Empirical approaches for the investigation of toxicant-induced loss of tolerance

Claudia Miller, Nicholas Ashford, Richard Doty, Mary Lamielle, David Otto, Alice Rahill, Lance Wallace

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


It has been hypothesized that sensitivity to low-level chemical exposures develops in two steps: initiation by an acute or chronic chemical exposure, followed by triggering of symptoms by low levels of previously tolerated chemical inhalants, foods, or drugs. The Working Group on Toxicant-induced Loss of Tolerance has formulated a series of research questions to test this hypothesis: Do some individuals experience sensitivity to chemicals at levels of exposure unexplained by classical toxicological thresholds and dose-response relationships, and outside normally expected variation in the population? Do chemically sensitive subjects exhibit masking that may interfere with the reproducibility of their responses to chemical challenges? Does chemical sensitivity develop because of acute, intermittent, or continuous exposure to certain substances? If so, what substances are most likely to initiate this process? An experimental approach for testing directly the relationship between patients' reported symptoms and specific exposures was outlined in response to the first question, which was felt to be a key question. Double-blind, placebo-controlled challenges performed in an environmentally controlled hospital facility (environmental medical unit) coupled with rigorous documentation of both objective and subjective responses are necessary to answer this question and to help elucidate the nature and origins of chemical sensitivity.

Original languageEnglish (US)
Pages (from-to)515-519
Number of pages5
JournalEnvironmental health perspectives
Issue numberSUPPL. 2
StatePublished - Mar 1997


  • Chemical challenges
  • Chemical exposure
  • Chemical sensitivity
  • Chemical testing
  • Environmental medical unit
  • Exposure chamber
  • Intolerance
  • Multiple chemical sensitivity
  • Sensitivity
  • Toxicant-induced loss of tolerance

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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