EMPIRICAL APPROACHES FOR THE INVESTIGATION OF TOXICANT-INDUCED LOSS OF TOLERANCE

It has been hypothesized that sensitivity to low-level chemical exposu res develops in two steps: initiation by an acute or chronic chemical exposure, followed by triggering of symptoms by low levels of previous ly tolerated chemical inhalants, foods, or drugs. The Working Group on Toxicant-induced Loss of Tolerance has formulated a series of researc h questions to lest this hypothesis: Do some individuals experience se nsitivity 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 d evelop because of acute, intermittent, or continuous exposure to certa in substances? If so, what substances are most likely to initiate this process? An experimental approach for resting directly the relationsh ip between patients' reported symptoms and specific exposures was outl ined in response to the first question, which was felt to be a key que stion. Double-blind, placebo-controlled challenges performed in an env ironmentally 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.