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III.
CARCINOGENIC EFFECTS
Human Studies
Comprehensive reviews of the human studies of dioxin exposure and cancer risk available at the time
the document entitled Health Effects of Chlorinated Dioxins and Dibenzofurans was written for the
Toxic Air Contaminant (TAC) program (CDHS, 1986) are found in US EPA (1984) and Veterans
Administration (VA) (1981, 1984).
Dioxins have never been intentional products. In human exposure studies, PCDDs (polychlorinated
dibenzo-p-dioxins) and PCDFs (polychlorinated dibenzofurans) have only been present as contaminants
of other toxic chemicals, such as herbicides. Hence all studies of human PCDD/PCDF exposures have
been studies of exposure to chemical mixtures that may have contained PCDD and PCDF.
VA (1981, 1984) summarized what is known about the presence of PCDD and PCDF in
commercially-used chemicals. In general, PCDDs and PCDFs may be present as contaminants in the
herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5T). Levels of 2,3,7,8-TCDD in 2,4,5-T have been
found as high as six parts per million (Rappe et al. 1982). Another widely used herbicide, 2,4--
dichlorophenoxyacetic acid (2,4-D) is generally regarded as uncontaminated with 2,3,7,8-
Tetrachlorodibenzo-p-dioxin (TCDD). Cochrane et al. (1982) did detect traces of di-, tri-, and
TetraCDD as high as one part per billion in technical grade 2,4-D from Canada. However, the
TetraCDD isomer found in these samples was the 1,3,6,8-TCDD isomer, not the more toxic
2,3,7,8-TCDD.
Agent Orange, which was a mixture of 2,4,5-T and 2,4-D, has been shown to contain 2,3,7,8-TCDD
concentrations as high as 15-47 parts per million with an average of about 2 ppm (VA 1981). PCDDs
and/or PCDFs have also been found in the parts per million range in commercially used polychlorinated
biphenyls (PCB), trichlorophenol (TCP), tetrachlorophenol, and pentachlorophenol (PCP) (Rappe et
al. 1982, Hardell 1983).
Several case/control studies have been conducted in Sweden and in New Zealand. In these countries,
phenoxyacetic acids and chlorophenols were used extensively for agriculture and forestry. After clinical
observations of several patients with soft-tissue sarcomas (STS) and a history of heavy exposure to
phenoxyacetic acids, Hardell and Sandstrom (1979) conducted a case/control study of STS and
herbicide exposure. Cases were drawn from a university hospital in Northern Sweden, and consisted of
52 adult males with STS diagnosed between 1970 and 1977. Controls were drawn from general
population registries, at a 4:1.matching ratio, and matched to cases on sex, age, place of residence, and
vital status (whether alive or deceased). The investigators considered only non-malignant deaths for
deceased controls. Study subjects (or their next of kin) provided exposure histories by a mailed
questionnaire with a telephone follow-up. The odds ratio (OR) for exposure to phenoxyacetic acids
only (excluding subjects exposed to chlorophenols) was 5.3 (95% confidence interval (95% CI)
2.4-11.5). For exposure to chlorophenols only (excluding those exposed to phenoxyacetic acids) the
OR was 6.6 (95% CI 2.1-20.9).
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