Principles of Toxicology
Yuan, Zhanpeng, Ph.D.
Tel.： 6875 9982; 139 8612 0848
E-mail: [email protected]
毒理学基础Essentials of Toxicology
武汉大学公共卫生学院毒理学系
• Touch up
• Review
• Further Clarify
Objectives
Contents
• General Principles of Toxicology
– Absorption-Distribution-Excretion
• General Classification of Toxicants
• Specific Discussion of Toxicants
Toxicology
• Toxicology is the study of poisons
• Poisons are chemical/physical agents that produce adverse responses in biological organisms
General Principles of Toxicology
• ADME
• Classifications of Toxicity
• Mechanisms of Toxicity
• Primary Determinants of Toxicity
• Toxicity Modifiers
• ETC.
ADME
• Toxicological Process
– Transport Process Mechanisms
– Toxicokenetics
– Toxicokenetics and PBPK modeling
Absorption-Distribution-Excretion
• Toxicological Process
Toxicokinetics
Classification of Toxicity
• Acute toxicity: adverse effect resulting from a single, usually large, exposure to a toxin
• Subacute toxicity: Somewhat acute, between acute and chronic (online med. dictionary)
• Chronic toxicity: harmful effect from repeated exposures to a toxin for 3+ months
• Therapeutic index• LD50/ED50
• Risk: probability that injury will result from exposure to a substance for given conditions, dose, and route
Mechanisms• Alterations in receptor-ligand interactions
– Nicotine, most drugs
• Alterations in membrane function– Local anesthetics, hydrocarbons
• Interference with cellular energy mechanisms– Cyanide, Pentachlorophenol
• Covalent binding to biomolecules– Organophosphates, alkylating agents
• Causing non-lethal alterations in somatic cells• Carcinogens, e.g. aflatoxin• Alterations in ligand-activated transcription factors, e.g. Dioxins
• By inducing programmed cell death (apoptosis), e.g. Acetaminophen
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