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Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM)
Arsenic Toxicity
Biological Fate
In humans, soluble forms of ingested arsenic are well absorbed (60% to 90% absorption) from the gastrointestinal tract. The amount of arsenic absorbed by inhalation has not been determined precisely, but is also thought to be in the range of 60% to 90%. Dermal absorption is generally negligible, although toxic systemic effects have resulted from rare occupational accidents where either arsenic trichloride or arsenic acid was splashed on workers' skin. There are no quantitative studies of this route of exposure, but it is of minor importance compared to other routes of exposure such as inhalation and ingestion.
Airborne arsenic in the workplace is generally in the form of arsenic trioxide. Its particle size determines whether arsenic will reach the lower respiratory tract or be deposited in the upper airways and be swallowed after mucociliary clearance. Autopsies performed on retired smelter workers show that insoluble arsenic-containing particles may remain in the lungs for years.
After absorption through the lungs or gastrointestinal tract, arsenic initially accumulates in the liver, spleen, kidney, lungs, and gastrointestinal tract. Clearance from these tissues, however, is rapid. Two to 4 weeks after exposure ceases, most of the arsenic remaining in the body is found in keratin-rich tissues such as skin, hair, and nails, and to a lesser extent, in bones and teeth.
Oxidation-reduction reactions result in some interconversion of As(V) and As(III) in vivo, thus blurring the distinction between these two groups of inorganic arsenicals. A portion of As(III) is methylated, predominantly in the liver, to methylarsonic acid and dimethylarsinic acid. The methylation process is the body's principal mechanism of detoxification; the resulting metabolites are less toxic and more readily excreted.
Methylation efficiency in humans appears to decrease at high arsenic doses. When the methylating capacity of the liver is exceeded, exposure to excess levels of inorganic arsenic results in increased retention of arsenic in soft tissues. Cell culture studies suggest that the methylating process is inducible, since pretreatment with small amounts of arsenic over a prolonged period increases the methylating efficiency when a large dose is subsequently applied. Fish arsenic is apparently not biotransformed in vivo, but is rapidly excreted unchanged in the urine.
Arsenic is excreted primarily through the kidneys. After low-level exposure to inorganic arsenic, most of the urinary arsenic is present as methylated metabolites. Other less important routes of elimination of inorganic arsenic include feces, sweat, skin desquamation, and incorporation into hair and nails.
After a single intravenous injection of radiolabeled trivalent inorganic As(III) in human volunteers, most of the arsenic was cleared through urinary excretion within 2 days, although a small amount of arsenic was found in the urine up to 2 weeks later. The biologic half-life of ingested fish arsenic in humans is estimated to be <20 hours, with total clearance in approximately 48 hours. Because arsenic is rapidly cleared from the blood, blood levels may be normal even when urine levels remain markedly elevated.
- Analysis of a spot sample of the patient's urine revealed 6,000 µg per liter (µg/L) (normal is <50 µg/L) as total arsenic. What factors could be responsible for this level, and what additional history would you elicit?
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