In Silico Toksikoloji Yöntemleri ve Uygulamaları Üzerine Araştırmalar

Abstract

The use of computer-assisted toxicology methods (in silico toxicology, computer-based toxicology etc.) in predicting preclinical toxicological endpoints, clinical side effects, and the metabolism of pharmaceutical substances has gained significant interest from the scientific community and the public. The increasing accessibility of these technologies for scientists and the regulations allowing their use for chemical risk assessment have further fueled this interest. In silico toxicology is seen as a reliable method not only in product development and pharmaceutical preparation but also in reducing lengthy and costly animal testing. An overview of in silico toxicology has been provided, and the fundamental concepts, current capabilities, and limitations of this technology have been discussed, experimental study using this technology has been presented, comparing the calculated LD50 and NOAEL values for the mentioned endpoints with experimental data. In this comparison, drug compounds with existing LD50 and NOAEL values in the literature were selected. The LD50 value was calculated using the QSAR Toolbox program, selecting time periods between 48 and 96 hours. Rats and mice, which have extensive data in the literature for these compounds, were chosen as the species. For NOAEL, no specific time range was selected, the most comparable data from existing databases were used for the comparison. For the compound Baclofen, which does not have existing LD50 and NOAEL values in the literature, calculations were performed. The LD50 value was found to be 940 mg/kg for oral administration in mice and 300 mg/kg for intraperitoneal (IP) administration in rats. The NOAEL value was found to be 20.1 mg/kg/day. Our results, obtained from QSAR and Read-Across methods, suggest that these values should be verified by comparing them with results obtained from comprehensive laboratory studies. This study serves as a preliminary investigation and is expected to contribute to the development of new strategies in this field.