Environmental toxicology of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans.
Few environmental compounds have generated as much interest and controversy within the scientific community and in the lay public as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Their ubiquitous presence in the environment and the risk of accidental exposure has raised concern over a possible threat of PCDDs or PCDFs to human health. The most extensively studied and potent isomer is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). Dioxin is a multisite toxicant in laboratory rodents resulting in a number of tissue-, species-, and sex-dependent responses. Much has been learned about the mechanism of dioxin's effects, especially for the induction of cytochrome P-450 enzymes. Binding of PCDDs and PCDFs to a receptor protein, termed the dioxin or Ah receptor, is necessary for most biological and toxic responses. The most common toxic response used for evaluating the human health risk posed by PCDDs and PCDFs is the hepatocarcinogenic response observed primarily in rodents. Despite extensive research efforts, the effects of PCDDs and PCDFs on humans are not well characterized. However, available data indicate there is good agreement between known effects of dioxin in laboratory animals and those described 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 interindividual variation in biological responses and the health risk posed by PCDDs and PCDFs.
Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
J P
JP
Vanden Heuvel
G
G
Lucier
D000818:Animals; D001572:Benzofurans / Q000009:adverse effects* / Q000633:toxicity; D000072338:Dibenzofurans, Polychlorinated; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004463:Ecology; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000633:toxicity; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000502:physiology; D015203:Reproducibility of Results
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug