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Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensitive Line (FSL) rats were selectively bred to be more sensitive to the OP diisopropylfluorophosphate (DFP) compared to their control counterparts, the Flinders Resistant Line (FRL) rats. The present paper will summarize evidence which indicates that the FSL rats exhibit certain similarities to individuals with MCS. In addition to their greater sensitivity to DFP, the FSL rats are more sensitive to nicotine and the muscarinic agonists arecoline and oxotremorine, suggesting that the number of cholinergic receptors may be increased, a conclusion now supported by biochemical evidence. The FSL rats have also been found to exhibit enhanced responses to a variety of other drugs, including the serotonin agonists m-chlorophenylpiperazine and 8-OH-DPAT, the dopamine antagonist raclopride, the benzodiazepine diazepam, and ethanol. MCS patients report enhanced responses to many of these drugs, indicating some parallels between FSL rats and MCS patients. The FSL rats also exhibit reduced activity and appetite and increased REM sleep relative to their FRL controls. Because these behavioral features and the enhanced cholinergic responses are also observed in human depressives, the FSL rats have been proposed as a genetic animal model of depression. It has also been reported that MCS patients have a greater incidence of depression, both before and after onset of their chemical sensitivities, so cholinergic supersensitivity may be a state predisposing individuals to depressive disorders and/or MCS. Further exploration of the commonalities and differences between MCS patients, human depressives, and FSL rats will help to elucidate the mechanisms underlying MCS and could lead to diagnostic approaches and treatments beneficial to MCS patients.
Patients with multiple chemical sensitivity (MCS) react to low levels of common environmental chemicals with various health complaints. The etiology and pathogenesis of MCS is not clear. Objective criteria for diagnosis are lacking. Usually there are no pathological somatic findings, while psychiatric morbidity is considerably high. Somatoform, mood and anxiety disorders are diagnosed most frequently. A subgroup of MCS patients may suffer from a special form of somatoform disorders related to the environment. Critics of a psychogenic model of MCS argue that psychiatric diagnoses are descriptive, and causality can not be derived from them. However, clinicians are expected to evaluate the most probable cause of the complaints and give therapeutic recommendations. There are promising therapeutic concepts for somatoform and other psychiatric disorders, but not for MCS. Double-blind challenge tests, but also therapy evaluation studies could contribute to a better understanding of the pathogenesis of MCS in the future.
People suffering from multiple chemical sensitivity (MCS) complain of a variety of symptoms that could impair cognitive and psychomotor function either directly or indirectly. This paper discusses the use of cognitive and psychomotor performance tests together with some experiment designs that could be considered for use to assess fitness of MCS sufferers for work or the efficacy of diagnostic, preventative, or therapeutic measures. The tests could also contribute to the body of objective information on MCS and help sway the opinion of those who are dubious of its authenticity. The credentials of cognitive and psychomotor performance tests are derived from their successful use in studying the effects of drugs, and the types of tests are illustrated by describing those used by the United Kingdom Defence Evaluation and Research Agency Chemical and Biological Defence Human Studies Group, which has been involved in the assessment of drugs and chemicals on work performance for many years. The tests include mathematical, verbal and spatial processing, tracking, reaction time, attention and vigilance, and memory tests. The discussion of experiment designs includes both repeated measures and parallel groups designs together with their advantages and disadvantages and some suggested modifications to accommodate the particular problems posed by MCS.
This paper summarizes the key features of the olfactory-limbic, neural sensitization model for multiple chemical sensitivity (MCS) and presents relevant data on chemically intolerant human subjects from laboratory studies using quantitative electroencephalography, polysomnography, neuropsychological tests, cardiovascular measurements, and blood markers. MCS is a poorly understood chronic, polysymptomatic condition in which some prior controlled research studies have failed to find evidence to differentiate active from placebo tests. Closer examination of past MCS research, however, reveals that studies have failed to incorporate the design and methodological approaches necessary to test for nonimmunological sensitization. Time-dependent sensitization (TDS) is a well-documented phenomenon in the pharmacology literature involving the progressive increase in a given response by the passage of time between the initial and subsequent exposures to a substance or a stressor. As in MCS, multiple, chemically unrelated agents can trigger TDS. Females time-sensitize more readily than do males. Pharmacological and nonpharmacological (stress) stimuli can cross-sensitize. Dopaminergic pathways in the brain and the hypothalamic-pituitary-adrenal axis are likely involved in TDS. Data on the symptomatology of MCS point to central nervous system involvement, including limbic regions that receive input from both olfactory (odor) and trigeminal (irritant) pathways. Limbic and mesolimbic brain regions are among the most sensitizable to repeated, intermittent environmental stimuli. Sensitizable individuals can show no difference or lesser responses to a test substance on initial exposure, but later exhibit much greater increases in responsivity on the next exposure after a period of days. For future research, it is essential to distinguish chemical intolerance symptoms such as derealization, sudden mood changes, musculoskeletal pain, menstrual dysfunction, and uncontrollable sleepiness from chemical phobia and avoidance behaviors. This model permits hypothesis-driven research on MCS and has major implications for interpretation of apparently positive and negative tests for "true" as opposed to "perceived" sensitivity to low levels of environmental chemicals.
The syndrome of multiple chemical sensitivities has many manifestations and undoubtedly many causes. Treatment must be individualized based on a thorough psychosocial and biological diagnostic evaluation. Careful listening, as is usually the case, not only results in a more complete history but also serves a critical therapeutic purpose in cementing a trusting, working partnership. Family dynamics, and larger social concerns, such as litigation, may figure importantly as obstacles to rehabilitation if they are ignored in treatment planning. In chronically disabled patients, the importance of psychosocial interventions is even greater but should not eclipse attention to relevant medical interventions. The most basic physiologic manipulation involves a program of environmental avoidance. Such a program should be applied with caution since it is not without risks of inadvertent exacerbation of medical and psychologic disabilities. Therefore, from a medical perspective, interventions should focus on improving chemical tolerance by the appropriate application of first aid, chronohygiene, nutrition, psychophysiology, and correction of microbiological disruptions. Thorough investigation for intercurrent disease and its appropriate management is paramount. Attempts to treat the entire problem by isolating attention to one area or based on a single theory are likely to fail.
Multiple chemical sensitivity syndrome (MCS) is believed to be a multiple organ disease caused by low-level exposure to chemical substances. It is characterized by central-nervous, gastrointestinal and irritative mucocutaneous symptoms. This phenomenon is not recognized in traditional medicine, opponents of the theory of a separate disease attributing all symptoms to psychopathological processes. Since this phenomenon is becoming increasingly prevalent in Western countries, appropriate strategies for its study need to be developed.
Multiple chemical sensitivity as a "disease" has emerged as a descendant of food allergy, which, in the 1920s and 1930s, was considered to be responsible for much human suffering and symptoms of disease. After the onmarch of the clinical ecological movement in the 1950s, interest has been focused on the environment, and concern about food allergies and chemical sensitivity has reached epidemic proportions. "Active hazardous waste sites" and "workers exposed to toxic chemicals" are at the top of the list of public worries. The public believes manufactured chemicals to be more dangerous than natural ones, although toxicologists regard the risks as equal. Originally, symptoms of patients were explained as "allergies", but since the 1960s the concept of "chemical sensitivities" has become a big-time diagnosis. The ideas of the clinical ecologists diffused rapidly into the community aided by public media. Today organizations like "Chemical Victims" and "National Foundation for the Chemically Hypersensitive" have thousands of members. Although the diagnosis of the disease is very vague, suffering patients believe that the clinical ecologists can offer them something that traditional medicine cannot: sympathy, recognition of pain and suffering, a physical explanation for their suffering, and active participation in medical care. Ecologic medicine thus soared in the patients' esteem, not just because of the content of the objective diagnoses that ecologic practitioners were able to supply, but because of the subjective nature of the doctor-patient relationship they were able to offer.
Multiple Chemical Sensitivity (MCS), an intolerance to everyday chemical and biological substances in amounts that do not bother other people, is a medically contested condition. In addition to symptoms and the ongoing difficulties of living with this condition, this hidden and stigmatized disability strongly impacts social relationships and daily life. Based on an ethnographic study, this article introduces the context of MCS in terms of cultural themes, the media, and the economic power of industries that manufacture the products that make people with MCS sick. Participants' experiences with family members and friends, in work and school settings, and with physicians exemplify the difficulties of living with MCS. I dedicate this article to Joan Ablon, my professor and mentor, whose work has always inspired my thinking and research topics.
Since symptoms typical for multiple chemical sensitivity (MCS) are induced by exposure to low levels of chemicals, we hypothesize that MCS represents an impaired recognition of odors or an increased emotional reaction to common odors. Twenty-five subjects with MCS, 20 women and 5 men, and 50 gender-and-age matched controls participated in this study. The University of Pennsylvania Smell Identification Test (UPSIT) and the Cross-Cultural Smell Identification Test (CC-SIT) were administered. In addition to selecting the most probable odor among the four, the subjects were asked their impression of each odor. Odor identifiability evaluated by the scores of two tests, were almost equal in MCS and control groups. The mean CC-SIT odor per person with pleasant feeling was lower in MCS than in controls. The mean odor per person creating an unpleasant sensation was higher in MCS than in the controls. Gingerbread was the only odor making MCS subjects more pleasant than the controls. Nine out of 40 UPSIT odors were felt as unpleasant by MCS subjects more than by controls. This study indicates that MCS subjects are able to identify the odors equally as well as the controls but feel unpleasant to a larger number of odors than the controls. Despite unknown mechanisms of the altered odor perception in MCS, the application of these tests for diagnostic procedure of MCS is proposed.
Whether persons with multiple chemical sensitivity syndrome (MCS) have immunological abnormalities is unknown. To assess the reliability of selected immunological tests that have been hypothesized to be associated with MCS, replicate blood samples from 19 healthy volunteers, 15 persons diagnosed with MCS, and 11 persons diagnosed with autoimmune disease were analyzed in five laboratories for expression of four T-cell surface activation markers (CD25, CD26, CD38, and HLA-DR) and in four laboratories for autoantibodies (to smooth muscle, thyroid antigens, and myelin). For T-cell activation markers, the intralaboratory reproducibility was very good, with 90% of the replicates analyzed in the same laboratory differing by < or = 3%. Interlaboratory differences were statistically significant for all T-cell subsets except CD4+ cells, ranging from minor to eightfold for CD25+ subsets. Within laboratories, the date of analysis was significantly associated with the values for all cellular activation markers. Although reproducibility of autoantibodies could not be precisely assessed due to the rarity of abnormal results, there were inconsistencies across laboratories. The effect of shipping on all measurements, while sometimes statistically significant, was very small. These results support the reliability of fresh and shipped samples for detecting large (but perhaps not small) differences between groups of donors in the T-cell subsets tested. When comparing markers that are not well standardized, it may be important to distribute samples from different study groups evenly over time.
The individually different effects of exposure to comparable levels of chemicals might be partly explained by dissimilar response sensitivity towards chemicals. Multiple chemical sensitivity (MCS) might be the clinical endpoint of this altered sensitivity. Concerning a subclinical range of chemical sensitivity, 'challenge studies' with people reporting chemical sensitivity are needed to improve the knowledge about such differences. The chemical and general environmental sensitivity questionnaire (CGES) is a standardized screening tool for the selection of this group. In the present study 24 healthy male volunteers, half of them classified as sMCS-subjects, were experimentally exposed to 2-butanone and ethyl benzene at different levels (TLV-level vs. odor threshold). The strength of self-reported sensory irritations (nasal and ocular) and symptoms of bad smell were assessed, prior, during, and after the 4 hours of exposure. The time courses of sensory irritations were affected by sMCS. Across all exposure periods sMCS-subjects showed increasing symptom scores while control-subjects did not. Symptoms of bad smell were affected by three exposure-related factors (substance, level, duration) without any additional influence from the sMCS factor. Starting from these results it could be concluded that the time-depending influence of reported chemical sensitivity is most prominent for subjective data of sensory irritations.
Multiple chemical sensitivity (MCS) is a syndrome in which multiple symptoms occur with low-level chemical exposure; whether it is an organic disease initiated by environmental exposure or a psychological disorder is still controversial. We report a 38-year-old male worker with chronic toluene exposure who developed symptoms such as palpitation, insomnia, dizziness with headache, memory impairment, euphoria while working, and depression during the weekend. Upon cessation of exposure, follow-up neurobehavioural tests, including the cognitive ability screening instrument and the mini-mental state examination, gradually improved and eventually became normal. Although no further toluene exposure was noted, non-specific symptoms reappeared whenever the subject smelled automotive exhaust fumes or paint, or visited a petrol station, followed by anxiety with sleep disturbance. During hospitalization for a toluene provocation test, there was no difference between pre-challenge and post-challenge PaCO(2), PaO(2), SaO(2) or pulmonary function tests, except some elevation of pulse rate. The clinical manifestations suggested that MCS was more relevant to psychophysiological than pathophysiological factors.
Multiple chemical sensitivity is a controversial diagnosis. Rigorous, controlled, laboratory-based research can reduce this controversy and lead to potential clinical confirmatory tests. The literature on human caffeine discrimination provides a rigorous methodology that can address reports that patients who suffer multiple chemical sensitivity (MCS) are sensitive to usually well-tolerated chemical doses; the studies require patients to discriminate caffeine from placebo under double-blind conditions. Several issues relevant to the conduct of caffeine discrimination studies using MCS patients as subjects are addressed; these issues include study design, determination of safe and tolerable training doses, and discrimination training. Such research will benefit patients and clinicians dealing with a diagnosis of MCS.
The lack of widely accepted, standardized, clinical and epidemiologic criteria for Multiple Chemical Sensitivity syndrome has led to confusion about the identification of the condition and has slowed pertinent research. In this article, the authors evaluated the psychometric properties of 2 sets of clinical/epidemiologic criteria for Multiple Chemical Sensitivity syndrome. In this cross-sectional survey of 1,166 patients who visited outpatient occupational, otolaryngology, allergy, and clinical ecological clinics, the authors used the aforementioned sets of criteria to (a) estimate the prevalence of the syndrome in these varied samples and (b) compare the current diagnostic practices of traditional physician specialists with those of clinical ecologists. The authors used a patient-completed questionnaire to assess the medical, psychosocial, and psychological status of patients who reported multiple chemical sensitivities. This approach enabled the formulation of 6 domains, which represented commonly observed characteristics of the syndrome. The authors used a physician-completed questionnaire to collect diagnoses of Multiple Chemical Sensitivity syndrome and other medical conditions. Domains, which were operationalized by the questionnaire and comprised the 2 sets of criteria for identification of the Multiple Chemical Sensitivity syndrome, had test-retest reliabilities that exceeded .75 and estimates of internal consistency that ranged between .59 and .94. Evidence of construct and face validity was considered acceptable. The overall clinic-based prevalences of Multiple Chemical Sensitivity syndrome, based on 6 and 4 domains, were 7% and 23%, respectively. Regardless of the identifying set of criteria used, physicians' diagnoses had relatively low sensitivities (range = 6-50%) and relatively high specificities (range = 82-99%). The study data suggested that the domains operationalized by the questionnaire had reasonable psychometric characteristics. Study data also support the fact that Multiple Chemical Sensitivity syndrome is often overlooked--even by those physicians who treat it most frequently--and that use of both sets of objective criteria for identifying the syndrome would greatly improve the sensitivity of physician diagnoses.
Many workers who speculate about multiple chemical sensitivity (MCS) have devised a large number of hypothetical constructs designed to explain the phenomena. Too often these are not logically connected to the larger body of scientific thought but instead appeal to ideas not documented in accessible literature and often appearing metaphysical in nature.
The phenomenon of multiple chemical sensitivities is a peculiar manifestation of our technophobic and chemophobic society. It has been rejected as an established organic disease by the American Academy of Allergy and Immunology, the American Medical Association, the California Medical Association, the American College of Physicians, and the International Society of Regulatory Toxicology and Pharmacology. It may be the only ailment in existence in which the patient defines both the cause and the manifestations of his own condition. Despite this, it has achieved credibility in workmen's compensation claims, tort liability, and regulatory actions, all of which are briefly reviewed.
Multiple chemical sensitivities (MCS) has become an increasingly frequent diagnosis assigned to patients with symptoms associated with exposures to environmental chemicals. Since the characteristic symptoms of MCS are triggered by very low concentrations of chemicals, in the range of olfactory thresholds, it is widely believed that the intranasal chemoreceptive senses are involved in the pathophysiology of MCS. Thus, the present study addressed both the olfactory and trigeminal systems: using a double-blind approach we investigated whether MCS patients show differences in responses after exposure to either room air or low concentrations of a widely used chemical agent (2-propanol). A total of 23 patients participated in the experiments (mean age 47 years; 13 female, 10 male). MCS was diagnosed according to Cullen's criteria Performance of the nasal chemical senses was established by means of chemosensory event-related potentials (CSERP) and subjective measures of olfactory function (odor discrimination, phenylethyl alcohol odor thresholds). CSERP were recorded in response to olfactory (H2S), and trigeminal (CO2) stimuli. The study provided three major results: (1) Approximately 20% of patients diagnosed with MCS presented symptoms regardless of the type of challenge, suggesting the susceptibility of MCS patients to unspecific experimental manipulations. (2) Changes in CSERP latencies indicated a change in the processing of both olfactory and trigeminal stimuli. (3) While odor threshold remained unchanged, the patients' ability to discriminate odors decreased after exposure to room air. In contrast, this decrease was less pronounced after exposure to 2-prop. Summarily, MCS patients respond to challenge with 2-prop with changes of chemosensory perception which might increase their susceptibility to environmentally volatile chemicals. Changes in the pattern of event-related potentials are interpreted as the possible change of the orientation of cortical generators, i.e., neuronal populations that were involved in the processing of chemosensory information. However, investigations in healthy controls are needed in order to draw further conclusions.