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METABOLSM OF PENTAVALENT AND TRIVALENT DIMETHYLARSENIC ARSENIC IN THE MOUSE
Citation:
HUGHES, M. F., B. ADAIR, B. C. EDWARDS, D. J. THOMAS, JOHN T. CREED, S. CONKLIN, M. STYBLO, V. DEVESA I PEREZ, AND E. M. KENYON. METABOLSM OF PENTAVALENT AND TRIVALENT DIMETHYLARSENIC ARSENIC IN THE MOUSE. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen after chronic exposure in either drinking water or the diet. DMA(V) is also a major urinary metabolite of mammals exposed to inorganic arsenic. In mice, iv and po administration of [14C]-DMA(V) results in rapid urinary elimination of unspecified [[14[C]. This study assessed the chemical form of the arsenicals excreted in urine by mice after exposure to DMA(V) or dimethylarsinous acid (DMA(III), iodide form), the putative reduced metabolite of DMA(V). Adult female B6C3F1 mice were administered po DMA(V) (0.6 or 60 mg As/kg) or DMA(III) (0.6 mg As/kg). Control mice were administered water. Following treatment, the mice were housed for 24 h in metabolism cages for collection of urine. Two methods were urinary arsenic analysis. Hydride-generation atomic absorption spectrometry (HG-AAS) was used to detect for DMA(V), DMA(III) and trimethylarsine oxide (TMAO). HPLC-ICP-MS was used to analyze for dimethylthioarsinic acid (DMTA) and trimethylarsine sulfide (TMAS). All five arsenicals were detected in the urine of control and treated mice; levels of each arsenical in urine of treated mice were five times or more higher than in urine of control mice. Urinary levels of DMA(V), TMAO and DMA(III) of treated mice were in the ppm range, except for DMA(III) in the low dose DMA(V) group, which was in the ppb range. Urinary levels of DMTA and TMAS of treated mice were in the ppb range. The rank order of arsenicals detected by HG-AAS in urine of DMA(V)-treated mice was DMA(V) > TMAO > DMA(III). In urine of DMA(III)-treated and control mice, the rank order of arsenicals detected by HG-AAS was TMAO > DMA(V) ≥ DMA(III). Similar values of DMTA and TMAS were detected in urine of each treatment group. TMAO is the predominant urinary metabolite of pentavalent and trivalent dimethylated arsenic administered to mice, which supports the hypothesis of oxidative methylation of arsenic. (This abstract does not represent U.S. EPA policy.)