Pathogenesis of limb and facial malformations induced by pyrimethamine in the rat.

The temporal sequence of morphological events resulting in limb and face malformations was studied in pyrimethamine (PY) treated female rats, 30 mg/kg of PY in a 10 ml/kg suspension of 0.9% NaCl were administered i.p. on days 12, 13 and 14 of gestation. Controls received only 0.9% NaCl solution. The females were killed at different stages of gestation (between 14 and 21 days). Early PY treated embryos showed mainly haematomas in the extremities and the mandibulo-maxillary areas. During the course of gestation, fewer haematomas and more malformations were observed. At term, malformations were observed in the same localisations where haematomas were previously seen.