Toxicological Reviews

, Volume 22, Issue 4, pp 247–261

Idiopathic Environmental Intolerance

Part 2: A Causation Analysis Applying Bradford Hill’s Criteria to the Psychogenic Theory


    • Behavioral MedicineMulti-Disciplinary Toxicology, Treatment and Research Center
  • Karen E. Binkley
    • Division of Clinical Immunology and AllergyUniversity of Toronto
  • Arthur Leznoff
    • Division of Clinical Immunology and AllergyUniversity of Toronto
  • Scott Phillips
    • Toxicology AssociatesMulti-Disciplinary Toxicology, Treatment and Research Center
Review Article

DOI: 10.2165/00139709-200322040-00006

Cite this article as:
Staudenmayer, H., Binkley, K.E., Leznoff, A. et al. Toxicol Rev (2003) 22: 247. doi:10.2165/00139709-200322040-00006


Toxicogenic and psychogenic theories have been proposed to explain idiopathic environmental intolerance (IEI). Part 2 of this article is an evidence-based causality analysis of the psychogenic theory using an extended version of Bradford Hill’s criteria. The psychogenic theory meets all of the criteria directly or indirectly and is characterised by a progressive research programme including double-blind, placebo-controlled provocation challenge studies. We conclude that IEI is a belief characterised by an overvalued idea of toxic attribution of symptoms and disability, fulfilling criteria for a somatoform disorder and a functional somatic syndrome. A neurobiological diathesis similar to anxiety, specifically panic disorder, is a neurobiologically plausible mechanism to explain triggered reactions to ambient doses of environmental agents, real or perceived. In addition, there is a cognitively mediated fear response mechanism characterised by vigilance for perceived exposures and bodily sensations that are subsequently amplified in the process of learned sensitivity. Implications for the assessment and treatment of patients are presented.

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© Adis Data Information BV 2003