Embryotoxicity of chromium: Distribution in pregnant mice and effects on embryonic cells in vitro

Abstract

The embryonic and fetal uptake of Na₂ ⁵¹Cr₂O₇(Cr VI) was about 10 times higher than that of ⁵¹CrCl₃(Cr III) when these two were given in the same doses i. v. to pregnant C57BL mice. On day 13 of gestation, embryonic concentrations were 12% (Cr VI) and 0.4% (Cr III) of the maternal serum concentration 1 h after injection to the mother. After injection of Cr(III) radioactivity was not detectable in embryonic structures in early gestation, when autoradiographic techniques were used. In late gestation, administration of both forms of Cr resulted in an accumulation in the calcified areas of the fetal skeleton. The radioactivity after administration of Cr(VI) may represent Cr(III) after reduction in the tissues. When added to chick limb bud mesenchymal cells in vitro, Cr(VI) inhibited chondrogenesis at a concentration of about 0.1 μg/ml medium, which is around 1/10 of the embryonic concentration achieved after giving teratogenic doses to pregnant mice. Cr(III) on the other hand did not show any overt cytotoxicity even at 15 μg/ml (∼ 500 times higher than the in vivo embryonic concentrations after teratogenic doses). Especially Cr(III) accumulated strongly in the visceral yolk sac, probably after binding to and transport by maternal serum proteins. The possibilities that Cr(III) excerts its teratogenic action by inhibiting embryotrophic nutrition is discussed.