Teratogenic effects of D-penicillamine in rats: relation to copper deficiency

The teratogenicity of D-penicillamine (DP) (dimethyl cysteine) was studied using the Sprague-Dawley rat. D-Penicillamine was fed during pregnancy at a level of 0 (control), 0.17, 0.83, or 1.66% of the diet. The frequency of resorptions, and the frequency and severity of malformations, increased with increasing levels of the drug. Maternal and fetal tissue copper levels were significantly lower in the DP groups than in controls, with the levels decreasing in a dose-related manner. Maternal and fetal zinc levels were lower in the 1.6% DP group than in controls. Maternal liver iron concentration was higher in the drug-fed rats than in controls, increasing in a dose-related manner. Fetal iron concentration was not consistently affected by the drug. Maternal and fetal manganese, calcium, and magnesium concentrations were similar among all groups. These results suggest that the teratogenicity of D-penicillamine may be due in part to induction of copper deficiency and, at high dose levels, zinc deficiency, caused by its chelating properties.