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High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
Published on: May 10, 2016
Interpreting 'dose-response' curves using homeodynamic data: with an improved explanation for hormesis
1Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth, Devon, UK. ardst@yahoo.co.uk
Abstract:
A re-interpretation of the 'dose-response' curve is given that accommodates homeostasis. The outcome, or overall effect, of toxicity is the consequence of toxicity that is moderated by homeodynamic responses. Equilibrium is achieved by a balance of opposing forces of toxic inhibition countered by a stimulatory response. A graphical model is given consisting of two linked curves (response vs concentration and effect vs concentration), which provide the basis for a re-interpretation of the 'dose-response' curve. The model indicates that such relationships are non-linear with a threshold, which is due to homeodynamic responses. Subthreshold concentrations in 'dose-response' curves provide the sum of toxic inhibition minus the homeodynamic response; the response itself is unseen in serving its purpose of neutralizing perturbation. This interpretation suggests why the alpha- and beta-curves are non-linear. The beta-curve indicates adaptive overcorrection to toxicity that confers greater resistance to subsequent toxic exposure, with hormesis as an epiphenomenon.
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