TOXICOLOGY

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TOXICOLOGY
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Toxicology

• Branch of science that deals with the adverse
  effects of xenobiotics on living systems
• Xenobiotic a chemical substance that is foreign
  to a living organism
• Incorporates knowledge from many scientific
  disciplines
• Biology, biochemistry, genetics, mathematics,
  medicine, pharmacology, physiology, etc.

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History of Toxicology

• Poisons recognized as early as 1500 B.C.
• All substances are poisons there is none that
  is not a poison. The right dose differentiates a
  poison and a remedy.
• Paracelsus (1493-1541)

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History Continued

• Field of toxicology rapidly expands in the 20th
  century
• Wiley Bill, 1906
• Copeland Bill, 1938
• Formation of FDA
• Delancy clause, 1958
• No carcinogens in food supply
• Genetic and developmental toxicology
• Rachel Carsons Silent Spring
• Thalidomide

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Terminology

• Poison
• Any agent that produces an adverse effect in a
  biological system
• Selective toxicity
• Chemical produces injury to one kind of organism
  without harming another kind of organism

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Terminology continued

• Dose-response relationship
• Individual
• Quantal
• LD50
• Dose needed to produce death in 50 of treated
  animals

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Routes/Sites of Exposure

• Gastrointestinal
• Lung
• Skin
• Intravenous

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Duration/Frequency of Exposure

• Acute
• Less than 24 hours
• Subacute
• Less than 1 month
• Subchronic
• 1-3 months
• Chronic
• More than 3 months

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Adverse Effects

• Local versus systemic
• Allergic
• Immediate versus delayed
• Reversible versus irreversible
• Idiosyncratic reactions

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Chemical Interactions

• Additive
• 235
• Synergistic
• 2220
• Potentiation
• 0210
• Antagonism
• 401

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Antagonism

• Functional antagonism
• Opposing physiological effects
• Chemical antagonism
• Inactivation
• Dispositional antagonism
• Alter concentration at target organ
• Receptor antagonism
• Competition at the receptor site

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Dose-Response Relationships

• Individual
• Response of one individual to a range of doses of
  a toxin
• Quantal
• Population effects
• All or none
• Normal frequency distribution
• Cumulative distribution
• Probit transformation

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Therapeutic Index

• Ratio of the dose which produces a toxic effect
  and the dose which produces a therapeutic effect
• TI LD50/ED50
• Margin of safety
• LD1/ED99
• Potency
• Efficacy

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