principles of toxicology yuan, zhanpeng, ph.d. tel. ： 6875 9982; 139 8612 0848 e-mail:...

Principles of Toxicology

Yuan, Zhanpeng, Ph.D.

Tel.： 6875 9982; 139 8612 0848

E-mail: zpyuan@whu.edu.cn

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

Thank you!