Development and Mechanistic Evaluation of a Lithocholic Acid Derivative as an Environmentally Safe Rodenticide

Control of rodents remains a critical global challenge due to their role in spreading zoonotic diseases and damaging ecosystems, but current rodenticides, such as anticoagulant rodenticides, have significant limitations, including the development of resistance in rodents and bioaccumulation leading to secondary toxicity in nontarget species. Dcha-20, a lithocholic acid derivative and vitamin D receptor agonist, was synthesized to potentially address these issues. This study investigates its rodenticidal efficacy, safety profile, and mechanism of action. The oral LD₅₀ estimate of Dcha-20 was 4.9 mg/kg in male and female rats, ranking it among the most potent of currently available rodenticides. Pharmacokinetic analysis revealed a short half-life and low bioavailability (4.5% in males and 12.8% in females), suggesting minimal risk of secondary toxicity. Unlike vitamin D₃, Dcha-20 impeded plasma calcium elevation observed with vitamin D₃, minimizing the risk of hypercalcemia in nontarget animals. Transcriptome analysis highlighted upregulation of pathways associated with vitamin D metabolism and inflammatory responses, indicating acute renal failure as the primary toxic mechanism. Histopathological and biochemical analyses confirmed renal damage, including elevated blood urea nitrogen and creatinine levels. Dcha-20 is stable to light and heat, unlike vitamin D₃ derivatives. These findings suggest that Dcha-20 is a promising candidate for safe, effective rodent control, with potential for large-scale use.