The September edition of Critical Reviews in Food Science and Nutrition ed Fergus Clydesdale( vol 49 issue 8 ) is devoted to Key events Dose Response Framework.
This is a systematic review of key events which occur between the initial dose of a biologically active substance and the effect.
The substance will be
1. ingested, absorbed ( which is liable to be modified by events in the intestine and stomach.)
2. transported or processed by metabolism
3. a interaction or process in the target tissue
4. ultimate effect of interest.
The evaluation of the benefits and risks of a chemical depend upon a knowledge of the dose response in the recipient. A threshold dosage for the biological effect may be defined.
However each human is individual and the biology and genetic make up will differ so it is important to be careful in being too specific about a response. The number of individuals studied, he sensitivity of the methods used to test the chemical’s effect and the frequency and length of the study measurements are important.
The concept of Mode of Action (MOA) is discussed. . A mode of action is a biologically plausible sequence of key events, starting with the interaction of an agent with a cell leading to a observable biological effect. A key event is an observable precursor step that is a necessary part of the mode of action.
The authors believe it is important to define these key events for any biological process.
Finally the review applies these principles to nutrition specifically vitamin A.
Julien et al 2009 The key events dose-response framework: a cross-disciplinary mode- of action base approach to examining dose-response and thresholds. Critical Reviews in Food Science and Nutrition ed Fergus Clydesdale vol 49 pp 682-689
Boobis et al 2009 Application of key events analysis to chemical carcinogens and non-carcinogns. Critical Reviews in Food Science and Nutrition ed Fergus Clydesdale vol 49 pp 690-707
Ross et al 2009 Applcation of a key events dose response analysis to nutrients: a case study with vitamin A ( retinol ) Critical Reviews in Food Science and Nutrition ed Fergus Clydesdale vol 49 pp 708-715

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