The relationship between the IC50, toxic threshold, and the magnitude of stimulatory response in biphasic (hormetic) dose–responses

Hormesis is a dose–response relationship characterized by a biphasic (U- or inverted U-shaped) response. We present the results of a study designed to assess the relationship between toxic potency (as measured by the IC50) and the magnitude of the hormesis stimulation. To facilitate this, we describe a new parameter (ΔX), which we define as the difference between the concentration (or dose) that inhibits 50% of the growth of the organism under study (IC50), and the concentration (or dose) of the respective toxicological threshold (either the benchmark dose (BMD) or zero equivalent point (ZEP)). Our analysis includes a subset of data from a previously published report describing a National Cancer Institute study that exposed yeast to putative anticancer agents in a high throughput assay. The toxic threshold used in this paper was the BMD5. Thus, the ΔX in this paper is defined as: ΔX = IC50 − BMD5. We have found that the ΔX and the magnitude of stimulation above the control response are inversely related. These findings describe the first known relationship between toxic potency and the magnitude of hormetic response and warrant further inquiry.