Dose Response

 

The dose-response relationship is an essential concept in toxicology. It correlates exposures with changes in body functions or health.

In general, the higher the dose, the more severe the response. The dose-response relationship is based on observed data from experimental animal, human clinical, or cell studies.

Knowledge of the dose-response relationship establishes:

  • Causality — that the chemical has induced the observed effects.
  • The threshold effect — the lowest dose where an induced effect occurs.
  • The slope for the dose response — the rate at which injury builds up.

Within a population, the majority of responses to a toxicant are similar; however, there are differences in how responses may be encountered – some individuals are susceptible and others resistant. As demonstrated in Animation 1, a graph of the individual responses can be depicted as a bell-shaped standard distribution curve. There is a wide variance in responses as demonstrated by the mild reaction in resistant individuals, the typical response in the majority of individuals, and the severe reaction in sensitive individuals.

 

Animation 1. A graph of individual responses to a substance, which generally take the form of a bell-shaped curve (view full-text, PDF version)

 

The dose-response curve is a visual representation of the response rates of a population to a range of doses of a substance, as demonstrated in Animation 2.

 

Animation 2. The graph of a dose-response relationship typically has an "s" shape. (view full-text, PDF version)

 

threshold for toxic effects occurs at the point where the body's ability to detoxify a xenobiotic or repair toxic injury has been exceeded. Most organs have a reserve capacity such that loss of some organ function does not result in decreased performance. For example, development of cirrhosis in the liver may not result in a clinical effect until over 50% of the organ has been replaced by fibrous tissue.

 

Knowledge Check

The quantity of a substance administered to an individual over a period of time or in several individual doses is known as the:
Fractionation of a total dose so that the total amount administered is given over a period of time usually results in:
The usual dosage unit that incorporates the amount of material administered or absorbed in accordance with the size of the individual over a period of time is:
The dose at which a toxic effect is first encountered is called the:
The dose-response relationship helps a toxicologist determine: