Subacute Oral Toxicity Evaluation of Red Pine Oil in Sprague-Dawley Rats: Safety Profiling for Potential Therapeutic Use.

Red pine oil (Pinus densiflora) is a monoterpene-rich essential oil with antimicrobial, antioxidant, and anti-inflammatory activities. While commonly used topically, its systemic safety following oral use remains underexplored, limiting its development as an oral therapeutic or supplement. This research aims to evaluate the subacute oral toxicity of red pine oil in Sprague-Dawley rats over 28 days, followed by a 14-day recovery phase. Male and female rats were assigned to six groups (n = 10/group) and administered red pine oil at 90, 270, or 1000 mg/kg body weight/day by oral gavage. All test preparations were diluted in fish oil; control groups received fish oil alone. Parameters evaluated included clinical signs, body weight, hematology, serum biochemistry, organ weights, and histopathology of major organs. Satellite groups assessed reversibility. No mortality, behavioral changes, or clinical signs of toxicity were observed. Red pine oil significantly increased hemoglobin, hematocrit, erythrocyte count, lymphocytes, and platelets in male rats, with values returning to baseline after recovery. Triglyceride levels were reduced in males at mid and high doses. Minor increases in AST and urea in high-dose females were not accompanied by histological abnormalities. Organ weights and tissue structures remained within normal limits. All observed effects were noncumulative and reversible. Red pine oil was well-tolerated at doses up to 1000 mg/kg/day, with no systemic or organ-specific toxicity. The established NOAEL was 1000 mg/kg BW. These findings support its safety for oral use and provide a scientific basis for further pharmacological studies.