Long-term in vivo carcinogenicity study of phenytoin (5,5-diphenylhydantoin) in F344 rats.

The carcinogenicity of phenytoin was studied in F344/DuCrj rats. Phenytoin was mixed with powdered basal diet at levels of 0 (control), 0.025 or 0.05% and groups of 50 male and 50 female rats were administered these doses ad lib. for 2 yr. Survival of the treated male and female rats was similar to that of the corresponding controls. There was a dose-related decrease in mean body weight of treated female rats, but body weights of treated male rats were similar to those of controls. A variety of tumours developed in all groups including the control group, but all of the neoplasms that were observed were histologically similar to known spontaneous tumours in this strain of rats and no statistically significant increase in the incidence of any particular tumour type was evident in the treated groups of either sex. Nor was there any evidence of accelerated tumour induction in any phenytoin-treated group. Thus, it is concluded that under the conditions used in this experiment phenytoin had no carcinogenic potential in F344 rats.