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Analysis of micronucleus induction of pyrimethamine in in vitro CHL cells and in in vivo mouse bone marrow cells.

In vivo and in vitro mutagenicity of pyrimethamine were examined in the micronucleus test. Pyrimethamine strongly induced micronuclei in a dose-dependent manner in the in vitro micronucleus test using the Chinese hamster lung (CHL) cell line, when treated at 0.2-1.6 micrograms/ml for 48 h. The in vivo micronucleus test was carried out in mice after the first, second, third and fourth administration of doses up to 40 mg/kg p.o. The results showed no increased frequency of micronuclei after any treatment, though pyrimethamine was shown to persist at levels > 2 micrograms/ml in plasma after a single oral administration of 50 mg/kg.