The Urinary Excretion of Arsenic Metabolites After a Single Oral Administration of Dimethylarsinic Acid to Rats

The biotransformation following oral administration of dimethylarsinic acid (DMA), an organoarsenical herbicide and the main metabolite of inorganic arsenic in mammals, was studied in rats. Male F344/DuCrj rats were administered a single dose of DMA (50 mg/kg) orally. Urine was collected at 0, 2, 4, 8, 10, 24, and 48 h after administration by forced urination. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry (IC-ICP-MS). The proportions of urinary elimination of DMA, trimethylarsine oxide (TMAO), methylarsonic acid (MMA), an unidentified arsenic metabolite, and arsenite were determined at various timepoints after administration. Unmetabolized DMA was the most common form excreted during the first 4 h. Thereafter, a gradual decrease in the proportion of DMA was observed, while progressive increases in those of TMAO, the unidentified metabolite, and arsenite occurred. The proportion of TMAO excreted amounted to over 50% of all arsenic in urine between 6 and 24 h. The proportion of the unidentified metabolite and arsenite were each approximately 10% at 10 and 24 h after administration. The findings indicate that DMA administered to rats was initially excreted as unchanged DMA, and later as the methylated metabolite, TMAO. Arsenite, a demethylated metabolite of DMA, also was excreted later than elimination of DMA and TMAO. The hypothesis of demethylation by intestinal microorganisms can be supported by comparing the metabolites following oral and intraperitoneal administration. The unidentified metabolite was readily decomposed by HCl but was left unchanged by NaOH; these findings suggest that it was present in a complexed form in urine.