Molecular underpinnings of developmental toxicity by the concept of “signal toxicity”

In “traditional toxicity,” a toxic substance reaches the target molecules, such as nucleic acids, proteins including enzymes, membranes, and other components in, on, or around the cell, and induces malfunction. In contrast, in “signal toxicity,” the chemical binds to a receptor and/or modulates the levels of its endogenous ligands. After that, the chemical itself is not important. The aberrant signal from the receptor initiates a cascade of molecular events that leads to various changes in the cells and organs. If the signal is abnormal for them in timing, kind, and amount, it may induce irreversible adverse effects if the organ is under development or maturation. This review summarizes the key characteristics of developmental toxicity referring to the concept of “signal toxicity.”