Uptake, distribution, and metabolism of trivalent arsenic in the pregnant mouse

To investigate the distribution of trivalent arsenic (arsenite) in the pregnant rodent, CD-1 mice were dosed with sodium arsenite by ip injection or by gavage on gestation d 18 (copulation plug day = d 1). Doses were 8 (ip) or 25 (po) mg/kg, and samples of maternal blood, liver, and kidneys, as well as fetuses and pooled placentas, were analyzed for total arsenic at intervals of up to 24 h. Fetal tissue was also analyzed for relative proportions of inorganic arsenic and methylated metabolites. Arsenic uptake was significantly greater in the injected mice and their fetuses (as a proportion of the administered dose), with levels highest at 10 min to 4 h in maternal tissues and 24 h in fetuses. Peak maternal arsenic levels (as microgram/g or microgram/ml) ranged from 2.36 (blood) to 26.15 (liver) for the ip injected and 1.25 (blood) to 17.64 (liver) for the gavaged treatment group. The rate of arsenic elimination from maternal samples was not significantly influenced by administration route, with first-order elimination rate constants (k) of 0.215 and 0.234 h-1 for the po and ip dosed mice, respectively. Fetal tissue arsenic peaks were 2.10 and 0.77 micrograms/g for the ip and po treatment groups, respectively. The proportion of methylated arsenic in fetuses increased to 79% in the ip treatment group and 88% in the po group by 24 h. Such results show that much of the arsenic reaching the mouse fetus has been methylated to less toxic metabolites. They also confirm that assumptions made regarding hazard to the fetus must reflect the likelihood that a portion of any maternal dose of inorganic arsenite reaching a fetus may have been methylated, and they support previous findings that arsenite is toxic to the conceptus at lower doses when given by injection than by gavage.