Toxicology of Cyanide

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Toxicology of Cyanide

• Steven Bryant
• Chem 471
• 11-11-02

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Outline of Presentation

• History of Cyanide
• General toxicity
• Mechanisms
• Antidotes
• Status of cyanide

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History of Cyanide

• Affects on biological organisms studied for
  nearly 200 years
• A German pharmacist, Schrader, noticed that
  hydrogen cyanide (HCN) was released when leaves
  of the cherry laurel and other rosaceous species
  were crushed
• Became a highly researched toxin in industry due
  to its frequent use in mining and metallurgy

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Non-Industrial Sources

• Found in some foods and plants almonds, millet
  sprouts, lima beans, bamboo shoots, cassava roots
  (tapioca), spinach, and soy
• Vitamin B12 is another source of cyanide, where
  it occurs as a part of the naturally occurring
  sugars or other complex organic compounds
• Other non-industrial sources of cyanide exposure
  burning of leaves or other yard waste, and from
  smoking cigarettes

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Industrial Sources

• Industry major source of cyanide in soil and
  water
• Sources of cyanide in water metal mining
  processes, organic chemical industries, publicly
  owned wastewater treatment plants, and iron and
  steel plants
• Gaseous sources of cyanide fumes of certain
  chemical industries, vehicle exhaust, and waste
  burning

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• Most common industrial forms of cyanide in the
  environment hydrogen cyanide, sodium cyanide,
  and potassium cyanide
• Cyanide salts and hydrogen cyanide are often used
  in metallurgy, photographic development, making
  plastics, fumigating ships, pesticides, and
  electroplating
• Cyanide contamination of the water/soil can be
  contributed to the use of certain road salts, as
  well as landfills

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Toxicity Regulations

• Government organizations, as well as worldwide
  organizations, have set recommended exposure
  levels
• EPA
• Amount of cyanide allowed in water is 200
  micrograms per liter of water.
• Limits of hydrogen cyanide stored in foods 5
  parts per million (ppm) for certain vegetables -
  250 ppm in some spices

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• EPA also sets spill regulations
• OSHA
• Permissible exposure limit for cyanide salts is 5
  mg of cyanide per cubic meter of air averaged
  over an 8-hour workday or 40-hour workweek
• NIOSH
• Recommended exposure levels of 5 mg/m3 for 10
  minutes for workers when exposed to calcium
  cyanide, hydrogen cyanide, potassium cyanide, and
  sodium cyanide.

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Routes of Exposure

• Routes inhalation, oral, or dermal exposure
• Once cyanide is absorbed, it is rapidly
  transported through the blood
• In the lungs, it can be distributed to the body
  within seconds and death can occur in minutes
• Oral Rapidly absorbed from the gastrointestinal
  tract
• Does not accumulate in tissue/blood in chronic
  exposure cases

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Effects on the Body

• Cyanide can affect vascular, pulmonary, central
  nervous, cardiac, visual, autonomic, endocrine,
  and metabolic systems
• Vascular system An initial transient increase,
  then a decrease in cardiac output
• Visual system A loss in the capacity to focus
• Pulmonary system Respiratory gasp caused by the
  stimulation of a chemoreceptor, followed by
  hyperventilation
• Central nervous system Decrease in awareness
  that can be followed by convulsions or loss of
  consciousness
• Metabolic system Decrease in energy production
  by the inhibition of the use of cytochrome oxidase

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Metabolic System Affects

• Blocking of the formation of adenosine
  triphosphate (ATP)
• ATP Immediate energy source for doing work in
  biological systems
• Blocking of ATP occurs when cyanide and carbon
  monoxide block the final step of electron
  transfer from cytochrome oxidase to oxygen.
  Electron flow and respiration are stimulated, but
  short-circuiting the proton current prevent ATP
  formation.4

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Metabolism of Cyanide
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Mechanism of Toxicity

• Two-step process
• First, HCN penetrates a protein crevice of
  cytochrome c oxidase and binds to the protein
• Then, the hydrogen cyanide binds to the trivalent
  iron ion of the enzyme, forming a relatively
  stable, but reversible, coordination complex
• Results increased blood glucose, pyruvic acid,
  lactic acid and nicotinamide adenine dinucleotide
  (NADPH) levels, and a decrease in the
  ATP/adenosine diphosphate (ADP) ratio.2

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Mechanism of Toxicity

• Acts as a strong nucleophile having multiple
  effects on the body
• In the neurons, there is an accumulation of
  intracellular calcium due to the cyanide
  nucleophile.
• Initiate the release of catecholamines from the
  adrenals and adrenergic nerve terminals. 5
• Release of excitatory neurotransmitters in the
  brain, inhibits the enzymes that protect the
  brain against oxidation energy
• The mitochondrial cytochrome c oxidase inhibition
  mechanism, discussed above, also causes central
  nervous system damage.

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Preferred Mechanism

• Not all metabolized products are bad
• Thiocyanate (SCN-), a far less toxic metabolite
• CN- S2O3-2 ? SCN- SO3-2
  
• More desirable and less toxic in the body, unlike
  the other cyanide products that are formed in the
  body

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Another Preferred Mechanism

• Amino acid cystine plays role in the safe removal
  
• Cystine and cyanide combine to form
  thiocyanoalanine

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Antidotes

• Methylene blue
• Produces methemoglobin, which binds the cyanide
  ion and prevents damage of the respiratory
  enzymes
• Amyl nitrite and sodium
• Much more effective in forming methemoglobin.5
• Found in Lilly cyanide kit

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Current Status

• Currently, cyanide is being produced from, as
  well as used in, industry
• It is still comes from yard waste burning,
  cigarette smoking, car exhaust, and many other
  sources
• EPA and OSHA try to keep these levels lower and
  safer for citizens and workers in industry
• Some cities limit yard waste burning to minimize
  pollutants

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References

• Conn, E.E et. al., Cyanide Compounds in
  Biology, John Wiley and Sons, Chichester, 1988.
• Harper, Carolyn Goldhaber, Susan. Toxicological
  Profile for Cyanide (Update). Research Triangle
  Institute, Atlanta, 1997.
• http//www.atsdr.cdc.gov/tfacts8.html. Accessed
  9/23/02. Last update June 11, 2001.
• Baskin, Steven I. Brewer, Thomas J. Medical
  Aspects of Chemical and Biological Warfare.
  Borden Institute, 1997.
• Arena, Jay M., Poisoning Toxicology..Symptoms..Tr
  eatments. Bannerstone House, Springfield, 1974.
• Elkins, Harvey B. Industrial Toxicology. John
  Wiley and Sons, New York, 1950.