The Interagency Workgroup on
Multiple Chemical Sensitivity
August 24, 1998
NRC Workshop on Multiple Chemical
AOEC Workshop on Multiple Chemical Sensitivity, 1991
Report on Biologic Markers in Immunotoxicology, 19923
ATSDR Expert Panel on Multiple Chemical Sensitivity, 1993
Chemicals and Neurobiologic Sensitivity, 1994
California Department of Health Services, 199454
NIEHS, MCS: Controlled Exposure Studies, 19955
EOHSI/NIEHS Conference, 199656
DHHS Report to Congress, 19987
Table of Contents
VII. Key Panels,
Workshops, and Reports: Recommendations
Since 1990, Federal Government agencies have sponsored or
cosponsored a number of expert panels and workshops concerning MCS. These meetings have
been important, because key researchers on chemical sensitivity and related areas have
participated in the development of recommendations pertinent to the condition. MCS patient
advocates and persons with MCS have also participated in some of the panels and workshops.
The workgroup recognizes the expertise used to develop the recommendations from these
meetings and is concerned that they not be lost to time. Moreover, it is important to
compare the status of the key recommendations to assess whether they are still relevant
for a better understanding of MCS. The key recommendations from federally sponsored panels
and workshops on MCS are given in Table
5. The key recommendations from individual panels and workshops are described in the
NRC Workshop on Multiple
Chemical Sensitivities, 1991
In March 1991, at the request of EPA, the National
Research Council (NRC) conducted a workshop to develop an MCS research agenda. The
participants included a wide range of scientific disciplines and philosophical views. The
meeting reported its findings and recommendations through three working groups: Research
Protocol for Clinical Evaluation, Exposures and Mechanisms, and Epidemiology.
Clinical Evaluation working group:
- Prospective longitudinal studies of exposure-based events are very important and should
- A research priority should be the study of the adaptation-deadaptation hypothesis, and
the study should be pursued using an ECU. In addition, a second approach should evaluate
individuals, over time, in their usual environment.
- Selection of research subjects should be based on the specific hypothesis to be tested
(e.g., symptom-based, exposure-based, and population-based).
- Development of a database of chemicals, foods, drugs, and signs and symptoms reported to
be associated with MCS is important.
Exposures and Mechanisms working group:
- Studies should include a comprehensive history, including exposures, physical
examination, and appropriate laboratory testing. Endpoints for response should include
immunologic, neurologic, endocrinological, psychological, social, and other markers or
- Dose-response relationships should be examined.
- Animal models should be developed that mimic the human syndrome.
- Tissues obtained by biopsy and necropsy from patients, animals, and their controls
should be evaluated for signs of pathologic change.
Epidemiology working group:
- The magnitude of the problem caused by MCS in the general population should be
- Multi-center, clinical case-comparison studies in occupational/environmental medicine
clinics should be an early priority.
- A broad set of symptom prevalences should be utilized that will allow flexible
construction of a variety of case definitions.
- Population-based methods, including construction of survey instruments, should be used
to determine the basic descriptive epidemiology of certain multiorgan disorders that have
been linked to MCS (e.g., systemic lupus erythematosus, scleroderma, multiple sclerosis,
and somatization disorder).
- Prompt studies of defined populations subjected to discrete and sudden chemical
exposures should be enacted to assess the initiation and natural history of sensitivity
syndromes involving environmental chemicals.
- Normal ranges for new test modalities, including the sensitivity and specificity of
screening techniques and biomarkers, should be determined.
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AOEC Workshop on Multiple Chemical
In September, 1991, the Association of Occupational and
Environmental Clinics (AOEC) held an MCS workshop in Washington, D.C. The workshop format
included plenary sessions and four work groups that focused on research needs in
characterizing patients, events, developing treatment strategies, and exploring possible
Characterizing Patients group:
- Develop a case definition for use in descriptive epidemiologic research and in challenge
Characterizing Events group:
- Determine incidence and prevalence of MCS, perhaps by using community-based studies and
existing surveys such as the National Health and Nutrition Examination Survey.
- Carry out prevalence surveys in specific occupational cohorts and cross-cultural studies
of "naive" populations (i.e., groups who are unaware of MCS).
- Perform longitudinal studies of populations exposed through "natural"
situations (e.g., "sick building" exposures).
- Develop case registries to follow the course of MCS patients.
- Carry out double-blind, placebo-controlled challenge studies, primarily inhalation
studies, including but not limited to chamber studies.
Treatment Methods group:
- Study the effects of early intervention in an exposed population (e.g., critical
- Perform randomized, controlled trials of therapies that have some reasonable theoretical
- Carry out studies of subjective outcomes, including belief structures of both patients
and healthcare providers.
- Perform challenge studies, primarily inhalation studies, including (but not limited to)
- Study olfactory function and the nasal-olfactory-limbic pathway.
- Develop studies of neuroimaging techniques (e.g., PET and SPECT) and studies of
- Conduct prospective studies of cohorts of persons sensitive to chemicals and of families
of MCS patients.
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Report on Biologic Markers in
In addition to the findings and recommendations from the
March 1991 NRC Workshop, in 1992, the NRC Subcommittee on Immunotoxicology, through its
Committee on Biologic Markers, published Biologic Markers in Immunotoxicology. The
report endorsed the recommendations from the NRC meeting held in 1991.
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ATSDR Expert Panel on Multiple
Chemical Sensitivity, 1993
In fiscal year 1993, Congress appropriated $250,000 to
ATSDR "[f]or chemical sensitivity/low level chemical and environmental exposure
workshops." The appropriation was in response to community concerns that chemical
releases from hazardous waste sites and pesticide applications were associated with MCS.
In response, ATSDR formed a 12-person panel to provide advice to the agency on projects
that would fulfill congressional intent. The panel comprised representatives from
academia, medicine, public health, and industry as well as several MCS patient advocates.
Government and outside observers were also present. In April 1991, the panel developed and
ranked ideas for MCS projects (Clean Sites, 1993).
- Convene a neurologic workshop with clinicians and neuroscientists to compare clinical
observations with animal and other neurologic research findings.
- Conduct a cross-sectional/prevalence epidemiologic study.
- Use a panel of experts with diverse interests to design and monitor a study that would
use an existing ECU. The project would involve testing the usefulness of techniques such
as double-blind, placebo-controlled challenge testing, provocation-neutralization, and
- ATSDR should convene an interagency committee and obtain funds for an environmental
unit. ATSDR should develop an educational workshop for other agencies to prepare them for
membership on the interagency committee.
- Convene a committee to define single or group phenomena to describe chemical sensitivity
- Convene an MCS panel to focus on developing a database, ways to piggy-back field-study
research, and a registry.
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Chemicals and Neurobiologic
In April 1994, as a part of ATSDR activities that
responded to the Congressional mandate to fund MCS workshops, and in response to the
recommendations of the expert panel meeting held in April 1993, a national meeting was
held in Baltimore, Maryland, to discuss low-level exposure to chemicals and neurobiologic
The conference did not formally adopt findings or recommendations. However, an overview
was prepared and presented (Kipen, 1994); this overview pointed out that some overall
recommendations could be made that do not necessarily represent consensus but may be
useful to interested parties:
- Establish a case definition with attention to its validity (e.g., content, criteria, and
- Explore large populations for salient characteristics of chemical sensitivity.
- Determine population prevalence of the various degrees of chemical sensitivity, with or
without co-morbid medical or psychiatric conditions.
- Undertake analytic epidemiology studies to ascertain risk factors and eventually design
- Focus on the olfactory system, both as a chemical sense organ and as an important
receptor for psychological cues.
- Focus on the immune system, especially its ability to be conditioned by psychological
stimuli; include the field of psychoneuroimmunology.
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California Department of Health
To further address the recommendations from the ATSDR
expert panel meeting held in 1993, a portion of the funds appropriated by Congress to
ATSDR were used to fund a grant to the California Department of Health Services (CDHS).
The grant's purpose was to develop a scientifically acceptable research design that could
identify persons with physiologically-based susceptibility to low levels of chemical
exposure. The grant included determining a case definition for MCS, designing survey
instruments, and selecting appropriate biomarkers to characterize individuals who report
sensitivities to multiple chemicals. In 1994, an expert panel was assembled by CDHS to
provide advice on how best to carry out these goals. In 1996, CDHS released a final report
on the project (CDHS, 1996).
- Rather than using a compromise definition, CDHS proposes the use of questionnaire data
to assemble diagnostic scales describing various characteristics and attributes of the MCS
- Population-based determinations of prevalence of MCS are an important step in evaluating
hypotheses about the mechanisms and etiology of this condition. Questions about the MCS
syndrome have been included in the 1995 California Behavioral Risk Factor Survey (BRFS).
CDHS has also proposed a more extensive study using the questionnaire they have developed.
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NIEHS, MCS: Controlled Exposure
As part of NIEHS activities related to the Superfund
Hazardous Substances Basic Research and Training Program, a workshop was held by the
Environmental and Occupational Health Sciences Institute, the University of Medicine and
Dentistry of New Jersey-Robert Wood Johnson Medical School, and Rutgers University. The
objective of the workshop was to develop a multidisciplinary research agenda for
elucidating possible mechanisms for MCS that involved investigators who realized the
interactive nature of the problem. The relevant disciplines included neuroscience,
immunology, epidemiology, exposure assessment, and environmental chemical engineering.
- Clear criteria are needed for the selection of subjects to participate in studies of
chemical sensitivities, for example, the inclusion/exclusion of MCS subjects with
co-morbid diagnoses. If subjects with other medical illnesses (e.g., asthma) are included,
the number of co-morbid diagnoses should be limited in any given study and controlled in
- Controlled exposure studies in which a carefully defined set of MCS subjects are exposed
to a chemical hypothesized to cause symptoms and in which objective and subjective
responses are measured is critical. At present, no controlled study has demonstrated a
relationship between chemical exposure and symptoms in this patient group.
- Effects of conditioning and sensitization need to be considered in research studies of
- Consideration should be given to single case designs as an alternative to group
comparisons, given the heterogeneity of subjects, symptoms, and chemical exposures.
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EOHSI/NIEHS Conference, 1996
In September 1996, the Environmental and Occupational
Health Sciences Institute (EOHSI) and NIEHS sponsored the Conference on Experimental
Approaches to Chemical Sensitivity, which was held in Princeton, New Jersey (Kipen and
Fiedler, 1997). It was conducted as a workshop in which experienced MCS clinicians who
could document patient characteristics worked with experimental investigators from
MCS-relevant disciplines to develop experimental approaches to MCS elucidation. Five
working groups addressed specific topics: empirical approaches for the investigation of
toxicant-induced loss of tolerance, Pavlovian conditioning and MCS, psychoneuroimmunology,
neurogenic inflammation, and testing the neural sensitization and kindling hypothesis.
Each group was composed of both persons who had experience in trying to treat MCS patients
and researchers who had developed research methods relevant to the MCS model under
discussion. Each group produced recommendations, which included the following (Bascom et
al., 1997; Bell et al., 1997; Cohen et al., 1997; Miller et al., 1997; Siegel et al.,
- Studies should be initiated to test hypotheses in the domain of nonneurogenic
inflammation, determining whether inflammation is present in symptomatic tissues of
patients who have MCS and if it is associated with a heightened neurosensory response.
- Conduct longitudinal studies to test hypotheses: (1) a psychoneuroimmunologic component
is correlationally or causally associated with development of MCS and (2) stress is
associated with MCS as a chronic disabling disease.
- Conduct double-blind, placebo-controlled challenge studies performed in an
environmentally controlled hospital facility coupled with rigorous documentation of both
objective and subjective responses.
- Conduct interviews with MCS patients to ascertain episodes consistent with a learning
interpretation of their symptoms.
- Conduct balanced placebo-controlled studies to separate the effects of chemical
expectation from chemical effects in MCS.
- Evaluate the possibility of olfactory hypersensitivity in MCS patients through further
- Systematically evaluate the efficacy of systematic desensitization as a treatment for MCS
- Consider single-case designs as an alternative to group comparisons, given the
heterogeneity of subjects, symptoms, and chemical exposures.
- Develop a generally accepted structured interview that is based on common patterns of
- One design for protocols to initiate and test for sensitization in MCS patients could
involve the same sensitization procedures but compare outcomes under conditions of masking
- Test the hypothesis that MCS patients are more susceptible to initiation of
context-dependent sensitization than are control subjects.
- Longitudinal studies with repeated measures would enable evaluation of fluctuations over
- Conduct laboratory animal studies to assess neural time-dependent sensitization
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HHS Report to Congress, 1998
In January 1998, the Acting Assistant Secretary for
Health, Department of Health and Human Services (HHS), submitted a report to Congress
entitled "Report to Congress on Research on Multiple Chemical Exposures and Veterans
with Gulf War Illnesses" (Eisenberg, 1998). The report was prepared in response to
House Report 105-205, which accompanied the U.S. Departments of Labor, Health and Human
Services, and Education and Related Agencies Appropriations Bill for fiscal year 1998. The
appropriations language states, "[T]he Committee believes that there is need to
conduct research as rapidly as possible into the possible links between chemical and
biological exposures and the illnesses suffered by tens of thousands of Persian Gulf War
veterans. The Committee believes it would be useful to support research in areas of
multiple chemical sensitivity; the definition of individual genetic differences in the
ability to metabolize environmental agents commonly encountered during the Persian Gulf
War; and the development of a better understanding of how multiple exposures of chemicals
interact to exert their toxicity on an organism. . . The Committee requests the Secretary
to submit a report by December 31, 1997, describing the Department's proposed Gulf War
illness research plan and a description of how funding will be allocated among the
agencies to implement the program."
The HHS report indicates that a representative will be located
in the Office of Public Health, Office of Secretary, as the principal official for the
research program stipulated by Congress. In fiscal year 1998, a consensus-building
conference will be held to "[f]ully characterize the nature of multiple chemical
exposures with the Gulf War veteran population and to relate this characterization to what
is known about Multiple Chemical Sensitivity (MCS) and related conditions and disorders
within civilian populations." CDC will be allocated $300,000 to conduct the
conference. Also, in fiscal year 1998, $400,000 will be added to an NIH grant entitled
"Chemical Mixtures in Environmental Health."
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5 lists, in descending order of concordance, the recommendations from the seven
meetings that are described in this section. There were four recommendations that had
support from five or more meetings:
- Conduct basic epidemiology,
- Conduct case-comparison studies,
- Develop a case definition for MCS, and
- Conduct challenge studies.
The specifics of these four recommendations varied across the seven meetings. For
example, all meetings recommended more research, although the specific types of research
varied with the meeting. The need for more basic epidemiologic data on MCS was a mutual
theme at all seven meetings.
This discussion of the previously held federally-supported meetings, while presenting
the formal recommendations, should not diminish the serious consideration that was given
to many other topics. The published proceedings should be reviewed for additional details.
As will be evident in the next section, only limited progress has been made by
agencies on many of the recommendations listed in Table
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