ners feasible, but challenges remain in the risk-assessment process because of the differing toxicity of individual PCBs.

Most in vivo animal studies and in vitro bioassays use commercially available, technical-grade mixtures of PCBs or individual congeners. PCBs present in the environment differ from commercially available mixtures, because different congeners are metabolized and biodegraded at different rates. Few studies have investigated the effects of environmentally altered mixtures of PCBs. The studies that have investigated those effects include field and controlled laboratory feeding experiments, but the co-occurrence of other toxicants, such as DDT, Toxaphene, and dieldrin, complicate their interpretation.

Commercial PCB mixtures elicit a broad spectrum of toxic responses that depend on several factors, including chlorine content, purity, dose, species, strain, age, and sex of animal, and route and duration of exposure. Immunotoxicity, carcinogenicity, neurotoxicity, and developmental toxicity, as well as the biochemical effects of commercial PCB mixtures, have been extensively investigated in various laboratory animals, fish, and wildlife species. The mechanisms and endpoints of PCB toxicity have been reviewed (Poland and Knutson 1982; Safe 1984; Barrett 1995; Silberhorn et al. 1990). Two main categories of PCBs have been designated based on mechanism of action: those that act through the arylhydrocarbon receptor (AhR) and those that do not.

AhR-Mediated Effects

The non- and mono-ortho-substituted PCBs are of particular concern, because these congeners can assume a planar or nearly planar conformation similar to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Safe 1990; Giesy et al. 1994a; Metcalfe and Haffner 1995) and have toxic effects qualitatively similar to TCDD. These compounds act by the same mechanism as TCDD, that is, by binding to and activating the AhR, a cytosolic, ligand-activated transcription factor (Poland and Knutson 1982; Gasiewicz 1997; Blankenship et al. 2000). Each polychlorinated dibenzo hydrocarbon (PCDH) binds with different affinity to the AhR and, therefore, has different potency for biological effects (Safe 1990; Ahlborg et al. 1994; van den Berg et al. 1998).

A great deal of work has been conducted on the toxicity of dioxin, and there is a large amount of data on dioxin-like effects. The data come from experimental and epidemiological studies. Epidemiological studies have been conducted in individuals exposed to dioxin occupationally, in the chemical and the agricultural industries, individuals exposed environmentally (e.g.,



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