Dibenzo‐ p ‐Dioxins: 2,3,7,8‐Tetrachlorodibenzo‐ p ‐Dioxin and Other Polychlorinated Dioxin‐Like Chemicals

Abstract

Abstract 2,3,7,8‐Tetrachlordibenzo‐ p ‐dioxin (TCDD) is often called the most potent toxic man‐made chemical. TCDD is the most toxic member of the polychlorinated dibenzo‐ p ‐dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar PCBs or “dioxin‐like” chemicals (DLCs). These chemicals have similar structures and toxicological effects. TCDD is considered the prototype of the DLCs due to its toxic potency, persistence in the environment and biological systems and because it is the most studied of the DLCs. While polychlorinated dibenzo‐ p ‐dioxins are a class of compounds with 75 possible congeners, as shown in the following structure, only those chlorinated in all the lateral positions are considered dioxins or DLCs. The lateral chlorines result in planar compounds and impart metabolic stability, biological potency, and environmental persistence. TCDD and other DLCs induce a broad range of biochemical and toxic responses. These effects are elicited through their binding and activating the Ah‐receptor (AhR), which is an intracellular protein that acts as a ligand‐activated transcription factor. The binding and activation of the AhR by DLCs initiate a cascade of biochemical, cellular, tissue, and organ‐level effects leading to developmental toxicity, immunotoxicity, reproductive toxicity, and carcinogenicity, among others.