Interpreting 'dose-response' curves using homeodynamic data: with an improved explanation for hormesis

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.

Keywords: acquired tolerance; control mechanism; homeodynamic; hormesis; α-curve; β-curve.

FIGURE 1

A graphic interpretation of the α- and β-curves based on a homeodynamic responses to toxic inhibition. The α-curve is indicated by a and b, and the β-curve by c and d. The responses (R) are indicated by a and c and the effects (E) by b and d. The inhibitor (I) applies to all graphs. The adjustment in rate due to sustained exposure x results cumulatively in an increase in growth y (see text for further explanation).

FIGURE 2

Acquired resistance due to pre-exposure. a. the results of an experiment using hydroids, showing the effects of copper on growth rate. The colonies indicated by the dashed line were pre-exposure to copper (10μg. ℓ ⁻¹ for 3 weeks) and the control group had not (redrawn from Stebbing, 1981a); b. indicates how at a given level of inhibition, the capacity to resist the effect of copper is enhanced by pre-exposure; c. indicates how at a given concentration of copper, growth rate is increased as a result of pre-exposure.