1. Allergic Reactions

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1. Allergic Reactions

• Chemical allergy is an immunologically mediated
  adverse reaction to a chemical
• Results from previous sensitization to the
  chemical or to a structurally similar one.

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2. Idiosyncratic Reactions

• Genetically determined abnormal reactivity to a
  chemical.
• Stevens-Johnson syndrome
• carbamazepine, phenytoin, allopurinol
• Usually qualitatively similar to that observed in
  other individuals but may take the form of
  extreme sensitivity/insensitivity to the
  chemical.
• Succinylcholine and prolonged apnea

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3. Immediate versus delayed Toxicity

• Immediate responses are those that occur rapidly
  after a single administration of a substance
• Delayed toxic effects are those that occur after
  a lapse of some time.
• Cancer is example of delayed (20-30 years)

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4. Reversible versus Irreversible Toxic Effects

• If a chemical produces pathological injury to a
  tissue the ability of that tissue to repair
  itself will determine whether the effect is
  reversible to irreversible.
• Liver regenerates rapidly
• CNS does not
• Carcinogenic and teratogenic effects are
  generally irreversible

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TH
Thalidomide
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C Concentration IRingestion rate EDexposure
duration AF Absorption factor BW body
weight ATAverage time
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• Calculating Reference Dose

• RfD(mg/kg/day) NOAEL(mg/kg/day) / Safety Factor
  (UF x MF)
• Safety factor of 100 usually used
• factor of 10 for human/animal response
  differences
• factor of 10 for inter-individual response
  differences
• additional safety factor of 10 applied if data
  are questionable

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Variation in Susceptibility
Why me, Doc? Ecogenetics Identify inherited
variation in susceptibility to specific exposure
of external agents
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Toxicology Data Network (TOXNET) Integrated
Risk Information System (IRIS)