Biotransformation of dimethylarsinic acid in mouse, hamster and man

Abstract

The metabolism of dimethylarsinic acid (DMA) a common pesticide and the main metabolite of inorganic arsenic in mammals, has been studied in mice, hamsters and man. Mice and hamsters were administered a single dose of 74As-DMA (40 mg As/kg body weight) orally, while a human subject ingested DMA corresponding to 0.1 mg As/kg body weight. Ion exchange chromatography, paper electrophoresis, thin layer chromatography as well as arsine generation--gas chromatography combined with atomic absorption spectrophotometry or mass spectrometry were used to characterize the arsenic metabolites in urine and feces collected over 48 hours after treatment. In mice and hamsters 3.5% and 6.4% of the dose, respectively, were excreted in urine in the form of trimethylarsine oxide (TMAO). No TMAO was found in feces. A DMA-complex was detected in urine and feces. It amounted to about 13% of the dose in mice and 15% in hamsters. About 80-85% of the dose was eliminated in urine and feces in the form of unmetabolized DMA. No demethylation of DMA to inorganic arsenic was observed. In man, about 4% of the dose was excreted in urine as TMAO and about 80% as DMA.

A concise review of the toxicity and carcinogenicity of dimethylarsinic acid

“…Yamauchi and Yamamura (1984) reported that 49% of a single oral dose of 50 mg/kg DMA was eliminated in the urine of Syrian golden hamsters within 5 days ( 36% in feces). Marafante et al (1987) reported similar findings in that 56% of a single oral dose of 40 mg (As)/kg DMA was eliminated in urine of male Syrian golden hamsters within 48 h (41% in feces). Gastrointestinal absorption of DMA may be more extensive in mice.…”

“…DMA is methylated to trimethylarsenic compounds to a small extent in mice, rats, hamsters and humans (Yamauchi and Yamamura, 1984;Marafante et al, 1987;Yoshida et al, 1997). Marafante et al (1987) reported that 3 and 6% of a single oral dose of 40 mg (As)/kg DMA was eliminated in urine as trimethylarsine oxide (TMAO) within 48 h in mice and hamsters, respectively; TMAO was not detected in the feces of either species in this study.…”

Advances made in Understanding the Effects of Arsenic Exposure on Humans

“…Upon exposure to arsenic, humans excrete significant amount of MMA which is about 10-20% of total urine arsenic 16 . In mammals DMA is the end point of arsenic metabolism and is not further methylated 17,18 . It is found that 40-60% of arsenic remains are retained in skin, hair, nails, muscle, teeth and bones even after exposure to arsenic is ceased (ATSDR case studies in environmental medicine, agency for toxic substances and disease registry) 19 .…”

Arsenic- Exposure, Mechanism of Action and Toxicity Analysis: A Prenatal View

“…The excreted dimethylated arsenic is roughly 50% and monomethylated is nearly 25% and the remaining is inorganic (Buchet et al 1981). MMA V and DMA V, the pentavalent metabolites have low toxicity as compared to arsenite or arsenate (Marafante et al 1987). An issue of National Health and Nutrition Examination Survey 2003-2004 on urinary arsenic suggests that as the total arsenic in the urine increases, there is increase in the percentage of methylated forms and as the total arsenic levels decreases in urine, inorganic arsenic is the leading element (Caldwell et al 2009).…”