Dose–response relationship
The dose–response relationship, or exposure–response relationship, describes the change in effect on an organism caused by differing levels of exposure (or doses) to a stressor (usually a chemical) after a certain exposure time, or to a food. This may apply to individuals (e.g.: a small amount has no significant effect, a large amount is fatal), or to populations (e.g.: how many people or organisms are affected at different levels of exposure).
Although dose and exposure are often interchangeably used, in the area of clinical pharmacology (the study of drugs), the two names are separated. The former means dosage or amount of dose administered to a person, whereas the latter means the time-dependent concentration (often in the circulatory blood or plasma) or concentration-derived parameters such as AUC (area under the concentration curve) and Cmax (peak level of the concentration curve) of the drug after its administration.
Studying dose response, and developing dose–response models, is central to determining "safe", "hazardous" and (where relevant) beneficial levels and dosages for drugs, pollutants, foods, and other substances to which humans or other organisms are exposed. These conclusions are often the basis for public policy.
The U.S. Environmental Protection Agency has developed extensive guidance and reports on dose-response modeling and assessment, as well as software. More relevant, the U.S. Food and Drug Adminstration has guidance to elucidate dose-response relationships during the drug development process.
Dose–response relationships generally depend on the exposure time and exposure route (e.g., inhalation, dietary intake); quantifying the response after a different exposure time or for a different route leads to a different relationship and possibly different conclusions on the effects of the stressor under consideration. This limitation is caused by the complexity of biological systems and the often unknown biological processes operating between the external exposure and the adverse cellular or tissue response.
A dose–response curve is a simple X–Y graph relating the magnitude of a stressor (e.g. concentration of a pollutant, amount of a drug, temperature, intensity of radiation) to the response of the receptor (e.g. organism under study). The response may be a physiological or biochemical response, or even death (mortality), and thus can be counts (or proportion, e.g., mortality rate), ordered descriptive categories (e.g., severity of a lesion), or continuous measurements (e.g., blood pressure). A number of effects (or endpoints) can be studied, often at different organizational levels (e.g., population, whole animal, tissue, cell).
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