Doseresponse Relationships

Toxicity is a relative measure of the ability of an agent to cause a harmful effect on a living organism. All substances have toxic properties. Even water is an irritant to the skin, and oxygen is toxic to humans at a high enough partial pressure and duration of exposure. On the other hand, some substances that are common industrial toxins are beneficial or even necessary to life at lower doses. This is particularly true with some of the metals, such as chromium or nickel. Even ionizing radiation can fit this category. Ultraviolet radiation from the sun converts 7-dehydrocholesterol in the skin into a form of vitamin D, a necessary nutrient. Figure 19.1 compares the type of response of necessary compounds with those that are not. Curve (a) represents the case in which the substance is a required nutrient; curve (b) is the case for a substance that is not required. For case (a) there is a deficiency of the compound below the concentration C1, whereas it is toxic above C2. Concentration C1 would be related to the minimum daily dietary requirement for the substance, and C2 is related to the experimental value, called the no observed adverse effect concentration (NOAEC).

The situation of curve (a) in Figure 19.1 brings to mind a famous statement by the sixteenth-century physician Paracelsus, often paraphrased as ''the dose makes the poison'': ''All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.''

Table 19.1 lists a number of substances that can be both toxic and essential. In the spirit of Paracelsus, then, we must be interested in determining the dose-response relationship: what dose of a toxin produces what level of undesirable effect. Leaving until later the discussion of selecting the particular effect of concern, and the experimental details, let us assume situations similar to the following examples:

1. Two hundred white rats are divided into 10 groups of 20; each rat receives a one-time subcutaneous (below the skin) injection of a quantity of a toxic substance

Environmental Biology for Engineers and Scientists, by David A. Vaccari, Peter F. Strom, and James E. Alleman Copyright © 2006 John Wiley & Sons, Inc.


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