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Principles of Toxicology Yuan, Zhanpeng, Ph.D. Tel. : 6875 9982; 139 8612 0848 E-mail: zpyuan@whu.edu.cn
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毒理学基础 Essentials of Toxicology 武汉大学公共卫生学院 毒理学系
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Touch up Review Further Clarify Objectives
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Contents General Principles of Toxicology –Absorption-Distribution-Excretion General Classification of Toxicants Specific Discussion of Toxicants
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Toxicology Toxicology is the study of poisons Poisons are chemical/physical agents that produce adverse responses in biological organisms
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General Principles of Toxicology ADME Classifications of Toxicity Mechanisms of Toxicity Primary Determinants of Toxicity Toxicity Modifiers ETC.
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ADME Toxicological Process –Transport Process Mechanisms –Toxicokenetics –Toxicokenetics and PBPK modeling
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Absorption-Distribution-Excretion Toxicological Process
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Toxicokinetics
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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 LD 50 /ED 50 Risk: probability that injury will result from exposure to a substance for given conditions, dose, and route
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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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