CHAPTER 2-62: DIOXINS

INTRODUCTION

Polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) are a group of highly toxic substances commonly known as dioxins. Dioxins are not produced commercially. They are formed during the production of certain organochlorines (eg, trichlorophenoxyacetic acid [2,4,5-T], hexachlorophene, pentachlorophenol); and by the combustion of these and other compounds, such as 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. There are 75 PCDD and 135 PCDF congeners. 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. Some dioxins are known animal carcinogens and are classified as human carcinogens by the EPA, the National Toxicology Program, and the IARC. TCDD is classified by IARC as a Group 1 human carcinogen. Human exposure leads to an overall increase in the rates of all cancers in exposed individuals.

TOXIC DOSE

Dioxins are extremely potent animal toxins. With the discovery of significant noncancer developmental abnormalities in environmentally exposed animals, the "no effect" level for exposure to dioxins is under reevaluation and is likely to be within an order of magnitude of current human dietary exposure. The oral 50% lethal dose (LD₅₀) in animals varies from 0.0006 to 0.045 mg/kg. Daily dermal exposure to 10–30 ppm in oil or 100–3,000 ppm in soil produces toxicity in animals. Chloracne is likely with daily dermal exposure exceeding 100 ppm. The greatest source of exposure for the general population is food, which is contaminated in minute quantities, usually measured in picograms (trillionths of a gram). Higher exposures have occurred through industrial accidents or intentional poisoning.

CLINICAL PRESENTATION

1. Acute symptoms after exposure include irritation of the skin, eyes, and mucous membranes and nausea, vomiting, and myalgias.

2. After a latency period that may be prolonged (up to several weeks or more), chloracne, porphyria cutanea tarda, hirsutism, or hyperpigmentation may occur. Elevated levels of hepatic transaminases and blood lipids may be found. Polyneuropathies with sensory impairment and lower extremity motor weakness have been reported. The Ukrainian president, Viktor Yushchenko, ...