Integrative In Silico Toxicity Assessment of Chlorfenapyr Using AI-Driven Platforms

Authors : Ünzile Yaman

Pages : 44-52

View : 30 | Download : 18

Publication Date : 2025-06-27

Article Type : Research Paper

Abstract :Chlorfenapyr is a pyrrole-class pesticide with a unique mechanism of action that disrupts mitochondrial oxidative phosphorylation. Despite its broad-spectrum insecticidal use, publicly available toxicological data on chlorfenapyr remain limited, particularly regarding organ-specific and long-term effects. To address this data gap, the present study implements a multi-model in silico toxicity assessment using three AI-based platforms—SwissADME, ProTox-II, and ADMETlab 2.0—to predict key toxicokinetic and toxicodynamic properties from the compound’s SMILES representation. Physicochemical and pharmacokinetic parameters such as molecular weight, lipophilicity, gastrointestinal absorption, and cytochrome P450 inhibition were consistently predicted across platforms. However, notable discrepancies emerged in blood–brain barrier (BBB) permeability and hepatotoxicity outcomes. Acute toxicity was estimated with a predicted LD₅₀ of 55 mg/kg (Class 3), while organ-specific risks included neurotoxicity and respiratory toxicity. Both platforms highlighted mitochondrial membrane potential disruption and oxidative stress pathways as probable mechanisms of toxicity. Toxicophore analysis further revealed substructures associated with non-genotoxic carcinogenicity, aquatic toxicity, and poor biodegradability, raising environmental safety concerns. By combining complementary model outputs, this AI-supported approach allows for scalable, reproducible, and ethically favorable screening of chemical hazards. The findings demonstrate that multi-endpoint in silico toxicology workflows can effectively identify early warning signals of compound toxicity and guide future experimental priorities—particularly for chemicals like chlorfenapyr, where experimental data are scarce and regulatory insight is urgently needed.
Keywords : ADMETlab2.0, Chlorfenapyr, hesaplamalı toksikoloji, ProTox-II, pestisit risk değerlendirmesi, SwissADME

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