On the issue of determining tolerable daily intake of total N-nitrosamines for toddlers

In Russia, assessment of food products that contain N-nitrosamines (NAs) conventionally focuses on the total N-nitrosodimethylamine and N-nitrosodiethylamine contents. Other NAs are also potential carcinogens and their non-carcinogenic effects require more profound investigation, especially upon low-dose exposures. A child body is more sensitive to NA exposures due to its morphofucntional peculiarities. This involves likely earlier manifestations of non-carcinogenic effects (for example, hepatotoxicity) due to, among other things, their unidirectional effects. More precise health risk assessment requires considering all NAs identified in food products. The present study continues and enlarges previous research works with their focus on experimental determination of N-nitrosamines toxicity in food for babies and toddlers. We assessed hepatotoxicity associated with harmful effects produced by N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodibutylamine, N-nitrosodipropylamine, N-nitrosopyrrolidine and N-nitrosopiperidine. Lower benchmark dose limit (BMDL) able to cause significantly more considerable hepatotoxic effects (judging from AST, ALT, GGT activity, levels of total bilirubin and alkaline phosphatase) was established through analyzing the total intake of N-nitrosamines identified in meat canned food for toddlers. Establishing BMDL for the total N-nitrosamine contents (0.175 µg/kg of body weight), below which no significant relation existed between likelihood of hepatotoxic effects and NAs dose, made it possible to calculate tolerable daily intake equal to 4.38 ng/kg of body weight considering a potential unidirectional hepatotoxic effects produced by six N-nitrosamines. This established TDI value is considerably lower than a previously established one (15.8 ng/kg of body weight per day) for the sum of four NAs (N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodibutylamine, and N-nitrosodipropylamine), which is probably due to the estimated unidirectional NAs effect. Combined exposure to a wider range of N-nitrosamines enhances harmful effects, which requires considering the whole range of these substances in health risk assessment. The study findings confirm that it is advisable to develop safe standards for the sum of NDMA and DENA; however, it is also necessary to consider developing safe standards for the analyzed range of six NAs in food products.