How Does Toxic Exposure Cause Children’s Disease?

Upon completion of this section, you will be able to

• describe the exposure-disease model.

The exposure-disease model is often used to conceptualize how toxicant exposure occurs and to identify the steps necessary to cause disease or other adverse health or developmental outcomes. The exposure-disease model depicts the relationship between an environmental contaminant and an adverse health effect. It predicts that the harm caused by a contaminant depends on its

• toxicity,
• route of exposure, and
• host factors.

No matter how toxic, no chemical can harm a person (child, adult, or both) unless exposure occurs. After a sufficient level of exposure (dose) to the chemical, biologic uptake, target organ contact, and biologic change can occur, all of which can lead to disease or other effects.

Steps that must occur for an environmental toxicant to cause disease.

• Environmental contamination (potential exposure): the exposure source and how the contaminant disperses in the environment.
• Exposure: For a toxicant to cause disease, exposure must occur. Exposure occurs through an exposure pathway between the contaminant in the physical environment and the exposed person.
• Biologic uptake: the process by which the transfer of substances from the environment to plants, animals, and humans occurs.
• Absorbed dose: how much of a toxicant is absorbed after an exposure occurs.
• Biologic changes: the chemical changes causing damage to tissues following a toxic exposure and an absorbed dose.
• Target organ: the organ or organs affected by an exposure to the toxicant. The “critical organ” is the most sensitive organ.
• Clinical disease: physical signs and symptoms resulting from a sufficiently absorbed toxicant dose.

Each of these steps will be defined further in the following text blocks.

Environmental contamination results from the release of a hazardous substance, whether manufactured or natural.

Environmental contaminants are found in

• air,
• water (both surface and groundwater),
• soil and sediments (soil found beneath bodies of water), and
• biota (game, domesticated animals, and crops).

For a toxicant to cause disease, exposure must occur. Exposure occurs through an exposure pathway between the contaminant in the physical environment and the exposed person.

An exposure pathway has five parts.

1. A source of contamination, such as an abandoned mine or industrial emissions.
2. An environmental medium and transport mechanism, such as water or movement through a groundwater aquifer.
3. A point of exposure, such as a private well.
4. A route of exposure, such as
   • eating,
   • drinking,
   • breathing,
   • touching,
   • transplacental exposure, and/or
   • intravenous exposure.
5. A receptor population, such as people potentially or actually exposed.

When all five parts are present, the exposure pathway is termed “a completed exposure pathway” [ATSDR 2005].

Biological uptake is the process by which the transfer of substances occurs from the environment to plants, animals, and humans.

When a completed exposure pathway exists, a toxicant dose is taken into the body. The amount of a toxicant absorbed into the body—not how much is present in the environment—determines disease risk.

Following the absorption of a poison or toxicant, biological changes in the body are the result of the toxicodynamics of the particular poison or toxicant. Toxicodynamics is the study of the cellular and molecular mechanisms of the action of a poison [University of Arizona Emergency Medicine Research Center 2003].

Whether biological changes occur in response to exposure depends on how much of a poison or toxicant dose a person has been exposed to and how much he or she has subsequently absorbed. The extent of such changes also depends on host factors, such as age and developmental stage.

Target organs are those that are sensitive to that specific poison or toxicant. Some poisons act by poisoning a specific step in cellular metabolism. Others attack specific organs: for example,

• lead attacks the nervous system,
• asbestos attacks the lungs, and
• cadmium attacks the kidneys.

Many factors determine whether a person exposed to a toxic substance develops a clinical disease. Among these are

• dose (amount x duration of exposure x frequency of exposure),
• age and developmental stage of the exposed person,
• preexisting health conditions, and
• genetic predisposition to the disease and other factors of increased susceptibility.

Special consideration must be given to toxic exposures during

• fetal life,
• infancy,
• childhood, and
• adolescence.

Considerations include increased exposures and increased vulnerabilities, such as critical periods of target organ development. These considerations are needed to assess children’s risk from a particular toxic exposure. For some toxicants, children may be less sensitive than are adults. But for most toxicants, the opposite is true.

Although clinical disease may result from a completed exposure pathway, the practitioner needs also to consider subclinical disease. For example, lead poisoning may result in loss of intelligence quotient (IQ) points in a young child. Although this adverse effect does not manifest as “clinical disease,” it might nonetheless become very important in that child’s life and health trajectory.

• The exposure-disease model posits that the harm caused by an environmental contaminant depends on its innate toxicity, the route of exposure, the exposure dose, and host factors.
• Children are often more susceptible to environmental toxicant exposures based on their increased exposure risk (resulting from factors such as diet and behavior) and increased vulnerabilities, including unique and sensitive periods of target-organ development.