Metabolism of inorganic arsenic and biomarkers of exposure

Humans as well as most mammals metabolize inorganic arsenic (Inorg As), a recognized human carcinogen, by methylation. The end-metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) are less toxic and more readily excreted in the urine than Inorg As. Generally, people exposed to arsenic have 10-30% Inorg As, 10- 20% MMA and 60-80% DMA in urine, with considerable interindividual variation. Little is known about factors influencing the metabolism in humans. The aim of the present study was to investigate such factors e.g. age, ethnicity, and pregnancy in people chronically exposed to arsenic via drinking water in two villages in northern Argentina. Also, transfer of arsenic to the fetus and human milk was studied. For assessment of arsenic exposure, total arsenic concentrations in drinking water, food, breast milk and blood (B- As) were determined using hydride generation atomic absorption spectrophotometry (HGAAS), after dry ashing. Concentrations of arsenic metabolites in urine (U-Asmet, i.e. Inorg As+MMA+DMA; direct HG-AAS) and B- As were used as biomarkers of exposure to Inorg As. In order to assess methylation capacity, arsenic metabolites in urine and plasma were speciated. using ionexchange chromatography and HG-AAS. Fetal exposure was investigated by determination of arsenic concentrations in cord blood, placenta, matemal blood and urine. The concentration of arsenic in drinking water in the villages was about 200 µg As/L, which is considerably higher than the drinking water guideline of 10 µg As/L recommended by the WHO. The staple food soup and maize porridge had the highest concentrations of arsenic (300-400 µg As/kg). The high arsenic exposure caused clearly elevated B-As and U-Asmet, in the investigated children (n=57, age 3-15 yrs) and women (n=39, age 18-66 yrs). The B-As (10 µg As/L) was 10 times higher and the U-Asmet (300-440 µg AsAL) was 30 times higher than in the control area, where the water contained