General Principles of Toxicology

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General Principles of Toxicology
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General Principles of Toxicology

• Mechanistic
• Toxicogenics
• Descriptive
• Toxicity Testing
• Safety evaluation
• Regulatory requirements
• Regulatory

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General Principles of Toxicology

• Forensic Toxiciology
• Clinical Toxicology
• Environmental Toxicology
• Ecotoxicology
• Developmental Toxicology
• Teratology
• Reproductive Toxicology

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General Principles of Toxicology

• Spectrum of Toxic Dose
• AGENT DOSE (mg/kg)
• Ethyl Alcohol 10,000
• Sodium Chloride 4,000
• Ferrous Sulfate 1,500
• Morphine Sulfate 900
• Phenobarbital Sodium 150
• Picrotoxin 5
• Nicotine 1
• D-Tubocurarine 0.5
• Hemicholinium-3 0.2
• Tetrodotoxin 0.1
• Dioxin (TCDD) 0.001
• Botulinum Toxin 0.00001

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General Principles of Toxicology

• Classification of Toxic Agents
• Toxin Of biologic origin
• Toxicant Anthropogenic origin

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General Principles of Toxicology

• Route and Site of Exposure
• Duration and frequency of exposure
• Acute dose occurs in less than 24 hour
• Ingestion
• Dermal
• Inhalation
• Intra-ocular
• Injection

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General Principles of Toxicology

• Sub-acute
• Less than one month by whatever route and
  repetition
• Sub-chronic
• Doses between one and three months
• Chronic
• Exposure for more than three months to lifetime

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General Principles of Toxicology

• Spectrum of Undesired effects
• Allergic Reactions
• Idiosyncratic reactions
• Immediate versus delayed toxicity
• Reversible versus irreversible toxics effecs
• Local versus systemic toxicity

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General Principles of Toxicology

• Interaction of chemicals
• Additive action
• 2 3 5
• Synergistic
• 2 2 20
• Potentiation
• 0 2 10
• Antagonism
• 4 6 8

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General Principles of Toxicology

• Types of antagonism
• Functional
• Opposite effects on the same physiologic function
• Chemical
• Chelators of metals
• Dispositional
• Changes in uptake, distribution or excretion
• Receptor
• blockers

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Lessons Learned 1

• Question All chemicals are toxic but
• Natural products are not poisons because they are
  beneficial
• Synthetic chemicals are more toxic than
  substances found in the natural environment
• Both natural and synthetic substances are toxic
  depending on the dose
• Two chemicals are equally toxic if they have the
  same LD50

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Lessons Learned 2

• On the basis of surface area, the ranking of dose
  per unit area
• Mouse, Rat, Rabbit, Guinea Pig, Cat, Monkey, Dog,
  Human
• Mouse, Rabbit, Rat, Guinea Pig, Cat, Dog, Monkey,
  Human
• Mouse, Rat, Guinea Pig, Rabbit, Cat, Monkey, Dog,
  Human
• Mouse, Rat, Guinea Pig, Rabbit, Cat, Dog, Monkey,
  Human