NPIP, NMOR and NMEA. The cancer risks of NPYR, NPIP, NMOR and NMEA was estimated to be lower than de minimis risk (i.e., a cancer risk of 10−6), and thus, can be ignored. The derived cancer risks of NDEA and NDBA exceeded de minimis risk, but did not exceed de manifestis risk (i.e., a cancer risk of 10−4), meaning that no imminent action is required for either chemical. However, because the high-end cancer risk (i.e., > 90th percentile) by NDMA intake exceeded de manifestis risk owing to its strong carcinogenicity and high daily intake rate, action to reduce the cancer risk from dietary intake of NDMA is strongly warranted. Because NDMA formation in foods is an unavoidable chemical reaction between NDMA precursors (i.e., nitrogen oxides and organic amines), we recommend focusing on reducing the contents of NDMA precursors in foods as a best management practice.

Elevated urinary levels of carcinogenic N-nitrosamines in patients with urinary tract infections measured by isotope dilution online SPE LC–MS/MS

Volatile N-nitrosamine (VNA) levels in South Korean and imported alcoholic beverages were determined between 1995 and 2002. A total of 147 alcoholic beverages, including lager beer, whisky, liqueurs and traditional Korean alcoholic beverages (Chungju, Takju and Soju), were analysed for their VNA content by GC-TEA. Of eight VNAs (N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosomorphorine (NMOR), N-nitrosodibuthylamine (NDBA), N-nitrosopiperidine (NPIP), N-nitrosodiprophylamine (NDPA) and N-nitrosodiphenylamine (NDPhA)) only NDMA was detected. In 1995, NDMA was detected in 79.3% of domestic beers; the average was 0.8 µg kg−1. Seven years later, the average NDMA level for 18 domestic beers was 0.3 µg kg−1 and it was positive in 55.6% samples. In whisky and liqueurs, NDMA levels averaged <0.1 µg kg−1 in both 1995 and 2002. Average NDMA levels of Chungju in 1995 were <0.1 µg kg−1, but NDMA was not detected in 2002. Takju had undetectable levels of NDMA both times. In 1995, NDMA was found in four of six Soju samples, but in 2002, NDMA could not be detected.

The biotransformation potential of six nitrosamines and their precursor secondary amines by a mixed methanogenic culture was investigated. Among the six nitrosamines tested, N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), and N-nitrosopyrrolidine (NPYR) were almost completely degraded but only when degradable electron donors were available. On the contrary, N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), and N-nitrosodibutylamine (NDBA) were not degraded. Three precursor secondary amines, corresponding to the three biodegradable nitrosamines, were also completely utilized even with very low levels of available electron donors. The secondary amine precursors of the three, nonbiodegradable nitrosamines were also recalcitrant. A bioassay conducted to elucidate the biotransformation pathway of NDMA in the mixed methanogenic culture using H(2) as the electron donor showed that NDMA was utilized as an electron acceptor and transformed to dimethylamine (DMA), which in turn was degraded to ammonia and methane. The H(2) threshold concentration for NDMA bioreduction ranged between 0.0017 and 0.031 atm. Such a high H(2) threshold concentration suggests that in mixed methanogenic cultures, NDMA reducers are weak competitors to other, H(2)-consuming microbial species, such as homoacetogens and methanogens. Thus, complete removal of nitrosamines in anaerobic digestion systems, where the H(2) partial pressure is typically below 10(-4) atm, is difficult to achieve.

An analytical method was developed for the determination of the extraction of volatile N-nitrosamine compounds including N-nitrosodimethylamine ( NDMA) , N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosopiperidine (NPIP), and N-nitrosopyrrolidine (NPYR) from salted aquatic products by gas chromatography-mass spectrometry (GC-MS). In this experiment, the separation and detection conditions were optimized for different extraction methods, solid-phase extraction columns, and chromatographic columns. The results showed that the linear correlation coefficients (R2) were higher than 0. 999 8 within 10 - 1 000 micro g/L, and the reproducibilities were good with the - relative standard deviations (RSD) less than 8%. The recoveries were 79% - 105%. It is noted that this method for the determination of volatile N-nitrosamine compounds in salted aquatic products was much more sensitivity and with a lower detection limits (0. 05 micro g/kg except NDPA) than the previously reported methods. This proposed method is rapid and convenient for the determination, and easy for the operation. It is appropriate for the determination of volatile N-nitrosamine compounds in various salted aquatic products.

N-nitrosamines are widespread in various bodies of water, which is of great concern due to their carcinogenic risks and harmful mutagenic effects. Livestock rearing, domestic, agricultural, and industrial wastewaters are the main sources of N-nitrosamines in environmental water. However, information on the amount of N-nitrosamines these different wastewaters contribute to environmental water is scarce. Here, we investigated eight N-nitrosamines and assessed their mass loadings in the Desheng River to quantify the contributions discharged from different anthropogenic activities. N-nitrosodimethylamine (NDMA) (< 1.6-18ng/L), N-nitrosomethylethylamine (NMEA) (< 2.2ng/L), N-nitrosodiethylamine (NDEA) (< 1.7-2.4ng/L), N-nitrosopyrrolidine (NPYR) (< 1.8-18ng/L), N-nitrosomorpholine (NMOR) (< 2.0-3.5ng/L), N-nitrosopiperidine (NPIP) (< 2.2-2.5ng/L), and N-nitrosodi-n-butylamine (NDBA) (< 3.3-16ng/L) were detected. NDMA and NDBA were the dominant compounds contributing 89% and 92% to the total N-nitrosamine concentrations. The mean cumulative concentrations of N-nitrosamines in the livestock rearing area (26 ± 11ng/L) and industrial area (24 ± 4.8ng/L) were higher than those in the residential area (16 ± 6.3ng/L) and farmland area (15 ± 5.1ng/L). The mean concentration of N-nitrosamines in the tributaries (22ng/L) was slightly higher than that in the mainstem (17ng/L), probably due to the dilution effect of the mainstem. However, the mass loading assessment based on the river's flow and water concentrations suggested the negligible mass emission of N-nitrosamines into the mainstem from tributaries, which could be due to the small water flow of tributaries. The average mass loads of N-nitrosamines discharged into the mainstem were ranked as the livestock rearing area (742.7g/d), industrial area (558.6g/d), farmland area (93.9g/d), and residential areas (83.2g/d). In the livestock rearing, residential, and industrial area, NDMA (60.9%, 53.6%, and 46.7%) and NDBA (34.6%, 33.3%, and 44.9%) contributed the most mass loads; NDMA (23.4%), NDEA (15.8%), NPYR (10.1%), NPIP (12.8%), and NDBA (37.8%) contributed almost all the mass loads in the farmland area. Photodegradation amounts of NDMA (0.65 ~ 5.25µg/(m3·day)), NDBA (0.37 ~ 0.91µg/(m3·day)), and NDEA (0 ~ 0.66µg/(m3·day)) were also calculated according to the mass loading. Quantifying the contribution of different anthropogenic activities to the river will provide important information for regional river water quality protection. Risk quotient (RQ) values showed the negligible ecological risks for fish, daphnid, and green algae.

The present work reports a rapid reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of seven volatile N-nitrosamines namely N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodiproylamine (NDPA), N-nitrosodi butylamine (NDBA), N-nitrosopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR) for monitoring food safety. A strategic experimental approach was implemented for the method development. The desired chromatographic separation was achieved on a Symmetry C18 (4.6 × 150 mm, 5 μm) column using gradient elution. The optimized mobile phase consisted of the 10 mM ammonium hydroxide pH = 8.9 and acetonitrile. The eluted compounds were monitored at 231 nm wavelength using spectrophotometric detector. The developed method separated seven compounds from each other within a run time of 10 min. The method is effective for the determination of presence of these carcinogenic compounds. The average extraction recovery of seven nitrosamines was found 84.5%; the precision of method was found less than 2.7% and accuracy was found between 95%-102.5%. The assay could be applied in food monitoring safety.

Objective : This research foucuses on the development of a liquid chromatographic method for the rapid and reliable separation and identification of major nitrosamine impurities, ensuring both short analysis time and adequate resolution. Given the toxicological relevance of nitrosamines, their occurrence in pharmaceutical formulations has raised substantial concerns, leading to the reassessment of multiple drug products. In response, reverse-phase HPLC with UV detection and LC-MS techniques have been widely applied as powerful analytical tools for their detection and control. Methods : The following impurities of the N-nitrosamine class are separated and identified by the LC-MS technique: NDMA (N-nitrosodimethylamine), NDEA (N-nitrosodiethylamine), NMEA (N-nitrosomethylethylamine) NDIPA (N-nitrosodiisopropylamine), NDBA (N-nitrosodibutylamine) NPIP (N-nitrosopiperidine). A standard solution of nitrosamines mix was prepared and subsequently diluted in methanol to achieve a final concentration of 20 µg/mL for each compound. The analysis was performed using a UHPLC chromatography system Flexar FX10 (Perkin Elmer) with MS QTOF (AB Sciex TripleTOF4600), Phenomenex Luna Omega 3 C18 (150x4.6mm, 3μm) column, column temperature 450C, mobile phase methanol and formic acid 0.1% in ultrapure water, gradient elution, flow 0.45 mL/min., injected volume 5 µl. The proposed LC-MS conditions are significantly improved compared to the European Pharmacopoeia recommendations for N-Nitrosamines impurities in active substances analysis. Results : Based on the mass fragmentation profiles of the six investigated nitrosamines, chromatographic separation was successfully accomplished in less than 25 minutes, with the elution sequence established as follows: NDMA, NMEA, NDEA, NPIP, NDIP, NDBA. Conclusions : The development of optimal chromatographic conditions allows further separation and identification of nitrosamines impurities in pharmaceutical products.

A gas chromatography-tandem mass spectrometry (GC-MS/MS) method was established for the determination of 10 volatile N-nitrosamines in meat products. The meat samples were extracted by simultaneous distillation extraction (SDE), and then a cleanup step involving the frozen fat removal method was applied. The analytes were quantified by the external standard method in multiple reaction monitoring (MRM) mode. Under the optimized conditions, the correlation coefficients of the standard calibration curves were greater than 0.99 in the range of 1.00-1000 μg/L. The limits of detection (LODs, S/N=3) and limits of quantification (LOQs, S/N=10) were 0.01-0.02 μg/kg and 0.04-0.07 μg/kg, respectively. The average spiked recoveries of the 10 volatile N-nitrosamines were 74.8%-94.3% at spiked levels of LOQ level, 1.0 and 2.0 μg/kg,and the relative standard deviations were less than 8.3%. Six volatile N-nitrosamines (N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine (NPIP), N-nitrosodibutylamine (NDBA) and N-nitrosodi-n-propylamine (NDPA)) were detected in different types of meat products, and each volatile N-nitrosamine in pickled meat products had the highest detection values. The developed method has the advantages of simplicity, sufficient extraction, high sensitivity, and low reagent dosage, in addition to proving suitable for the daily testing requirements of a large number of samples in the laboratory.

ABSTRACTA compilation of volatile N-nitrosamine levels in processed (e.g., cured, canned, smoked) meat and poultry products is presented. Over 1800 samples of processed meat products including bacon, ham, salami, sausage, and various other processed meat and poultry products have been examined for the presence of eight volatile N-nitrosamines. The database compiled from the literature is based on 25 references published for the period of 1985 to 2018 from 14 countries. N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP), and N-nitrosopyrrolidine (NPYR), are the most frequently identified volatile N-nitrosamines occurring in processed meat and poultry products. N-nitrosodiethylamine (NDEA), and N-nitrosodibutylamine (NDBA) are also frequently observed to a lesser extent. The processed meat and poultry products with the highest levels of volatile N-nitrosamines were pork (fried, fat only eaten), poultry (fried), poultry (spiced, grilled), and bacon (fried).

Simultaneous determination of low molecular weight nitrosamines in pharmaceutical products by fast gas chromatography mass spectrometry