Acute and Subacute Toxicity Study of α-Arbutin: An In Vivo Evidence

Abstract

α-Arbutin, a glucoside of hydroquinone, is utilized as a skin-lightening agent that inhibits human tyrosinase activity. Although it exhibits antioxidant and anti-inflammatory properties, limited research exists on its toxicological effects. This research investigates the oral toxicity of α-arbutin in both acute and subacute settings using Sprague-Dawley rats as test subjects. Female Sprague-Dawley rats underwent acute oral toxicity testing in accordance with OECD TG 425 guidelines. The rats received oral doses of 175, 550, 1750, and 2000 mg/kg. Additionally, a subacute oral toxicity study following OECD TG 407 protocols was performed on both male and female rats. In this study, the animals were given daily oral doses of 250, 500, 1000, and 2000 mg/kg for 28 days. During acute and subacute oral toxicity assessments, no deaths or observable changes in behavior were noted at the administered doses. Examination of gross anatomy showed a significant decrease in the relative spleen weight of rats given α-arbutin at 250 mg/kg compared to the control group. Male rats treated with α-arbutin exhibited markedly non-significantly increased levels of AST, ALT, and chloride ions. In contrast, mean corpuscular hemoglobin concentration levels notably decreased at lower α-arbutin doses relative to the control group. Brain histopathology of male rats revealed moderate inflammation with pyknotic nuclei, whereas the cortex showed extensive epithelial cell necrosis following the administration of 2000 mg/kg of α-arbutin. The results showed that when given for a short time, α-arbutin is nontoxic till 2000 mg/kg. The median lethal dose (LD₅₀) of α-arbutin is more than 2000 mg/kg. A long-term toxicity study may be performed to validate the result. This study evaluated the acute and subacute oral toxicity of α-arbutin in Sprague-Dawley rats. No mortality or significant behavioral changes were observed up to 2000 mg/kg. However, at higher doses, male rats exhibited elevated liver enzymes and chloride ions, along with brain inflammation and cortical necrosis. Overall, α-arbutin showed no remarkable toxicity at tested doses, with an LD₅₀ exceeding 2000 mg/kg, warranting further long-term safety assessments.

Keywords: OECD guideline; acute toxicity; drug discovery; drug safety; subacute toxicity; toxicity; α‐arbutin.