Arsenic Toxicity
What is the Biologic Fate of Arsenic in the Body?
Course: WB 1576
CE Original Date: October 1, 2009
CE Renewal Date: October 1, 2011
CE Expiration Date: October 1, 2013
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Learning Objective |
Upon completion of this section, you will be able to
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Introduction |
The primary routes of arsenic entry into the body are ingestion and inhalation. Dermal absorption also occurs, but to a lesser extent. The half-life of inorganic arsenic in humans is about 10 hours [Rossman 2007]. Arsenic undergoes biomethylation in the liver. Approximately 70% of arsenic is excreted, mainly in urine [Rossman 2007]. Arsenic is excreted in the urine; most of a single, low-level dose is excreted within a few days after ingestion. |
Gastro-Intestinal Tract |
For soluble trivalent arsenic compounds, approximately 95% of the ingested dose is absorbed from the gastrointestinal (GI) tract [Rossman 2007]. |
Lungs |
Airborne arsenic in the workplace is generally in the form of arsenic trioxide [Ishinishi et al. 1986]. The amount of arsenic absorbed by inhalation has not been determined precisely, but it is thought to be within 60% to 90% [Yip and Dart 2001]. Smaller particles are deposited more deeply in the respiratory tract. |
Dermal Absorption |
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. |
Distribution |
After absorption through the lungs or GI tract, arsenic is widely distributed by the blood throughout the body. [ATSDR 2007] Most tissues rapidly clear arsenic, except for skin, hair, and nails [Lansdown 1995]. Two to four weeks after exposure ceases, most of the arsenic remaining in the body is found in keratin-rich tissues such as
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Metabolism |
Arsenic is absorbed into the blood stream at the cellular level and is taken up by
Reduction of arsenate (As V) to arsenite (As III) is needed before methylation can occur. This reaction requires glutathione (GSH) [Miller et al. 2002; Vahter et al. 1983]. A portion of arsenite (As III) is methylated in the liver by enzymatic transfer of the methyl group from S-adenosylmethionine (SAM) to methyl arsonate (MMA V) and dimethyl arsenate (DMA V) [Aposhian et al. 2004; Styblo et al. 2002]. The resulting metabolites are more readily excreted. Methylation has long been considered the main route of arsenic detoxification, but more recently there has been a growing body of literature supporting other detoxification mechanisms. For example, a number of animal species lack arsenic methylation and excrete inorganic arsenic [Vahter 2002]. The implication is that there may be other more important arsenic detoxification mechanisms in mammals. Other studies have suggested additional detoxification mechanisms such as
There have also been studies of arsenic metabolism suggesting that methylation of inorganic arsenic may be a toxification, rather than a detoxification pathway and that trivalent methylated arsenic metabolites, particularly monomethylarsonous acid (MMA III) and dimethylarsinous acid (DMA III), are "unusually capable of interacting with cellular targets such as proteins and DNA" [Kitchin 2001]. Methylation efficiency in humans appears to decrease at high arsenic doses. Patterns of methylated arsenic species in urine are similar between siblings and between siblings and parents, which suggests that arsenic methylation is genetically linked [Chung et al. 2002]. 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. |
Excretion |
Arsenic is excreted in the urine primarily through the kidneys. Humans excrete a mixture of inorganic, monomethylated, and dimethylated (but not trimethylated) forms of arsenic. The pentavalent metabolites MMA V and DMA V are less toxic than arsenite or arsenate [Marafante et al. 1987].
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Key Points |
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