The discovery, importance and significance of monomethylarsonous acid (MMAIII) in urine of humans exposed to inorganic arsenic

Using a newer and more specific method of analysis (Le et al., 2000. Environ. Health Perspect,, 108, 1015-1018), monomethylarsonous acid (MMA(III)) has been detected for the first time in the urine of some humans exposed to inorganic arsenic in their drinking water. We studied subjects in Romania who had been exposed to 2.8, 28.5, 84.1 or 161 mug As/l in their drinking water. In the latter two groups, the MMA(III) was 11 and 7% of the urinary arsenic, while the MMA(V) was 14 and 13%, respectively. Of our 58 subjects, 17% had MMA(III) in their urine. MMA(III) was not found in the urines of any of the group with the lowest As exposure. The concentrations of MMA(III) in mate Golden Syrian hamster livers were determined 15 h after administration of a single intraperitoneal dose of [As-73]arsenate. Metabolites of inorganic arsenate present in hamster liver after 15 It were observed in the following concentrations (ng/g liver +/- SEM); MMA(III), 38.5 +/- 2.9; DMA(III), 49.9 +/- 10.2; arsenite, 35.5 +/- 3.0; arsenate, 118.2 +/- 8.7; MMA(V), 31.4 +/- 2.8; and DMA(V), 83.5 +/- 6.7. MMA(V) reductase activity, the rate-limiting enzyme of inorganic arsenic metabolism, was determined in tissues of male Golden Syrian hamsters. The specific activity of this enzyme in the brain > bladder > spleen > liver > lung > heart > skin > kidney > testis. This is the first identification of MMA(III) in urine and MMA(III) and DMA(III) in liver and indicates that the significance of various arsenic species in mammalian tissue and urine needs to be re-examined and re-evaluated as to their role in the toxicity and carcinogenicity of inorganic arsenic.