Chemical Information Review Document for Arbutin [CAS No. 497-76-7] and Extracts from Arctostaphylos uva-ursi

Arbutin is found in the dried leaves of a number of different plant species including bearberry (Arctostaphylos uva-ursi). The leaves and leaf extracts from uva ursi are used in non-prescription medicinal products mainly to treat urinary tract infection, cystitis, kidney stones, and as a diuretic. The active component, arbutin, is converted to hydroquinone (HQ) which has antimicrobial, astringent, and disinfectant properties. Arbutin is also an inhibitor of melanin formation and is use in some skinlightening products. It is rapidly metabolized and excreted in rats as unchanged arbutin and in humans as HQ, HQ glucuronide, and HQ sulfate. HQ induced renal tubule adenomas in male rats and liver adenomas and thyroid gland follicular cell hyperplasia in mice. It was negative in the Ames assay but induced mutations and micronuclei in mouse L5178Y lymphoma and chromosome aberrations and sisterchromatid exchange in Chinese hamster ovary cells. Side effects reported from the ingestion of dried uva ursi leaves included nausea and vomiting, irritability, insomnia, and an increased heart rate. Extremely high doses can cause ringing in the ears, shortness of breath, convulsions, collapse, and delirium. Uva ursi has also been linked with albuminuria, hematuria, and urine cast; liver damage is also a risk with long-term use. In vitro studies of human melanocytes exposed to arbutin at concentrations below 300 μg/mL reported decreased tyrosinase activity and melanin content with little evidence of cytotoxicity. Arbutin did not induce mutations in hamster V79 cells, except after preincubation with β-glycosidase. Bone marrow micronuclei were not induced in mice after oral treatment with arbutin, and a mixture of uva ursi extracts did not induce micronuclei in cultured human lymphocytes.