Embryotoxicity of Arsenite and Arsenate: Distribution in Pregnant Mice and Monkeys and Effects on Embryonic Cells in Vitro

Abstract

The distribution of ⁷⁴As-labelled arsenate and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondro-genic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the ⁷⁴As-arsenic appeared to pass the mouse placenta relatively freely and approximately to the same extent. The retention time in maternal tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution picture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50~ 5-10 μM), while arsenate seemed to be without effect at concentrations up to 200 μM (highest tested). Arsenate, however, showed a potentiation of the arsenite toxicity.