ENVIRONMENTAL TOXICOLOGY OF POLYCHLORINATED DIBENZO-P-DIOXINS AND POLYCHLORINATED DIBENZOFURANS

Few environmental compounds have generated as much interest and contro versy within the scientific community and in the lay public as polychl orinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans ( PCDFs). Their ubiquitous presence in the environment and the risk of a ccidental exposure has raised concern over a possible threat of PCDDs or PCDFs to human health. The most extensively studied and potent isom er is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). Dioxin is a multisite toxicant in laboratory rodents resulting in a number of ti ssue-, species-, and sex-dependent responses. Much has been learned ab out the mechanism of dioxin's effects, especially for the induction of cytochrome P450 enzymes. Binding of PCDDs and PCDFs to a receptor pro tein, termed the dioxin or Ah receptor, is necessary for most biologic al and toxic responses. The most common toxic response used for evalua ting the human health risk posed by PCDDs and PCDFs is the hepatocarci nogenic response observed primarily in rodents. Despite extensive rese arch efforts, the effects of PCDDs and PCDFs on humans are not well ch aracterized. However, available data indicate there is good agreement between known effects of dioxin in laboratory animals and those descri bed in epidemiological studies for effects in humans. The sequence in events initiated by the Ah receptor interacting with dioxin-responsive genes and ending with altered patterns of differentiation and growth must be sought in order to understand tissue, species, sex. and interi ndividual variation in biological responses and the health risk posed by PCDDs and PCDFs.