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1. Allergic Reactions

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. 2. Idiosyncratic Reactions. Genetically determined abnormal reactivity to a chemical.

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1. Allergic Reactions

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  1. 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.

  2. 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

  3. 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)

  4. 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

  5. TH Thalidomide

  6. C: Concentration IR:ingestion rate ED:exposure duration AF: Absorption factor BW: body weight AT:Average time

  7. 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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