Meta-Analysis of Dioxin Cancer Dose Response for Three Occupational Cohorts. (Research)

By Crump, Kenny S.; Canady, Richard et al. | Environmental Health Perspectives, May 2003 | Go to article overview

Meta-Analysis of Dioxin Cancer Dose Response for Three Occupational Cohorts. (Research)


Crump, Kenny S., Canady, Richard, Kogevinas, Manolis, Environmental Health Perspectives


This article presents a meta analysis of data from three cohorts occupationally exposed to TCDD and related compounds. A statistically significant (p = 0.02) trend was found in total cancer mortality with increasing dioxin exposure. The trend tests show an increase in total cancer at cumulative TEQ (unit of measurement for TCDD-like compounds that is defined as the amount of TCDD that would produce the same toxicity as a mixture of TCDD-like compounds) serum levels that would result from lifetime intake of 7 pg TEQ/kg body weight/day, with no increase at 6 pg/kg/day. A linear dose response provided a good fit to the combined data and predicted an E[D.sub.01] (dioxin exposure resulting in a 0.01 increase in lifetime risk of cancer mortality) of 45 pg/kg/day (95% confidence interval, 21-324). The U.S. Environmental Protection Agency estimates that current lifetime human exposures to dioxin average approximately 1 pg/kg/day (99% percentile: 3 pg/kg/day). Although it appears unlikely that current exposures through foods would reach either 7 pg/kg/day or the E[D.sub.01], our analysis argues for careful consideration of the upper ranges of long-term average exposures for dioxins. Key words: carcinogen, dioxin, dose-response assessment, meta-analysis, occupational cohorts. Environ Health Perspect 111:681-687 (2003). doi:10.1289/ehp.5831 available via http://dx.doi.org/ [Online 30 October 2002]

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In 2000 the U.S. Environmental Protection Agency (U.S. EPA) released a draft risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxin-like compounds that evaluated the current state of knowledge regarding exposures and health effects of these compounds (U.S. EPA 2000). Included in this assessment was an estimate derived from epidemiological data of the 1% effective dose, E[D.sub.01], defined as the lifetime average body burden of TCDD that would increase the lifetime risk of cancer (all kinds) mortality by 1%. Exposures to other dioxin-like compounds were accounted for by using toxicity equivalence factors (TEQ) to express the amount of all dioxin-like compounds in a mixture in TEQ units, defined as the amount of TCDD that would produce the same toxicity. The U.S. EPA risk assessment was criticized by Start (2001), who showed that the epidemiologic data used by the U.S. EPA was consistent with an elevated background cancer risk of about 32% relative to comparison populations and no dioxin effect.

The U.S. EPA E[D.sub.01] estimate was based on data from three occupational cohorts: 5,172 workers from 12 U.S. chemical plants studied by the National Institute for Occupational Safety and Health--the "NIOSH cohort" (Aylward et al. 1996; Fingerhut et al. 1991), 1,189 workers at a chemical plant in Hamburg, Germany--the "Hamburg cohort" (Flesch-Janys et al. 1998), and 243 workers exposed as a result of an uncontrolled release in 1953 of TCDD from an autoclave being used for trichlorophenol production at a BASF AG plant in Ludwigshafen, Germany--the "BASF cohort" (Ott and Zober 1996). The NIOSH cohort was by far the largest of the three, not only in terms of the number of workers exposed but also in terms of the number of cancers observed during follow-up.

Recently, an additional 6 years of follow-up was conducted for the NIOSH cohort (Steenland et al. 1999), and, more important, a new exposure assessment was developed that allowed an estimation of TCDD exposure for all members of the cohort (Steenland et al. 2001). This information was not available in time to be incorporated into the U.S. EPA (2000) assessment. We incorporated this new information from the NIOSH cohort, along with the information previously available for the Hamburg and BASF cohorts, into a risk assessment similar to that conducted by the U.S. EPA. We compared results of this risk assessment to those obtained by the U.S. EPA and by Starr (2001). We also compared our results to risk estimates based only on the NIOSH cohort (Steenland et al. …

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