title: Plasma dioxin levels and cause-specific mortality in an occupational cohort of workers exposed to chlorophenoxy herbicides, chlorophenols and contaminants.
abstract: 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.
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Daisy
authors.initials: D
authors.lastname: Boers
authors.forename: Lützen
authors.initials: L
authors.lastname: Portengen
authors.forename: Wayman E
authors.initials: WE
authors.lastname: Turner
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
mesh_terms: D002423:Cause of Death; D002617:Chemical Industry; D002733:Chlorophenols / Q000009:adverse effects*; D006540:Herbicides / Q000009:adverse effects*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced / Q000401:mortality*; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000401:mortality*; D009784:Occupational Diseases / Q000139:chemically induced / Q000401:mortality*; D016273:Occupational Exposure / Q000009:adverse effects*; D009790:Occupations; D000072317:Polychlorinated Dibenzodioxins / Q000097:blood*; D016016:Proportional Hazards Models
chemical_list: D002733:Chlorophenols; D006540:Herbicides; D000072317:Polychlorinated Dibenzodioxins