Regulatory safety evaluation of key lime (Citrus aurantiifolia) peel ethanol extract: Acute, 90-day repeated-dose, and genotoxicity studies.

Key lime (Citrus aurantiifolia) peel, a major by-product of juice processing, is rich in flavonoids and other bioactives. To support its safe use as a food-derived ingredient, we chemically characterized key lime peel ethanol extract (KLPE) and conducted a full toxicological evaluation under OECD Test Guidelines (No. 420, 408, 471, 473, 474) and in compliance with GLP. The program included acute oral toxicity, a 90-day repeated-dose study with a 28-day recovery, and in vitro and in vivo genotoxicity assays. KLPE caused no mortality or clinical signs, and body weight, food intake, hematology, and organ weights were comparable to controls. No histopathological lesions or genotoxic effects were observed. Both the LD50 and the No Observed Adverse Effect Level (NOAEL) exceeded 2000 mg/kg BW/day, the highest dose tested, indicating a wide safety margin. These results provide regulatory-grade evidence confirming the safety of KLPE for human consumption and support its application as a functional food and nutraceutical ingredient in global markets.