Distribution, metabolism, and fetal uptake of pentavalent arsenic in pregnant mice following oral or intraperitoneal administration.
The relative percentages of inorganic versus methylated arsenic (7440382) in fetuses and maternal and fetal uptake of arsenic were quantitated following oral or intraperitoneal administration of arsenic to pregnant mice. Pregnant CD-1-mice were administered oral doses of 40mg/kg or intraperitoneal (IP) doses of 20mg/kg sodium- arsenate (7778430) on day 18 of gestation. Mice were sacrificed 1, 2, 4, 6, 12, 18, or 24 hours later, and individual fetuses, pooled placentas and maternal blood, urine, liver and kidneys were analyzed for total arsenic. Some of the fetal tissue was also analyzed for the arsenic metabolites, monomethylarsonic-acid (124583) (MMA) and dimethylarsinic-acid (75605) (DMA). Following oral administration, fetal arsenic levels peaked at 6 hours and placental levels peaked at 1 hour, while both fetal and placental arsenic levels peaked at 2 hours following IP administration. The peak fetal arsenic levels following oral administration were almost five times greater than peak levels following IP administration. Maternal livers contained more arsenic following oral administration than after IP administration, while arsenic levels in all other tissues were higher following IP administration. Methylated arsenic, predominantly in the form of DMA, was recovered from fetal tissue at all sampling times, and percentages of inorganic versus methylated arsenic were similar following either route of administration. The authors conclude that these results are consistent with the differences observed in teratogenicity, fetotoxicity, and maternal toxicity following intraperitoneal versus oral administration of arsenic, and support the concept that the effects on the conceptus are related to peak levels.