In order to understand how toxins cause a harmful change in organs, tissues, cells, or biochemicals, it is first necessary to have knowledge of normal physiology and
anatomy. In the initial section, we present an overview of normal physiology, especially as related to the normal body components and how they function. While we indicate how some xenobiotics can damage the different body components, detailed examples of toxic cellular and biochemical reactions will be covered in later sections.
The body is immensely complex with numerous components, all which perform precise functions necessary for the body to maintain health and well being. Malfunction of any component can result in a breakdown of a portion of the body, commonly referred to as disease. Toxins can damage an organ or organ system so that it can not function properly, leading to death or sickness of the organism (for example, liver or kidney failure). However, in nearly all cases, the toxin actually exerts its harmful effect directly on specific cells or biochemicals within the affected organ. These cell and chemical changes in turn cause the tissue or organ to malfunction.
Most toxins are usually specific in their toxic damage to particular tissues or organs, referred to as the "target tissues" or "target organs". Toxic effects may in fact affect only a specific type of cell or biochemical reaction. For example, the toxic effect of carbon monoxide is due to its' binding to a specific molecule (hemoglobin) of a specific cell (red blood cell). Another example of a highly specific effect is that of organophosphate toxins, which inhibit an enzyme (acetylcholine esterase), responsible for modulating neurotransmission at nerve endings.
On the other hand, the effect of some toxins may be generalized and potentially damage all cells and thus all tissues and all organs. An example is the production of free radicals by whole body radiation. Radiation interacts with cellular water to produce highly reactive free radicals that can damage cellular components. The result can be a range of effects from death of the cell, to cell malfunction, and failure of normal division (e.g., cancer). An example of a multi-organ chemical toxin is lead, which damages several types of cells, including kidney cells, nerve cells, and red blood cells.
The body is a remarkable complex living machine consisting of trillions of cells and multitudes of biochemical reactions. Each cell has a specific function and they work in concert to promote the health and vitality of the organism. The number and types of toxic reactions is likewise very large. While this tutorial can not possibly present all these types of cellular and biochemical toxic reactions, it is our goal to provide an overview of the primary toxic mechanisms with a few examples that illustrate these mechanisms. It is important to understand that changes at one level in the body can affect homeostasis at several other levels.
The understanding of the cellular and chemical toxicity is growing rapidly and there is already extensive literature in that regard. A listing of all the excellent books pertaining to this subject is beyond the scope of this tutorial. While other references were occasionally consulted, the textbooks listed below have served as the primary resources for this tutorial.
F. Lu. Taylor & Francis, Washington, D.C. 1996.
Casarett and Doull's Toxicology.
C. Klaassen. McGraw-Hill Companies, Inc., New York. 1996.
Essentials of Environmental Toxicology.
W. Hughes. Taylor & Francis, Washington D.C. 1996
Anatomy & Physiology.
V. Scanlon and T. Sanders. F.A. Davis Company, Philadelphia. 1995.
N. Stacey. Taylor & Francis, London, U.K. 1993.
Introduction to Chemical Toxicology.
E. Hodgson and P. Levi. Appleton and Lange, Norwalk, CT. 1994
Mechanisms and Concepts in Toxicology.
W. N. Aldridge. Taylor & Francis, London, U.K. 1996
Principles of Biochemical Toxicology.
J. A. Timbrell. Taylor & Francis LTD, London. 1987.
Principles of Toxicology.
K. Stine and T. Brown. CRC Lewis Publishers, Boca Raton, FL. 1996.
Encyclopaedia of Toxicology.
P. Wexler. Academic Press, Inc. 1998.
Health Effects of Hazardous Materials.
N. Ostler, T. Byrne, and M. Malchowski. Prentice-Hall, Inc. 1996.
Armed Forces Institute of
Washington, D.C. 1999.