Use and Safety of Tyrphostin AG17 as a Stabilizer in Foods and Dietary Supplements Based on Toxicological Studies and QSAR Analysis.

This study evaluated two formulations of L-carnitine, which were developed and impregnated in an oil-based self-emulsifying system (SEDDS), the first with tyrphostin AG17 and the second without the addition of tyrphostin AG17. The formulation with tyrphostin AG17 showed the presence of stable microvesicles up to 498 h after its preparation. To establish a robust safety profile in compliance with modern regulatory frameworks and the 3Rs principle (replacement, reduction, and refinement), a toxicological evaluation was conducted integrating an in silico quantitative structure-activity relationship (QSAR) analysis with confirmatory in vivo subchronic toxicity studies. The QSAR analysis, performed using the OECD QSAR Toolbox and strictly adhering to Organization for Economic Co-operation and Development (OECD) validation principles, predicted an acute oral LD50 of 91.5 mg/kg in rats, a value showing high concordance with the historical experimental data (87 mg/kg). Furthermore, computational modeling for repeated-dose toxicity yielded a no-observed-adverse-effect level (NOAEL) of 80.0 mg/kg bw/day, a no-observed-effect level (NOEL) of 60.4 mg/kg bw/day, and an ADI = 56 mg/day. These computational findings were substantiated by a 90-day subchronic toxicity study in male Wistar rats, where daily intragastric administration of tyrphostin AG17 at doses up to 1.75 mg/kg resulted in not statistically significant hematotoxic activity (