Comparison of teratogenic effects of aspirin and hydroxyurea in the Fischer 344 and Wistar strains

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Abstract
The Fischer 344 rat is being used increasingly in toxicology studies. There have been few reports in which rats of this strain were used in teratology and reproduction studies, but comparison of teratologic data with other toxic end points and kinetic information would be greatly facilitated by using the same strain. Therefore, the embryotoxic effects of two positive teratogens, aspirin and hydroxyurea, were compared in Fischer rats and in the commonly used Wistar rats. Aspirin was administered in single oral doses of 500 and 625 mg/kg on d 10; hydroxyurea was injected ip at 500 mg/kg on d 11. Dams were sacrificed on d 20 and fetuses examined for skeletal and visceral defects. Male and female fetal weights and lengths were significantly reduced in treated groups in both strains. Both teratogens caused a significant increase in resorptions in Wistar and Fischer rats. A wide variety of skeletal alterations were induced by both teratogens in both strains. These included extra ribs, fused or missing ribs, extra thoracic and lumbar vertebrae, split vertebral centra, and missing vertebrae. Only a small number of Fischer fetuses exhibited visceral malformations such as hydrocephaly and cleft palate. The frequency of soft‐tissue malformations, including cleft palate and severe cardiac anomalies, was much higher in Wistar fetuses.