An Overview of the Effects of Dioxins and Dioxin-Like Compounds on Vertebrates, as Documented in Human and Ecological Epidemiology

Abstract

Dioxins and dioxin-like compounds are primary examples of persistent organic pollutants that induce toxicity in both wildlife and humans. Over the past 200 years these compounds have been almost exclusively generated by human activity and have left a string of disasters in the wake of their accidental release. Most recently, the contamination of the Irish pork supply with dioxins resulted in an international recall of all Irish pork products. Epidemiologic data on human and ecological dioxin exposures have revealed a common pattern of biological response among vertebrate species, which is mediated through activation of the Aryl hydrocarbon Receptor (AhR). These AhR-mediated effects include profound consequences on the vertebrate individual exposed in early-life, with respect to myriad developmental endpoints including neurologic, immunologic, and reproductive parameters. Humans appear to be susceptible to these effects, in a manner similar to that of the laboratory and wildlife species which have demonstrated such outcomes. Furthermore, epidemiologic data suggest that there is little or no margin of exposure for humans, with respect to these developmental effects. Given these concerns, prudent public health policy should include the continued reduction of exposures.

Polychlorinated dibenzo-p-dioxins, furans, and biphenyls (PCDDs/PCDFs and PCBs) in breast milk and early childhood growth and IGF1

“…Epidemiological studies of possible effects of background levels of these chemicals are, however, scarce (White & Birnbaum 2009).…”

Ligand Promiscuity of Aryl Hydrocarbon Receptor Agonists and Antagonists Revealed by Site-Directed Mutagenesis

“…The prototypical and most studied AhR ligand is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant and known human carcinogen (3). However, numerous other halogenated aromatic hydrocarbons (HAHs), polycyclic aromatic hydrocarbons (PAHs), and PAH-like compounds have also been described that possess high affinity for the AhR and can activate AhR-dependent signal transduction and produce diverse biological/toxic effects in various species (1,4). The AhR-mediated toxic and biological effects are produced by metabolically stable dioxin-like HAH ligands, including TCDD, 2,3,7,8-tetrachlorodibenzofuran (TCDF), 3,3=, 4,4=,5-pentachlorobiphenyl (PCB126), and others.…”

Water exposure assessment of aryl hydrocarbon receptor agonists in Three Gorges Reservoir, China using SPMD-based virtual organisms

“…The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that responds to exogenous and endogenous chemicals with the induction or repression of expression of a large battery of genes and production of a diverse spectrum of biological and toxic effects in a wide range of species and tissues (Beischlag et al, 2008;Denison et al, 2011;White and Birnbaum, 2009). Most of the AhR ligands which have been characterized, such as some of the halogenated aromatic hydrocarbons (HAHs) and nonhalogenated polycyclic aromatic hydrocarbons (PAHs), are exogenous to the body.…”