Overview and justification of a toxicological experiment design for establishing risk assessment indicators

Tóm tắt

N-nitrosamines in food products are a serious health threat due to their carcinogenic and non-carcinogenic effects on the kidneys, spleen, GIT, and liver. Meat products are a major source of their exposure. Within a joint Russian-Vietnamese study, health risks for the Vietnam population were assessed using the methodology developed in the Eurasian Economic Union. As a result, unacceptable risk levels associated with Nnitrosodimethylamine (NDMA) in meat products were established for children under 6 years and adults 18-50 years old. However, the reference dose for NDMA established by the US EPA is based on limited data and requires experimental definition. The objective of this study is to overview the publications devoted to the study of the toxic effects of N-nitrosamines and to justify an experiment design for identifying and validating biomarkers of exposure and response upon N-nitrosamines’ exposure. In conformity with the international standards OECD and GLP principles, a design is going to be created for a 180-day experimental study of NDMA chronic toxicity using Wistar rats. The number of animal groups exposed to NDMA is four, and one group is control. Oral exposure to NDMA will take place using gavage 7 days a week. The experiment involves monthly monitoring of biochemical indicators (AST, ALT, and GGT) and NDMA levels in blood. The created design is expected to help establish points of departure (reference level, benchmark dose level) for chronic exposure as well as provide significant data for risk assessment. Taking into account three established approaches used in experimental studies to refine risk assessment’s parameters, the Benchmark dose (BMD) method was selected for this experiment’s design.