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4. What happens to arsenic in the body?

  • 4.1 What happens to arsenic absorbed by the body?
  • 4.2 What are the indicators of arsenic exposure?

4.1 What happens to arsenic absorbed by the body?

The source document for this Digest states:

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.

Source & ©: IPCS "Environmental Health Criteria for Arsenic and Arsenic compounds", 
EHC 224, Chapter 1: Summary, section 5

4.2 What are the indicators of arsenic exposure?

The source document for this Digest states:

Levels of arsenic or its metabolites in blood, hair, nails and urine are used as biomarkers of arsenic exposure. Blood arsenic is a useful biomarker only in the case of acute arsenic poisoning or stable chronic high-level exposure. Arsenic is rapidly cleared from blood, and speciation of its chemical forms in blood is difficult. Arsenic in hair and nails can be indicators of past arsenic exposure, provided care is taken to prevent external arsenic contamination of the samples. Arsenic in hair may also be used to estimate relative length of time since an acute exposure. Speciated metabolites in urine expressed either as inorganic arsenic or as the sum of metabolites (inorganic arsenic + MMA + DMA) provide the best quantitative estimate of recently absorbed dose of arsenic. However, consumption of certain seafood, mainly seaweed and some bivalves, may confound estimation of inorganic arsenic exposure because of metabolism of arsenosugars to DMA in the body or the presence of DMA in the seafood. Such food should be avoided for 2–3 days before urine sampling for monitoring of exposure to inorganic arsenic.

Source & ©: IPCS "Environmental Health Criteria for Arsenic and Arsenic compounds", 
EHC 224, Chapter 1: Summary, section 5

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