Kojic acid, the chemical name 5-hydroxy-2-hydroxymethyl-4-pyrone, is used in cosmetic products as a skin whitening or depigmenting agent. Kojic acid is a chelating agent produced by several species of fungi, especially Aspergillus oryzae, which has the Japanese common name of koji. It is a by-product in the fermentation process of malting rice, when producing sake (Japanese rice wine). It is used in food and cosmetics to help preserve against color changes. Kojic acid also has antibacterial and antifungal properties. Kojic acid markedly inactivated isolated tyrosinase by chelation. In cultured human melanocytes, tyrosinase activity per well was slightly reduced at the concentration range between 0.1 mM and 0.5 mM but was rapidly dose-dependently reduced at higher concentration. The inhibitory effect of kojic acid on tyrosinase activity in the cell culture system is smaller than that of arbutin at concentrations that do not affect cell viability, even though marked inactivation was observed in isolated tyrosinase. There are conflicting reports on the effectiveness in kojic acid. [Maeda and Fukuda]. Kojic acid may take two to three months to show efficacy and thus may seem rather slow to be effective.  However, kojic acid does not have any side effects during the 10- to 20-month period during normal application on the skin. Kojic dipalmitate is mentioned in the Inventory of Cosmetic Ingredients, but derivative esters of Kojic acids are also used. The substance is listed as an emollient, whereas Kojic acid itself is listed as an antioxidant. Results of the range finding test indicated that the LD50 was in the range of 4000 to 16000 mg/kg bw. In the main experiment lethargy, piloerection, abnormal body carriage, ataxia and depressed respiration rate were observed shortly after dosing. These signs were accompanied by gasping amongst mice treated at 6400 mg/kg bw. Bodyweight increases of rats treated at 16000 mg/kg bw were slightly depressed during the first week. Recovery of survivors was apparently complete within four days of dosing. Autopsy revealed congestion of the lungs and pallor of the liver, kidneys and spleen in animals died after treatment. The LD50 and its 95% confidence limits were calculated to be 5100 (3900 – 6700) mg/kg bw. No erythema or oedema occurred in the test performed. Kojic acid was not considered to be an irritant to rabbit skin. In the preliminary test and in the first experiment, 3% Kojic acid aqueous solution caused no eye disturbances. In the second experiment mild transient hyperemia was observed in 2 of 4 animals. No other inflammatory changes or corneal disturbances were observed. Eye irritability was reported to be very weak. In the supplementary test no specific response was observed for up to 72 hours. Two out of 20 animals showed a positive reaction, indicating a sensitising potential of the substance. Kojic acid is sensitising in humans. Based on the information provided, margins of safety of respectively 35 (face and hands), 58 (hands) and 88 (face) have been calculated suggesting that the use of Kojic acid at a maximum concentration of 1.0% in skin care formulations poses a risk to the health of the consumer. In addition, other parts of the skin might be exposed to Kojic acid. Kojic acid has the potential to induce skin sensitisation. Relevant data on kinetics of Kojic acid after dermal application may be submitted to refine the MOS approach..

Source: Dweck, Anthony. Handbook of Natural Ingredients (Dweck Books 4) . Dweck Data.