Tissue dosimetry, metabolism and excretion of pentavalent and trivalent dimethylated arsenic in mice after oral administration

Journal Article · Fri Feb 15 04:00:00 EST 2008 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2007.10.011· OSTI ID:21077918

Devesa, Vicenta ^[1]; Adair, Blakely M ^[2]; Conklin, Sean D; Creed, John T ^[3]; Styblo, Miroslav ^[4]; Kenyon, Elaina M; Thomas, David J ^[2]

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1. University of North Carolina at Chapel Hill, Center for Environmental Medicine, Asthma and Lung Biology, Chapel Hill, NC 27599 (United States)
2. U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711 (United States)
3. U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, Cincinnati, OH 45268 (United States)
4. University of North Carolina at Chapel Hill, Department of Pediatrics, School of Medicine, Chapel Hill, NC 27599 (United States)

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic in mice after acute oral administration. Adult female mice were administered [{sup 14}C]-DMA(V) (0.6 or 60 mg As/kg) and sacrificed serially over 24 h. Tissues and excreta were collected for analysis of radioactivity. Other mice were administered unlabeled DMA(V) (0.6 or 60 mg As/kg) or dimethylarsinous acid (DMA(III)) (0.6 mg As/kg) and sacrificed at 2 or 24 h. Tissues (2 h) and urine (24 h) were collected and analyzed for arsenicals. Absorption, distribution and excretion of [{sup 14}C]-DMA(V) were rapid, as radioactivity was detected in tissues and urine at 0.25 h. For low dose DMA(V) mice, there was a greater fractional absorption of DMA(V) and significantly greater tissue concentrations of radioactivity at several time points. Radioactivity distributed greatest to the liver (1-2% of dose) and declined to less than 0.05% in all tissues examined at 24 h. Urinary excretion of radioactivity was significantly greater in the 0.6 mg As/kg DMA(V) group. Conversely, fecal excretion of radioactivity was significantly greater in the high dose group. Urinary metabolites of DMA(V) included DMA(III), trimethylarsine oxide (TMAO), dimethylthioarsinic acid and trimethylarsine sulfide. Urinary metabolites of DMA(III) included TMAO, dimethylthioarsinic acid and trimethylarsine sulfide. DMA(V) was also excreted by DMA(III)-treated mice, showing its sensitivity to oxidation. TMAO was detected in tissues of the high dose DMA(V) group. The low acute toxicity of DMA(V) in the mouse appears to be due in part to its minimal retention and rapid elimination.

• OSTI ID: 21077918
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 227; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARSENIC
BLADDER
CARBON 14
CARCINOGENS
DOSES
DOSIMETRY
EXCRETION
LIVER
METABOLISM
METABOLITES
MICE
ORAL ADMINISTRATION
OXIDATION
OXIDES
RADIOACTIVITY
RATS
SULFIDES
TOXICITY
URINE