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.

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.

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.

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 aminotransferases and blood lipids may be found. Polyneuropathies with sensory impairment and lower extremity motor weakness have been reported. The Ukrainian president, Viktor Yushchenko, was poisoned with TCDD in 2004 and exhibited many of the classic signs and symptoms, including chloracne.
3. Death in laboratory animals occurs a few weeks after a lethal dose and is caused by a “wasting syndrome” characterized by reduced food intake and loss of body weight. Death from acute toxicity in humans is rare, even in cases of intentional poisoning.

Is difficult and rests mainly on a history of exposure; the presence of chloracne (which is considered pathognomonic for exposure to dioxins and related compounds) provides strong supporting evidence. Although many products previously contaminated with dioxins are no longer produced in the United States, exposures to PCDDs and PCDFs occur during many types of chemical fires, and the possibility of exposure can cause considerable public and individual anxiety. Dioxins are classified by the WHO as among the most environmentally persistent of all organic pollutants.

1. Specific levels. It is difficult and expensive to detect dioxins in human blood or tissue, and there is no established correlation with symptoms. There are many congeners of PCDDs, PCDFs, and PCBs; the individual contribution of each one to toxicity is assessed by using toxic equivalence factors (TEFs) established by the World Health Organization, based on relative potency estimates for each congener (TCDD by definition has a TEF of 1). Testing is not clinically indicated unless there has been a massive exposure. The WHO is a source of information regarding certified laboratories outside the United States; testing in the United States is performed by the CDC/NCEH (National Center for Environmental Health). As a result of more stringent controls over environmental exposures, the human body burden of dioxins has decreased over the last 30 years. Unexposed persons have a mean of 5.38 pg of 2,3,7,8-TCDD per gram of serum lipid, compared with workers producing trichlorophenols, who had a mean of 220 pg/g. The highest recorded level is 144,000 pg/g of blood fat in a patient with few adverse health effects other than chloracne.
2. Other useful laboratory studies include glucose, electrolytes, BUN, creatinine, liver aminotransferases, CBC, and urinary uroporphyrins (if porphyria is suspected).

1. Emergency and supportive measures. Treat skin, eye, and respiratory irritation symptomatically.
2. Specific drugs and antidotes. There is no specific antidote.
3. Decontamination
   1. Inhalation. Remove victims from exposure and give supplemental oxygen if available.
   2. Eyes and skin. Remove contaminated clothing and wash affected skin with copious soap and water; irrigate exposed eyes with copious tepid water or saline. Personnel involved in decontamination should wear protective gear appropriate to the suspected level of contamination.
   3. Ingestion. Administer activated charcoal if conditions are appropriate (see Table I-37). Gastric emptying is not necessary if activated charcoal can be given promptly.
4. Enhanced elimination. Since dioxins are lipid soluble, lactation significantly enhances elimination. Elimination of dioxins may be enhanced through administration of olestra, a nonabsorbable fat substitute that increases fecal excretion. Low-density lipoprotein (LPL)-apheresis has also been used to lower body burden of dioxins, but entails risk. Unfortunately, clinical studies of methods to enhance elimination have been extremely limited and are not conclusive; however, olestra administration has lowered the half-life of TCDD from 5-10 years to 1-2 years.