Toxicology and Carcinogenesis Studies of 8-Methoxypsoralen (CAS No. 298-81-7) in F344/N Rats (Gavage Studies)

摘要

Oral administration of 8-methoxypsoralen followed by exposure to longwave ultraviolet light (primarily ultraviolet A, 320-400 nm) is used in the treatment of vitiligo and psoriasis. 8-Methoxypsoralen also occurs naturally in a variety of vegetables. Toxicology and carcinogenesis studies of 8-methoxypsoralen without ultraviolet A were conducted by administering USP-grade 8-methoxypsoralen (99% pure) in corn oil by gavage to groups of F344/N rats once or for 16 days, 13 weeks, or 2 years. In vitro genetic toxicology tests were performed with bacteria and mammalian cells. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of 8-methoxypsoralen (without ultraviolet radiation) for male F344/N rats, as shown by increased incidences of tubular cell hyperplasia, adenomas, and adenocarcinomas of the kidney and carcinomas of the Zymbal gland. There was no evidence of carcinogenic activity of 8-methoxypsoralen for female F344/N rats given the chemical at 37.5 or 75 mg/kg per day for 2 years.