Dose–response relationship

Food Toxicology 2(2+0)
Lesson 4 : General Principles of Toxicology

Dose–response relationship

No chemical agent is entirely safe and no chemical agent should be considered entirely harmful. The single most important factor determining the potential harmfulness or safeness of a compound is the relationship between the concentration of the chemical and the effect produced on the biological mechanism. A chemical can be permitted to come in contact with a biological mechanism without producing an effect on the mechanism, provided the concentration of the chemical agent is below a minimal effective level. Dose–response refers to the relationship between the exposure dose of a substance and the response of the organism ingesting the substance. A dose–response relationship is determined by experiments, usually done with laboratory animals, in which groups of individuals are dosed with the substance over a range of concentration. The animals are observed for symptoms for an endpoint, which must be measurable and quantifiable. The endpoint can be a physiological response, a biochemical change, or a behavior response. It is important to keep in mind that, when measuring the toxicity of a substance, the endpoint selected is relevant to organisms of the same species as well as among different species. Endpoints often selected for toxicity studies include, among others, the effective dose (ED) and the lethal dose (LD). ED endpoints are usually therapeutic efficacies, such as the dose to produce anesthesia or analgesia. For acute toxicity studies, a measure of LD 50 is often used.

The calculated LD 50 is the statistically estimated dose that when administered to a population will result in the death of 50% of the population. Some individuals within a population show an intense response whereas others show a minimal response to the same dose of the toxicant. For a lethal compound at a particular dose, some animals will succumb to the dose whereas others will not. Thus, it is difficult to predict beforehand what effect a compound under study will have on an individual within a population. Some animals respond at low doses whereas others do at high doses, with the majority responding at around the median dose.


Last modified: Monday, 26 March 2012, 1:41 PM