In vivo dominant lethal effect of pyrimethamine in male mouse germ cells

Pyrimethamine is used for treatment of malaria and toxoplasmosis. The embry otoxicity and clastogenicity of pyrimethamine is known and our aim was to i nvestigate its dominant lethal effect in vivo. For this purpose, we used th ree groups of Swiss-albino male mice and a control group. We injected males with doses of 16, 32 or 64 mg/kg pyrimethamine and housed them with 10 fem ales/male for each mating interval. Females were sacrificed and their uteri were evaluated for dominant lethality. As a result of this study we found that pyrimethamine induced dominant lethal mutations in the third, fourth a nd sixth weeks at the 64 mg/kg dose level, without the effect being dose-de pendent. We conclude that pyrimethamine is a suspected germ cell mutagen.