MCS Position Statement

Multiple chemical sensitivity (MCS) is an environmental illness (EI) in which negative neurological, pulmonary, cardiac, and rheumatic health effects, among others, are experienced from exposure to common environmental chemicals including fragrances, cleaners, pesticides, and other petrochemicals at concentrations that are below regulatory toxicity thresholds and that are normally deemed as safe.1-2 In 1989, consensus criteria were established for the diagnoses and definition of MCS and they were revised in 1999.3 The case criteria define MCS for diagnostic purposes as meeting six criteria: 3

1. The condition is chronic.
2. Symptoms recur reproducibly with repeated chemical exposure.
3. Symptoms recur in response to lower levels of chemicals than previously tolerated.
4. Symptoms appear in response to multiple chemically unrelated substances.
5. Symptoms improve or resolve when chemical incitants are removed.
6. Multiple organ systems are affected.

This paper will support the position that MCS is a disorder of organic biological origin induced by toxic environmental insults, and requires immediate recognition in the workplace, medical community, school system, and public places across America; and that it is crucial that environmental toxicants are identified and reduced or effectively regulated and enforced through legislation to prevent additional injury to citizens.

Current Evidence of MCS

Nuclear medicine utilizes SPECT (Single Photon Emission Computerized Tomography) technology to perform brain scans which records brain functioning by measuring perfusion (blood flow).4 MCS patients commonly have a lower baseline flow of blood to the brain, and develop further decreases in brain perfusion upon exposure to perfumes and petrochemicals.5-7 Individuals with chronic symptoms show long-term reduced blood flow to the brain and reduced ability of the brain to take up the tracer substance in the early phase of injection, indicating a pattern of neurotoxic metabolic abnormality.7-11 Over 90% of MCS patients exhibit a pattern of neurotoxic metabolic abnormalities in the brain that is consistent with toxic encephalopathy, but that is not consistent with the changes associated with psychiatric disease.10-11 SPECT brain scans on MCS patients with chronic symptoms following toxic exposure to various petrochemical, perfume, and related compounds have thus provided evidence to support an organic, biological basis to MCS when compared with healthy control subjects.6-11

Numerous studies have documented toxic encephalopathy and other adverse reactions resulting from low level chronic exposure to various chemicals.12-15 Researchers have identified numerous physiological abnormalities in MCS subjects, including cardiac abnormalities16-18, reactive upper airway disease155, vasculitis19, thrombophlebitis20, impaired Phase 1 and Phase II detoxification clearance16, glutathione depletion16,21, tinnitus22, thyroid and adrenal abnormalities23, gastrointestinal disturbances155, T-cell activation/impaired NK cell function/auto-immune disorders16,25-26, vitamin and mineral deficiencies16,27, nuerocognitive decline16,28-29, rhinitis30, sinusitis30, respiratory inflammation17, abnormal methacholine challenge17, somatosensory abnormality31, peripheral neuropathy16, sleep disturbance32, impaired balance16, and elevated levels of xenobiotics25 among others.

Mast cell activation and disorders of porphyrin metabolism have also been linked to MCS.16,33 Those with mastocytosis can be exquisitely sensitive to even small amounts of chemicals.33 A group of MCS patients tested for mast cell disease showed some patients actually had mastocytosis and others were found to have a mast cell disorder.33 Porphyrin enzyme abnormalities have also been shown to manifest in blood enzyme deficiencies and chemical sensitivity in 86% of subjects.34

Research suggests substantial individual differences in chemical sensitivity, often spanning orders of magnitude.35 There are more than 40 studies on MCS published from the United States, Canada, Europe, Japan, and Australia which have shown that most cases of MCS are initiated after one or more exposures to organic solvents and three classes of pesticides.157,163 The pattern of causality by chemical exposure is well documented.157,163,165 Evidence now shows that genes controlling the activity of enzymes known to have roles in the metabolism of these organic solvents and pesticides, also have roles in determining increased susceptibility to MCS.163,165 The epidemiological evidence and genetic evidence of causality is further supported by the Hill criteria, which was developed to determine the likelihood of a causal role for environmental factors in disease.163-165

Genetic differences relating to detoxification processes are present more often in those with MCS than those without.67 Five genetic polymorphisms have a statistically significant role in determining MCS prevalence.67 People with a ''high'' expression of two specific genes (CYP2D6 and NAT2) were shown to be 18 times more likely to have MCS.67 Each of these genes encodes proteins that metabolize chemicals previously implicated in MCS, notably some organophosphorus pesticides (PON1 and PON2 genes) and the organic solvents (CYP2D, NAT1 and NAT2 genes). 67 Chemicals shown to initiate MCS must be in a specific chemical form to be active; therefore, individuals who metabolize them at different rates vary in their susceptibility to MCS.67 Genetic predisposition for MCS may involve altered biotransformation of environmental chemicals.66 Haley found similar, confirmatory results with the PON1 gene in studies of the Gulf War syndrome veterans65, findings that have been confirmed by Furlong, Hulla, and Thier.156-158

Another study analyzed genetic variants of four genes: NAT2, GSTM1, GSTT1, and GSTP1. The GST- genes code for enzymes in the glutathione system, the body’s frontline defense against xenobiotics.37 Individuals who are NAT2 slow acetylators and those with homozygously deleted GSTM1 and GSTT1 genes are significantly more likely to develop chemical sensitivity.37 Glutathione S-transferases act to inactivate chemicals; people without these GSTM1 and GSTT1 genes are less able to metabolize environmental chemicals.37 Glutathione S-transferases play a crucial role in the process of detoxification of chemicals.37 The deletion of another gene, the GSTP1 gene, leaves individuals more susceptible to developing MCS, as lack of these genes means a loss of protection from oxidative stress.37

MCS may also be caused by low molecular weight chemicals that bind to chemoreceptors on sensory nerve C-fibers leading to the release of inflammatory mediators.38 Brain inflammation, biochemistry, oxidative stress, excitotoxicity and other interrelated mechanisms are correlated with symptoms of MCS.39,163 An accumulating body of consistent and well-documented evidence implicates elevated nitric oxide (NO) and peroxynitrite (ONOO-) as the etiology of the central nervous system and peripheral tissue sensitivities seen in MCS and other multi-system illnesses, including fibromyalgia (FM), chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD), and Gulf War syndrome.39 Peroxynitrite (ONOO-) is oxidized from nitric oxide.39-40 Excess peroxynitrite, implicated in MCS and related illnesses, depletes energy stores, which in turn causes extreme fatigue.39-40 Peroxynitrite also increases the permeability of the blood brain barrier; excess levels allow chemicals greater chemical access to the brain.40 Breakdown of the blood brain barrier has been shown in MCS patients by Kuklinski and in animal models of MCS by Abou-Donia.161-162 The key effect of nitric oxide (NO) in the body is inhibition of cytochrome P-450 activity and slowing degradation of hydrophobic organic chemicals.39-40 Excess nitric oxide levels, as found in MCS patients, slows down the body’s natural detoxification processes leaving chemical toxicants in the body for a longer period of time.39-40 A reduced blood-brain barrier and increased time to naturally detoxify the body may render MCS patients subject to permanent and long-term brain and nervous system damage and toxic encephalopathy. At least thirteen stressors are implicated as initiators that begin the NO/ONOO cycle of biochemistry in these multi-system illnesses through chronic low-level exposure or a sudden acute exposure to an inciting agent, including carbon monoxide exposure, organophosphate poisoning , and ionizing radiation exposures.39,41

Prior Paradigms

There have been various claims that MCS is caused by some ill-defined and unsupported psychogenic mechanisms.42-44,50 One such theory suggests that MCS may be a Pavlovian learned fear response.44 There is no supporting evidence for the claim of a Pavlovian learned response, as Pavlovian conditioning requires the formation of an association between a conditioned stimulus (CS) and an unconditioned stimulus (US) through repetition in order for learning to occur.45 The subject would have to know, understand, and connect the dangers of chemical ingredients of the same nature as incitants, despite these ingredients being generally regarded as safe and, in the case of fragrances and many cleaning chemicals, unlabeled on the product under HHS § 720.9 of the Food and Drug Administration.46 It is quite conceivable that MCS patients learn of the chemical content of common products used in the environment after they develop MCS, when they are thus forced to educate themselves in order to practice avoidance to improve and ultimately remain well. Subjects reliably react to fragrances in provocation tests in which their nose was clamped, showing symptoms were not transmitted via the olfactory nerve, since the subjects could not smell the perfume.47-48,60-61 Much like those unaware of chemical exposure to virtually odorless products, such as carbonless copy paper or sick buildings, patients with MCS also react to chemicals which are odorless, giving no hint of impending exposure and invalidating the theory of MCS being a fear induced olfactory response or learned behavior.24,47-48,60

Psychological proponents have also purported that co-occurring depression and/or anxiety in a portion of subjects causes MCS.50-51 If this were true, then 100%, or at least a statistically significant proportion, of the subjects would have co-occurring mental illnesses, and that illness would likely have been present prior to MCS onset. Since that is not the case and the rate of co-occurring mental illness in MCS patients is similar to that of other physiologically based chronically ill populaces, then depression and/or anxiety may be ruled out as an etiologic mechanism and instead considered reactionary.52-57 Further evidence against this theory is provided by statistics that show psychotherapy and psychoactive drugs intended to cure MCS have been shown to be more likely to harm patients than help them.58 A study shows 80% of MCS patients report no benefit from psychotherapy to cure MCS and 15% have reported further harm.58 Though 65% find psychotherapy helpful to cope with the dramatic life changes MCS bestows upon them, psychotherapy is obviously not a cure, as MCS is not a psychologically mediated disease.58 Further, psychiatric drugs such as Zoloft, Prozac, Elavil, and other antidepressants were reported to harm an average of 60% of those who tried them and had no effect on an additional 25%.58 Drugs such as Valium and Xanax proved to harm 45% and had no effect on an additional 30%.58 There is not a single empirical study that shows any significant remission rate in the symptoms of a cohort of environmental illness patients from counseling or psychiatric drug therapy.

Proponents of a psychological etiology claim that MCS defies classification as a disease because it supposedly lacks evidence, and has no consistent characteristics or objective measurable features; however, all these proponents have shown is their own failure to read and cite the numerous studies in the peer-reviewed literature that report the physiological, biochemical, and genetic findings of MCS.17,30,38,58-62,76 Further, they have failed to provide any explanation for the factors distinguishing the chemicals involved in MCS from those that have no role; they have not shown how a psychological mechanism could stand behind an odorless chemical producing symptoms or a benign odiferous chemical failing to produce symptoms.63 They have also ignored the prospects for objective biomarker tests for MCS that have been published by Kimata, Millqvist, Bell and Fox and their respective colleagues, each of which is based on measurable physiological changes in response to low level chemical exposures in MCS patients.17,58-62 They have disregarded SPECT imaging results showing brain changes which are inconsistent with psychiatric disease and indicate a biological origin for MCS in neurotoxicity.7-11 More importantly, they have overlooked the genetic data of Schnakenberg, McKeown-Eyssen and her colleagues, and the earlier work of Haley and his colleagues showing that the chemicals initiating MCS act as toxicants, not as odors generating some strictly olfactory response.37,65.67 The proponents have given complete disregard to the genetic roles that meet Hill criteria and which are, by definition, causal, as subjects have no idea what forms of these genes they carry and consequently, their psychology cannot be influenced by the perception that they should be more susceptible.37,65.67,163-164 Genetic studies, coupled with known biochemical functions of the genes involved, are the recognized approach to determining the biological mechanism of MCS.66-67 These specific studies provide significant confirmation of the toxicogenic roles of chemicals previously implicated in MCS.66-67

In the past, MCS patients have been labeled as being psychogenic, largely due to the outward symptoms of physiological neurotoxicity.28,58 Patients with MCS may develop hyperactivity in deep structures of the brain during chemical exposure, explaining the emotional liability some experience, on a physiological rather than psychological basis.68 Petrochemicals and organic solvents are known etiologic mechanisms with an organic basis that induce depression, anxiety, panic attacks, and other apparent mental disorders via known organic etiologic mechanisms; but these manifestations resolve when incitants are removed, thus distinguishing them from true psychiatric illnesses.69-71 The evidence is now abundant that MCS is a true organic, biological illness.17,61-63 Patients may be helped with detoxification protocols, biochemical stabilizing therapy, and/or exposure education, and should not be sent for useless, and often harmful, psychiatric treatment and medications to cure MCS.17,61-63 Patients with MCS desire qualified medical care and the opportunity to return to a full life and career.27,73-73 Many report that they had successful, professional careers prior to becoming ill and reported that they would happily resume their old lives if they found relief from their MCS.28,72-73 This relief includes the recognition and acceptance of MCS, access to proper medical treatment, and accommodations in the school system, workplace, and public community.28,72-73

Prevalence

A surprising number of people report sensitivity to ordinary everyday chemicals.74-81 The figures range from an average of eleven to seventeen percent, with spikes as high as thirty percent of subjects who report reactions to multiple chemical incitants.74-81 The figures reveal that at least two percent, and as many as six percent, have been so bothered by chemical exposures that they sought medical care and received a doctor-diagnosis of multiple chemical sensitivity (MCS).79,81 Applying the case definition criteria3 to the average reported chemical sensitivity, it appears that 1.5 out of 10 people suffer from MCS.74-81

Health care utilization costs directly related to MCS have been estimated at approximately $1,581 annually per patient.82 The United States Population is estimated to be 302.8 million.83 Prevalence studies predict that approximately 15% of the United States population, now estimated at 302.8 million, suffers from MCS; therefore, direct health care utilization costs amount to a staggering $71.8 billion dollars per year.74-82 Estimated costs for MCS and other disorders linked to neurotoxicity amount to an additional $81.5 to $167 billion annually in lost productivity.84 Cumulative social and economic costs identified in four case studies of illnesses that are candidates for environmental causation totaled between $568 billion and $793 billion dollars per year.85

Evidence of the Toxicity of Everyday Chemicals

Various studies of product safety generating EPA safe limits have failed to consider the impact of combined exposures in day-to-day living, which add to the body burden of chemicals in humans and must be utilized, expelled, or stored.2,86-116 Many of the chemicals that act as MCS incitants, including fragrances, cleaning products, air fresheners, fabric softeners, disposable diapers, and pesticides, have been scientifically shown to elicit symptoms of toxicity in “normals” at levels of common, and often unavoidable, exposure in the environment. 117-128,130.134,136 At the time the Toxic Substances Control Act (TSCA) of 1976 was passed, the chemical industry effectively grandfathered substances already on the market and exempted them from testing.160 Europe has taken a more pro-actively protective stance than the United States through REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances) legislation.159 The aim of REACH is to improve the protection of human health and the environment through the better and earlier identification of the intrinsic properties of chemical substances.159 Products used by United States consumers on a daily basis are continually and routinely recalled for toxic effects, as recent recalls of lead tainted toys, popcorn flavoring, and FEMA trailers, to name a few, demonstrate.138-140

After inhalation, chemicals enter the limbic system, affecting the hypothalamus and pituitary; and through pituitary control, elicit some symptoms though affecting adrenal, thyroid and reproductive function.130-132 Tests have shown verifiable and chronic changes in brain function after petrochemical exposure and determined that exposure to chemicals through inhalation may aggravate the allergic lung inflammation.64,128,129,132, 135 Developing organisms are generally recognized as differentially sensitive to chemical exposure because of toxicokinetic and/or toxicodynamic factors.141

Fragrances have been shown to cause sensory irritation, pulmonary irritation, decreases in expiratory airflow velocity, and alterations of the functional observational battery in mice, indicative of neurotoxicity after an hour of normal level exposure to common cologne. The severity of the symptoms increased after mice were repeatedly exposed to the fragranced product.117 Subsequent analysis of the test atmosphere revealed the presence of chemicals with known irritant and neurotoxic properties, providing a toxicological basis to explain human complaints of adverse reactions to fragrances.117

The use of consumer cleaning agents and air freshener may yield high levels of volatile organic compounds (VOC’s).133-134 Consumer cleaning products were shown to contain glycol ethers, which are regulated toxic air contaminants, as well as terpenes, which can react with ozone to form a variety of secondary pollutants such as formaldehyde and ultrafine particles.133 Known chemical toxicants are emitted during air-freshener use, including d-limonene, dihydromyrcenol, linalool, linalyl acetate, beta-citronellol, alpha-pinene, beta-pinene, 3-carene, camphene, benzyl propionate, benzyl alcohol, bornyl acetate, isobornyl acetate, and benzaldehyde.118,133-134 Maternal depression has been significantly associated with air freshener use in the home136 and one name brand air freshener, which contains short chain aliphatic hydrocarbons, was shown to induce fatal ventricular fibrillation.119 Air fresheners, at concentrations to which individuals are actually exposed, have been linked to increases in sensory and pulmonary irritation, decreases in airflow velocity, and abnormalities of behavior as measured by the functional observational battery score, providing a toxicological explanation for human complaints of adverse reactions to air fresheners.120

Laundry products, particularly fabric softener emissions, have been shown to induce sensory irritation, pulmonary irritation, mild inflammation of the lungs, and airflow limitation in mice.121 Dry laundry and linen, like that which consumers wear and sleep on, was shown to emit sufficient chemical residue to cause sensory irritation.121 Analysis of the emissions of a dryer sheet revealed concentrations of the respiratory irritants isopropylbenzene, styrene, trimethylbenzene, phenol, and thymol, and induced respiratory affects when left in a room overnight with mice.121 The results of this study provide a toxicological basis for human complaints of adverse reactions to fabric softener emissions.121

Pesticides are known endocrine disruptors and have been shown to delay sexual maturity and interfere with sex hormone synthesis, and have been linked to increased malaise, chronic illness, asthma, mortality, cancer, leukemia, lupus, Parkinson disease, diabetes, and decreased neuropsychologic functioning scores, neurobehavioral performance, cognitive function, psychomotor function, sensory/motor function, and nerve conduction.123-127,137

Disposable diapers have been demonstrated to emit mixtures of chemicals with documented respiratory toxicity, inducing sensory irritation, reduced mid-expiratory airflow velocity, increased respiratory rates, and increased tidal volume.122

Advanced stages of multiple chemical sensitivity can lead to organ failure.144-145 Many observable and empirical, scientific facts accompany MCS including SPECT scan changes, vitamin deficiencies, mineral deficiencies, excess amino acid deficiency, and disturbed lipid and carbohydrate metabolism.2,7,9,146 While the germ theory of illness was the main threat to health, the zeal to kill germs with chemical toxicants has now created a health paradigm shift in which chemicals have become the main threats to health, as many diseases are now being linked to chemical and toxic origin.

Worldwide Recognition

The Centers for Disease Control (CDC) recently recognized chemical sensitivity as a symptom of myalgic encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS).147 Studies have shown that removal of incitants and proper environmental control is the most efficacious treatment known to date.58,148-151 Ninety-five percent of patients report improvement upon practicing avoidance and 94% report improvement upon moving to a chemical free living space.58 Clearly educating patients to avoid chemical irritants and toxicants is most helpful.58,148-151

MCS is already formally recognized by the national health care system in Germany.152 The Danish Environmental Protection Agency has already concluded that there is ample evidence that MCS is due to environmental contaminants and has taken initiative to minimize off-gassing materials in the indoor environment in efforts to prevent the development of new cases of MCS.152 The government of Sweden recognizes electrical sensitivity as a disability.152 Canada has also recognized MCS and has taken preventive measures by limiting the use of pesticides, fragrances, and other toxicants.152 Diagnostic criteria for MCS have been accepted internationally and are currently under review to consider new findings; the recognition of MCS at all levels of government is steadily increasing.152 We are now seeing public policy and regulations advance towards protecting people from tobacco smoke, pesticides, fragrances, vehicle exhaust, and other chemicals in public places.152 More than one half of the states in the US have already provided a proclamation deeming at least one day or month dedicated for MCS and/or Toxic Injury Awareness.153

Therefore, it is essential that MCS be immediately and fully recognized in America as an organic physiological disorder induced by toxic environmental insults. Environmental toxicants and irritants from perfumes, smoke, pesticides, industry, and building materials must be reduced or effectively regulated through legislation and enforcement to prevent injury to all citizens. Immediate accommodation with a safe environment for school, work, and housing should be granted to MCS victims who are still capable of working, while those permanently injured should receive disability benefits. The Americans with Disabilities Act must be enforced, to provide the same rights to MCS patients as other disabilities, with protection from abuse, harassment, and discrimination. As new information is published regarding MCS, it is crucial that it be communicated to the medical and public communities. Accurate, objective information which is free from conflicts of interests, ties to the chemical industry, and connections to the pharmaceutical industry must be rigorously researched and widely disseminated. Funding is immediately and direly needed for additional investigation into the etiology, treatment, and prevention of this costly, devastating, and disabling disorder.

The future of America is in our collective hands. It is crucial that industrial financial gain must not be permitted to compromise the health and well being of all citizens. There are alternatives to the toxic products and pollution man has created. A shift to these safer alternatives will be market-driven as accurate information on risks becomes readily available; meanwhile informed and enlightened regulation is highly encouraged in order to prevent MCS in the future and allow current patients to engage fully in society as productive members without threat of further injury. We must never forget that many MCS patients can and do function normally in exposure free conditions. It is time to move past the view that science does not a grasp of MCS.154 Sufficient clear and present evidence is currently available to show that MCS is real and disabling, and to justify, indeed to demand, immediate action.