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. Touch up Review Further Clarify Objectives

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 in biological 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 LD 50 /ED 50 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

64. Thank you!