In this chapter, the committee reviews the epidemiological, bioassay, and mode of action evidence and then presents conclusions regarding both qualitative and quantitative measures of carcinogenicity of TCDD, other dioxins, and DLCs.

Epidemiological Evidence

The epidemiological evidence that provided the basis for EPA’s assessment consists primarily of studies following four cohorts. Of these, the Reassessment reviewed in detail those related to the three cohorts that provided quantitative dose-response estimates linking serum dioxin to cancer mortality (Ott and Zober 1996; Becher et al. 1998; Steenland et al. 2001). The cohorts were quite variable in size and exposure ranges. Ott and Zober (1996) studied a relatively small number of men exposed to an accidental release of dioxin in 1953 (N = 243, 13 cancer deaths). Becher et al. (1998) examined a cohort of 1,189 men employed in pesticide and herbicide production, from which 124 cancer deaths were identified. The third cohort represents a large occupational population originally studied by Fingerhut et al. (1990, 1991), who examined 5,172 male employees in 12 manufacturing facilities. An update on this cohort was provided by Steenland et al. (1999), who applied “job-exposure matrix”2 estimates to 5,132 workers in the original cohort who were followed for 6 more years. The total number of cancer deaths in this cohort was 377. In 2001, Steenland et al. updated this study again on a subcohort of 3,538 workers (with 256 cancer deaths) and used data from 170 members of this cohort for which estimated external exposures and known serum dioxin levels were available to establish a quantitative dose-response assessment.

Each study identified a cohort of workers who had been employed in industrial settings in which dioxin was a by-product. These settings included pesticide production (Ott and Zober 1996; Becher et al. 1998) or chemical plants more broadly (Steenland et al. 2001). In each instance, current serum dioxin measurements were available for a subset of workers. Development of exposure estimates for the entire cohort required two extrapolations: from current serum dioxin measurements to historical exposure levels using estimates of serum dioxin half-life, and from workers with current serum dioxin measurements to those without by linking available serum dioxin measurements to job characteristics based on knowledge of the industrial processes. Although these extrapolations decrease the accu-

2

A “job-exposure matrix” refers to an algorithm by which experience in particular jobs are assigned estimated exposure levels. Each job (a row of the matrix) has a corresponding series of exposure levels assigned (columns).



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