Self-reported Multiple Chemical Sensitivity Research Articles

Multiple Chemical Sensitivity.

Multiple Chemical Sensitivity (MCS), a condition also known as Chemical Sensitivity (CS), Chemical Intolerance (CI), Idiopathic Environmental Illness (IEI) and Toxicant Induced Loss of Tolerance (TILT), is an acquired multifactorial syndrome characterized by a recurrent set of debilitating symptoms. The symptoms of this controversial disorder are reported to be induced by environmental chemicals at doses far below those usually harmful to most persons. They involve a large spectrum of organ systems and typically disappear when the environmental chemicals are removed. However, no clear link has emerged among self-reported MCS symptoms and widely accepted objective measures of physiological dysfunction, and no clear dose-response relationship between exposure and symptom reactions has been observed. In addition, the underlying etiology and pathogenic processes of the disorder remain unknown and disputed, although biologic and psychologic hypotheses abound. It is currently debated whether MCS should be considered a clinical entity at all. Nevertheless, in the last few decades MCS has received considerable scientific and governmental attention in light of the many persons reporting this illness. In this review, we provide a general overview of the history, definition, demographics, prevalence, and etiologic challenges in defining and understanding MCS.

INDOOR AIR QUALITY AND HEALTH IN NEWLY CONSTRUCTED APARTMENTS OF INDONESIA: CASE STUDY ON THE EFFECT OF MODIFICATION

In Indonesia, sick building syndrome (SBS) and related health problems are suspected among the residents in emerging new urban houses constructed of modern building materials without sufficient material standards or minimum ventilation rates. First, this study investigates the current conditions of indoor air quality (IAQ) and health in newly constructed high-rise apartments in major cities of Indonesia, in contrast with traditional landed houses, the so-called Kampongs. Concentrations of formaldehyde and TVOC were measured, whereas a face-to-face interview was conducted. A total of 896 respondents were interviewed, and 207 rooms were measured during 2017-2019. The results showed that overall, the newly constructed apartments recorded higher formaldehyde levels compared to Kampongs. The status of the self-reported multiple chemical sensitivity (MCS) among occupants was significantly different between the two building types. Furthermore, the occupants with higher levels of TVOC, in particular, were associated with the higher MCS risks, especially in the apartments. Second, we conducted a modification project in several apartment units of Surabaya to examine the effects of exhaust fans on IAQ. In most units, the concentrations of both formaldehyde and TVOC were reduced after the modification. Further, a follow-up measurement was conducted in the same units for about a month.

Indoor air quality and self-reported multiple chemical sensitivity in newly constructed apartments in Indonesia

There is a possibility that sick building syndrome has already spread widely among newly constructed residential buildings in developing countries. This study investigates the current conditions of IAQ and their effects on health among occupants in two representative types of residential buildings in Jakarta and Surabaya: high-rise apartments and traditional landed houses. A total of 707 respondents were interviewed and 125 rooms were measured during 2017–2018. The results indicated that approximately 40–50% of the respondents in the newly constructed apartments showed some degrees of MCS risk. Formaldehyde and TVOC concentrations in apartments were especially critical. Furthermore, the respondents with a higher MCS risk were found to be exposed to increased TVOC concentrations in the apartments. Other than the IAQ, higher levels of stress are probably one of the most influential factors, followed by gender (females), occupation, window-opening, frequency of cleaning, the prevalence of allergic diseases and possession of AC.

Life indicators, illness characteristics, and psychosocial concomitants of self-reported multiple chemical sensitivity: A two-year longitudinal study

Life indicators, illness characteristics, and psychosocial concomitants were measured in a large sample of persons self-reporting multiple chemical sensitivity. Cross-sectional data are presented for 305 persons who responded to written surveys. Examined are employment status, income, relationship status, illness characteristics such as length, severity, and age respondents became sensitive, money spent on physicians and on home alterations, situations reported to cause the initial sensitization, and the psychosocial measures of social support and psychosocial adjustment to illness. In addition, relevant life indicators are re-examined two years later and presented for 209 persons who continued to participate. This paper examines life indicators for persons of four levels of severity of condition and three courses of condition over time.

Self-reported multiple chemical sensitivity symptoms and personal volatile organic compounds exposure concentrations in construction workers

The relationship between high chemical compound exposure and human health has been an important worldwide issue. High exposure to chemical compounds can make harmful health effect. One of the mostly risky groups to this high exposure to chemical compounds is the construction worker. In this study, their exposure level and self-reported Multiple Chemical Sensitivity were investigated. In the first part of this study, self-reported symptom surveys and personal six Volatile Organic Compounds (VOCs) exposure measurements were conducted with three categories of construction employment, including exterior workers, interior workers, and office workers. The job category with the greatest exposure to VOCs was the interior workers, followed by office workers, and then exterior workers. However, based on the self-reported symptom surveys, office workers demonstrated a relatively high risk for Multiple Chemical Sensitivity (MCS) among the three job categories. From these results, it was uncertain that whether this was characteristic of office workers in general, or only office workers in the construction business. To determine this, the same surveys and measurements were conducted with office workers outside the construction business. University students were also surveyed as a comparison group. The results determined that office workers outside the construction business meeting the operational criteria for MCS were similar to construction office workers. This similarity was not nearly so pronounced when the construction office workers were compared to the university students. High chemical exposure level to interior workers and high MCS symptom of office workers should be considered and improved for each job group's health.

Impact of self-reported multiple chemical sensitivity on everyday life: A qualitative study

Multiple chemical sensitivity (MCS) is a descriptive term covering symptoms attributed to exposure to common airborne chemicals. There are no internationally accepted criteria, but it has been suggested that MCS is a chronic and disabling condition. However, details of the impact of MCS on everyday life are limited. To describe the impact of MCS on everyday life, strategies for managing the condition, and experiences with healthcare management. A focus group study was conducted, including two interviews with a sample of six women and six men between 27 and 78 years of age, a duration of MCS of at least 1 year, and with different occupational conditions. MCS may severely influence different aspects of everyday life, including lifestyle, social relations, and occupational conditions. Avoiding common airborne chemicals was the most prevalent coping strategy, which implied creating a chemical-free living space and limiting social activities. Experiences with healthcare management were overall reported as negative in terms of not receiving acknowledgement of the reported symptoms. MCS may have serious implications for daily functioning. Further research on individual consequences and the social and psychological factors that may be associated with MCS is needed in order to add to our understanding of this condition and to the provision of more satisfactory healthcare.

General practitioners’ experiences with provision of healthcare to patients with self-reported multiple chemical sensitivity

Objective. To describe general practitioners’ (GPs’) evaluation of and management strategies in relation to patients who seek medical advice because of multiple chemical sensitivity (MCS). Design. A nationwide cross-sectional postal questionnaire survey. The survey included a sample of 1000 Danish GPs randomly drawn from the membership list of GPs in the Danish Medical Association. Setting. Denmark. Results. Completed questionnaires were obtained from 691 GPs (69%). Within the last 12 months 62.4% (n = 431) of the GPs had been consulted by at least one patient with MCS. Of these, 55.2% of the GPs evaluated the patients’ complaints as chronic and 46.2% stated that they were rarely able to meet the patients’ expectations for healthcare. The majority, 73.5%, had referred patients to other medical specialties. The cause of MCS was perceived as multi-factorial by 64.3% of the GPs, as somatic/biologic by 27.6%, and as psychological by 7.2%. Partial or complete avoidance of chemical exposures was recommended by 86.3%. Clinical guidelines, diagnostic tools, or more insight in the pathophysiology were requested by 84.5% of the GPs. Conclusion. Despite the lack of formal diagnostic labelling the patient with MCS is well known by GPs. The majority of the GPs believed that MCS primarily has a multi-factorial explanation. However, perceptions of the course of the condition and management strategies differed, and many GPs found it difficult to meet the patients’ expectations for healthcare. The majority of the GPs requested more knowledge and clinical guidelines for the management of this group of patients.

Sequence Variations in Subjects with Self-Reported Multiple Chemical Sensitivity (sMCS): A Case-Control Study

Polymorphisms in several genes contribute to interindividual differences in the metabolism of xenobiotics, and may lead to toxicity and disease. The balance between activation and/or detoxification processes may influence an individual's susceptibility to disease. One postulated mechanism underlying multiple chemical sensitivity (MCS) is based on increased metabolism of xenobiotics. The aim of the present study was to determine such polymorphisms in cases with self-reported MCS (sMCS) and controls. sMCS cases (14 men, 45 women, mean age: 48 yr) and controls (14 men, 26 women, mean age: 44 yr) of the same anthroposphere were characterized using the MCS-questionnaire from Hüppe and coworkers (2000) and a standardized questionnaire for living conditions and living factors. Allelic frequencies of genomic variations for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were determined. The MCS questionnaire from Hüppe et al. (2000) differentiated between cases and controls with 87.5% sensitivity and 90% specificity. Compared to controls the sMCS cases had lower exposures, especially to odorous factors, and worse social conditions. No significant differences of the allelic distribution of genetic polymorphisms in the genes for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were found between cases and controls. The results are in contrast to the study of McKeown-Eyssen and coworkers (2004) but in accordance with the German MCS multicenter study. Although the MCS questionnaire from Hüppe et al. (2000) allowed us to differentiate sMCS cases and controls, it was not strong enough for a discrimination based on sequence variations in genes for enzymes involved in xenobiotic metabolism. Therefore, further research needs to focus on a unique phenomenological characterization of MCS.

The German Multicentre Study on Multiple Chemical Sensitivity (MCS)

In this multicentre study on multiple chemical sensitivity (MCS) 291 consecutive environmental medicine (EM) outpatients were examined in several environmental medicine outpatient centres/units throughout Germany in 2000/2003. Of the EM outpatients, 89 were male (30.6%) and 202 were female (69.4%), aged 22-80 (mean 48 years, S.D.=12 years). The sample was representative for university-based environmental outpatient departments and represented a cross-sectional study design with an integrated clinical-based case-control comparison (MCS vs. non-MCS). Three classifications of MCS were used: self-reported MCS (sMCS), clinically diagnosed MCS (cMCS), and formalised computer-assisted MCS with two variants (f1MCS, f2MCS). Data were collected by means of an environmental medicine questionnaire, psychosocial questionnaires, the German version of the Composite International Diagnostic Interview (CIDI), and a medical baseline documentation, as well as special examinations in partial projects on olfaction and genetic susceptibility markers. The hypothesis guided evaluation of the project showed that the patients' heterogenic health complaints did not indicate a characteristic set of symptoms for MCS. No systematic connection could be observed between complaints and the triggers implicated, nor was there any evidence for a genetic predisposition, or obvious disturbances of the olfactory system. The standardised psychiatric diagnostics applying CIDI demonstrated that the EM patients in general and the subgroup with MCS in particular suffered more often from mental disorders compared to an age and gender matched sample of the general population and that in most patients these disorders commenced many years before environment-related health complaints. Our results do not support the assumption of a toxicogenic-somatic basis of the MCS phenomenon. In contrast, numerous indicators for the relevance of behavioural accentuations, psychic alterations or psychosomatic impairments were found in the group of EM-outpatients with subjective "environmental illness".

Pilotstudie zu Lebensgewohnheiten und Lebensumfeld von Patienten mit selbstberichteter multipler Chemikaliensensitivität, Duftstoffallergien oder Polyposis nasi

Background: Environmental factors are discussed as possible causes and/or triggers of multiple chemical sensitivity (MCS), fragrance allergies (FA) and polyposis nasi (PN). Ajoint effect organ of MCS, FA and PN is the respiratory tract. Therefore, aim of the present study was to characterize and compare living conditions and living factors of persons with self-reported MCS (sMCS), FA or PN. Material and methods: Dependence of variable distribution of a standardized questionnaire of living conditions and living factors was investigated between the patient groups using Pearsons Χ 2 test. In case of significance, pairwise comparisons were done with Fisher's exact test and were Bonferroni adjusted. Results: The sMCS-group consisted of 14 men and 45 women, the FA group of 19 men and 25 women and the PN group of 42 men and 27 women. Questionnaire variables with a significantly different distribution between the patient groups were: chemicals as suspected cause of health disturbances (p < 0.001), use of perfume (p < 0.001), mould exposure at home (p = 0.035), age of furniture at home (p = 0.001), use of disinfections (p = 0.006), insecticides (p = 0.004), daily time spent at home (p = 0.032), exposures to photocopying machines (p < 0.001) and to odors (p < 0.001) at workplace. Mainly, the questionnaire variables investigated were significantly different distributed between the sMCS- and the FA-/PN groups. Conclusions: The different distribution of the questionnaire variables investigated between the sMCS-, FA- and PN group regarded environmental factors with odorous components. Reactions to these factors were lesser pronounced in the FA- than in the sMCS group. In the PN group no environmental association was observed.

Assessment of environmental worry in health-related settings: Re-evaluation and modification of an environmental worry scale

The aim of this article was to re-evaluate and possibly modify the standardized Environmental Worry Scale (EWS) by Hodapp et al. [1996. Evaluation eines Fragebogens zur Erfassung von Umweltbesorgnis. Z. Gesundheitspsychologie IV(1), 22–36] with regard to its content and structure. In order to do this, 161 participants were chosen as a reference group to take part in a survey. The data were analyzed and a factor analysis yielded two instead of one component of worry, namely “personal” and “general” environmental worry, leading to a new evaluation method. This revised evaluation method was then applied to patients ( n=227) with or without self-reported multiple chemical sensitivity (MCS) and thus used in the context of reported health complaints. The outlined results indicate that the assessment of worry as proposed by Hodapp et al. [1996. Evaluation eines Fragebogens zur Erfassung von Umweltbesorgnis. Z. Gesundheitspsychologie IV(1), 22–36] should be elaborated by the newly developed evaluation method with which a ratio determined by “personal” and “general” worry can be calculated. In addition to analyzing the absolute quantity of worry, the calculated ratio allows to draw conclusions on the structure of worry. It will be discussed to what extent the results present new insights into the role of worry among patients suffering from environmental diseases.

Eye blinks as indicator for sensory irritation during constant and peak exposures to 2-ethylhexanol

Two experiments were performed to re-evaluate the sensory irritating properties of 2-ethylhexanol in relation to dose and time and to examine the usability of electromyographic eye blink recordings as indicator of sensory irritation. Mean exposure levels of 1.5, 10 and 20 ppm were realized in experimental models simulating either constant or variable 4 h exposure. Each study was carried out with two subject samples, healthy young men with self-reported multiple chemical sensitivity (sMCS) and age matched controls. Although 2-ethylhexanol exposure was below the occupational threshold limit value of 50 ppm, the study revealed strong dose–response relationships between airborne solvent concentrations and blink rates. During 40 ppm peak exposures the blink rate increased threefold. In the course of 4 h, exposure blink rates increased significantly showing no adaptation. Subjects with sMCS revealed, with one exception at start of exposure, no significantly higher blink rates than controls. The results indicate that the irritative potential of 2-ethylhexanol is higher than commonly expected. In both exposure scenarios with either constant or peak exposures, electromyographic eye blink recordings were an appropriate method for the examination of acute sensory irritations in time.

Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor and histamine in patients with self-reported multiple chemical sensitivity

Plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor, but not histamine, were elevated in patients with self-reported multiple chemical sensitivity (sMCS). Exposure to volatile organic compounds (VOC) increased plasma levels of all parameters in these patients, while it had no effect in normal subjects or patients with atopic eczema/dermatitis syndrome (AEDS). Exposure to VOC also enhanced skin wheal responses induced by histamine in patients with sMCS, while it failed to do so in normal or AEDS subjects. These results indicate that exposure to VOC may enhance neurogenic inflammation with concomitant enhancement of histamine-induced responses.

477 Diverging trends of subjective, autonomic, and inflammatory responses in young adults with self-reported multiple chemical sensitivity (SMCS)

The origin of idiopathic environmental intolerances (IEIs) is an open question. According to the psychological approaches, various top-down factors play a dominant role in the development of IEIs. The general psychopathology model assumes a propensity towards mental ill-health (negative affectivity) increases the probability of developing IEIs. The attribution model emphasizes the importance of mistaken attribution of experienced somatic symptoms; thus, more symptoms should lead to more IEIs. Finally, the nocebo model highlights the role of expectations in the development of IEIs. In this case, worries about the harmful effects of environmental factors are assumed to evoke IEIs.We estimated cross-lagged panel models with latent variables based on longitudinal data obtained at two time points (six years apart) from a large near-representative community sample to test the hypothesized associations. Indicators of chemical intolerance, electromagnetic hypersensitivity, and sound sensitivity fit well under a common latent factor of IEIs. This factor, in turn, showed considerable temporal stability. However, whereas a positive association was found between IEIs and increased somatic symptoms and modern health worries six years later, the changes therein could not be predicted as hypothesized by the three psychological models. We discuss the implications of these results, as well as methodological aspects in the measurement and prediction of change in IEIs.

Perceived treatment efficacy for conventional and alternative therapies reported by persons with multiple chemical sensitivity.

Multiple chemical sensitivity (MCS) is a condition in which persons experience negative health effects in multiple organ systems from exposure to low levels of common chemicals. Although symptoms experienced from particular chemicals vary across persons, they are generally stable within persons. The sensitivities often spread over time, first to related chemicals and then to other classes of chemicals. This study examined self-reported perceived treatment efficacy of 101 treatments used by 917 persons with self-reported MCS. Treatments examined included environmental medicine techniques, holistic therapies, individual nutritional supplements, detoxification techniques, body therapies, Eastern-origin techniques, newer therapies, prescription items, and others. The three most highly rated treatments were creating a chemical-free living space, chemical avoidance, and prayer. Both creating a chemical-free living space and chemical avoidance were rated by 95% of respondents as helpful. Results for most therapies were mixed. Participants had consulted a mean of 12 health care providers and spent over one-third of their annual income on health care costs. We discuss this drain on personal resources and describe respondents' attitudes toward the possibility of healing from MCS.

Application of Quick Environment Exposure Sensitivity Inventory (QEESI©) for Japanese population: study of reliability and validity of the questionnaire

A standardized questionnaire has not been established for screening or diagnostic assessment of patients with multiple chemical sensitivity (MCS) in Japan. In the US, Miller and Prihoda (1999a,b) developed a questionnaire that could be used internationally, the Quick Environment Exposure Sensitivity Inventory (QEESI), to assist researchers and clinicians in evaluating patients and populations for chemical sensitivity. The Japanese version of QEESI was subsequently translated by Ishikawa and Miyata (1999). The present study was performed to investigate the reliability and validity of QEESI (Japanese version) for research purposes and for evaluation of patients with MCS in Japan. A total of 498 subjects were recruited from the general population of Miyagi prefecture, Japan. The factor structure in QEESI was analyzed with 40 items on four subscales except for the items in 'Masking' using principal components analysis with Promax rotation. The results showed that 30 items on three subscales, 'Chemical Inhalant Intolerances,' 'Symptom Severity,' and 'Life Impact' except for 'Other Intolerances' were consistent with those reported for the US population by Miller and Prihoda (1999a). Cronbach's alpha reliability coefficient ranged between 0.87 and 0.94 indicating high internal consistency in the 30 items on three subscales. Next, we compared the mean scores on three subscales of QEESI in two groups: 131 self-reported MCS group who were new outpatients at the Environmental Medical Center in Kitasato Institute Hospital, and 131 members of the general population (controls) who were matched for both gender and age with the self-reported MCS group. Mean scores on each subscale for the self-reported MCS group were significantly greater than those for controls (P <0.001). Mean scores on all of the 30 items on three subscales for the self-reported MCS group were also significantly greater than for the controls (P <0.001). These findings indicated that the 30 items on three subscales in QEESI can be used for surveys and for diagnostic assessment of patients with MCS as well as for comparative studies between patients in Japan and in other countries.

Breathing and Heart Rate during Experimental Solvent Exposure of Young Adults with Self-Reported Multiple Chemical Sensitivity (sMCS)

This paper deals with the assumption that young adults with self-reported multiple chemical sensitivity (sMCS) show a heightened sensitivity of autonomic functions during experimental solvent exposure. Male sMCS-subjects were selected (out of n=274) on the base of a German questionnaire on chemical and environmental sensitivity (CGES). Two independent experiments were carried out, each with 12 sMCS-subjects and 12 age-matched control-subjects. In experiment I two concentrations of the solvents ethyl benzene (10 and 98 ppm) and 2-butanone (10 and 189 ppm) were used. Experiment II investigated 2-propanol (35 and 190 ppm) and 1-octanol (0.1 and 6.4 ppm). The low concentrations correspond nearly to the olfactory thresholds while the high concentrations correspond to the German occupational threshold limit values (MAC). The exposure duration under each condition was 4 h. The sequence of the four exposure conditions was random including intervals of at least 2 days without exposure. During the exposure physiological changes of breathing rate and heart rate were recorded. Two 30 min intervals with a sedentary position of the subjects at the beginning and end of exposure were chosen for analyses. Neither in experiment I nor in experiment II significant specific reactions to the type or level of the exposures were found. The autonomic functions in both experiments revealed alterations within the exposure sessions. The heart rate in experiment II and the breathing rate in both experiments decreased significantly during the analyzed 30 min intervals. Furthermore, in both experiments the heart rates decreased significantly from beginning to end of exposure. Only in experiment I the mean breathing rate of sMCS-subjects was generally higher compared to the control-subjects. Regarding the assumption of a heightened sensitivity of sMCS-subjects the two experiments yielded controversial results. Thus, the hypothesis of stronger responses of autonomic functions of sMCS-subjects provoked by various exposure scenarios remains open.

Psychophysiological functions of subjects with self-reported multiple chemical sensitivity (sMCS) during experimental solvent exposure

AbstractThe study examined the assumption of a higher sensitivity of autonomic functions of subjects with self-reported multiple chemical sensitivity (sMCS) during environmental exposure. The hypothesis was tested in a laboratory study with standardized exposures.Twelve healthy male subjects (26.4±5.4y) with and 12 male control subjects (25.7±3.8y) without self-reported multiple chemical sensitivity (sMCS), selected by a questionnaire, were included in the experimental study. At four different days the subjects were exposed in a random order to solvents for four hours: 10ppm or 98ppm ethyl benzene, 10ppm or 189ppm 2-butanone. Heart rate and breathing rate were analysed for two 30-minutes periods of vigilance testing at the beginning and end of exposure.In sMCS-subjects both functions were elevated at the beginning of the testing periods with a tendency to decrease over the 30-minutes periods. Control subjects revealed a relatively constant level (breathing rate) and a small increase (heart rate) during the periods. These group differences were obvious for all experimental conditions across substances and levels of exposures. Furthermore, the mean of the breathing rate of sMCS-subjects was generally higher compared to the control subjects. While the assumption of a generally altered sensitivity of autonomic functions of sMCS-subjects to environmental changes seems to be supported, no specific reactions to the type or level of the chemical exposure were found.

Time courses of sensory irritations due to 2-butanone and ethyl benzene exposure: Influences of self-reported multiple chemical sensitivity (sMCS)

AbstractThe 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 sub-clinical 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 24healthy 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’, the relevance of toxic, neurobiological and psychic effect mechanisms

The review deals mainly with the key question of chemical causation of multiple chemical sensitivity (MCS). There are only few human studies with valid information on chemical exposure and in no study the chemical toxic causation hypothesis is supported. The animal model of olfactory-limbic/neural sensitization is of heuristic value to explain MCS phenomena and includes both chemical and non-chemical Stressors. However, in animal studies seldom chemical substances and exposure levels were used which might be of relevance in the formation of MCS. The problem is demonstrated for toluene exposures in human and animal sensitization studies. In accordance with the sensitization hypotheses, human studies prove a generalized vulnerability to environmental stimuli in subjects with self-reported MCS. However, study designs do not allow to deduce whether the strong responsivity is a premorbid or comorbid phenomenon or is related to exposure. Alternative study approaches to evaluate dose-response relationships are proposed.