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  Toxicology
Information
Brief
Entry And Fate Of Chemicals In Humans

Publication Date: 9/93

ROUTES OF ENTRY

Chemicals, including pesticides, are widely distributed in the environment. Therefore there are many possible sources of exposure to these chemicals for humans. Substances which are in ambient and indoor air may be inhaled into the lungs while those in water or food may be ingested or inhaled through mist or steam (such as in the shower). Direct contact with the chemical is the most prevalent way environmental chemicals can penetrate the skin, but exposure through the skin may also occur as a result of contact with chemical contaminants in air and water (for example bathing or swimming).

A single chemical can enter the body through all three routes of exposure -- inhalation, ingestion and skin penetration (dermal exposure). A compound, such as chloroform, which evaporates readily and which may be found in drinking water illustrates this point. When this water is used for drinking, ingestion is the route of exposure. When it is used for showering, exposure may occur due to inhalation of the steam or mist and from direct contact through the skin. Similarly, pesticide use can involve more than one route of exposure if precautions are not taken. A pesticide which is sprayed can be inhaled during use; penetrate through the skin during mixing and application; and be ingested through food if not washed off hands or food before eating.

ABSORPTION, DISTRIBUTION AND FATE

Once a chemical enters the body, it is often absorbed into the bloodstream and can move throughout the body. The amount absorbed and the rate of absorption depend on the chemical and the route of exposure. This movement of the substance through the bloodstream is called distribution. Through distribution a chemical can come into contact with all parts of the body, not only the original site of entry. In some cases, such contact, distant from the site of entry, can lead to adverse health effects. For example, ingestion of the pesticide parathion into the stomach can lead to damage to the lungs.

Once a chemical is absorbed into the bloodstream, it can have several different fates. In many cases, it is rapidly removed from the body through the urine or feces. In other situations, it may be stored in various parts of the body, such as fat or bone, and remain in the individual for many years. A compound may also lead to a toxic effect through interaction with certain organs or tissues in the individual or with other compounds in the body.

Often, a substance which is absorbed into the body interacts with particular body chemicals and is changed into one or more other chemicals. This process is called metabolism and the products are called metabolites. Metabolism may lead to products which are easier for the body to excrete and so can protect the body from possible adverse effects. In other cases, however, the metabolites may be more toxic than the original chemical which was absorbed. The variety of products resulting from metabolism may have the same possible fates as the original chemical -- storage, excretion or toxicity.

CHEMICAL PROPERTIES

The particular properties of the absorbed chemical are quite critical to its fate in the body. Certain chemicals are very resistant to metabolism and readily dissolve in fat so that they tend to be stored. Dieldrin is a good example of this type of compound. Other chemicals are more rapidly metabolized and excreted and are gone before they can cause adverse effects. The organophosphate pesticides tend to behave this way at low doses.

AN INDIVIDUAL'S CHARACTERISTICS

The characteristics of the individual who is exposed are also very important in the fate of the chemical. The age, sex, genetic background, previous exposures, diet and other factors play important roles in the way that the body interacts with a chemical and in turn the potential for adverse effects. Thus, the characteristics of both the chemical and the exposed individual are important factors determining the fate of the chemical in the body.

THE TIME COURSE FOR EXPOSURE

In the case of a single event exposure, it is the total amount of chemical to which a person is exposed that determines the severity of the toxic effect, if any. The greater the amount of exposure, the greater the potential for adverse health effects. In some cases, this is due solely to the inherent toxicity of the chemical and, in others, also to the overwhelming of the body's ability to respond. In the latter case, the body may not be able to metabolize the chemical rapidly enough to prevent an increase in concentration to toxic levels. In such a situation, there is a clear threshold above which toxic signs and symptoms appear

In the case of (repeated) multiple exposures to a chemical, it is not only the total amount of exposure, but also the rate or timing of exposure that is quite important. All processes in the body normally proceed at specific rates so that metabolism, excretion and storage occur during a particular period of time after a chemical is absorbed. For a one occurrence exposure, the time needed for the various processes that breakdown the compound to be completed will determine the length of time that a toxic response, if any, persists.

However, if there are repeated exposures to the same chemical, the situation is more complicated. If there is enough time between exposures so that all of the chemical from the initial exposure is excreted, and no effects persist, then each exposure is essentially independent of the previous one and can be treated as a single exposure. However, if the time between exposures is so short that some of the chemical remains from the first exposure, then a buildup of the chemical can occur. Over time this buildup can lead to levels which are toxic.

The total amount of exposure can have different results depending on whether the exposure occurred all at once or repeatedly over time (the time course of exposure). A high dose given once may have a toxic effect while the same total dose given in small amounts over time will not. For example, drinking several ounces of alcohol at once may cause inebriation while drinking one ounce every few hours may not. Also, a particular dose given a few hours apart may have an adverse effect while the same total dose given a few days apart will not.

SUMMARY

The possible toxic effects of exposure to a particular chemical depends on many factors. These include the characteristics of the chemical and the individual exposed; the route of exposure; the total dose and the time course of exposure. Unfortunately, scientists have not been able to determine exactly how each of these factors will affect any specific individual so that present understanding of chemical exposures provides only general guidance. Minimizing exposure will minimize the potential for adverse effects. In addition, a general knowledge of all the contributing factors will help reveal the situations which have the most potential for adverse health effects and can aid in determining the best ways to manage chemicals.