The Mode of Absorption, Distribution, and Elimination of Toxic Materials
Authors: Dinman Bertram D. , Dinman Jonathan D. 
Published: August 2005

Abstract

The toxicity of materials and the hygienic standards governing their use are of obvious importance in the practice of health protection; however, they should not be confused with the
hazard
of the usage of such materials. As this chapter will attempt to demonstrate, there are multiple physical and biological factors which will under various conditions of exposure determine the risk associated with workplace chemicals.

Multiple physical factors will determine whether chemical agents ever reach target tissues to produce toxic sequella. Gases may replace all the air in the atmosphere, but the amount of vapor in the atmosphere at any time is limited by the vapor pressure of the liquid or solid from which it arises. By contrast, the amount of suspended particulate matter in the atmosphere (e.g., dust, mist, or fume) is not limited by vapor pressure. It is well established that particulates may adsorb gases and vapors, thereby altering, and in some instances increasing, their physiological action. This follows because gas or vapors sorbed on particulates must follow the same physical principles governing the deposition of such particles in the pulmonary tree. Because particulates are more likely than gases to impinge on various portions of respiratory tract surfaces, the physiological consequences of particulate inhalation may be more significant than would be the case for gas or vapor molecules that less readily deposit and are exhaled. In addition to these purely physical considerations outside the body, other biophysical factors in the body, for example, pH, p
K

a

, lipid/water partition coefficient, and dissociation characteristics, discussed in this chapter also determine whether the xenobiotic and tissue target ever have the opportunity to interact.

Similarly, a multiplicity of biological variables determine whether a material will ever reach a target site. In the course of a material's absorption into the body, transport to, and entering a specific target organ or being eliminated, numerous conditions must be met before the cellular target site may be reached. The blood supply, conditions of vascular and cell permeability, integrity of the mucociliary escalator system, actions of neurohumoral mediators, and so on all determine whether cellular target molecules ever are at risk. Finally, even if the extensive complex of preconditions are met so as to permit the occurrence of xenobiotic‐target cell interactions, biosystems possess intrinsic capacities for the obviation of temporary and/or persistent dysfunction, viz., cellular repair or removal of aberrant cellular transformations. For example, repair of the consequences of ionizing radiation upon DNA base sequences once believed improbable have been extensively studied. At present, a number of specific, individual mechanisms for functional restitution of such alterations have been described. In addition, where damaged cells have been functionally altered such as to cause subsequent dysfunctional behavior, events leading to the programmed death, viz., apoptosis, of such cells effectively terminate their ability to reproduce such defective progeny. Discussion of these reparative and damage control mechanisms are briefly noted in the chapter.
To plan the prevention of injury from toxic materials in industry, it is essential to have a clear understanding of the dynamics of how materials enter the body, how they are handled therein, and how they are eliminated. To comprehend these processes more clearly, one need understand the mechanics of respiration and circulation and their role in the kinetics of absorption, transport, body cellular uptake, and body elimination. Many of these processes require comprehension of the gas laws and the ability to apply them to the solution of gases in liquids and specifically in the body fluids.

On the basis of such understanding it will become apparent why the occurrence of exposure to a toxic material is not
per
se tantamount to the risk of an untoward effect. Indeed, after review of this chapter, it would seem that, given all the conditions required before toxicity occurs, such an outcome is less probable than no event at all.