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

  • J Xenobiot. 2026 Jun 1;16(3):100. doi: 10.3390/jox16030100.
Zaina Kalaji  1  2 ,  Ibrahim Hachim  1  2 ,  Marwa Almazrouei  1 ,  Hanaa Habbal  1 ,  Vidya Bijosh Mohan  1 ,  Mohammad G Mohammad  1  3 ,  Rifat Hamoudi  1  2  4  5  6  7 ,  Rabih Halwani  1  8  9  10  11
Affiliations
  • 1. Research Institute of Medical and Health Sciences, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
  • 2. Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
  • 3. Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
  • 4. Division of Surgery and Interventional Science, University College London, London NW3 2PF, UK.
  • 5. Biomedically Informed Artificial Intelligence Laboratory (BIMAILab), University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
  • 6. Center of Excellence for Precision Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
  • 7. ASPIRE Precision Medicine Research Institute Abu Dhabi, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
  • 8. Health and Wellbeing, NEOM, Tabuk P.O. Box 11149, Saudi Arabia.
  • 9. King Saud University Celiac Disease Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh P.O. Box 2454, Saudi Arabia.
  • 10. Prince Fahad Bin Sultan Chair for Biomedical Research, University of Tabuk, Tabuk P.O. Box 11149, Saudi Arabia.
  • 11. College of Medicine, Alfaisal University, Riyadh P.O. Box 2454, Saudi Arabia.
PMID: 42346422 DOI: 10.3390/jox16030100
Abstract

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.

Keywords
Larixyl acetate; OECD Test Guideline 412; intranasal delivery; subacute toxicity.
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