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World Health Organization : Year 2000 ; World Health Organization, Programme on Chemical Safety, No. 00.8, Pages P1-104: IPCS Training Module No. 4 General Scientific Principles of Chemical Safety

By L. Fishbein

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Book Id: WPLBN0000182627
Format Type: PDF eBook
File Size: 7.0 MB
Reproduction Date: 2005

Title: World Health Organization : Year 2000 ; World Health Organization, Programme on Chemical Safety, No. 00.8, Pages P1-104: IPCS Training Module No. 4 General Scientific Principles of Chemical Safety  
Author: L. Fishbein
Volume:
Language: English
Subject: Health., Public health, Wellness programs
Collections: Medical Library Collection, World Health Collection
Historic
Publication Date:
Publisher: World Health Organization

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Fishbein, L. (n.d.). World Health Organization : Year 2000 ; World Health Organization, Programme on Chemical Safety, No. 00.8, Pages P1-104. Retrieved from http://worldlibrary.org/


Description
Medical Reference Publication

Excerpt
FOREWORD The principal focus of this work is to mher the objectives of the IPCS in its elaboration and evaluation of the effects of chemicals on human health and the environment and the development of methodology, testing methods and risk evaluation by highlighting the basic tenets of the cornerstone, toxicology. Toxicology is increasingly recognized to be a dynamic discipline where change is being driven by both technological and conceptual advances. Hence this report will reflect the panoply of interactions between chemicals and living organisms via the broad spectrum of animal studies which measure the toxic effects resulting fiom both short-term and long-term exposures at low and hgh concentrations of agents, interspecies extrapolations, mechanism of bioactivation and detoxification as well as toxicokinetics and toxicodynamics. The essentials of toxicology are extended into risk assessment (and its limitations and uncertainties) including hazard identification, dose response, exposure assessment, risk characterization and risk management. Risk assessment is recognized to be not one procedure with one outcome, but a complex of related activities, all of which inform an overall judgement as to health risk. Future developments in the many areas of testing and harmonization of cancer and non-cancer risk assessments are also featured. This training module builds on and updates the original text (post Task Group draft, April 1995) of the IPCS document (originally intended for publication in the Environmental Health Criteria series) entitled General Principles and Methods for Chemical Safety (Human Health Protection). In-place of the many original textual references, a selected bibliography has been added.

Table of Contents
CONTENTS GENERAL SCIENTIFIC PRINCIPLES OF CHEMICAL SAFETY Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii 1 . CHEMICAL SAFETY FOR HUMAN HEALTH PROTECTION: CONCEPTS AND APPLICATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 Definition of chemical safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 The need for chemical safety and human health protection . . . . . . . . . . . 1 1.3 Historical development of chemical safety . . . . . . . . . . . . . . . . . . . . . . . . 2 1.4 Chemical safety concepts and application . . . . . . . . . . . . . . . . . . . . . . . . 4 1.4.1 Universe of chemicals to be tested . . . . . . . . . . . . . . . . . . . . . . . 13 1.5 International dimension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2 . PRINCIPLES OF TOXICITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2.1 Manifestations and mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2.1.1 Homoeostasis and adaptive changes . . . . . . . . . . . . . . . . . . . . . . 18 2.1.2 Acute versus chronic exposure . . . . . . . . . . . . . . . . . . . . . . . . . . 20 2.1.3 Mechanisms of toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 2.1.3.1 Inhibition of specific enzymes . . . . . . . . . . . . . . . . . . . . 23 2.1.3.2 Induction of specific enzymes . . . . . . . . . . . . . . . . . . . . 24 2.1.3.3 Genotoxicity and carcinogenicity . . . . . . . . . . . . . . . . . 29 2.1.4 Local versus systemic effects; routes of exposure . . . . . . . . . . . . 33 2.1.5 Primary and secondary effects . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.1.6 Target organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 2.1.6.1 Site of exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 2.1.6.2 Site of metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 2.1.6.3 Site of accumulation . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 2.1.6.4 Sites of excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 2.1.6.5 Sites of special sensitivity . . . . . . . . . . . . . . . . . . . . . . . 41 2.2 Toxicokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 2.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 2.2.2 Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 2.2.3 Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 2.2.4 Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 2.2.4.1 Modulation of metabolism . . . . . . . . . . . . . . . . . . . . . . 51 2.2.4.2 Metabolic activation . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 2.2.4.3 Species and individual differences in metabolism .... 52 2.2.5 Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 2.2.6 Kinetic modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

 

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