Principles of Toxicology

1. Principles of Toxicology Yuan, Zhanpeng, Ph.D. Tel.：6875 9982; 139 8612 0848 E-mail: zpyuan@whu.edu.cn

2. 毒理学基础Essentials of Toxicology 武汉大学公共卫生学院 毒理学系

3. Objectives • Touch up • Review • Further Clarify

4. Contents • General Principles of Toxicology • Absorption-Distribution-Excretion • General Classification of Toxicants • Specific Discussion of Toxicants

5. Toxicology • Toxicology is the study of poisons • Poisons are chemical/physical agents that produce adverse responses inbiological organisms

7. General Principles of Toxicology • ADME • Classifications of Toxicity • Mechanisms of Toxicity • Primary Determinants of Toxicity • Toxicity Modifiers • ETC.

8. ADME • Toxicological Process • Transport Process Mechanisms • Toxicokenetics • Toxicokenetics and PBPK modeling

10. Absorption-Distribution-Excretion • Toxicological Process

32. Toxicokinetics

45. 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

46. 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