Arsenic Methylation in Humans

Creselius (1977) reported the urinary excretion of MMA and DMA by a volunteer who had ingested wine containing 63//g iAs. To date, a number of studies have examined the methylation of As in humans during environmental or occupational exposure to different forms of As. In addition, several laboratory experiments have been performed on volunteers administered with single or repeated doses of arsenicals. The main purpose of this work has been to characterize the kinetic behavior of iAs and organoAs compounds and to find reliable markers of exposure of humans to As. 

GaAs workers. Exposure to higher levels of As in copper smelting resulted in increased urinary excretion of iAs, MMA, and DMA. Urinary excretion of TMA was not increased under high exposure conditions and can be used to monitor the dietary intake of TMA species such as arsenobetaine. The results of this study emphasize again the need for complete speciation in evaluating exposure to As in humans. 

DMA to be the major As metabolite (70% of urinary As). Notably, the significant increase in the amount of MMA was found in urine of As-exposed individuals accompanied by a decrease in the amount of DMA. This alteration in the ratio of MetAs species in urine could reflect dosage-dependent changes in metabolism of iAs. Thus, the urinary ratio of MMA/ DMA may be an appropriate indicator of iAs exposure in humans and warrants examination in other As-exposed and control populations. 

Based on a 10-kg body weight, this yields an intake of 1.5//g As/kg/day, which is less than the WHO/FAO provisional tolerable weekly intake of iAs (2.1//g Askg May ) (Joint WHO/FAO 1989). In the absence of data on the species of As present in foods, it is widely assumed that dietary As is primarily organoAs species (e.g., arsenobetaine and arsenocholine) which are relatively nontoxic. However, it has been reported that 5%-12% of the As in freshwater fish is present as iAs (Norin et al. 1985). To better assess the role of diet in the intake of iAs, additional data are needed on the chemical form of As in food. 

P) Influence of Disease Status on Methylation. Liver disease has been shown to change capacity for As methylation in humans (Buchet et al. 1984). Although the cumulative urinary excretion of As in 24 h after i.v. injection of 7.14//g As Vkg was unaffected by the presence or absence of liver disease, liver disease status did affect the MM A and DMA in urine, resulting in reduced MM A and increased DMA. In individuals without liver disease n = 13), MMA represented 12.3% 2.8% and DMA 23.3% 6.4% of the cumulative 24-h urinary As (Geubel et al. 1988). In patients with liver cirrhosis injected i.v. with 7.14//gAs Vkg, the proportion of MMA and DMA in cumulative 24-h urine was 4.7% 3.3% and 40.4% 16.6% n = 38), respectively. Notably, carbon tetrachloride-induced liver cirrhosis increases the urinary excretion of DMA in male golden Syrian hamsters (Takahashi et al. 1988). 

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