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

Environ Health Perspect. 1998 Apr;106 Suppl 2(Suppl 2):655-62. doi: 10.1289/ehp.98106655.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzofurans / adverse effects*
  • Benzofurans / blood
  • Chemical Industry
  • Cohort Studies
  • Dioxins / adverse effects*
  • Dioxins / blood
  • Dose-Response Relationship, Drug
  • Germany / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / etiology
  • Neoplasms / mortality*
  • Occupational Exposure*
  • Risk Assessment

Substances

  • Benzofurans
  • Dioxins