EXPERIMENTAL STUDIES ON THE LONG-TERM EFFECTS OF METHYLPHENIDATE HYDROCHLORIDE

Toxicology and carcinogenesis studies of methylphenidate hydrochloride , a drug used in the treatment of attention-deficient disorders, were performed in F344 rats and B6C3F1 mice. In these studies, methylphenid ate hydrochloride was administered for 2 years at doses of 0, 100, 500 or 1000 ppm in the feed to rats and at doses of 0, 50, 250, 500 ppm t o mice in groups that consisted of 50 animals/dose/sex/species. The av erage amount of methylphenidate consumed per day was estimated to be 4 -47 mg/kg/day for rats and 5-67 mg/kg/day for mice. Survival was simil ar in dosed and control groups. An increase in benign tumors of the li ver and increased liver weights were observed in male and female mice at the high dose. An increase in hepatoblastomas was also seen in high dose male mice. Methylphenidate was not mutagenic in the Salmonella a ssay system, and it is hypothesized that this tumorigenic effect might be due to nongenotoxic effects of the chemical such as an increase in cell proliferation. Increased incidences of neoplasms were not seen i n rats. However, there was a notable decrease in mammary gland fibroad enomas in female rats and a marginal decrease in benign pheochromocyto mas in male rats. Epidemiology studies of methylphenidate have found n o evidence of a carcinogenic effect in humans and like our findings in rats, report a less than expected rate of cancers in patients taking methylphenidate.