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

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 [CI] 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% CI 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% CI 0.82, 1.79), increasing to 1.73 (95% CI 1.21, 2.40) in the last quartile (greater than or equal to 2503.0 ng/kg x years). For ail 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% CI 1.13, 2.29) and the fourth quartile (greater than or equal to 5217.7 ng/kg x years TEQ, SMR 1.64, 95% CI 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.