Principles of Toxicology

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Principles of Toxicology

• Activities in Toxicologic Science
• Toxicology is a
• Mechanistic
• Descriptive
• Regulatory
• Forensic
• Clinical
• Environmental
• Inhalation

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Spectrum of Toxic Dose

• A poison is any substance by any route at any
  time which causes a deleterious response or
  effect in an organism

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Classification of Toxic Agents

• Toxin versus toxicant

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Characteristics of exposure

• The substance itself or the product it becomes

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Route and site of exposure

• Skin
• Optic
• Oral
• Inhalation
• Injection
• Arterial
• Venous

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Duration and Frequency of Exposure

• Acute
• Subacute
• Subchronic
• Chronic

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Spectrum of Undesired Effects

• Intended
• Unexpected
• Adverse
• Toxic

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Categories -

• When offered a choice, ask for less.
• Additive - 1 plus 1 equals 2
• Potentiation 0 2 10
• Synergism 2 2 12
• Antagonism 4 6 8 or 4 0 2

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Type of Interaction

• Functional
• Dispositional
• Chemical
• Receptor

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Reactions

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

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Tolerance

• Accomodation
• Disposition
• Sequestration
• detoxication

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Dose Response

• Individual or Graded, Dose-Response Relationships
• Quantal or Population, Dose Response Relationship

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Therapeutic Index

• TI equals LD50 divided by ED50
• The LD50 is
• The ED50 is

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Margin of Safety

• MOS equals LD1 divided by the ED99
• The LD1 is
• The ED99 is ..

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Species Differences

• Rodents are not small humans
• They are different
• Rodent (Rat, Mouse, Hamster) versus Lagomorphs
  versus Canus versus Felines versus Swine versus
  Primates

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Testing Paradigms

• Acute
• Death
• Irritation
• Skin Draize Test
• Eye
• Sensitization
• MK
• Buehler Open Epicutaneous

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Testing Paradigms (Continued)

• Sub-Chronic (28 Day)
• Sub-chronic (90 Day)
• Chronic (two years)
• Lifetime (whose?)

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Testing Costs and Times
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