Exposures and Mechanisms

WORKING GROUP II

There are clinical reports of a syndrome which has been described as follows: Chemicals (odorous and nonodorous VOC's, solvents, pesticides, etc.) cause a 'sensitization' (induction phase) in a subset of individuals. Upon subsequent exposure to lower concentrations, these individuals may respond in a polysymptomatic fashion (triggering). This 'sensitivity'' may spread to other chemicals, foods or drugs. The underlying mechanism(s) is unknown at present but may include immunological, neurological, endocrinological, psychological, or other factors.

Currently, there is insufficient objective evidence for the entity called multiple chemical sensitivity caused by chemical exposures. Research is needed to test characteristics of the entity and define mechanisms that may be involved. Therefore the following research approaches are suggested.

HUMAN STUDIES

Following a comprehensive history, including environmental exposures, physical examination and appropriate laboratory testing, subjects diagnosed with MCS and control individuals, should be challenged by exposure to a mixture of offending agents determined historically. A double blind controlled procedure should be employed. The possible role of ''adaptation" and "deadaptation" should be considered in the protocol. Endpoints for response should include immunologic, neurologic, endocrinologic, psychologic, social, etc. markers or measures. Dose-response relationships should be examined.

A second approach could be evaluation of individuals, over time, in their usual environment.

OTHER EXPERIMENTAL APPROACHES

Animal models should be developed that manic the human syndrome. Exposures and



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OCR for page 9
Multiple Chemical Sensitivities: A Workshop Exposures and Mechanisms WORKING GROUP II There are clinical reports of a syndrome which has been described as follows: Chemicals (odorous and nonodorous VOC's, solvents, pesticides, etc.) cause a 'sensitization' (induction phase) in a subset of individuals. Upon subsequent exposure to lower concentrations, these individuals may respond in a polysymptomatic fashion (triggering). This 'sensitivity'' may spread to other chemicals, foods or drugs. The underlying mechanism(s) is unknown at present but may include immunological, neurological, endocrinological, psychological, or other factors. Currently, there is insufficient objective evidence for the entity called multiple chemical sensitivity caused by chemical exposures. Research is needed to test characteristics of the entity and define mechanisms that may be involved. Therefore the following research approaches are suggested. HUMAN STUDIES Following a comprehensive history, including environmental exposures, physical examination and appropriate laboratory testing, subjects diagnosed with MCS and control individuals, should be challenged by exposure to a mixture of offending agents determined historically. A double blind controlled procedure should be employed. The possible role of ''adaptation" and "deadaptation" should be considered in the protocol. Endpoints for response should include immunologic, neurologic, endocrinologic, psychologic, social, etc. markers or measures. Dose-response relationships should be examined. A second approach could be evaluation of individuals, over time, in their usual environment. OTHER EXPERIMENTAL APPROACHES Animal models should be developed that manic the human syndrome. Exposures and

OCR for page 9
Multiple Chemical Sensitivities: A Workshop parameters measured in the animal model should mimic those measured in humans wherever possible. Tissues obtained by biopsy and necropsy from patients, animals and their controls should be evaluated for pathologic changes. In addition, functional and morphological changes in cells and tissues should be evaluated using in vitro techniques. ADDITIONAL NEEDS Attempts should be made to develop a data base of chemicals, foods and drugs, and associated signs and symptoms, which have been reported to be associated with MCS. Evaluation of this data base should be explored to identify possible linkages between exposure and mechanisms.