Idiopathic environmental intolerance: Part 1: A causation analysis applying Bradford Hill's criteria to the toxicogenic theory

Toxicol Rev. 2003;22(4):235-46. doi: 10.2165/00139709-200322040-00005.


Idiopathic environmental intolerance (IEI) is a descriptor for a phenomenon that has many names including environmental illness, multiple chemical sensitivity and chemical intolerance. Toxicogenic and psychogenic theories have been proposed to explain IEI. This paper presents a causality analysis of the toxicogenic theory using Bradford Hill's nine criteria (strength, consistency, specificity, temporality, biological gradient, biological plausibility, coherence, experimental intervention and analogy) and an additional criteria (reversibility) and reviews critically the scientific literature on the topic. The results of this analysis indicate that the toxicogenic theory fails all of these criteria. There is no convincing evidence to support the fundamental postulate that IEI has a toxic aetiology; the hypothesised biological processes and mechanisms are implausible.

Publication types

  • Review

MeSH terms

  • Animals
  • Causality
  • Environmental Exposure / adverse effects*
  • Evidence-Based Medicine
  • Humans
  • Multiple Chemical Sensitivity* / epidemiology
  • Multiple Chemical Sensitivity* / etiology
  • Pharmacoepidemiology / methods*
  • Toxicology / methods*