The teratogenic activity of a thalidomide analogus EM12 in rats on a low-zinc diet.

The relationship between the teratogenicity of EM12, 2-(2,6-dioxopiperiden-3'-yl) phthalimidine, a stable analogue of thalidomide, and zinc status in the maternal animal was investigated using pregnant rats on a low-zinc diet (1 ppm zinc, days 0--14 gestation) as the experimental model. Previous studies with this compound in rats fed a commercial diet at oral doses up to 250 mg/kg per day for three days and intravenous doses up to 10 mg/kg per day for three days failed to produce "typical" thalidomide malformations. However, when a dose of 150 mg/kg was given intraperitoneally to rats on a low-zinc diet, typical thalidomide malformations occurred with an incidence of 57.5%.