NTP Technical Report on the Perinatal Toxicology and Carcinogenesis Studies of 5,5-Diphenylhydantoin (Phenytoin) (CAS No. 57-41-0) in F344/N Rats and B6C3F1 Mice (Feed Studies)

摘要

Chronic toxicity and carcinogenicity studies were conducted to determine the effects of 5,5-diphenylhydantoin in the diet given to rats and mice during the adult (F1) period only (a typical carcinogenicity study); to determine the toxic and carcinogenic effects in rats and mice receiving perinatal (F0) exposure only (dietary exposure of dams prior to breeding and throughout gestation and lactation); and to determine the effects of combined perinatal and adult exposure. Under the conditions of these 2-year, adult-only, dietary exposure studies, there was equivocal evidence of carcinogenic activity of 5,5-diphenylhydantoin in male F344/N rats based on marginally increased incidences of hepatocellular neoplasms. There was no evidence of carcinogenic activity of 5,5-diphenylhydantoin in female F344/N rats given 240, 800, or 2,400 ppm. There was no evidence of carcinogenic activity of 5,5-diphenylhydantoin in male B6C3C1 mice given 30,100, or 300 ppm. There was clear evidence of carcinogenic activity of 5,5-diphenylhydantoin in female B6C3F1 mice based on increased incidences of hepatocellular neoplasms.