An IARC evaluation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans as risk factors in human carcinogenesis

The International Agency for Research on Cancer (IARC) Monographs program reevaluated polychlorinated dibenzo-p-dioxins and evaluated polychlorinated dibenzofurans as possible carcinogenic hazards to humans in February 1997, using the most recent epidemiologic data on exposed human populations, experimental carcinogenicity bioassays in laboratory animals, and supporting evidence on relevant mechanisms of carcinogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was evaluated as carcinogenic to humans (IARC group 1 classification) on the basis of limited evidence of carcinogenicity to humans derived from follow-up of workers who had been heavily exposed in industrial accidents and sufficient evidence of carcinogenicity in experimental animals. The evaluation also considered the following supporting evidence: TCDD is a multisite carcinogen in experimental animals and has been shown by several lines of evidence to act through a mechanism involving the aryl hydrocarbon receptor; this receptor is highly conserved in an evolutionary sense and functions the same way in humans as in experimental animals; tissue concentrations of TCDD are similar in heavily exposed human populations in which an increased overall cancer risk was observed and in exposed rats that developed tumors in carcinogenicity tests. Other polychlorinated dibenzo-p-dioxins, the nonchlorinated dibenzo-p-dioxin, and polychlorinated dibenzofurans were evaluated as not classifiable as to their carcinogenicity to humans (group 3).