Attenuation of exposure-response curves in occupational cohort studies at high exposure levels

Leslie Stayner, Kyle Steenland, Mustafa Dosemeci, Irva Hertz-Picciotto

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


Numerous occupational cohort mortality studies have observed exposure-response curves to have an increasing slope at low exposure levels that attenuates or even turns negative at high exposure levels. Examples discussed in this paper include dioxin, silica, 1,3-butadiene, cadmium, beryllium, radon daughters, diesel fumes, nickel, arsenic, and hexavalent chromium. Possible explanations for this phenomenon include (i) bias introduced by the healthy worker survivor effect, (ii) a depletion of the number of susceptible people in the population at high exposure levels, (iii) a natural limit on the relative risk for diseases with a high background rate, (iv) mismeasurement or misclassification of exposures, (v) the influence of other risk factors that vary by the level of the main exposure, and (vi) the saturation of key enzyme systems or other processes involved in the development of disease.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalScandinavian Journal of Work, Environment and Health
Issue number4
StatePublished - Aug 2003


  • Epidemiology
  • Flat dose-response

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Toxicology
  • Geography, Planning and Development
  • Health, Toxicology and Mutagenesis


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