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SPECIFYING THE PERMISSIBLE DAILY EXPOSURE TO N-NITROSAMINES BY ALIMENTARY INTAKE WITH FOOD USING EXPERIMENTAL STUDIES
Abstract
More sensitive methods to determine chemicals in food enable us to assess the contaminant danger in the product. It is of help when evaluating the speed and conditions of their formation in the food and studying long-term carcinogenic and acute toxic effects on the body. The results of exposure to contaminants on the body as biomarkers of the effect in a controlled experiment on laboratory animals and the further use of the results obtained in the risk assessment might serve as conditions for establishing or reviewing the standards for the content of the studied chemicals contained in food. Hygiene regulations of the Russian Federation related to N-nitrosamines in infant food state a standard for their content based on the lowest detection level. A critical stage by developing the maximum permissible levels of chemicals is the working-out of acceptable daily intake (ADI). Since medico-biological studies of the baby?s health status are challenging from the point of view of medical ethics, it is advisable to develop ADI using a simulation experiment as per health risk criteria. The developed method for measuring the N-nitrosamines content in food has a more sensitive detection level. It results in assessing the impact of the determined N-nitrosamines at concentrations below the previously established lowest detection level (LDL). When specifying ADI, we used the results obtained during an experiment on laboratory animals. We focused on the N-nitrosamines content found by chemical analytical method in canned meat of one batch. The impact of N-nitrosamines in baby canned meat was assessed using 120 white Wistar rats. Biomarkers of hepatotoxicity (alanine transaminase, aspartate transaminase, gamma glutamine transferase) were studied to assess the effect of the sum of N-nitrosamines. Statistical processing was carried out using the Statistica 6.0. A statistically significant difference between animal groups was assessed using the Mann-Whitney U-test. Mathematical modeling was carried out and modifying factors were determined to find the reference levels. As a result, we stated NOAEL at the level of 0.00064 mg/kg per day. Based on the results of an experiment to determine the inactive dose (BMDL) of N-nitrosamines from canned meat intended for infants, a mathematical simulation of the "dose-effect" relationship was carried out. While simulating, reliable cause-effect relationships were established between the level of contamination of the sum of N-nitrosamines in canned meat and an increase in the values of biomarkers of hepatotoxicity. The lowest level equal to 0.00063 mg/kg per day was selected from all the control levels obtained during the simulation of the "dose-effect" relationship. As a result of the calculation, ADI was established at the level of 0.000016 mg/kg per day taking into account modifying factors. The obtained ADI will be helpful by further establishing the maximum permissible level of the sum of N ? nitrosamines in baby canned meat.
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