N-nitroso Compounds Research Articles

Carcinogenic effects of N-nitroso compounds in the environment

N-nitroso compounds (NOC) are produced by the acid catalyzed reaction of nitrite with certain nitrogen compounds. The gastrointestinal tract (GI) is the main site for the formation of reactive nitrogen species (RNS). Bacteria present on the GI tract surface reduced the dietary nitrate or nitrite into Nitric oxide NO and other related compounds. The clinical sign of NOC carcinogenicity varies according to species, dose, and route of administration. Humans are exposed to preformed N-nitroso compounds and endogenous NOC via the environmental food chain. Several NOC are potential human carcinogens, including DENA and NDMA, but evidence from population studies is inconsistent.

N-nitrosoethylenethiourea formation at environmentally-relevant concentrations of ethylenethiourea in a pooled groundwater sample

N-nitroso compounds form from the interaction between nitrosatable precursors and nitrite under acidic conditions. A majority of N-nitroso compounds tested show evidence of carcinogenicity in animal models. Formation of N-nitroso compounds may occur from exposure to precursors in drinking water, but the extent of formation depends on a number of factors, including concentration of substrates, presence of catalysts and inhibitors, and pH. The objective of this study was to examine these factors in pesticide-associated N-nitroso (PANN) compound formation in drinking water. In preliminary screening experiments, nine nitrosatable pesticides and degradation products were individually reacted at environmentally-relevant concentrations (≤ 20 μg L‐−1) with sodium nitrite (NaNO2) and hydrochloric acid (HCl) in ultra-pure water. Only ethylenethiourea (ETU) showed evidence of PANN compound formation in initial experiments and was further tested for N-nitrosoethylenethiourea (N-ETU) formation in a pooled groundwater sample (comprised of five tap water samples combined into one homogenous sample) collected from an agricultural region of Prince Edward Island in Canada, where nitrate contamination is a known concern. Evidence of N-ETU formation in the groundwater sample was observed within 30 min at concentrations 7.5, 10, and 20 μg L−1. Analysis of target compounds and semi-target PANN compounds was performed using ultra-high pressure liquid chromatography coupled with high resolution orbital ion trap mass spectrometry. These preliminary experiments serve to inform about potential PANN compound formation in groundwater. The results of this study suggest that ETU is capable of forming potentially carcinogenic N-ETU in water containing nitrite/nitrate at trace concentrations under acidic conditions. Thus, these findings suggest that N-ETU formation may be a concern for individuals exposed to low concentrations of ETU in groundwater.

Drinking-water nitrate and cancer risk: A systematic review and meta-analysis

Background Nitrate is an inorganic compound that occurs naturally in all surface and groundwater, although higher concentrations tend to occur only where fertilizers are used on the land. The regulatory limit for nitrate in public drinking water supplies was set to protect against infant methemoglobinemia, but other health effects were not considered. Risk of specific cancers and congenital disabilities may be increased when the nitrate is ingested, and nitrate is reduced to nitrite, which can react with amines and amides by nitrosation to form N-nitroso compounds which are known animal carcinogens. This study aims to evaluate the association between nitrate ingested through drinking water and the risk of developing cancers in humans. Methods We performed a systematic review following PRISMA and MOOSE guidelines. A literature search was performed using PubMed, EMBASE, the Cochrane Library databases, Web of Science and Google Scholars in the time-frame from their inception to January 2020, for potentially eligible publications. STATA version 12.0 was used to conduct meta-regression and a two-stage meta-analysis. Results A total of 48 articles with 13 different cancer sites were used for analysis. The meta-regression analysis showed stomach cancer had an association with the median dosage of nitrate from drinking water (t = 3.98, p = 0.0001, and adjusted R-squared = 50.61%), other types of cancers didn’t show any association. The first stage of meta-analysis showed there was an association only between the risk of brain cancer & glioma (OR = 1.15, 95% CI: 1.06, 1.24) and colon cancer (OR = 1.11, 95% CI: 1.04, 1.17) and nitrate consumption in the analysis comparing the highest ORs versus the lowest. The 2nd stage showed there was an association only between the risk colon cancer (OR = 1.14, 95% CI: 1.04, 1.23) and nitrate consumption in the analysis comparing all combined higher ORs versus the lowest. Conclusion This study showed that there is an association between the intake of nitrate from drinking water and a type of cancer in humans. The effective way of controlling nitrate concentrations in drinking water is the prevention of contamination (water pollution). Further research work on this topic is needed.

Ingestion of nitrate and nitrite from drinking water and diet and cancers of the gastrointestinal tract in Iowa women

Background: Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potent animal carcinogens in the gastrointestinal tract. Methods: We evaluated nitrate ingestion from public drinking water supplies (PWS), private well use, and dietary nitrate and nitrite intakes in relation to incidence (through 2014) of cancers of the esophagus (n=37), stomach (97), small intestine (47), liver (56), and gallbladder (66) in the Iowa Women’s Health Study (42,000 women ages 50-75 in 1986). Historical nitrate measurements from PWS were linked to the enrollment address by duration. We computed average concentrations and number of years >5 mg/L NO3-N (½ the maximum contaminant level [MCL]). Dietary nitrate and nitrite were estimated using a food frequency questionnaire. We used Cox proportional hazards models to compute hazard ratios (HR) and 95% confidence intervals (CI). Results: In adjusted models, liver cancer risk was elevated among private well users (HR=2.5, CI 0.8-8.5) and those with any years >5 mg/L NO3-N (HR=2.0, CI 0.8-4.9); there was no association with average concentrations (HRper1mg/L NO3-N =1.1, CI 0.7-1.7). Private well use and PWS nitrate concentrations were not associated with other cancers. Dietary nitrate and nitrite from plants was inversely associated with small intestine (HRQ4vsQ1=0.4, CI 0.1-0.9) and gall bladder cancer (HRQ4vsQ1=0.3, CI 0.1-0.8), respectively; there were no associations for the other cancers. Nitrite intake from processed meats was associated with increased risk of stomach (HRnitriteQ4vsQ1=1.7, CI 1.0-3.0) and elevated risk of liver cancer (HRnitriteQ4vsQ1=1.8, CI 0.8-4.0) but was inversely associated with small intestine cancer (HRnitriteQ4vsQ1=0.4, CI 0.1-1.0). Power was limited, but there was no evidence for effect modification by vitamin C and red meat, factors affecting nitrosation. Conclusion: We found novel suggestive evidence that private well use and PWS nitrate may increase liver cancer risk. These associations should be evaluated in studies with larger case numbers.

Effect of the growth medium composition on nitrate accumulation in the novel protein crop Lemna minor

Duckweed is a potential alternative protein source for food and feed. However, little is known about the nitrate accumulation in this plant. A high nitrate level in vegetables can indirectly lead to an elevated intake of nitrites and N-nitroso compounds, increasing the risk of diseases for humans and animals. This research hypothesizes that the nitrate accumulation of Lemna minor differs between growing media. Additionally, it evaluates whether legal safety levels of nitrate for human and animal intake are exceeded. The duckweed was grown on (i) rainwater, and (ii) three synthetic media containing different nutrient levels. Furthermore, (iii) biological effluent of swine manure treatment and (iv) aquaculture effluent from pikeperch production were used, as these are potential media for closing nutrient loops in the agriculture sector. It was found that nitrate levels increased with the increasing availability of macronutrients in the water, and pH showed a particularly strong negative correlation with the nitrate levels in the plant. Nevertheless, nitrate content never exceeded 530 mg NO3 kg−1 fresh weight. To conclude, Lemna minor's nitrate content was below safety limits for human consumption in all tested growing media; however, a potential risk for ruminants was observed as these are more sensitive to nitrate conversions in their gastro-intestinal track.

Betel Quid Health Risks of Insulin Resistance Diseases in Poor Young South Asian Native and Immigrant Populations.

Betel quid, traditionally prepared with areca nut, betel leaf, and slaked lime, has been consumed for thousands of years, mainly in the form of chewing. Originally used for cultural, medicinal, and ceremonial purposes mainly in South Asian countries, its use has recently spread across the globe due to its psychoactive, euphoric, and aphrodisiac properties. Now it is widely used as a social lubricant and source of financial profit. Unfortunately, the profit motive has led to high rates of habitual consumption with eventual conversion to addiction among young girls and boys. Moreover, the worrisome practice of including tobacco in quid preparations has grown, particularly among pregnant women. Major health concerns include increased rates of malignancy, oral pathology, and cardiovascular, hepatic, fertility, metabolic, and neuropsychiatric disorders. Metabolic disorders and insulin resistance disease states such as type 2 diabetes, obesity, and metabolic syndrome contribute to cognitive decline and neurodegeneration. Mechanistically, the constituents of areca nut/betel quid are metabolized to N-nitroso compounds, i.e., nitrosamines, which are carcinogenic at high doses and cause insulin resistance following chronic low-level exposures. From an epidemiological perspective, the rising tide of insulin resistance diseases including obesity, diabetes, and dementias that now disproportionately burden poor countries has been propagated by rapid commercialization and enhanced access to betel quid. Public health measures are needed to impose socially and ethically responsible barriers to yet another cause of global health disparity.

Reduction of Nitrite in Meat Products through the Application of Various Plant-Based Ingredients.

Nitrite is the most commonly applied curing agent in the meat industry, and is known to affect human health. Nitrites impart a better flavor, taste and aroma; preserve the red-pinkish color of the meat; and prevent the risk of bacterial contamination of the cured meat, especially from Clostridium botulinum. Unfortunately, recent research has demonstrated some negative effects of this technique. Certain N-nitroso compounds have been shown to stimulate gastric cancer; therefore, most of the research groups are studying the effects of nitrates and nitrites. In this review, we discuss the various food sources of nitrites and nitrates and their current legal requirements for use in meat products. We also discuss the possible changes that might come up in the regulations, the concerns associated with nitrates and nitrites in meat products, and the use of plant-based nitrite and nitrate substitutes. All these topics will be considered with respect to ensuring a high level of microbiological protection, oxidative stability and acceptable sensory quality (color, taste and smell) in meat products.

Pathways for N-Nitroso Compound Formation: Secondary Amines and Beyond

Recent drug recalls (e.g., valsartan and ranitidine) linked to the discovery of nitrosamine impurities have led to increased regulatory scrutiny in the manufacturing process of marketed medicines, notably for determining any sources of risk for nitrosamine (or related N-nitroso compound) formation within the manufacturing process. This review seeks to aid the risk assessment process through identifying known conditions and reactants through which N-nitroso compounds can be formed.

Intestinal microbiota and its association with colon cancer and red/processed meat consumption.

The human colon harbors a high number of microorganisms that were reported to play a crucial role in colorectal carcinogenesis. In the recent decade, molecular detection and metabolomic techniques have expanded our knowledge on the role of specific microbial species in promoting tumorigenesis. In this study, we reviewed the association between microbial dysbiosis and colorectal carcinoma (CRC). Various microbial species and their association with colorectal tumorigenesis and red/processed meat consumption have been reviewed. The literature demonstrated a significant abundance of Fusobacterium nucleatum, Streptococcus bovis/gallolyticus, Escherichia coli, and Bacteroides fragilis in patients with adenoma or adenocarcinoma compared to healthy individuals. The mechanisms in which each organism was postulated to promote colon carcinogenesis were collated and summarized in this review. These include the microorganisms' ability to adhere to colon cells; modulate the inhibition of tumor suppressor genes, the activations of oncogenes, and genotoxicity; and activate downstream targets responsible for angiogenesis. The role of these microorganisms in conjugation with meat components including N-nitroso compounds, heterocyclic amines, and heme was also evident in multiple studies. The outcome of this review supports the role of red meat consumption in modulating CRC progression and the possibility of gut microbiome influencing the relationship between CRC and diet. The study also demonstrates that microbiota analysis could potentially complement existing screening methods when detecting colonic lesions.

Reduction in biogenic amines in douchi fermented by probiotic bacteria.

Ecology studies showed that esophageal and gastric cancers are directly correlated with the consumption of processed foods. The carcinogenicity of traditional Chinese fermented foods such as douchi (fermented black beans or fermented black soybeans) is due to the presence of carcinogenic N-nitroso compounds, which are derived from biogenic amines. Among the various biogenic amines that can act as precursors of N-nitroso compounds, histamine and tyramine are considered to be the most toxic and are of public health concern when present in food. We have examined some douchi products on the market, and significant amounts of histamine and tyramine were found. The use of fermentation starters generated by subculturing fermented products with unknown microbiota would induce the risk of biogenic amines. As the microbiota used in fermentation is a crucial factor in determining the biogenic amines of fermented food, it is hypothesized that the possible harmful effects of douchi can be minimized through the use of fermentation starters composed of probiotic bacteria. This is the first study to investigate the potential of using probiotic bacteria in manufacturing douchi. Lactobacillus rhamnosus GG (LGG), Lactobacillus casei Shirota (LcS) and Escherichia coli Nissle 1917 (EcN) were used to ferment black beans in this study, and no tyramine was detected in black bean samples incubated with these three strains anaerobically at 37°C or 20°C. The starter culture strains, temperature and presence of oxygen during the incubation period were found to be critical to the generation of biogenic amines. The findings of this study can provide evidence-based insights and warrant further investigations on the potential of reducing the harmful compounds in food fermented with probiotic bacteria as well as the sensory evaluation of douchi fermented with probiotic bacteria.

Mechanistic Hypotheses on Colorectal Cancer and Red Meat Intake: A Review

Red meat is classified as probably carcinogenic to humans by International Agency for Research on Cancer (IARC) based on evidence on how it may affect the development of colorectal cancer, the third most common cancer worldwide. A plethora of scientific experiments prevailing to establish a positive association between red meat and colorectal cancer suggested different mechanistic hypotheses in order to explain such a phenomenon. This paper aims to discuss major hypotheses related to how red meat consumption may lead to colorectal cancer. Such hypotheses involve the role of natural compounds present in red meat (such as lipid, protein, N-glycolylneuraminic acid and heme iron) and neoformed substances during meat processing (such as heterocyclic amines, polyaromatic hydrocarbons and N-nitroso compounds).

Ingested Nitrate and Nitrite and Bladder Cancer in Northern New England.

N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study. Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N) and average daily nitrate intake (mg/d) from 1970 to diagnosis/reference date (987 cases and 1,180 controls). We estimated overall and source-specific dietary nitrate and nitrite intakes using a food frequency questionnaire (1,037 cases and 1,225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). We evaluated interactions with factors that may affect N-nitroso compound formation (i.e., red meat, vitamin C, smoking), and with water intake. Average drinking water nitrate concentration above the 95th percentile (>2.07 mg/L) compared with the lowest quartile (≤0.21 mg/L) was associated with bladder cancer (OR = 1.5, 95% CI = 0.97, 2.3; P trend = 0.01); the association was similar for average daily drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest versus lowest quintile OR for nitrate = 1.4, 95% CI = 1.0, 2.0; P trend = 0.04; OR for nitrite = 1.5, 95% CI = 1.0, 2.1; P trend = 0.04, respectively), but not other dietary sources. We observed positive interactions between drinking water nitrate and red meat (P-interaction 0.05) and processed red meat (0.07). Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer.

Effect of lifestyle and dietary factors in the development of brain tumors.

Introduction:A brain tumor occurs when neurons are mutated and thus abnormal cells are formed. Glioma and meningioma are the two most common types, comprising approximately 75% of all brain tumors. The incidence rate of all primary brain tumors was 15.80/100,000 person-years in females and 14.33/100,000 person-years in males. An association of higher risk of brain tumors in adults with cured meat and fruit/vegetable consumption, the primary source of dietary N-nitroso compounds, is seen. Cigarette smoking is a major source of chemical carcinogens. The present study aimed at determining the effects of lifestyle and dietary habits in the development of brain tumor.Methods:The study aimed at the assessment of various dietary factors, lifestyle, and occupational and personal habits in patients diagnosed with brain tumor in a rural tertiary health-care hospital, using a structured questionnaire and statistical analysis.Results:It was observed that – (1) people with stressful, sedentary lifestyle and wrong diet and those addicted to alcohol consumption and the habit of cigarette smoking have higher risk of brain tumors; (2) males are more prone to brain tumors; and (3) among subtypes, majority had glioblastoma and the least had meningioma and opdivoglioblastoma and according to location, majority had cerebellopontine angle tumor and the least had left thalamic glioma and multicentric glioma. Primary care to preoperative brain tumor patients should be given in terms of preventing exposure to radiations, avoiding cigarette smoking, providing healthy diet, and avoiding chronic stress and environmental pollution and postoperative patients should be taken care including avoiding infections by maintaining proper hygiene and providing healthy diet for their speedy recovery.Conclusion:People with stressful life condition, wrong diet, and sedentary lifestyle and those addicted to alcohol, with the habit of cigarette smoking, have higher risk of brain tumors. Males are more prone to brain tumors.

A Review of the In Vivo Evidence Investigating the Role of Nitrite Exposure from Processed Meat Consumption in the Development of Colorectal Cancer.

The World Cancer Research Fund (WCRF) 2007 stated that the consumption of processed meat is a convincing cause of colorectal cancer (CRC), and therefore, the public should avoid it entirely. Sodium nitrite has emerged as a putative candidate responsible for the CRC-inducing effects of processed meats. Sodium nitrite is purported to prevent the growth of Clostridium botulinum and other food-spoiling bacteria, but recent, contradictory peer-reviewed evidence has emerged, leading to media reports questioning the necessity of nitrite addition. To date, eleven preclinical studies have investigated the effect of consuming nitrite/nitrite-containing meat on the development of CRC, but the results do not provide an overall consensus. A sizable number of human clinical studies have investigated the relationship between processed meat consumption and CRC risk with widely varying results. The unique approach of the present literature review was to include analysis that limited the human studies to those involving only nitrite-containing meat. The majority of these studies reported that nitrite-containing processed meat was associated with increased CRC risk. Nitrite consumption can lead to the formation of N-nitroso compounds (NOC), some of which are carcinogenic. Therefore, this focused perspective based on the current body of evidence links the consumption of meat containing nitrites and CRC risk.

Impact of high drinking water nitrate levels on the endogenous formation of apparent N-nitroso compounds in combination with meat intake in healthy volunteers

BackgroundNitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds (NOCs), which are known to be carcinogenic in animals. Humans can be exposed to nitrate via consumption of drinking water and diet, especially green leafy vegetables and cured meat. The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly. Therefore, in the present pilot study, we examined the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs, taking into account the intake of vitamin C, a nitrosation inhibitor.MethodsTwenty healthy subjects were randomly assigned to two groups consuming either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks. Drinking water nitrate levels were kept low during the first week (< 1.5 mg/L), whereas in week 2, nitrate levels in drinking water were adjusted to the acceptable daily intake level of 3.7 mg/kg bodyweight. At baseline, after 1 and 2 weeks, faeces and 24 h urine samples were collected for analyses of nitrate, apparent total N-nitroso compounds (ATNC), compliance markers, and genotoxic potential in human colonic Caco-2 cells.ResultsUrinary nitrate excretion was significantly increased during the high drinking water nitrate period for both meat types. Furthermore, levels of compliance markers for meat intake were significantly increased in urine from subjects consuming processed red meat (i.e. 1-Methylhistidine levels), or unprocessed white meat (i.e. 3-Methylhistidine). ATNC levels significantly increased during the high drinking water nitrate period, which was more pronounced in the processed red meat group. Genotoxicity in Caco-2 cells exposed to faecal water resulted in increased genotoxicity after the interventions, but results were only significant in the low drinking water nitrate period in subjects consuming processed red meat. Furthermore, a positive correlation was found between the ratio of nitrate/vitamin C intake (including drinking water) and the level of ATNC in faecal water of subjects in the processed red meat group, but this was not statistically significant.ConclusionsDrinking water nitrate significantly contributed to the endogenous formation of NOC, independent of the meat type consumed. This implies that drinking water nitrate levels should be taken into account when evaluating the effect of meat consumption on endogenous formation of NOC.Trial registrationDutch Trialregister: 29707. Registered 19th of October 2018. Retrospectively registered.

Ingested nitrate and nitrite and bladder cancer in Northern New England

OPS 36: Health effects of dietary exposures, Room 210, Floor 2, August 27, 2019, 4:30 PM - 5:30 PM Background/Aim: N-nitroso compounds (NOCs) are hypothesized human bladder carcinogens. Nitrate and nitrite are NOC precursors; sources include contaminated drinking water and diet. We examined nitrate and nitrite ingestion and bladder cancer risk in the New England Bladder Cancer Study, a population-based case-control study in Maine, New Hampshire, and Vermont. Methods: Using historical nitrate measurements for public water supplies, measured and modeled values for private wells and self-reported water intake, we estimated average nitrate concentrations (NO3-N mg/L) and average daily nitrate intake (mg/day) from 1970 to diagnosis/reference date for 987 cases and 1180 controls. We also estimated source-specific (animal, plant, processed meat) dietary nitrate and nitrite intakes using a food frequency questionnaire (1037 cases and 1225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, gender, smoking, disinfection by-products, and other factors. We evaluated interactions with factors affecting NOC formation (i.e., red and processed meat, vitamin C, smoking). Results: Average drinking water nitrate concentration above the 95th percentile (>2.07 mg/L) compared with the lowest quartile (<=0.21 mg/L) was associated with bladder cancer risk (OR=1.50, CI: 0.97-2.32; p-trend=0.01); the association was similar for average drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest vs. lowest quintile OR=1.42, CI: 1.01-1.98; p-trend=0.04; OR=1.48, CI: 1.04-2.09; p-trend=0.04, respectively), but no trends for other sources. Risk was highest among those with >2.07 mg/L NO3-N and >median red or processed meat intake vs <0.21 mg/L NO3-N/< median intakes (OR=2.61, CI: 1.33-5.11 and OR=3.47 CI: 1.75-6.87; p-interaction=0.05 and 0.07, respectively). We observed no interaction with vitamin C or smoking. Conclusions: Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer especially among those with high red or processed meat intake

Effect of Dietary Red Meat on Colorectal Cancer Risk-A Review.

Heme iron overload has been implicated as the main cause of the increased risk of cancer due to the consumption of red meat. However, fish and shellfish, teas, and spices contain up to five times more iron than red meat. There is insufficient evidence that iron intake in dietary red meat is the primary causal factor for colorectal cancer. In addition, harmful substances produced during the preparation of red meat, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), N-nitroso compounds, and acrylamide, are extrinsic factors that increase carcinogenicity. HCAs are produced during the cooking of red meat, poultry meat, and fish. PAHs may also be produced during the cooking of diverse food groups, such as dairy products, fruits, vegetables, and cereals. The average daily intake of red meat among Korean individuals is 62 g; the amount of PAHs entering the body via red meat is less than the average amount of PAHs the body is exposed to in the air. Therefore, it is difficult to conclude that dietary red meat is the main cause of colorectal cancer. Rather, there may be an intricate influence of multiple factors, including fruit and vegetable intake, alcohol consumption, smoking, overweight, obesity, and stress.

Substrate Promiscuity of ortho-Naphthoquinone Catalyst: Catalytic Aerobic Amine Oxidation Protocols to Deaminative Cross-Coupling and N-Nitrosation

ortho-Naphthoquinone-based organocatalysts have been identified as versatile aerobic oxidation catalysts. Primary amines were readily cross-coupled with primary nitroalkanes via deaminative pathway to give nitroalkene derivatives in good to excellent yields. Secondary and tertiary amines were inert to ortho-naphthoquinone catalysts; however, secondary nitroalkanes were readily converted by ortho-naphthoquinone catalysts to the corresponding nitrite species that in situ oxidized the amines to the corresponding N-nitroso compounds. Without using harsh oxidants in a stoichiometric amount, the present catalytic aerobic oxidation protocol utilizes the substrate promiscuity feature to provide a facile access to amine oxidation products under mild reaction conditions.

Safety Assessment of PCA (2-Pyrrolidone-5-Carboxylic Acid) and Its Salts as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reassessed the safety of 2-pyrrolidone-5-carboxylic acid (PCA) and sodium PCA; the Panel added 3 previously unreviewed salts (calcium, magnesium, and potassium) of PCA to this safety assessment. 2-Pyrrolidone-5-carboxylic acid and its salts are reported to function in cosmetics as skin conditioning agents-humectants. The Panel reviewed the data from the 1999 report of PCA and sodium PCA, as well as additional data included in this report, to determine the safety of these ingredients. The Panel concluded that PCA and its salts are safe in cosmetics in the present practices of use and concentration; additionally, these ingredients should not be used in cosmetic products in which N-nitroso compounds can be formed.

Inulin-fortification of a processed meat product attenuates formation of nitroso compounds in the gut of healthy rats

Intake of red and processed meat has been suspected to increase colorectal cancer risk potentially via endogenous formation of carcinogenic N-nitroso compounds or increased lipid and protein oxidation. Here we investigated the effect of inulin fortification of a pork sausage on these parameters. For four weeks, healthy Sprague-Dawley rats (n = 30) were fed one of three diets: inulin-fortified pork sausage, control pork sausage or a standard chow diet. Fecal content of apparent total N-nitroso compounds (ATNC), nitrosothiols and nitrosyl iron compounds (FeNO) were analyzed in addition to liver metabolism and oxidation products formed in liver, plasma and diets. Intriguingly, inulin fortification reduced fecal ATNC (p = 0.03) and FeNO (p = 0.04) concentrations. The study revealed that inulin fortification of processed meat could be a strategy to reduce nitroso compounds formed endogenously after consumption.