Substantiating indicators for assessing population health risks based on experimental investigation applying biomarkers of effect produced by n-nitrosamines

N-Nitrosodimethylamine (NDMA) is a nitrosamine with established hepatotoxicity. However, unlike its well-studied carcinogenic effects in model organisms, quantitative indicators for assessing non-carcinogenic risks under chronic exposure remain undetermined. In the context of hepatotoxicity, key biomarkers include aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Analyzing changes in activity of these enzymes in controlled experimental conditions allows for identifying dose-response relationships even for non-specific liver injury markers.

The study aimed to establish health risk assessment indicators based on experimental research using biomarkers of effect established for N-nitrosamines.

A 6-month toxicological experiment was conducted on Wistar rats randomly divided into five groups that were administered different oral doses of NDMA to interpolate the dose-response curve.

Dose-effect relationships were assessed using nonlinear regression analysis. Safe exposure levels for NDMA were deter-mined using the Benchmark Dose Lower Limit (BMDL) approach with the sliding window method. Statistical analysis was per-formed using the Mann-Whitney U-test. Uncertainty factors were applied when converting BMDL to a reference dose (RfD).

Among the analyzed hepatotoxicity biomarkers, GGT demonstrated the highest diagnostic sensitivity and a pronounced dose-dependent response (p ≤ 0.05). Mathematical modeling of the GGT-NDMA dose relationship yielded statistically significant indicators characterizing hepatotoxic effects. Based on significant biomarker excess, a BMDL of 0.0055 mg/kg body weight was established, and an RfD was substantiated for chronic NDMA exposure equal to 5.73•10 –6 mg/kg body weight. Dose – response indicators were established (b0 = -2.94, b1 = 35.96) for assessing non-carcinogenic risks associated with liver dysfunction. Thus, this study provides quantitative indicators for evaluating health risks under chronic NDMA exposure.