title: Estimation of the cumulated exposure to polychlorinated dibenzo-p-dioxins/furans and standardized mortality ratio analysis of cancer mortality by dose in an occupationally exposed cohort.
abstract: For a cohort of 1189 male German former herbicide and insecticide workers with exposure to polychlorinated dibenzo-p-dioxins and -furans (PCDD/F), we report an extended standardized mortality ratio (SMR) analysis based on a new quantitative exposure index. This index characterizes the cumulative lifetime exposure by integrating the estimated concentration of PCDD/F at every point in time (area under the curve). Production department-specific dose rates were derived from blood levels and working histories of 275 workers by applying a first-order kinetic model. These dose rates were used to estimate exposure levels for all cohort members. Total mortality was elevated in the cohort; 413 deaths yielded an SMR of 1.15 (95% confidence interval [Cl] 1.05, 1.27) compared to the mortality of the population of Germany. Overall cancer mortality (n = 124) was significantly increased (SMR = 1.41, 95% Cl 1.17, 1.68). Various cancer sites showed significantly increased SMRs. The exposure index was used for an SMR analysis of total cancer mortality by dose. For 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) a significant trend (p = 0.01) for the SMRs with increasing cumulative PCDD/F exposure was observed. The SMR in the first exposure quartile (0-125.2 ng/kg x years) was 1.24 (95% Cl 0.82, 1.79), increasing to 1.73 (95% Cl 1.21, 2.40) in the last quartile (> or = 2503.0 ng/kg x years). For all congeners combined as toxic equivalencies (TEQ) using international toxic equivalency factors, a significant increase in cancer mortality was observed in the second quartile (360.9-1614.4 ng/kg x years, SMR 1.64; 95% Cl 1.13, 2.29) and the fourth quartile (> or = 5217.7 ng/kg x years TEQ, SMR 1.64, 95% Cl 1.13, 2.29). The trend test was not significant. The results justify the use of this cohort for a quantitative risk assessment for TCDD and to a lesser extent for TEQ.
authors.affiliation: Center for Chemical Workers' Health and Hamburg State Department of Work, Health, and Social Affairs, Germany. flesch@uke.uni-hamburg.de
authors.forename: D
authors.initials: D
authors.lastname: Flesch-Janys
authors.forename: K
authors.initials: K
authors.lastname: Steindorf
authors.forename: P
authors.initials: P
authors.lastname: Gurn
authors.forename: H
authors.initials: H
authors.lastname: Becher
mesh_terms: D000328:Adult; D000368:Aged; D001572:Benzofurans / Q000009:adverse effects* / Q000097:blood; D002617:Chemical Industry; D015331:Cohort Studies; D004147:Dioxins / Q000009:adverse effects* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000401:mortality*; D016273:Occupational Exposure; D018570:Risk Assessment
chemical_list: D001572:Benzofurans; D004147:Dioxins