Arsenic

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Arsenic

• Elizabeth Love
• ENSC 531

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Arsenic

• Background Information
• Chemical Forms
• Uses
• Sources
• Exposure
• Mechanism of Toxicity
• Detoxification
• Acute and Chronic Health Effects
• Regulation

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Background Information

• Ancient substance
• Natural forms
• In the earths crust and in minerals and ores that
  contain various heavy metals
• Anthropogenic forms
• i.e. Resulting from industrial processes
• The use/source will determine the chemical form
  and the chemical form will influence its
  transport and toxicity

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Chemical Forms

• There are numerous arsenic compounds
• A basic knowledge of the chemical forms is
  necessary in understanding arsenic transport and
  toxicity
• Arsenic can be inorganic or organic and trivalent
  (arsenite) or pentavalent (arsenate)
• Generally the inorganic forms and the trivalent
  forms are more harmful
• Methylation of inorganic or organic forms results
  in chemical forms that are more easily
  volatilized and transported

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Uses of Arsenic Containing Products

• Peak use was for agricultural pesticides during
  the 18th and 19th century
• Replaced during the sixties by synthesized
  organic pesticides
• Past uses Medicinal, veterinary metal alloys,
  semi-conductors, pigments, dyes and glass
• Current uses Primarily as a wood preservative,
  also for heart worm and some herbicides

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Arsenic Sources

• Natural
• Volcanoes, fire, geothermal wells,
  weathering/leaching of rocks that contain arsenic
  and methylation that mobilizes many forms
• Anthropogenic
• Smelting, mining, waste incineration, and
  combustion of wood or coal
• Anthropogenic sources produce arsenic whose
  chemical forms can result in accumulation and
  toxic effects, whereas the natural sources
  generally produce chemical forms that are less
  harmful

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Arsenic Exposure

• Ingestion, inhalation and dermal absorption
• Ingestion is the main route because arsenic is
  present in water and on many food products,
  especially marine food products
• Inhalation and dermal absorption are typically
  related to occupational exposures
• Once arsenic has been absorbed it is quickly
  transported in the blood through the body

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Mechanisms of Arsenic Toxicity

• The complexity of forms and biotransformations
  make it difficult to asses the toxicity of all
  arsenic compounds, but one form that is fairly
  well understood is the trivalent form of arsenic
• Trivalent forms are responsible for most of the
  toxic effects produced in biological systems
• The trivalent forms exert their toxicity by
  disrupting protein and enzyme systems

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Mechanisms of Arsenic Toxicity Cont.

• The trivalent forms can
• Alter sulfydryl-containing proteins and enzyme
  systems
• Inhibit succinic dehydrogenase
• Uncouple oxidative phosphorylation by mimicking a
  phosphate
• Cells begin to accumulate arsenic through active
  transport, that would normally be transporting
  phosphate, which leads to a stimulation of the
  mitochondrial ATPase

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Mechanisms of Arsenic Toxicity Cont.

• Arsenic can inhibit the energy linked functions
  of mitochondria through two mechanisms
• Compete with the phosphate
• Inhibit the reduction of NAD
• Both mechanisms can lead to impaired respiration,
  which can result in the production of reactive
  oxygen species (ROS)

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Detoxification

• The greatest physiological distinction of arsenic
  toxicity is between the tri- and pentavalent
  forms
• The pentavalent form is less harmful, but it can
  be reduced to the trivalent form
• A good proportion of the trivalent form can be
  detoxified by undergoing methylation in the liver
• Other forms can undergo a detoxifying glutathione
  conjugation
• Excretion is primarily in the urine

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Acute and Chronic Health Effects

• Acute
• Large doses (70 180 mg) can induce death or
  cause sensory loss in the peripheral nervous
  system
• Symptoms fever, anorexia, melanosis, cardiac
  arrhythmia, skin irritation, stomach ache,
  vomiting and decreased production of red and
  white blood cells
• Chronic
• Health effects neurotoxicity, liver damage,
  reproductive problems, skin changes (often
  associated with cancer) and cancer

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Regulation

• In an attempt to provide some level of protection
  from toxic substances the EPA sets standards on
  the allowable levels of exposure
• Drinking water was recently lowered from 50 ppb
  to 10 ppb
• There are also restrictions on industrial
  releases and pesticides
• OSHA set a permissible exposure limit of 10 ug/m3
  in an 8 hour period for particles in an
  occupational setting

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Works Cited

• ATSDR. (2002). ATSDR-ToxFAQs Arsenic Homepage
  of ATSDR, Online. Available
  http//www.atsdr.cdc.gov 2002, September 22.
• National Research Council (1999). Arsenic in
  drinking water. National Academy Press,
  Washington, D.C.
• Selene, C. PhD, Odin, M.M., Gloria, S.W. PhD, and
  Little S. PhD (2000). Toxicological profile for
  arsenic. U.S. Department of Health and Human
  Services Public Health Survey.
• Klassen, C.D. (1996/2001). Casarett and Doulls
  Toxicology The basic science of poisons (CD).
  McGraw Hill, New York.
• Yu, M.H. (2001). Environmental Toxicology
  Impacts of environmental toxicity on living
  systems. Lewis Publishers, Boca Rotan, Florida.