Environmental Health Perspectives 105, Supplement 2, March 1997 working group report


Empirical Approaches for the Investigation of Toxicant-induced Loss of Tolerance

Claudia Miller,1 Nicholas Ashford,2 Richard Doty,3 Mary Lamielle,4 David Otto,5 Alice Rahill,6 and Lance Wallace7


1 Department of Family Practice, University of Texas Health Science Center at San Antonio, San Antonio, Texas
2 Center for Technology, Policy and Industrial Development, Massachusetts Institute of Technology, Boston, Massachusetts
3 Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
4 National Center for Environmental Health Strategies, Voorhees, New Jersey
5 U.S. Environmental Protection Agency, Research Triangle Park, North Carolina
6 Department of Environmental Medicine, University of Rochester, Rochester, New York
7 Office of Research and Development, U.S. Environmental Protection Agency, Warrenton, Virginia

Abstract
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. -- Environ Health Perspect 105(Suppl 2):515-519 (1997)

Key words: chemical challenges, chemical exposure, chemical testing, chemical sensitivity, environmental medical unit, exposure chamber, intolerance, multiple chemical sensitivity, sensitivity, toxicant-induced loss of tolerance

This paper is based on a work group discussion at the Conference on Experimental Approaches to Chemical Sensitivity held 20Ð22 September 1995 in Princeton, New Jersey. Manuscript received at EHP 6 March 1996; manuscript accepted 16 August 1996.

This document has been reviewed by the U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency.

Address correspondence to Dr. C.S. Miller, Environmental and Occupational Medicine. Department of Family Practice, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7794. Telephone: (210) 567-4557. Fax: (210) 567-4579. E-mail: millercs@uthscsa.edu

Abbreviations used: EMU, environmental medical unit; POMS, Profile of Mood States; UPSIT, University of Pennsylvania Smell Identification Test.

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Last Update: March 25, 1997