The elimination of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) was investigated in a group of n = 43 exposed workers with 2 blood measurements and n = 5 workers with 3 measurements. Under the assumption of a one-compartment, first-order kinetic model the median half-life for 2,3,7,8-TCDD was 7.2 yr, while for the other dioxins the estimates were between 3.7 yr for 1,2,3,4,6,7,8-HpCDD (hepta-chlorinated) and 15.7 yr for 1,2,3,7,8-PCDD (penta-chlorinated). For the furans median half-lives between 3.0 yr for 1,2,3,4,6,7,8-HpCDF and 19.6 yr for 2,3,4,7,8-PCDF were observed. There was no indication for a deviation from a first-order kinetic. Increasing age and percent body fat were associated with increasing half-life for most of the congeners. Smokers in general had a faster decay than non- and ex-smokers. In summary, the higher chlorinated PCDD/F like TCDD appear to be highly persistent in humans with half-lives ranging between 4 and 12 yr.

The relation between mortality (all cause; cancer; cardiovascular diseases (International Classification of Diseases, Ninth Revision (ICD-9), codes 390-459); ischemic heart diseases (ICD-9 codes 410-414)) and exposure to polychlorinated dibenzo-p-dioxins and -furans (PCDD/F) was investigated in a retrospective cohort study. The cohort consisted of 1,189 male workers in a chemical plant in Hamburg, Federal Republic of Germany, who had produced phenoxy herbicides, chlorophenols, and other herbicides and insecticides known to be contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin and other, higher chlorinated dioxins and furans. The authors reported previously on cancer mortality in this cohort for the follow-up period 1952-1989. The current study covers the years 1952-1992 and investigates the relation of PCDD/F exposure to mortality using a quantitative estimate of PCDD/F exposure for the whole cohort derived from blood and adipose tissue levels measured in a subgroup (n = 190). Quintiles and deciles of these estimates served as dose parameters in the estimation of relative risks (RRs), using year-of-birth stratified Cox regression. An unexposed cohort of gas workers served as an external reference group. The total mortality was elevated in all dose groups. The highest relative risk was observed for the highest 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decile (RR = 2.43, 95% confidence interval (CI) 1.80 to 3.29). Cancer mortality and mortality due to ischemic heart diseases showed a dose-dependent relation with TCDD and all PCDD/F combined. The highest relative risks for cancer (RR = 3.30, 95% CI 2.05 to 5.31) and ischemic heart diseases (RR = 2.48, 95% CI 1.32 to 4.66) were observed in the highest PCDD/F exposure group. The pattern of effects and tests for trend were similar when the lowest exposure group within the chemical worker cohort served as the reference, but the relative risks were smaller and the confidence intervals were larger. Potential confounding exposures complicate the interpretation of the internal comparison. These findings indicate a strong dose-dependent relation between mortality due to cancer or ischemic heart diseases and exposure to polychlorinated dioxins and furans.

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)

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.ImagesFigure 1

The elimination of beta-hexachlorocyclohexane (beta-HCH) in humans was investigated in a group of 40 former workers of a lindane-producing plant by analyzing at least 2 blood specimens (3 specimens in 3 workers) from different time points. Assuming a first-order kinetic model for excretion, the median half-life of beta-HCH is 7.2 yr calculated by concentrations in whole blood and 7.6 yr calculated by concentrations in extractable lipids. In univariate analyses an influence of age, percent body fat, and liver disease (additionally in whole blood an influence of contents of extractable lipids) on clearance was observed. All factors show a positive correlation with half-life. According to a multiple regression model, influence of percent body fat calculated according to Deurenberg et al. (1991) is an important covariate in the description of the variations of the clearance rate (calculated on the basis of extractable lipids) of beta-HCH. The data support the assumption of first-order kinetics.