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Original article
Plasma dioxin levels and cause-specific mortality in an occupational cohort of workers exposed to chlorophenoxy herbicides, chlorophenols and contaminants
  1. Daisy Boers1,
  2. Lützen Portengen1,
  3. Wayman E Turner2,
  4. H Bas Bueno-de-Mesquita3,
  5. Dick Heederik1,
  6. Roel Vermeulen1
  1. 1Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands
  2. 2Division of Environmental Health Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
  3. 3Centre for Nutrition and Health The National Institute for Public Health and Environmental Protection (RIVM), Bilthoven, The Netherlands Centre for Nutrition and Health
  1. Correspondence to Roel Vermeulen, Department of Environmental Epidemiology, Utrecht University, Institute for Risk Assessment Sciences, PO Box 80178, 3508 TD, Utrecht, The Netherlands; r.c.h.vermeulen{at}


Background We recently reported increased risks for all cancers and urinary cancers in workers exposed to chlorophenoxy herbicides using data from the Dutch herbicide cohort study. These risks could not be linked to the qualitative exposure proxies available. Here, we re-investigate exposure–response relationships using a (semi)quantitative measure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

Methods Plasma TCDD levels of 187 workers were used to develop a predictive model for TCDD exposure. Cox proportional hazards model was used to investigate associations between time-varying TCDD exposure and cause-specific mortality. Sensitivity analyses were performed to assess the impact of key assumptions in exposure assessment.

Results Predicted TCDD levels were associated with mortality from all causes (HR 1.08; 95% CI 1.03 to 1.13), ischaemic heart disease (IHD; HR 1.19; 95% CI 1.08 to 1.32) and non-Hodgkin's lymphoma (NHL; HR 1.36; 95% CI 1.06 to 1.74). No relationships were found between TCDD exposure and mortality from all cancers, respiratory or urinary cancers, which were previously linked to qualitative proxies of TCDD exposure in this cohort. Sensitivity analyses showed that results were relatively robust to slight changes in exposure estimation.

Conclusions Modelled TCDD exposure does not explain the previously reported increased risks for cancer mortality in this cohort except for a possible association with NHL. A small increase in ischaemic heart disease was observed, however we cannot exclude that this finding was due to residual confounding. Although risk estimates for some of the rarer outcomes were still rather imprecise, we do not expect more precise estimates from longer follow-up of this cohort due to the long time-span since last exposure to TCDD.

  • TCDD
  • modelling
  • cause-specific mortality
  • occupational exposure
  • chlorophenoxy herbicides
  • epidemiology
  • dioxins

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  • The Central Bureau of Statistics (CBS) Netherlands provided data on causes of death used in this investigation.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Utrecht Medical Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.