Evidence From Humans
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Mortality study of chemical workers exposed to dioxins: follow-up 23 years after chemical plant closure
Manuwald, U., Velasco Garrido, M., Berger, J., Manz, A., Baur, X. Occup Environ Med. 2012. 69:9, .
Topic area
Environmental pollutant - Dioxin TCDD
Study design
Retrospective cohort
Funding agency
German Federal Ministry of Labour and Social Affai
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analyses based on menopausal status
Number in Cohort
Cohort: 398
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
398 female employees of a chemical plant in Hamburg, Germany, who worked full-time for at least 3 months between 1952 and 1984, followed for vital status in community registries through 2007. A pathologist determined cause of death from death certificates.
Comment about participation selection
At the time of this study, 76% of the workers (men and women) with known vital status had worked for more than 1 year at the plant.
Exposure Investigated
Exposures investigated
Cumulative occupational exposures to TCDD based on complete work history at the plant. Exposure level in each workplace estimated based on prior analysis of TCDD measured in adipose tissue and blood in some workers.
How exposure was measured
Job history Estimates from previous biological sample
Exposure assessment comment
There is some concern about exposure misclassification because the SMR for all cancer was lower among men with biological measures of TCDD as compared to among men with estimated TCDD exposure. No such comparisons between biological and estimated body burdens were reported for women. It is not clearly stated, but it appears that all women in the cohort had estimated, rather than measured exposure.
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.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Strength of associations reported
Female breast cancer mortality compared to Hamburg population:
Overall: SMR 1.86 (95% CI 1.12-2.91)

Estimated TCDD (ppt):
Q1 (2 cases) SMR 0.84 (95% CI 0.09-3.03)
Q2 (6 cases) SMR 2.80 (95% CI 1.02-6.10)
Q3 (2 cases) SMR 0.70 (95% CI 0.08-2.52)
Q4 (9 cases) SMR 3.22 (95% CI 1.47-6.10)
Author address
Institute for Occupational and Maritime Medicine, Hamburg, Germany.
Reviewers Comments
Because the general population was chosen as the comparison population, these results may be underestimated due to the healthy worker effect. The authors note that associated toxic agents, such as beta-hexachlorocyclohexane, benzene, asbestos, and other by-products in the chemical manufacturing process may act as confounders in the study. Mortality is an insensitive measure of risk.
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