A 55-week chronic toxicity study of dietary administered kojic acid (KA) in male F344 rats

Abstract

-A chronic toxicity study of kojic acid (KA) was performed using male F344 rats by dietary administration at concentrations of 0 (control), 0.5 and 2.0% for 55 weeks. Body weight gain was suppressed in the 2.0% group. The major hematological findings were decreased red blood cell (RBC) count and hematocrit (Ht) values at both 0.5 and 2.0%. In serum biochemistry, increased aspartate -hepatocytes and proliferation of bile ductules in both treatment groups, and hypertrophy of hepatocytes, granulomas and proliferation of bile ducts in the 2.0% group were increased in incidence, and numbers and areas of glutathione-S of the 2.0% group. In the thyroids, diffuse follicular cell hyperplasia at 0.5 and 2.0% and focal follicular cell hyperplasia and follicular adenoma at 2.0% were increased. A thyroid follicular carcinoma was also observed at 2.0%. Additionally, increased incidences of hyaline casts and basophilic tubules in the kidneys at 2.0% and microgranulomas containing crystals in the lung in both treatment groups were noted. At 2.0%, hypertrophy of cortical cells in zona fasciculata was also increased in the adrenals. In conclusion, no observed adverse effect level of KA was below 0.5%, which is equivalent to 227 mg/kg body weight/day in male rats.

Final Report of the Safety Assessment of Kojic Acid as Used in Cosmetics

“…Male F344 rats were used in a 55-week toxicity dietary study of kojic acid. 93 The 7-week-old rats were divided into groups of 20 and received 0%, 0.5%, or 2.0% kojic acid (equivalent to 0, 227, or 968 mg/kg body weight/d, respectively). One week prior to treatment, rats received a single subcutaneous injection of 5 mL/kg saline.…”

“…The study concluded that the NOAEL of kojic acid was below 0.5% (227 mg/kg body weight/d). 93 Carcinogenicity studies are summarized in Table 5.…”

Endocrine Disruption by Mixtures in Topical Consumer Products

“…Some skin whitening agents used in cosmetics are known or suspected endocrine actives. Kojic acid has been demonstrated to interfere with either iodine organification or iodine uptake by the thyroid, resulting in altered thyroid functions [109,110]. Another compound used in skin whitening is resorcinol, which, as previously mentioned, has similar effect on thyroid function and hormone production.…”

Antimelanogenic activities of piperlongumine derived from Piper longum on murine B16F10 melanoma cells in vitro and zebrafish embryos in vivo: its molecular mode of depigmenting action

“…Although arbutin and kojic acid are popular in the cosmetic industry, several reports have found safety issues when these chemicals are used in pharmaceutical products [8][9][10]. Arbutin has remained in use in the cosmetic industry, but since 2001, other hydroquinones have not been used in skin-lightening formulations in the European Union [9].…”