What is the Origin of Nonmonotonic Dose-Response?

The recognition of NMDR relationships emerged primarily from the study of endocrine-disrupting chemicals (EDCs) and their effects on hormone systems. Traditional toxicology assumed a monotonic response, but the discovery that EDCs could exert potent effects at very low, environmentally relevant doses challenged this long-held paradigm. The term highlights the complex, non-linear dynamics inherent in receptor-mediated endocrine signaling.

What is the Mechanism of Nonmonotonic Dose-Response?

The mechanism is typically explained by the presence of multiple receptor types or distinct signaling pathways that exhibit varying binding affinities for the substance. For instance, a low concentration of a hormone may selectively activate a high-affinity receptor, initiating a specific response. Conversely, a higher concentration might saturate that receptor while also activating a lower-affinity receptor or an opposing pathway, thereby diminishing or reversing the initial effect and creating the characteristic nonmonotonic curve.

Nonmonotonic Dose-Response

Meaning

A Nonmonotonic Dose-Response (NMDR) relationship is a pharmacological or toxicological phenomenon where the magnitude of a biological effect does not increase or decrease consistently with an increasing dose of a substance. This response often presents as a U-shaped or inverted U-shaped curve, indicating that low doses can sometimes elicit a greater or different effect than much higher doses. This pattern is particularly relevant in endocrinology due to the high-affinity, complex nature of hormonal signaling at low concentrations.