Sodium-arsenite (7784465) was administered to pregnant mice in order to determine the distribution of trivalent arsenic in tissues. CD-1- mice were mated and the day on which a copulation plug was observed was designated gestation day one. Pregnant mice were injected intraperitoneally (IP) on gestation day 18 with a dose of 8mg/kg sodium-arsenite or were given a dose of 25mg/kg by gavage (per oral, PO). Treated females were sacrificed at 0.5, 1, 2, 4, 6, 12, 18, or 24 hours following dosing. Fetuses, placentas, blood, liver, and kidneys were analyzed for total arsenic (7440382). Fetuses were also analyzed to determine the relative proportions of inorganic arsenic and arsenic metabolites in fetal tissue. Inorganic arsenite readily entered the maternal blood following either IP or PO administration. Uptake was greater and more rapid in the injected mice and their fetuses. Arsenic levels were higher in the blood and other tissues of injected mice than in mice treated orally, even though the dose was only one third as great. Maternal arsenic levels peaked at 24 hours. Arsenic peaks in fetal tissue were 2.10 and 0.77micrograms/gram for the IP and PO treated groups. By 24 hours, the proportion of methylated arsenic in fetuses treated IP was 79 percent while that in the PO group was 88 percent. A significant amount of arsenic which reached the mouse fetus had been methylated and these metabolites were less toxic to the fetus. The authors conclude that inorganic arsenite administered to the pregnant mother is transferred via the placenta to the fetus. Fetotoxicity depends upon the route of administration and stage of gestation.
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