PRINCIPLES OF TOXICOLOGY - Biology East Borneo

2 Absorption, Distribution, andElimination of Toxic AgentsABSORPTION, DISTRIBUTION, AND ELIMINATION OF TOXIC AGENTSELLEN J. O’FLAHERTYThis chapter explains fundamental principles of toxicology, and discusses• The broad principles that govern transfer of molecules across membranes• The factors that influence absorption of foreign compounds from the GI tract and the lung,and across the skin• Simple kinetic models that describe disposition (distribution and elimination)• Mechanisms of elimination (biotransformation and excretion)2.1 TOXICOLOGY AND THE SAFETY AND HEALTH PROFESSIONSOccupational health specialists, including toxicologists, rely upon human and animal data to determinesafe exposure levels. If effects observed in workers can be reproduced in a laboratory animal, it becomespossible to investigate the mechanisms that might reasonably be expected to produce such effects. Onthe other hand, shedding light on the mechanism by which a designated effect is produced in a test animalspecies may make it easier to find ways to prevent such effects from occurring in humans. Such anunderstanding may also help to identify subtle or delayed effects that have not been observed in workers,but to which health professionals should be alerted.The uncertainties associated with converting test results in small animals to predictions relevant tohumans are frequently stressed. Quantitative differences among species do exist. Occasionally, thesedifferences can be so great that they obscure fundamental similarities. Physiological and biochemicalattributes characteristic of a particular species can shift patterns of absorption, distribution, metabolism,excretion, or effect in significant ways. Nonetheless, the basic principles that control these processesare the same for all mammalian species. These principles will be surveyed in this chapter.Toxic Agents and the BodyFigure 2.1 will be referred to several times during this chapter. It is a schematic overview of the behaviorof a foreign compound as it enters the body, is distributed into tissues, exerts an effect, and is eliminated.A toxicant is absorbed into the body and then into the blood. From the blood, it is simultaneouslyeliminated and distributed to various tissues, including the target tissue. The target tissue is the tissueon which the toxicant exerts its effect.Principles of Toxicology: Environmental and Industrial Applications, Second Edition, Edited by Phillip L. Williams,Robert C. James, and Stephen M. Roberts.ISBN 0-471-29321-0 © 2000 John Wiley & Sons, Inc.35