Distribution, metabolism, and fetal uptake of pentavalent arsenic in pregnant mice following oral or intraperitoneal administration

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Abstract
Pregnant CD‐1 mice were treated with 20 (i.p.) or 40 (p.o.) mg/kg sodium arsenate on gestation day 18 (plug = day 1). Individual fetuses, pooled placentas and maternal blood, urine, liver, and kidneys were obtained from three or more litters at intervals up to 24 hours following treatment. Acid‐digested samples were analyzed for total arsenic by hydride generation atomic absorption spectrophotometry. The rate of arsenic elimination from maternal samples was not influenced by administration route. First‐order elimination followed a brief period of distribution, and the biological half‐life was approximately 10 hours. Arsenic was found in most samples, with mean peak concentrations expressed as μg As/gm (wet wt.) or /ml (values listed are post‐treatment sampling times in minutes or hours and concentrations for i.p. and for p.o. treated groups, respectively) as follows: fetuses–2, 3.5; 6, 0.8, placentas–2, 9.3; 1, 2.3, blood–10 minutes, 6.9; 1, 2.0, urine–1, 712; 2, 342, kidney–20 minutes, 25.4; 1, 11.0, liver–0.5, 7.9; 1, 11.7. By 24 hours, arsenic levels in fetuses and placentas had declined to 0.22 μg/gm and 0.74 μg/gm for i.p. and 0.33 μg/gm and 0.57 μg/gm for p.o. treatments, respectively. Fetal arsenic uptake and loss were more rapid following i.p. than p.o. treatments, and although the i.p. dose was only half that used p.o., peak fetal As+5 was almost fivefold higher following i.p. treatment. These results agree with the finding that oral dosing of pregnant mice with arsenate has less effect on the conceptus than does treatment by injection. Arsenic metabolites (mono‐ and dimethyl arsenic) were quantitated in fetuses and ranged up to 83% of total fetal arsenicals by 24 hours.
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