Evidence From Humans
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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
Flesch-Janys, D., Steindorf, K., Gurn, P., Becher, H. Environ Health Perspect. 1998. 106 Suppl 2, 655-62.
Topic area
Environmental pollutant - Dioxin
Study design
Occupational cohort
Study Participants
Number of Cases
No breast cancer deaths
Number in Cohort
Cohort: 1,189 males
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Females excluded. Cohort of pesticide workers in Hamburg, Germany: high compared to low workers within the cohort and cohort compared with population of Germany.
Exposure Investigated
Exposures investigated
Cumulative exposure based on integrated estimate for every time (area under the curve), combining blood levels with job history.
How exposure was measured
Job history Biological Other: Environmental model
Exposure assessment comment
Combination of biomarker and back estimation of exposure for multiple jobs provides a sophisticated estimate of cumulative exposure. Peak exposure may still be an important variable.
Statistical Analysis
Breast cancer outcome investigated
Mortality from breast cancer: male
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Gender, age, calendar year. Breast cancer risk factors not adequately controlled.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Description of major analysis
Standardized mortality ratio by quartile.
Strength of associations reported
No breast cancer deaths were expected and none occurred.
Results Comments
Elevated female breast cancer risk was observed in an earlier report from this cohort; but females are excluded from this later analysis.
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.
Author address
Center for Chemical Workers' Health and Hamburg State Department of Work, Health, and Social Affairs, Germany. flesch@uke.uni-hamburg.de
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