Limb anomalies produced by 2,2'-dipyridyl in rats

The teratogenicity of 2,2'-dipyridyl (DIP), a chelator for ferrous iron, was investigated by administration of single dose of 60 or 75 mg/kg intraperitoneally to pregnant SD rats on days 11.5-14.5. Fetuses examined on day 21 were decreased in weight, and had defects chiefly in the limb. The type and incidence of limb defects differed according to day of treatment. Digital malformations in the forelimb and long-bone defects in the hindlimb were produced with high incidence by treatment on day 12.5, and the frequency of digital malformations in the hindlimb was increased by treatment on day 13.5. Light and electron microscopic examinations revealed the delay of mesenchymal condensation and destruction of mesenchymal cells in the forelimb bud in the early stage after day 12.5 treatment. The normal increase of DNA, protein, collagen and glycosaminoglycan contents in the forelimb bud was markedly inhibited by the treatment. The incorporation activities for [14C]proline and [14C]glucosamine of the forelimb bud were reduced to 50-60% of the control. These results indicate that DIP has potent teratogenic and cytotoxic effects on the development of the rat limb bud.