Embryotoxicity and fetal toxicity of nickel in rats

Abstract

Embryotoxicity and fetal toxicity of nickel chloride (NiCl 2) and nickel subsulfide (Ni 3S 2) were studied in Fischer rats. Injection of NiCl 2 (16 mg of Ni/kg, im) on Day 8 of gestation reduced the mean number of liver pups per dam and resulted in diminished body weights of fetuses on Day 20 of gestation and of weanlings at 4 to 8 weeks after birth. Injection of Ni 3S 2 (80 mg of Ni/kg, im) on Day 6 of gestation reduced the mean number of live pups per dam. No congenital anomalies were found in fetuses from any Ni-treated dams, including dams that received 10 im injections of NiCl 2 (2 mg of Ni/kg, twice daily, on Days 6–10 of gestation). 63NiCl 2 (12 mg of Ni/kg, im) was administered to a group of nonpregnant female rats and to groups of pregnant rats on Day 8 or 18 of gestation. After 24 hr, the relative concentrations of 63Ni in tissues were: kidney > serum > adrenal ⋍ lung ⋍ ovary > spleen ⋍ heart ⋍ liver > skeletal muscle. Pituitary 63Ni concentrations were much higher in pregnant rats than in nonpregnant females. 63Ni concentrations in products of conception (embryos and embryonic membranes) on Day 9 and in placentas on Day 19 were equivalent to 63Ni concentrations in adrenal, lung, and ovary tissues of the dams. Autoradiography of fetuses and placentas on Day 19 of gestation showed 63Ni localization in fetal urinary bladders and in the basal laminae and yolk sacs of the placentas. These studies show (a) that im injection of NiCl 2 and Ni 3S 2 during early gestation causes embryonic mortality at dosages that do not cause maternal mortality, and (b) that 63Ni(II) can cross the feto-maternal barriers and enter the fetuses during late gestation.