DIOXINS

Dioxins are a class of halogenated aryl hydrocarbons, formed during chemical synthesis when chlorophenols are used in the starting material. The three most widely studied sources of dioxins are the manufacturing of the herbicide Agent Orange, the manufacturing of the microbicide hexachlorphene, and the chlorine bleaching of wood pulp. Other sources include combustion of wastes that contain chlorine residues in plastics, and combustion in engines where a chlorinated product has been used as a fuel additive.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the prototype for the toxicity of this chemical class, which also includes chlorinated dibenzofurans. TCDD is one of the most highly toxic chemicals tested in several laboratory animal species. The acute LD50 (the lethal dose that will kill 50 percent of test animals) in guinea pigs (the most susceptible species) is in the microgram per kilogram range; the toxicity in rodents varies by species and strain of animal. The reason for this variation is that TCDD operates through a specific protein called the aryl hydrocarbon receptor (AhR), and the level of this protein and its ancillary proteins varies across species. TCDD is teratogenic in mice and carcinogenic in rats and mice, and is classified as a probable human carcinogen based on animal data and epidemiological studies. The most common human finding observed in high level occupational and accidental exposures is chloracne, a skin disorder. Several epidemiology studies have been conducted in worker cohorts, and in veterans and residents of Vietnam, with inconsistent results. However, it is generally accepted that TCDD has the potential to be a human carcinogen and teratogen, and exposures should be reduced to an absolute minimum.

The controversy surrounding this class of compounds stems from five areas. First, TCDD is highly toxic having carcinogenic, teratogenic, immunotoxic, and endocrine modulation properties. Second, there are over 200 analogs and congeners of the dioxins and benzofurans, with varying qualitative and/or qualitative toxicity. Toxic Equivalent Factors (TEFs) have been developed based on the ability of the analogs and congeners to bind to the AhR and induce a family of enzymes in a manner similar to TCDD. Third, TCDD is very persistent in soil and in animal tissues (including humans). Half-life estimates range from months to several years. Dioxins also bioaccumulate in the food chain. Hence, the potential is there for the compounds to accumulate in human tissue. Fourth, the extent of toxicity in humans has not been well defined. Fifth, dioxins are produced as combustion products when chlorine is available in the burning process. This area is of particular importance because of the incineration of municipal waste that contains bottles made from chlorinated plastics.

A great deal of research has gone into the generation and control of dioxin emissions from incinerators. One confounding factor is that incinerators may not be the only point source for dioxins, and fewer chemical plants are using starting materials that will lead to major releases of dioxins as in the past. Wood pulp and paper bleaching in the United States and Canada has minimized or eliminated the use of chlorine bleaches, but the contamination that exists is very persistent. The search for other sources of dioxins continues.

Some polychlorinated biphenyls (PCBs), another class of chlorinated hydrocarbons, mimic the biological activity of dioxins.

Michael Gallo

(see also: Carcinogen; Carcinogenesis; Endocrine Disrupters; PCBs; Persistent Organic Pollutants [POPs]; Pollution; Toxicology )