An IARC Evaluation of Polychlorinated Dibenzo-p-Dioxins and Polychlorinated Dibenzofurans as Risk Factors in Human Carcinogenesis

Abstract

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).

Significant issues raised by meta-analyses of cancer mortality and dioxin exposure.

“…The evidence from these three occupational cohorts thus indicates nothing at all about the human carcinogenicity of non-TCDD congeners, and this evaluation is entirely consistent with the International Agency for Research on Cancer's 1997 assessment of the evidence regarding these substances (McGregor et al 1998):…”

“…We also conclude that Crump et al's extrapolation (Crump et al 2003) from Steenland et al's TCDD analyses (Steenland et al 1999(Steenland et al , 2001) to one based on TEQ is unjustified and overreaching because neither the epidemiologic data nor their meta-analysis of it support the inference that TEQ exposures close to background are likely to be carcinogenic to humans (Flesch-Janys et al 1998;McGregor et al 1998). Their extrapolation from TCDD to TEQ is especially troubling because it raises unnecessary concerns about the safety of our food supply.…”

Toxicogenomic investigation of Tetrahymena thermophila exposed to dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

“…DDT has been found to be estrogenic [1], TBT is believed to cause androgenic effects [5], and TCDD affects a wide range of complicated biological processes and is thought to be nongenotoxic [44]. Accordingly, microarray analysis of exposure of Tetrahymena to the toxicants suggested that the functions of the differentially expressed genes varied among toxicant-treated sets.…”

Sawmill Chemicals and Carcinogenesis

“…They have been long known as being carcinogenic to laboratory animals, causing a wide range of tumors (66)(67)(68)(69), and are now confirmed as being carcinogenic to humans (7,(67)(68)(69)(70)(71)(72). TCDD causes cancer in multiple species, multiple strains, both sexes, and in multiple organs and tissues (66)(67)(68)(69). TCDD causes cancer by multiple routes, various durations of exposure, and ranges of exposure concentrations (66).…”