Environmental toxicology of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans.

Abstract

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.

Carcinogenicity of TCDD: Experimental, Mechanistic, and Epidemiologic Evidence

“…P-450-dependent enzyme activities, mRNA, or protein. Vanden Heuvel et al (147,148) showed that TCDD-mediated increases in CYP1A1 mRNA were detectable following a single dose of 0.1 ng/kg, which produces a concentration of TCDD in the liver equivalent to a chronic dose of 2-5 pg/kg per day.…”

Photodegradation of Polychlorinated Dibenzo-p-dioxins in Liquid Samples by Near UV Light Irradiation

“…(1). The 75 PCDD homologs show different toxicities depending on the degree of chlorination and on the position of the chlorine atoms in the dibenzo ring, the most toxic ones being the tetrachlorosubstituted (2,3). They are chemically stable and able to bioaccumulate in organisms and are thus extremely significant for the environment (4)(5)(6).…”

Chemicals and Cancer in Humans: First Evidence in Experimental Animals

“…Obviously, if humans are not exposed to a chemical carcinogen, then the expectation that that chemical will be a carcinogenic hazard to humans must be recognized as not being readily possible. Yet, even this apparent comfort might be short-lived because other laboratory chemical curiosities or industrial intermediates have had or do exhibit widespread human exposure: examples are vinyl chloride (27)(28)(29)(30), methyl isocyanate (31), tetrachlorodibenzo-p-dioxin (32,33), and 1,3-butadiene (34,35). Further, the concept of "safe" exposure levels to carcinogens accepts the erroneous concept of threshold (36).…”