Preclinical Safety Evaluation of the Khaolaor Ya-Kwad-Samarn-Lin Wound-Healing Formulation Following 28-Day Oral Administration in Wistar Rats

Abstract

Toxicity data following repeated administration are essential for evaluating the systemic safety of herbal wound-healing formulations.  Therefore, this study aimed to evaluate the 28-day repeated-dose oral toxicity of Khaolaor Ya-Kwad-Samarn-Lin (KLO), a Thai herbal formulation. The experimental protocol was adapted from OECD Test Guideline 407, and KLO was administered once daily by oral gavage at doses of 0.1, 1, and 5 mg/kg body weight/day. Mortality, clinical signs, behavioral changes, body-weight gain, food and water consumption, relative organ weights, gross necropsy findings, and histopathological changes were assessed. No mortality, treatment-related clinical signs, behavioral abnormalities, changes in body-weight gain, food or water consumption, or relative organ weights were observed in KLO-treated rats. Gross necropsy and histopathology revealed no treatment-related lesions. Isolated hematological changes were observed in high-dose male rats, including decreased mean corpuscular volume and granulocyte percentage; however, these changes showed no clear dose-response relationship and were not supported by clinical observations, organ-weight changes, gross pathological findings, or histopathological evidence. Overall, repeated oral administration of KLO did not produce detectable treatment-related adverse systemic toxicity. The no-observed-adverse-effect level (NOAEL) for KLO was determined to be 5 mg/kg body weight/day, the highest dose tested.