Kinetics and metabolism
Absorption of arsenic in inhaled airborne particles is highly dependent on the solubility and the size of particles. Both pentavalent and trivalent soluble arsenic compounds are rapidly and extensively absorbed from the gastrointestinal tract. In many species arsenic metabolism is characterized by two main types of reactions: (1) reduction reactions of pentavalent to trivalent arsenic, and (2) oxidative methylation reactions in which trivalent forms of arsenic are sequentially methylated to form mono-, di- and trimethylated products using S-adenosyl methionine (SAM) as the methyl donor and glutathione (GSH) as an essential co-factor. Methylation of inorganic arsenic facilitates the excretion of inorganic arsenic from the body, as the end-products MMA and DMA are readily excreted in urine. There are major qualitative and quantitative interspecies differences in methylation, to the extent that some species exhibit minimal or no arsenic methylation (e.g. marmoset monkey, guinea-pig, chimpanzee). However, in humans and most common laboratory animals, inorganic arsenic is extensively methylated and the metabolites are excreted primarily in the urine. Factors such as dose, age, gender and smoking contribute only minimally to the large inter-individual variation in arsenic methylation observed in humans. However, lower methylation efficiency in children has been observed in only one study out of three. Studies in humans suggest the existence of a wide difference in the activity of methyltransferases, and the existence of polymorphism has been hypothesized. Animal and human studies suggest that arsenic methylation may be inhibited at high acute exposures. The metabolism and disposition of inorganic arsenic may be influenced by its valence state, particularly at high dose levels. Studies in laboratory animals indicate that administration of trivalent inorganic arsenic such as As2O3 and arsenite initially results in higher levels in most tissues than does the administration of pentavalent arsenic. However, the trivalent form is more extensively methylated, leading to similar long-term excretion. Ingested organoarsenicals such as MMA, DMA and arsenobetaine are much less extensively metabolized and more rapidly eliminated in urine than inorganic arsenic in both laboratory animals and humans.
The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on 8790 women who had recently been pregnant in an area of Inner Mongolia, China known to have a gradient of drinking water arsenic exposure. This study observed increased systolic blood pressure levels with increasing drinking water arsenic, at lower exposure levels than previously reported in the literature. As compared to the referent category (below limit of detection to 20Â ÎĽg of As/L), the overall population mean systolic blood pressure rose 1.29Â mmÂ Hg (95% CI 0.82, 1.75), 1.28Â mmÂ Hg (95% CI 0.49, 2.07), and 2.22Â mmÂ Hg (95% CI 1.46, 2.97) as drinking water arsenic concentration increased from 21 to 50, 51 to 100, and >Â 100Â ÎĽg of As/L, respectively. Controlling for age and body weight (n =Â 3260), the population mean systolic blood pressure rose 1.88Â mmÂ Hg (95% CI 1.03, 2.73), 3.90Â mmÂ Hg (95% CI 2.52, 5.29), and 6.83Â mmÂ Hg (95% CI 5.39, 8.27) as drinking water arsenic concentration increased, respectively. For diastolic blood pressure effect, while statistically significant, was not as pronounced as systolic blood pressure. Mean diastolic blood pressure rose 0.78Â mmÂ Hg (95% CI 0.39, 1.16), 1.57Â mmÂ Hg (95% CI 0.91, 2.22) and 1.32Â mmÂ Hg (95% CI 0.70, 1.95), respectively, for the overall population and rose 2.11Â mmÂ Hg (95% CI 1.38, 2.84), 2.74Â mmÂ Hg (95% CI 1.55, 3.93), and 3.08Â mmÂ Hg (95% CI 1.84, 4.31), respectively, for the adjusted population (n =Â 3260) at drinking water arsenic concentrations of 21 to 50, 51 to 100, and >Â 100Â ÎĽg of As/L. If our study results are confirmed in other populations, the potential burden of cardiovascular disease attributable to drinking water arsenic is significant.
Keywords: Arsenic; Drinking water; Blood pressure; Cardiovascular disease; Post-natal; Reproductive health; Women; Inner Mongolia, China