Four thousand eighty inbred rats were maintained from weaning on various different concentrations of N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA). The principal aim was to characterize the dose-response relationship for the effects of these agents on esophageal cancer (NDEA) or on various types of liver cancer (NDEA and NDMA), although NDEA also caused a few tumors of the nasopharynx and NDMA also caused a few tumors of the lung. The numbers of tumors of mesenchymal and Kupffer cells in the liver were too few to allow easy characterization of the dose-response relationships, and although NDMA induced large numbers of bile duct neoplasms, NDEA did not. Thus, the four principal dose-response relationships studied were of NDEA on esophageal or liver cells and of NDMA on bile duct or liver cells. At doses sufficiently high for the median time to death from the disease of interest to be estimated, relationships were observed of the general form (Dose rate) x (median)n = constant where n was about 2.3 for the first three relationships and about 1 for the last one (NDMA on liver cell tumors). By contrast, at doses sufficiently low for longevity to be nearly normal (median survival about 2.5 years), there remained no material dependence on the dose rate of the age distribution of the induced neoplasms. At these low dose rates, the number of liver (but not of esophageal) neoplasms induced by treatment was simply proportional to the dose rate. This finding is not surprising, since the background incidence of liver (but not of esophageal) neoplasms was appreciable. The linear relationship observed at low dose rates (below 1 ppm) suggests that under these experimental conditions, among rats allowed to liver their natural life span, a dose of 1 ppm of NDEA or NDMA in the drinking water will cause about 25% to develop a liver neoplasm, a dose of 0.1 ppm will cause about 2.5% to do so, and a dose of 0.01 ppm will cause about 0.25% to do so, etc., with no indication of any \"threshold.\" (At these low dose rates, the incidence of liver neoplasms appears likely to exceed greatly that of esophageal neoplasms.) In addition, even quite low dose rates of the test agents caused a variety of nonneoplastic liver abnormalities (e.g., hyperplastic nodules, or shrinkage of hepatocytes) at a frequency roughly proportional to the dose rate.

Effects on 4080 rats of chronic ingestion of n-nitrosodiethylamine or n-nitrosodimethylamine - a detailed dose-response study - fundamental carcinogenic processes and their implications for low-dose risk assessment - reply

Background In recent years, carbon quantum dots (CQDs) has received a lot of attentions owing to their great physical and optical properties. There are different kinds of carbon sources applied in various fields, however, CQDs used in the food industry have higher requirements for their safety. Therefore, it is the best way to use natural materials for preparing CQDs without the participation of chemicals. Up to now, there are many natural food products for preparing CQDs. However, food waste is often overlooked. Actually, food waste is rich in carbon sources. And the efficient utilization of food waste plays a positive role in economic benefit and environmental pollution. Scope and approach Proper use of food waste as carbon source not only facilitates food safety detection but also increases byproduct value. This paper was intended to review the research progress of food waste utilization as carbon precursor and applications in food safety detection. The approaches of preparing CQDs from different sorts of food wastes, the characteristics and applications of CQDs were described in detail. Particularly the applications in food quality and safety detection including food additives, heavy metal ions were also elaborated. Key findings and conclusions Currently, food waste as carbon source could be divided into plant byproducts, animal food byproducts and food processing byproducts. Moreover, there are many applications of food waste as carbon precursor in CQDs technology to detect food additives and heavy metal ions. However, detection of pathogens and other harmful substances in food industry is rare. Last but not least, it was concluded that food waste had potential to prepare CQDs and be applied to food safety detection.

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Food waste as a carbon source in carbon quantum dots technology and their applications in food safety detection

Starters are microbial cultures used to promote and conduct the fermentation of meat products. Bacteria, particularly lactic acid bacteria (LAB) and coagulase-negative staphylococci (CNS), as well as yeasts and molds, may be used as starters. They can increase the safety of fermented meat products by means of rapid matrix acidification or due to the production of antimicrobial substances, such as bacteriocins. Besides, starters may help to standardize product properties and shorten ripening times. Safety of fermented meat products may be jeopardized by microbiological, namely foodborne pathogens (Salmonella spp., Listeria spp., etc), and chemical hazards, particularly biogenic amines, nitrosamines, polycyclic aromatic hydrocarbons (PAH), and mycotoxins. Biogenic amines (BA) are potentially unsafe nitrogenous compounds that result from the decarboxylation of some amino acids. Some microorganisms may be responsible for their formation. Starters can cause a fast pH decrease, inhibiting the development of microorganisms with amino acid decarboxylative ability, thus preventing the accumulation of BA in fermented meat products. Besides, starters can compete with the autochthonous, non-starter microbiota throughout ripening and storage, thus reducing BA production. Some strains of Lactobacillus sakei and Lactobacillus plantarum have been shown to reduce the formation/accumulation of BA. On the other hand, Staphylococcus xylosus and Debaryomyces hansenii strains have been reported to degrade BA in food. PAH are organic compounds containing multiple aromatic rings and produced by the incomplete combustion of organic matter, such as the wood used for smoking meat. Mixed starters containing Lactobacillus spp., Gram-positive catalase-positive cocci and yeasts have been used in the manufacturing of traditional meat sausages. However, the effect of starters on reducing the accumulation of PAH is poorly understood. Starters may also be engaged in competitive exclusion, outcompeting the spoiling or deteriorating autochthonous microbiota. For example, Pediococcus acidilactici has been shown to inhibit Listeria monocytogenes in meat products. Additionally, the role of molds, such as Penicillium nalgiovense, in the competitive exclusion of undesired filamentous fungi, has also been demonstrated. Most of these undesired fungi produce mycotoxins, secondary metabolites capable of causing disease. The current review addresses the role of starters on the microbiological and chemical safety of fermented meat products.

/pdf/role-of-starter-cultures-on-the-safety-of-fermented-meat-2scbb7kx7j.pdf

Role of Starter Cultures on the Safety of Fermented Meat Products.

Previous studies have shown inconsistent associations between red and processed meat intake and breast cancer risk. N-nitroso compounds and heme iron have been hypothesized as contributing factors. We followed 193,742 postmenopausal women in the NIH-AARP Diet and Health Study and identified 9,305 incident breast cancers (1995-2006). Dietary intake was assessed using a food frequency questionnaire at baseline. We adjusted daily intakes of meat, nitrite and heme iron for energy intake using the nutrient density method. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) by quintiles of dietary exposures for all breast cancer, by stage (in-situ, localized, regional/distant) and by estrogen/progesterone receptor (ER/PR) status using Cox proportional hazards regression. Total red meat intake was positively associated with risk of regional/distant cancer (p-trend = 0.02). The risk was 25% higher in the highest vs. lowest intake quintile (95% CI = 1.03-1.52). Higher processed red meat intake (Q5 vs. Q1) was associated with 27% higher risk of localized breast cancer (95% CI = 1.01-1.27, p-trend = 0.03) and a 19% higher risk of regional/distant cancer (95% CI = 0.98-1.44, p-trend = 0.10). In addition, higher nitrite intake from processed red meat was positively associated with localized cancer (HR for Q5 vs. Q1 = 1.23, 95% CI = 1.09-1.39, p-trend < 0.0001). Heme iron intake was positively associated with breast cancer risk overall and all cancer stages (p-trend = 0.02-0.05). No heterogeneity was observed in risk associations by hormone receptor status. Our findings suggest that high consumption of red meat and processed meat may increase risk of postmenopausal breast cancer. Added nitrite and heme iron may partly contribute to these observed associations.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.29901

Red and processed meat, nitrite, and heme iron intakes and postmenopausal breast cancer risk in the NIH-AARP Diet and Health Study.

The Panel on Food Additives and Nutrient Sources added to Food (ANS) provided a scientific opinion re-evaluating the safety of sodium nitrate (E 251) and potassium nitrate (E 252) when used as food additives. The current acceptable daily intakes (ADIs) for nitrate of 3.7 mg/kg body weight (bw) per day were established by the SCF (1997) and JECFA (2002). The available data did not indicate genotoxic potential for sodium and potassium nitrate. The carcinogenicity studies in mice and rats were negative. The Panel considered the derivation of an ADI for nitrate based on the formation of methaemoglobin, following the conversion of nitrate, excreted in the saliva, to nitrite. However, there were large variations in the data on the nitrate-to-nitrite conversion in the saliva in humans. Therefore, the Panel considered that it was not possible to derive a single value of the ADI from the available data. The Panel noticed that even using the highest nitrate-to-nitrite conversion factor the methaemoglobin levels produced due to nitrite obtained from this conversion would not be clinically significant and would result to a theoretically estimated endogenous N-nitroso compounds (ENOC) production at levels which would be of low concern. Hence, and despite the uncertainty associated with the ADI established by the SCF, the Panel concluded that currently there was insufficient evidence to withdraw this ADI. The exposure to nitrate solely from its use as a food additive was estimated to be less than 5% of the overall exposure to nitrate in food based on a refined estimated exposure scenario. This exposure did not exceed the current ADI (SCF, 1997). However, if all sources of exposure to dietary nitrate are considered (food additive, natural presence and contamination), the ADI would be exceeded for all age groups at the mean and the highest exposure.

Re‐evaluation of sodium nitrate (E 251) and potassium nitrate (E 252) as food additives

The Panel on Food Additives and Nutrient Sources added to Food (ANS) provided a scientific opinion re-evaluating the safety of potassium nitrite (E 249) and sodium nitrite (E 250) when used as food additives. The ADIs established by the SCF ([, 1997]) and by JECFA ([, 2002]) for nitrite were 0–0.06 and 0–0.07 mg/kg bw per day, respectively. The available information did not indicate in vivo genotoxic potential for sodium and potassium nitrite. Overall, an ADI for nitrite per se could be derived from the available repeated dose toxicity studies in animals, also considering the negative carcinogenicity results. The Panel concluded that an increased methaemoglobin level, observed in human and animals, was a relevant effect for the derivation of the ADI. The Panel, using a BMD approach, derived an ADI of 0.07 mg nitrite ion/kg bw per day. The exposure to nitrite resulting from its use as food additive did not exceed this ADI for the general population, except for a slight exceedance in children at the highest percentile. The Panel assessed the endogenous formation of nitrosamines from nitrites based on the theoretical calculation of the NDMA produced upon ingestion of nitrites at the ADI and estimated a MoE > 10,000. The Panel estimated the MoE to exogenous nitrosamines in meat products to be < 10,000 in all age groups at high level exposure. Based on the results of a systematic review, it was not possible to clearly discern nitrosamines produced from the nitrite added at the authorised levels, from those found in the food matrix without addition of external nitrite. In epidemiological studies there was some evidence to link (i) dietary nitrite and gastric cancers and (ii) the combination of nitrite plus nitrate from processed meat and colorectal cancers. There was evidence to link preformed NDMA and colorectal cancers.

Dario Battacchi

Papers

Re-evaluation of potassium nitrite (E 249) and sodium nitrite (E 250) as food additives

Re‐evaluation of sodium nitrate (E 251) and potassium nitrate (E 252) as food additives

Methodologies in the re-evaluation of nitrates and nitrites by the European Food Safety Authority (EFSA)