In Silico Toksikoloji Yöntemleri ve Uygulamaları Üzerine Araştırmalar
Date
2024Author
Karaca, Gökhan Egemen
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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.