Kojic Acid

Clinically effective copper-chelating tyrosinase inhibitor with decades of use for melasma and senile pigmentation at 1–2.5%. EU-restricted to 1% in face and hand products under Regulation 2024/996 (placement deadline 1 November 2025; withdrawal deadline 1 May 2027). Japan quasi-drug since 1988; suspended 2003 over rodent liver tumour data; reinstated 2005 after transdermal exposure confirmed negligible at 1% (peak plasma 1.54 ng/mL). Two persistent clinical challenges: aqueous oxidation instability requiring pH optimization, antioxidant co-formulants, or anhydrous vehicles; and contact sensitization in approximately 1–2% of users—a meaningful rate for leave-on products. Kojic acid dipalmitate ester addresses both liabilities at the cost of slower bioactivation. Effective within constraints but requires careful concentration and formulation engineering.

No specific FDA concentration restriction for cosmetic brightening use. Typically used at 1–2.5% in OTC brightening products. Not classified as a drug at cosmetic concentrations. Not GRAS-listed for OTC skin bleaching.