Phenotypic Subacute Toxicity Assessment of Intranasally Administered Larixyl Acetate: Implications for Potential...

Larixyl acetate, a primary component of Larch turpentine, is a naturally occurring compound with a broad spectrum of medicinal properties, including anti-inflammatory effects. It is a potent and selective inhibitor of TRPC6, a widely expressed Ca²⁺ channel that is involved in many respiratory diseases. Despite its demonstrated efficacy, it lacks a well-defined preclinical and phenotypic safety profile, which limits its therapeutic potential and implementation. In this study, female BALB/c mice were used to assess the toxicity of intranasally administered Larixyl acetate through a subacute model based on OECD Test Guideline 412, followed by a detailed analysis of physical, blood, biochemical, and tissue changes at the administration sites and beyond. Within the study's 30-day timeframe, our results show no statistically significant differences (p > 0.05) in any of the examined toxicity parameters between the controls or three treatment groups (0.5, 1, and 2 mg/kg). While no pharmacokinetic data were obtained to confirm local or systemic exposure of Larixyl acetate, these findings are crucial for establishing a solid foundation for future therapeutic endeavors, especially in the context of TRPC6-driven respiratory diseases.