Nitrite is abundantly used not only in the food industry but also in various chemical reactions such as diazotization to furnish azo-dye compounds and the Sandmeyer reaction. When a secondary amine ...is in the presence of nitrite, residual levels of nitrite ions can potentially form corresponding N-nitrosamines, many of which are known to be carcinogenic. The carcinogenicity concerns with N-nitrosamines resulted in worldwide recalls of numerous marketed pharmaceutical products since 2018. Therefore, the residual nitrite assay is a critical part of N-nitrosamine risk assessment, as many components present in drug products including not only the drug substance but also excipients can be a potential source of nitrite ions. While ion chromatography serves as a primary analytical tool for the nitrite ion assay, leveraging the Griess reaction shows several benefits over ion chromatography, which includes rapid and visible responses as well as flexibility of sample preparations in organic solvent. In order to simplify the Griess reaction method and enhance reactivity toward the nitrite ion, a series of probe molecules was designed and synthesized. Upon exposure to the nitrite ion, molecular probes undergo diazotization followed by intramolecular cyclization to form benzoccinnoline, which elicits dramatic absorption and emission changes as a signal readout for the nitrite assay. The reactivity toward the nitrite ion depends on nucleophilicity as well as electron-withdrawing/donating properties of substituents on probe molecules. Among a series of probe molecules, comparative kinetic studies revealed that the para-sulfonamide-substituted molecule (probe 1) has the highest reactivity with no-detectable side reaction. With probe 1, method validation was performed with two representative excipients, microcrystalline cellulose and dicalcium phosphate dihydrate, which demonstrated excellent accuracy, linearity, precision, and multilevel spike/recovery as well as very low detection limit (sub-parts-per-billion level) when coupled with a fluorescence detector. This new probe molecule offers low detection limits and wide flexibility in terms of sample preparation in a higher composition of organic solvent. Such flexibility of solvent choice enables a broader application of the method to any components in drug products including API, process intermediates, and excipients.
We investigated the effects of Lactobacillus pentosus inoculation on N-nitrosamines (NAs) contents and bacterial communities in dry fermented sausages. Culture-dependent and culture-independent ...(high-throughput sequencing) methods were employed to evaluate the bacterial communities. The results showed that inoculation with L. pentosus improved the microbiological quality of dry fermented sausages by enhancing the competitiveness of dominant bacteria and inhibiting the growth of undesirable microbes. At the end of ripening, NA content, nitrite residue, carbonyl content, total volatile basic nitrogen, pH value, and water activity of the sausages inoculated with L. pentosus were lower than the control (p < 0.05). L. pentosus showed nitrite depletion ability in Mann–Rogosa–Sharp broth. The bacteria obtained from L. pentosus-inoculated sausages significantly degraded NAs in phosphate-buffered saline (p < 0.05). Thus, L. pentosus can reduce NA levels in dry fermented sausages directly by degrading NAs and indirectly by decreasing their precursors (nitrite, amines) or inhibiting NA formation under conditions of lower pH and water activity, which may be attributed to the higher microbiological quality. Thus, L. pentosus is a potential starter culture for improving safety in the production of dry fermented sausages.
•N-Nitrosamines were reduced in the sausages inoculated with Lactobacillus pentosus.•Bacterial communities in dry sausages were constructed.•L. pentosus directly depleted nitrite.•L. pentosus inhibited both protein oxidation and degradation.•Bacteria from L. pentosus-inoculated sausages directly degraded N-nitrosamines.
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 than67% 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.
► Nitrosamines have carcinogenic properties and they can originate from food products. ► The meat processing temperature and addition of sodium nitrite have also affected the N-nitrosamine yields. ► ...N-Nitrosodimethylamine (NDMA) is reported as one of the most common nitrosamines.
The influence of biogenic amines (i.e. putrescine, cadaverine, spermidine and spermine) on the N-nitrosamine formation in heated cured lean meat was studied in the presence or absence of sodium nitrite and at different meat processing temperatures. Experimental evidence was produced using gas chromatography with thermal energy analysis detection (GC–TEA). Concentration of N-nitrosamines was modelled as a function of the temperature and the nitrite concentration for two situations, i.e. presence or absence of added biogenic amines to the meat. The significance of the influence of the changing parameters was evaluated by ANOVA (Analysis of Variance).
It was found that higher processing temperatures and higher added amounts of sodium nitrite increase the yields of N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP). Spermidine and putrescine amplify the formation of NDMA, but spermine and cadeverine do not influence the formation of this N-nitrosamine. Spermidine and cadeverine cause a significant increase of NPIP. Beside N-nitrosopyrrolidine (NPYR) in some rare cases, no other volatile N-nitrosamines are detected.
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.
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•Most N-nitrosamines increased from source water to finished water in autumn or winter.•The seasonal cancer risk for N-nitrosamines in drinking water was characterized firstly.•The resulting average individual DALYs lost was 4.43 × 10−6 ppy, mainly from liver cancer.•The multiple regression model for total N-nitrosamines in drinking water was developed.
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.
•The distribution of N-nitrosamine carcinogenic potencies is log-normal.•Parametric methods allow for increased statistical power when estimating features of interest.•Structure based subclasses of N-nitrosamines show different potencies.
N-nitrosamines, which are classified as carcinogens by IARC and US EPA, can be easily found in various foods. They are reaction products between nitrogen oxide and secondary amines, but can also be ...generated during fermentation. Ever since the 1960s, when nitrite, used as a preservative in processed meats, was suspected to generate N-nitrosamines, the usage of the food additive has been debated. However, the benefit of nitrite in food supply could not be ignored and the risk-benefit analysis has become a key issue in the use of the additive. For a risk analysis, an accurate estimation of the hazardous material is necessary; therefore, analytical methods for nitrosamines have continuously evolved from the 1950s. Solid supported liquid-liquid extraction and solid phase extractions have replaced the distillation for the clean-up steps, and tandem mass spectrometry is employed for higher selectivity and sensitivity. In the present study, for a better estimation of N-nitrosamine intake, the total diet study samples were prepared for the N-nitrosamines analysis. In order to obtain the most sensitive results, a partial preparation procedure was developed and modified for different food matrices. Among seven N-nitrosamines (N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitrosomorpholine) analyzed in the present study, N-nitrosodiethylamine has shown the highest detection rate in agricultural foods, while N-nitrosodimethylamine has appeared most frequently in livestock and fishery food products. The concentration of N-nitrosodimethylamine was the highest in seasoning.
The effects of different nitrite levels (50, 100, and 150 mg/kg meat) and dry-frying temperatures (100, 150, 200 and 250 °C) on the moisture movement, colour, sensory variables and residual nitrite ...and N-nitrosamine levels in smoked bacon were investigated. Increasing the dry-frying temperatures significantly increased the cooking loss and decreased the moisture content (P < 0.05). The bacon L*-values showed an increasing trend at first and then decreased, with the highest value of the bacon with 150 mg/kg nitrite was obtained at 100 °C and 150 °C. In addition, a*-values were significantly affected by the nitrite level and dry-frying temperature (P < 0.05), with the highest value of the bacon samples with 100 and 150 mg/kg nitrite observed at 250 °C. The residual nitrite content level initially increased (from unheated control to 150 °C) and then decreased (from 150 to 250 °C) sharply with increasing dry-frying temperatures in the bacon samples with the same sodium nitrite levels. N-methyl-N-nitrosoaniline (NMPhA) and N-nitrosomorpholine (NMOR) were measured in a number of smoked bacon samples, and a significant positive correlation (R2 = 0.772) was found for N-nitrosamines (NA) contents and nitrite levels (P < 0.05). The maximum levels of NMPhA and NMOR were detected when the bacon with 150 mg/kg sodium nitrite was pan-fried at 200 °C and 150 °C, respectively.
•NaNO2 and fried temperature were responsible for quality and NAs formation of bacon.•NMPhA and NMOR in salted bacon were detected during pan-fried process.•NMOR and NMPhA in bacon (150 mg/kg NaNO2) cooked at 150 and 200 °C was the largest.•Bacon cured with 100 mg/kg NaNO2 and cooked below 200 °C is recommended.
N-nitrosamines are potent carcinogens, particularly N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), which are commonly found in a variety of foods and drinking water. We calculated ...the food and drinking water intakes of NDMA, NDEA, and total volatile nitrosamines (TVNA) by Chinese residents in different provinces by multiplying the reported total diet study results by the nitrosamine contents in food and drinking water. The weighted content of nitrosamines in each category of foods and the concentration of nitrosamines in drinking water was obtained through literature review. The exogenous NDMA, NDEA and TVNA intakes of adult residents in 20 provinces ranged from 171 to 425 ng/d, 41 to 140 ng/d and 373 to 1028 ng/d, respectively. The main contributors to NDMA and TVNA intakes were vegetables, cereals, aquatic products, and meats while the main sources of NDEA intake were vegetables and cereals. The average total NDMA intake per capita in China (251 ng/d) was similar to that in Germany in 1991 (231 ng/d) but higher than that in the United States (136 ng/d), Canada (87.6 ng/d) and France (188 ng/d). Large differences in nitrosamine intakes were observed between the coastal provinces and inland provinces. Drinking water was estimated to contribute 13.1%, 1.3% and 10.8% of the exogenous intakes of NDMA, NDEA and TVNA, respectively. Based on our results, we recommend setting the NDMA drinking water criterion of 40 ng/L. Overall, this study presents basic information regarding nitrosamines intake via food and drinking water in China that will facilitate risk assessment, generation of health advisories and policy making.
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•First analyzing nitrosamine intake via food & water per capita in Chinese provinces•Weighted nitrosamine content in 12 categories of foodstuffs was calculated firstly.•Vegetables, aquatic products, cereals and meats contribute greatly to NDMA intake.•Vegetables and cereals contribute greatly to NDEA intake.•On average, drinking water contributes 13.1% of NDMA intake averagely in China.
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.
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•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 CO2 capture systems but can be safely mitigated by electrochemical decomposition enabling widescale deployment of CO2 capture systems to reach worldwide decarbonization targets.
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