Dioxins
Polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) are a group of highly toxic substances commonly known as dioxins. Dioxins are not produced commercially. PCDDs are formed during the production of certain organochlorines (eg, trichlorophenoxyacetic acid [2,4,5-T], hexachlorophene, pentachlorophenol); PCDDs and PCDFs are formed by the combustion of these and other compounds, such as polychlorinated biphenyls (PCBs [See Polychlorinated Biphenyls (PCBs)]), as well as the incineration of medical and municipal waste. Agent Orange, an herbicide used by the United States during the Vietnam War, contained dioxins (most importantly, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], the most toxic and extensively researched dioxin) as contaminants. Some PCBs have biological activity similar to that of dioxins and are identified as “dioxin-like.” The most common route of exposure to dioxins in the United States is through dietary consumption.
Mechanism of toxicity. Dioxins are highly lipid-soluble and are concentrated in fat, and they bioaccumulate in the food chain. Dioxins are known to bind to the aryl hydrocarbon receptor protein (AhR) in cytoplasm, form a heterodimer with nuclear proteins, and induce transcription of multiple genes. AhR activation by dioxins causes disruption of biochemical pathways involved in development and homeostasis. As a result, the timing of exposure as well as dose determines toxicity. Dioxins also have endocrine disruptor effects, and exposure may result in reproductive and developmental defects, immunotoxicity, and liver damage. Dioxins are known animal carcinogens and are classified as human carcinogens by the EPA, the National Toxicology Program, and the IARC. Human exposure leads to an overall increase in the rates of all cancers in exposed individuals.
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