COLLABORATIVE WORK TO EVALUATE TOXICITY ON MALE REPRODUCTIVE ORGANS BY REPEATED DOSE STUDIES IN RATS : 21)COMPARISON OF THE EFFECTS OF 2-AND 4-WEEKS PYRIMETHAMINE TREATMENT IN RATS

Abstract

Pyrimethamine (PYR), clinically used as an antimalarial or antiparasitic agent, is known to exert testicular toxicity in rats on oral administration for 8 weeks. This study was performed to examine whether 2-weeks daily repeated doses of PYR might induce detectable toxicity on the male reproductive organs in rats. PYR was orally administered to Slc:SD male rats at doses of 12.5, 25 or 50 mg/kg for 2 weeks, or 6.25, 12.5 or 25 mg/kg for 4 weeks. No effects were seen in any group on physical examination and body weight measurement. Gross findings in autopsy exhibited no abnormalities in any of the animals. There were no meaningful changes in the weights of reproductive organs, or in the number and activity of sperm in the epididymides. Loss and degenerative changes of pachytene spermatocytes in stages I to III seminiferous tubules were observed in the rats given 50 mg/kg PYR for 2 weeks. From the results obtained, it is concluded that 2-weeks repeated dosing with PYR is sufficient to detect toxicity on male reproductive organs in rats using histopathological examination.