Various pathways are used, the principal route being dependent on the current environment of the cell. Resulting metabolites are monomethylarsonous acid, MMA(III), and dimethylarsinous acid, DMA(III). Methylation had been regarded as a detoxification process, but reduction from +5 As to +3 As may be considered as a bioactivation instead. Another suggestion is that methylation might be a detoxification if "As[III] intermediates are not permitted to accumulate" because the pentavalent organoarsenics have a lower affinity to thiol groups than inorganic pentavalent arsenics. Gebel (2002) stated that methylation is a detoxification through accelerated excretion. With regard to carcinogenicity it has been suggested that methylation should be regarded as a toxification.Arsenic, especially +3 As, binds to single, but with higher affinity to vicinal sulfhydryl groups, thus reacts with a variety of proteins and inhibits their activity. It was also proposed that binding of arsenite at nonessential sites might contribute to detoxification. Arsenite inhibits members of the disulfide oxidoreductase family like glutathione reductase and thioredoxin reductase.The remaining unbound arsenic (≤ 10%) accumulates in cells, which over time may lead to skin, bladder, kidney, liver, lung, and prostate cancers. Other forms of arsenic toxicity in humans have been observed in blood, bone marrow, cardiac, central nervous system, gastrointestinal, gonadal, kidney, liver, pancreatic, and skin tissues. Heat shock response
Another aspect is the similarity of arsenic effects to the heat shock response.
The Environmental Protection Agency, for example, has estimated the total national annualized cost of treatment, monitoring, reporting, record keeping, and administration to enforce the MCL rule to be approximately $181 million. Most of the cost is due to the installation and operation of the treatment technologies needed to reduce arsenic in public water systems. Pregnancy
Arsenic exposure through groundwater is highly concerning throughout the perinatal period. Pregnant women are a high-risk population because not only are the mothers at risk for adverse outcomes, but in-utero exposure also poses health risks to the infant. There is a dose-dependent relationship between maternal exposure to arsenic and infant mortality, meaning that infants born to women exposed to higher concentrations, or exposed for longer periods of time, have a higher mortality rate.Studies have shown that ingesting arsenic through groundwater during pregnancy poses dangers to the mother including, but not limited to abdominal pain, vomiting, diarrhea, skin pigmentation changes, and cancer. Research has also demonstrated that arsenic exposure also causes low birth weight, low birth size, infant mortality, and a variety of other outcomes in infants. Some of these effects, like lower birth-rate and size may be due to the effects of arsenic on maternal weight gain during pregnancy.