Over the last 20 years physicians and scientists at the Environmental Health Center-Dallas have had an opportunity to observe over 20,000 patients who had chemical sensitivity problems. These patients were studied under various degrees of environmental control. This experience is unique in the world and has resulted in numerous peer-reviewed scientific articles, chapters in books, and books on this subject. Studies have resulted in over 32,000 challenge tests by inhalation, oral or injection methods, of which 16,000 are double blind. Blood chemical levels and fat biopsies for organic hydrocarbons number over 2,000, while the measurement of immune parameters is over 5,000 tests. Objective brain function tests have been accomplished in over 5,000 patients. Other objective tests, like computerized balance studies, depollutant enzyme levels, and autonomic nervous system changes, as measured by the Iriscorder, number near 1,000.

We wish to share our findings with the participants of the Japanese Society of Clinical Ecology for the study of chemical sensitivity.
 

To demonstrate cause-and-effect proof of environmental influences on an individual’s health, one must understand several important principles and facts. These principles involve those of total body load (burden), adaptation (masking, acute toxicological tolerance), bipolarity, biochemical individuality, the spreading phenomenon, and the switch phenomenon. Each principle will be discussed separately.
 

Some individuals, for example, are born with significantly lower quantities of specific enzymes (it may be 75%, 50%, or even 25% of the normals). Their response to environmental stimuli is often considerably weaker than those born with 100% of the normal detoxifying enzymes and immune parameters. Examples are the babies with phenylketonuria or the individuals with transferase deficiency, who do well until exposed to their environmental triggers, and then damage sets in. There are over 2,000 genetically transmitted metabolic errors, suggesting that most of the population will have at least one abnormality.⁴¹ Toxic volatile organic chemicals have been shown by Laseter to bioconcentrate in the fetus, increasing the acquired burden in some babies.⁴² It is well known that some individuals acquire their toxic load at work or around their homes.⁴² This changes with different seasons and weather conditions, giving variable effects and responses over time. Extreme care must be taken in evaluation of each patient, who may exhibit unique clinical responses due to his specific biochemical individuality. As an example, it is well known that not all patients will exhibit every reported symptom associated with systemic lupus erythematosus (SLE). Similarly, each patient exposed to the same environmental pollutant will react with his or her unique complex of symptoms. Because this vital fact is misunderstood, many studies are flawed when the wrong signs and symptoms are assessed for that individual.
 

Spreading may occur for many reasons. It may be due to a failure of the detoxification mechanisms’ oxidation, reduction, degradation, and conjugation brought about by pollutant overload, or it may occur because of depletion of the nutrient fuels of the enzyme or coenzyme, nutrient fuels, such as zinc, magnesium, all B vitamins, amino acid, or fatty acid. This depletion may account for the increasing inability of the body to detoxify and respond appropriately. The blood brain barrier or peripheral cellular membranes of the skin, lung, nasal mucosa, and gastrointestinal or genitourinary systems may be damaged, allowing previously excluded toxic and nontoxic substances to penetrate to areas that increase the risk of harm. Physiologic parameters including immune or pharmacologic releasing mechanisms, such as serotonin, kinin, and other vasoactive amides, may become so damaged that they are triggered by many toxic, then nontoxic (e.g., food) substances in addition to the specific one to which they initially reacted. It is well substantiated that antigen recognition sites may be disturbed or destroyed by pollutant overload. Hormone deregulation (feedback mechanisms) may occur, allowing for still greater dysfunction and sensitivity.¹⁵²

In contrast to patients who experience increased sensitivity to multiple triggering agents, some chemically sensitive patients may have one isolated organ involved in their disease process for years only to have dysfunction spread to other organs as their resistance mechanisms break down. This kind of spreading from one to another or multiple end-organs enables the progression of hypersensitivity and the eventual onset of fixed-named disease.¹⁵²

The switch phenomenon is the changing of pollutant-stimulated responses from one end-organ response to another. This change usually occurs acutely, but it may occur over a much longer period of time. This phenomenon was first described by Savage in the 1800s. He observed that when mental patients were at their worst they usually had a remission of their asthma or sinusitis. When they were better mentally and they were seen in the outpatient clinic, they had a much higher incidence of sinus and asthma problems. Randolph and most other environmentally oriented physicians have also observed this phenomenon. At the EHC-Dallas, we have observed similar occurrences in our patients, and, in fact, take cognizance of this phenomenon when evaluating therapy outcome.¹⁵²

In observing thousands of controlled challenges in the environmental unit, we have seen the target organ responses of many of our patients switch to several different ones during a long (i.e, 24h) reaction. Often, we have seen, for example, transient brain dysfunction followed by arthralgia, followed by diarrhea, followed by arrhythmia.¹⁵²

The switch phenomenon has also been seen following unsuspected or unrecognized pollutant exposures. For example, an individual sprays his home with pesticides and subsequently visits a neurologist with complaints of headaches and a rheumatologist with symptoms of arthritis. Never noticing or suspecting a connection between his exposure and the onset of his symptoms, he fails to disclose to either doctor symptoms unrelated to their specialty or the fact of his exposure. Instead, he submits to symptomatic treatment by both physicians. His health my temporarily improve, but in all likelihood, his total body load will remain elevated and he will become increasingly vulnerable to additional exposures that result in a still greater variety of symptoms.¹⁵²

Even when therapy for pollutant injury appears to have been effective, the switch phenomenon may be disguising the fact that the body is still harboring a pollutants. In this case, a new set of symptoms may begin indicating that a pollutant response has simply switched to another end-organ. This phenomenon occurs frequently when symptom-suppressing medication therapy or inadequate environmental manipulation is used over a period of time. For example, a patient may have his sinusitis cleared by medication (e.g., cortisone), but later since the cause has not been eliminated, he may develop arthralgia and eventually arthritis, or his colitis may have cleared only later to have cystitis develop. Because the occurrence of switch phenomenon is both common and insidious, it is essential that physicians monitor their patients for the onset of any new symptoms or problems.¹⁵²

The switch phenomenon with its cluster of disparate symptoms signals a problem that is a part of a larger pattern needing further investigation. If physicians were cognizant of this phenomenon during initial patient evaluation, they could help curtail a lifelong progression of illness through better diagnosis and treatment.¹⁵²

In order to accomplish concise studies of the chemical sensitivity phenomena, one must understand some facts about environmental pollutants.

Modern technology’s rapidly accelerating rate of growth has produced a wide variety of chemical products that contribute to the total chemical environment. Recent studies show that nearly 50% of the global atmospheric pollutants are generated by man (either isolated from natural products or synthesized), and the ubiquitous nature of the toxic chemical agents is widely appreciated.^8,13,14 It has been estimated that more than 2,000 new chemical compounds are introduced annually and that over 60,000 different organic chemicals are used commercially today.

The widespread presence of hazardous chemicals has rendered critical the environmental sensitivity problems described by Randolph⁴³ almost 40 years ago. While celebrated instances of gross contamination have long been the object of professional attention, only recently have literally thousands of synthetic chemical products, heretofore believed innocuous, been incriminated as agents of homeostatic dysfunction.^{11, 14} Current data affirm the view that standard methods for the determination of chemical incitants may no longer be effective.^{1, 7, 8, 26} With the finding that sensitivities can occur from subthreshold and picomolar quantities of chemicals has come the discovery that standard procedures such as skin prick or scratch tests often fail to demonstrate positive reactions that are otherwise verifiable.

Recent literature confirms the harmful effects of chemical incitants, like formaldehyde,^44,45 phenol,^45,46 some pesticides,⁷ chlorine,⁴⁷ and petroleum alcohol.⁴⁸ Commonly encountered chemicals like glycine, ^{9, 49} DDT, toluene, and turpentine,^50-52 and drugs such as hydralazine have been found to induce advanced-staged disease process.⁵³

A number of familiar metals have also been incriminated, among them nickel, cobalt, chromium,⁵⁴ aluminum,⁵⁵ mercury,⁵⁶ and platinum.⁵⁷ Other common environmental chemical incitants include xylene,⁵⁸ various acrylates,⁵⁹ and acrylated prepolymers,⁶⁰ benzoyl peroxide, carbon tetrachloride,⁶¹ sulfates,⁶² and dithiocarbamates,⁶³ and diisocyannates.⁶⁴
 

 City water, much of it secondhand, often contains from 100 to 10,000 times as many synthetic compounds as natural spring water.⁶⁶ This, coupled with the rapid growth in the use of synthetic chemicals, has focused concern on the chemical quality of drinking water.¹³ Although microbes are important, attention is now being drawn to the microchemical contaminants. Advances in analytic chemistry have been able to reveal chemical contaminants in the parts-per-billion or parts-per-trillion range. It is a serious mistake to assume that extensive contamination of drinking water with "low" levels of synthetic pollutants is "normal." These chemicals are widespread, and we should not be lulled into assuming these contaminants are innocuous. Examination of our ground water has revealed many hundreds of toxic chemicals in these ranges.^67,68

Many examples of water contamination include Times Beach, Missouri, with winter floods flushing dioxin-contaminated oil used 20 years ago, Niagra’s Love Canal area, Waterbury, Connecticut, and Middleboro, Kentucky.⁶⁹

In many cases, deadly materials have been accumulating for years in dumps and landfills. In the United States, some 80,000 pits and toxic waste lagoons hold chemicals ranging from carbon tetrachloride to discarded mustard-gas bombs.⁶⁸ Slowly escaping from burial sites, these leftovers directly contaminate our ground water. Polluted ground water exists at 347 of the nations 418 worst chemical dumps, and probably is occurring in the rest.⁶⁸ Laseter⁷ and others⁷⁰ have shown that a virtual organic chemistry laboratory exists in most drinking water.

In the early 1980s, California, New York, New Jersey, Arizona, Nova Scotia, and Pennsylvania condemned dozens of public water supply wells due to trichlorethylene or tetrachloroethylene pollution.⁷¹ Leaking fuel tanks contaminated nine Kansas public water supplies in 1981.⁷¹ Officials in New Mexico identified 25 cities where hydrocarbons and solvents contaminated the ground water.⁷¹ Analysis of New Orleans drinking water alone revealed the presence of thirteen halogenated hydrocarbons.

Sources of water pollution fall into three major categories: (1) municipal sewage; (2) agricultural wastes; and (3) industrial wastes. Approximately 55% of the water treated in municipal plants is from homes, while another 45% is from industry. Agricultural wastes include those from livestock and toxic chemicals (pesticides, herbicides, fertilizers), and farm runoff collects in rivers, lakes, and ground water. Industrial wastes, however, contain some of our more toxic substances. Over one-half of the total volume of industrial wastes come from paper mills, organic chemical manufacturing plants, petroleum companies, and steel manufacturing. The major pollutants are chemical by-products, oil, grease, radioactive waste, and heat. Other sources of contamination are drinking water disinfectants and by-products⁶⁸; it should be remembered that chlorine, interacting with organic material, produces toxic trihalomethanes and other organochlorines. Alternatives to treating water with chlorine include ozone, chloramines, ultraviolet irradiation, iodination, or home reverse osmosis and charcoal filtration.⁶⁸

Chloride, added at many sewage treatment plants, can also react with organic matter in the water to form chlorinated hydrocarbons, many of which are also known to cause cancer. Copper sulfate, aluminum sulfate, and fluorine are other major contaminants that may add to the total body burden.⁶⁸

Over a thousand different toxic chemicals have been found in public water supplies, including pesticides, herbicides, industrial solvents, and polychlorinated biphenyl, just to name a few.

Inorganic pollutants include arsenic, cadmium, chromium, copper, manganese, mercury, silver, and selenium.¹³ The use of inorganic arsenic insecticides has led to high arsenic levels in some water supplies.¹³ Barium (greater than 1 mg/L) has toxic effects on the heart, blood vessels, and nerves,⁶⁸ while cadmium at levels greater than 0.01 mg/L has adverse arterial effects. At levels greater than 1 mg/L or 1 ppm, the following metals found as water contaminants have produced severe chronic toxicity: antimony,⁷² beryllium,⁷³ cobalt,⁷³ gold,⁷³ iodine,¹³ lithium,⁷³ mercury,¹⁴ and vanadium.⁷³

In Minamata, Japan, between 1953 and 1960, various plastic companies dumped methylmercury chloride into the water, producing 50 to 85 ppm or 12 mercury in nearby fish. After ingesting these mercury-contaminated fish, 406 people died, and the adverse toxicological effects in developing children are continuing to be measured.⁷⁵

A recently completed study⁷⁶ found that skin absorption contributed from 29 to 91% of the total body dose of pollutants (from water), with an average of about 64%. This is even more important when one looks at the large number of volatile organic compounds found in our drinking and bath water.

Radiation occurs in some waters in the form of radon, a naturally occurring radionuclide that seeps from rock and may be concentrated in airtight homes, especially the basements. At this stage, more information is needed to fully assess its effects. It probably, however, can increase the total body load.

In 1965, a serious drinking-water problem was seen in 40% of patients hospitalized for a program of comprehensive environmental control.^1,77,78 Today it is up to 80%. We have found that patients susceptible to water contaminants virtually always exhibit multiple sensitivities, with advanced and severe environmental reactions, especially to airborne chemicals.¹ Interestingly, water sensitivity in children was found to increase on a circadian and seasonal basis.⁷⁹ Increased severity was seen during June and July or in September and October, when grass, pollen, and mold counts were also high.⁷⁹ Some ECU patients had difficulty with waters containing high levels of sodium, others with calcium, and still others with high bicarbonate waters. A few individuals tolerated distilled water, even though it contained some hydrocarbon residuals. Hundreds of outpatients have shown symptoms in reaction to both chlorinated and nonchlorinated waters, including numerous spring, charcoal-filtered, and distilled waters. If these water-induced symptoms remain undiscovered, food and chemical testing may be distorted. It is vital to test and find safe water before proceeding with other testing in these severely sensitive individuals.
 

The literature abounds with reports of chemical sensitivities^{80, 81} to many additives. Contaminant reactions complicate the study of food sensitivity, forcing one to define more clearly the nature of the incitant, not only as it is encountered in foods but also as it is encountered in the air and water. Bell⁸² has reported urticarial reactions and immunological changes to exposures to a number of food additives. Condemi⁸³ and Bell both suggest that food dyes may trigger reactions in sensitive individuals, including conditions commonly thought to be psychogenic or certain forms of hyperactivity.^{28, 84-89} Lindemayer⁹⁰ has associated urticarial reactions with several additives such as hydroxybenzoic acid propylester, benzoic acid, sodium benzoate, Ponceau rouge, and indigo carmine. Monroe’s data indicate a causal role played by tartrazine azo dyes and salicylates in the provocation of vascular alterations.³⁶ Other additives, including sodium nitrite and sodium glutamate, have been found to trigger migraine phenomena in susceptible patients.⁹¹

Sulfur dioxide¹⁶ and sodium salicylate can provoke asthmatic reactions⁹² while aspirin-like food contaminants and dyes may trigger urticaria, angioedema, bronchoconstriction and purpura.⁹³ An even wider variety of symptoms, including severe gastrointestinal disorder, has been associated with sensitivities to aniline, commonly found rapeseed oil.⁹⁴

In our experience, natural toxic components of foods, such as alkaloids, phenols, lectins, etc. must also be accounted for when one studyies the secondary food sensitivity that occurs from pollutant overload in the chemically sensitive individual. Therefore, three factors must be considered when evaluating the total food load. These are manmade pollutant contamination, natural toxic effects of foods, and food sensitivity. Failure to consider all three in the chemically sensitive patient may color or negate an otherwise clearly defined case of chemical sensitivity.
 

There exist widespread reports of sensitivities to chemicals in textiles, including synthetic acrylic fibers,¹¹⁴ polyester spin finishes,¹¹⁵ the epoxy resins, and synthetic clothing.¹¹⁶ Products such as fabric spray starch may also be considered toxic for the chemically sensitive individual,¹¹⁷ for whom even the metallic buttons on blue jeans may trigger reactions to nickel.¹¹⁸ Formaldehyde⁴⁴ on synthetics or tetrachloroethylene from dry-cleaned clothing can also causee problems.

Household cleaning products, particularly those containing formaldehyde, phenols, and chlorine, are hazardous for many patients. Several laundry products and detergents may be identified as household incitants,¹¹⁹ as well as a number of products use to clean and polish furniture.¹²⁰

The very construction of many homes may prove dangerous for the chemically sensitive patient. Data suggests that chemicals contained in wood preservatives (e.g., pentachlorophenols) are environmental incitants capable of triggering a variety of symptoms.^121-123 Others report problems with reactions to formaldehyde-containing pressed board, carpets, plywood and petrochemical contaminants.¹²⁴

Current data confirm earlier findings regarding the hazards of pesticides¹²⁵ such as 2,4-DNP and fungicides.¹²⁶ Moreover, research increasingly suggests the possibility of sensitivities to apparently innocuous items such as rubber bands,¹²⁷ coins,¹²⁸ epoxy,¹²⁹ and countless paper products.^{130, 131} Pesticides, along with oil, gas, or coal, are major offenders for sensitive individuals.

Research shows house plants^{132, 133} and common insects¹³⁴ can now be viewed as environmental incitants or causes of homeostatic dysfunction. In addition, sensitivities to cold and heat³⁶ and to contaminants in household water supplies have been associated with symptoms ranging from urticaria to severe respiratory distress.

Used routinely in the home, natural gas heat and stoves and insecticides and termite proofing chemicals can be prime offenders in chemical sensitivity. One must consider these potential sources of contaminants when developing studies on chemical sensitivity. In our experience, failure to evaluate building and home environments before challenge testing will often invalidate the results of challenge studies for the diagnosis of chemical sensitivity.
 

Type II cytotoxic damage may occur with direct injury to the cell. A clinical example of this is seen in patients exposed to mercury.¹³⁷ A group in Minamata, Japan, developed neurological disease from eating fish exposed to toxic methyl mercury chloride. Mercurial pesticides fall into this category. Twenty percent of the patients with immunological involvement seen at the EHC-Dallas seem to fall into this Type II category.

Type III shows immune complexes of completment and gamma globulin damaging the vessel wall. A clinical example of this is lupus vasculitis. Numerous chemicals, including procainamide and chlorothiazide, are known to trigger the autoantibody reaction of lupus-like reactions. Many other toxic chemicals can also trigger the autoimmune response.¹³⁸ Other chemicals, such as vinyl chloride, will produce micro aneurysm of small digital arterioles, probably due to this mechanism.^{51, 139}

Type IV (cell-mediated) immunity occurs with triggering of the T-lymphocyte. Numerous chemicals such as phenol, pesticides, organohalides, and some metals will also alter immune responses, triggering lymphokines, and producing the Type IV reactions.¹³⁸ Clinical examples are polyarteritis nodosa, hypersensitivity angitis, Henoch-Schonlein pupura, and Wegener’s granulomatosis.^{1, 139} A recent study done at the Environmental Health Center-Dallas on 104 proven chemically-sensitive individuals (70 vascular, 27 asthmatic, and 7 rheumatoid), comparing them with 60 nomral controls, showed that those manifesting a chemical sensitivity through their vascular tree had suppression of the suppressor T-cells (greater than 4 S.D.).⁴⁷ Clearly the larger portion of our patients with immunological involvement fall into the Type III and IV categories.
 

Triggering of the enzyme detoxification, mostly in the systems of liver and respiratory mucosa, plays an important role in clearing pollutants. It occurs, however, to a lesser extent in all systems. Foreign compound biotransformations have considerable variability, depending on genetic factors, age, sex, nutrition, health status, and the size of the dose.

The metabolism of foreign compounds usually occurs in the microsomal fraction (smooth endoplasmic reticulum) of liver cells. A few biotransformations are nonmicrosomal (redox reactions involving alcohols, aldehydes, and ketones). There are basically four biotransformation categories: oxidation, reduction, degradation, and conjugation.

The first three biotransformation pathways for xenobiotics are the same pathway that the body uses to process food and nutrients. If these enzyme systems ar overutilized by competing foreign pollutants, inadequate handling of food proteins can result, with the subsequent induction of food sensitivities. However, because these detoxification pathways are dependent on nutrient and mineral cofactors, these systems are inducible by appropriate oral or systemic supplementation. Such supplementation serves as an important factor in stabilizing and treating patients with chemical sensitivity. The fourth category of biotransformation, that of conjugation, is almost exclusively for handling foreign compounds. Conjugation appears to be uniquely utilized for the catabolism of foreign compounds, using amino acids and their derivatives with peptide bonds and carbohydrates and their derivatives with glucide bonds. Simpler compounds like sulfate and acetate are also involved in conjugation with linkage of ester bonds. Activated conjugated compounds plus specific enzymes are often detoxified by coupling with coenzymes, e.g., coenzyme A with acetate and other short-chain fatty acids. Adenosine or phosphoadenosine phosphate is detoxified with a methyl group from sulfate methionine, or the ethyl group from ethionine. Similarly, uridine and phosphate with glucose and glucuronic acids.^{140, 141}

There are generally five major categories of foreign-compound conjugative processes.¹⁴⁰ These are the following: (1) acetylation through coenzyme A, for detoxifying aromatic amines and sulfur amides; (2) peptide conjugation with glycine, glutamine and taurine and aromatic carboxylic acids to hippuric acid; (3) sulfonation with glutathione (containing cysteine) and microsomal enzyme conjugation for multi-ring systems such as naphtahlene, anthracene, and phenoanthracene, which eventually results in benign mercapturic acids or alternatively benign sulfate esters; (4) alkylations by methionine of amines, phenols, thiols, noradrenaline, histamine, serotonin, pyridine, pyrogallol, ethylmucaptin sulfites, selenites, and tellurites; (5) glucuronation—Glucuronides detoxify pesticides, alcohols, phenols, enols, carboxylic acid, amino hydroxamines, carbamides, sulfonamide and thio.^{140, 141} All of these processes are dependent upon nutrient fuels to keep these processes running efficiently. Toxic chemicals disturb the supply of the nutrient fuels by (1) producing poor quality food; (2) reducing intake; (3) reducing normal absorption; (4) setting up competitive absorption in the gut with nutrients; (5) imbalancing intestinal flora; (6) disturbing transport mechanisms; (7) disturbing proper decomposition and metabolism; (8) causing renal leaks; and (9) directly damaging nutrients. If nutrient inadequacy occurs, normal metabolism is overloaded and disturbed, resulting in selective changes in the pools of nutrients such as vitamins, minerals, amino acids, enzymes, lipids, and carbohydrates. Once this occurs, there is a vicious cycle of dysmetabolism often with production or worsening of chemical sensitivity. These detoxification and metabolic defects are often measureable and have been accomplished in over 2,000 chemically sensitive patients.
 

Challenge tests are the cornerstone of confirmatory diagnosis. These may be accomplished through oral, inhaled, or intradermal challenges. Care should be taken to rule out inhalant problems with pollen dust, and molds. Food sensitivity occurs in approximately 80% of the people with chemical sensitivity and must be evaluated. When diagnosing chemical sensitivity, one must investigate water contaminant sensitivities, as 90% of people with chemical sensitivity have water contaminant reactions.⁴ This can be checked by placing the patient on less chemically-contaminated, carcoal-filtered, distilled, or glass-bottled spring water for four days, with subsequent rechallenge of the patient’s regular drinking water. This procedure will often elicit a reaction to the water pollutants in the sensitive individual.

Patients frequently know where and when the onset of their problems occurred, e.g., sudden exposure to pesticides, working around printing machines, factory machines, etc. They usually develop increased odor perception to gasoline, perfumes, new paints, car exhausts, gas stoves, fabrics, clothing or carpeting stores, chlorine and Clorox, and cigarette smoke. Not only will they find these smells offensive, but may have marked reactions to them as well. Other symptoms can range from the almost universally seen fatigue, to classic end-organ failures. Physical findings frequently are vascular in nature, with edema, petechiae, spontaneous bruising, purpura, or peripheral arterial spasm. Frequently there is flushing, adult-onset acne, and a yellowness of the skin without jaundice. Chronic, nonspecific inflammation is usually a significant sign, e.g., colitis, cystitis, vasculitis, etc. Laboratory findings are often nonspecific, e.g., sedimentation rates may increase or liver profile may be mildly off. Fifteen percent of environmentally sensitive patients have positive C-reactive proteins. Twenty-five percent show abnormal serum complement parameters. Fifty percent of the chemically sensitive patients have depressed T cells. Twenty-five percent have impaired blastogenesis, and twenty-five percent have impaired delayed hypersensitivity, as evidenced by cell-mediated immunity skin tests. Of the patients with T-cell abnormalities, the depletion of the suppressor cells is seen, by over four standard deviations from a control group of normals.¹⁴¹ Ten percent of these patients have elevated IgE or IgG. Patients with recurring infections have impaired phagocytosis and killing capacity. Very accurate blood measurements are now available for the chlorinated pesticides as well. The following were found in over 200 chemically sensitive patients:

Fat biopsies have been preferred on many patients with over 100 different compounds studied. Often, there is more in the fat than blood in some cases such as organochlorine insecticides and more in the blood such as seen with substances such as 2-methylpentane and 3-methylpentane.

Skin biopsies of bruising and petechiae reveal perivascular lymphocyte infiltrates around the vessel wall in chemically sensitive patients.

Challenge tests can be done by the sublingual or intradermal route. The efficiency of these tests is now well established as numerous studies (several double-blind) have now been done.^{4, 24, 47, 142-145} These need to be done since 80% of chemically sensitive individuals are food sensitive. Blind intradermal challenge for chemicals can now be done with terpenes, petroleum derived ethanol, glycerine, formaldehyde, phenol, perfume, and newsprint, whereby production of symptoms will help establish the patient’s chemical sensitivity.

Over 200,000 intradermal challenges of chemicals have been performed under environmentally-controlled conditions at the EHC-Dallas. These are clearly reliable, especially as they meet the positive criteria of sign and symptom reproduction, wheal growth, and negative palcebo response.

Inhalation challenge is another method for the diagnosis of chemical sensitivity, done under varying degrees of environmentally controlled conditions. For best results one uses an anodized aluminum and glass booth to do ambient dose challenge of any toxic chemical in an environmentally controlled hospital setting. Some studies done in our center, under strictly controlled conditions in an environmental unit, showed significant findings (4 S.D.) of the chemical reactors over the controls when using <0.20 ppm formaldehyde, <0.0025 ppm phenol, <0.33 ppm chlorine, <0.50 ppm petroleum derived ethanol, <0.034 ppm of the pesticide 2,4,DNP, along with three placebos. These tests have been used in over 3,000 patients with over 99% accuracy. Similar studies can be done in the office setting, although controls are much more difficult and one finds many more placebo reactions. This is because environmentally controlled conditions are generally much more difficult to achieve and patients are often studied in the masked or adapted state, wherein symptoms may not be perceived. With the inhaled challenges, one can measure and plot blood levels, immune parameters, metabolic changes as well as sign and symptom scores.

Vitamin and intracellular mineral levels are needed to evaluate completely the chemically sensitive individual. In our center, analysis of more than 300 chemically sensitive patients showed the following deficiencies: B₆=64%; B₂=30%; B₁=29%; folic acid=27%; vitamin D=24%; B₃=19%; vitamin C=6%; vitamin B₁₂=3%. Of 190 chemically sensitive patients with mineral deficiencies, 88% had chromium deficiency,40% magnesium, 35% sulfur, 12% selenium, and 8% zinc.

A recent advance in the investigation of chemically sensitive patients is with brain function imaging by means of a SPECT scan (single photon emission computer tomography). This scanning technique gives a metabolic or "biochemical activity" picture of the intracranial structures using a tracer that has been tagged with radioactive technetium-99.

Many chemically sensitive patients report problems with memory, concentration, mood swings with irritability and poor mental organizational skills. These symptoms may have physiological triggers but may be mistaken for psychiatric symptomatology. A pattern commonly seen in the chemically sensitive patient closely resembles that of a neurotoxic affect on brain activity, with a pattern of diffuse intracerebral defects. This is frequently associated with neurocognitive symptoms, chemical exposures, and chemical sensitivity. Frequently temporal lobe asymmetry is also seen, along with a mismatch between the brain blood flow and the amount of biological or biochemical activity.¹⁵³

In a recently completed study comparing chemically sensitive patients, healthy volunteer controls and nonchemically sensitive patients, over 90% of the chemically sensitive patients had an abnormal brain scan of a neurotoxic pattern. Twenty-five out of 25 controls have been normal, and none of the nonchemically sensitive patients scaanned have shown a neurotoxic pattern.

This SPECT scanning technology provides evidence that the chemically sensitive patients are frequently found to have an abnormal cerebral metabolism, exhibiting a diffuse focal defect pattern that has previously been associated mostly with neurotoxic injury. The diffuse defect pattern may explain, in part, the complex neurocognitive symptoms that are frequently reported by chemically sensitive patients.
 

Injection therapy for inhalants, foods, and some chemicals will also help this problem.^{24, 144, 145, 147-150} Low-dose sublingual therapy in patients with allergic rhinitis was effective.¹⁵¹ These treatments can be done daily, but usually they are done every four to seven days. In our opinion, a properly balanced rotary diet is essential in treating the patient with food sensitivity, whether or not it may be induced by chemical overload. Vitamin and mineral supplementation is often necessary to replace the deficiencies that occur from the direct toxic damage, exhausted enzymatic detoxification pathways, and from the direct competition absorption. In rare cases, nutritional replacement with intravenous hyperalimentation is needed for severely debilitated patients. Techniques should be developed for monitoring and evaluating the outcome. Heat depuration physical therapy has been used a the Environmental Health Center-Dallas in over 1,000 patients. Clearly, this modality will mobilize toxics and allow them to be eliminated from the body.
 

2. Dickey, L. D. (Ed.). (1976). Clinical ecology. Springfield, IL:Charles C. Thomas.

3. Bell, I. R. (1982). Clinical ecology. Bolinas, CA: Common Knowledge Press.

4. Rea, W. J., & Mitchell, M. J. (1982, Sept./Oct.21-31). Chemical sensitivity and the environment. Immun. Allergy Prac.

5. Wordan, J. I. (1954). The effect of air in concentrations and polarity on the C0₂ capacity of mammalian plasma. Fed Proc, 13, 557.

6. Choy, R. V. S., Monro, J. A., & Smith, C. W. (Year?) Electrical sensitivities in allergy patients. Clin Ecol, 4(3), 93-102.

7. Laseter, J. L., DeLeon, I. R., Rea, W. J., & Butler, J. R. (1983). Chlorinated hydrocarhon pesticides in environmentally sensitive patients. Clin Ecol, 2(1), 3-12.

8. National Research Council. (1981). Indoor pollutants. Washington, D. C.: Natl. Academy Press.

9. Gilpin, A. (1978). Air pollution (2nd ed.). St. Lucia, Queensland: University of Queensland Press.

10. Wark, K., & Warner, C. (1961). Air pollution: Its origin and control. New York: Harper & Row.

11. Adelman, R. C. (1979). Loss of adaptive mechanisms during aging. Fed Proc, 38, 1968-1971.

12. Stokinger, H. E. (1965). Ozone toxicology: A review of research and industrial experience, 1954 - 1962. Arch Environ Health, 110, 719.

13. The National Research Council. (1977). Water hardness and health. In Drinking water and health (pp. 439-447). New York: National Academy of Science.

14. Winslow, S. G. (1981). The effects of environmental chemicals on the immune system: A selected bibliography with abstracts. Oak Ridge, TN: Toxicology Information Response Center, Oak Ridge National Laboratory.

15. Calabrese, E. J. (1977). Pollutants and high-risk groups. The biological basis of increased human susceptibility to environmental and occupational pollutants. New York: Wiley Interscience.

16. Freedman, B. J. (1980). Sulphur dioxide in foods and beverages:its use as a preservative and its effect on asthma. BrJ Dis Chest, 74 (2), 128-134.

17. Davidson, M., & Fienleib, M. (1972). Disulfide poisoning: A review. An Heart J, 83, 100.

18. Innami, S., Tojo, H., Utsuja, S., Nakamura, A., & Nagazama, S. (1974). PCB toxicity and nutrition I. PCB toxicity and vitamin A. Jap J Nutr, 32, 58-66.

19. Villeneune, D. C., Grant, D. L., Phillipos, W. E. J., Clark, M. L., & Clegg, D. J. (1971). Effects of PCB administration on microsomal enzyme activity in pregnant rabbits. Bull Environ Contam Toxicol, 6, 120.

20. Rea, W. J., Johnson, A. R., Smiley, R. E., Maynard, B., & Dawkins-Brown, 0. (1986). Magnesium deficiency in patients with chemical sensitivity. Clin Ecol, 4 (1), 17-20.

21. Pan, Y., Johnson, A. J., & Rea, W. J. (1987-88). Aliphatic hydrocarbon solvents in chemically sensitive patients. Clin Ecol, 5(3), 126-131.

22. Olson, K. R., et al. (1982). Amanita phalloides-type mushroom poisoning, West J Med, 37, 282.

23. Brostoff, J., & Challacombe, S. (1987). Food allergy and intolerance. London: Bailliere Tindall.

24. Rapp, 0.J. (1978). Double-blind confirmation and treatment of milk sensitivity. Med J Aust, 1, 571-572.

25. Rea, W. J., Pan, Y., et al. (1987). Toxic volatile organic hydrocarbons in chemically sensitive patients. Clin Ecol, 5(2), 70-74.

26. Hill, Johanna. (1987, Oct. 29). Peptides and their receptors as the biochemicals of emotion. Proceedings of the American Acad. Envir. Med. Annual Mtg., Nashville, TN.

27. Ader, Robert. (1987, Oct. 29). Behavioral influences of immunity. Proceedings of Amer. Acad. Envir. Med. Annual Mtg., Nashville, TN,

28. King, D. S. (1981). Can allergic exposure provoke psychologi cal symptoms? A double-blind test. Biol Psychiat, 16, 3-19.

29. Randolph, T. G. (1987). Specific adaptation. Ann Allergy, 40, 333-45.

30. Mustafa, M. G., & Tierney, D. F. (1987). Biochemical and metabolic changes in the lung with oxygen, ozone, and nitrogen dioxide toxicity. Am Rev Resp Dis, 118 (6).

31. Stokinger, H. E., & Coffin, D. L. (1968). Biological effects of air pollutants. In A. C. Stern (Ed.), Air pollution. New York: American Press.

32. Rinkel, Randolph, T. G., & Zeller, M. (1951). Food allergy. Norwalk, CT: New England Foundation of Allergic and Environmental Disease, rpt.

33. Selye, H. (1946). The general adaptation syndrome and the diseases of adaptation. J Allergy, 17, 23.

34. Jollow, D. J., et al. (1977). Biological reactive intermediates: Formation, toxicity, and inervation. New York.

35. Wand, A. M., et al. (1976). Immunological mechanisms in the pathogenesis of vinyl chloride disease. Brit Med JI, 6015, 936-938.

36. Rea, W. J., Peters, D. W., Smiley, R. E., et al. (1981). Recurrent environmentally triggered thrornbophlebitis. Ann Allergy, 47, 338-344.

37. Savage, G. H. (1884). Insanity and allied neuroses. Philadelphia: Lea and Febiger.

38. Rowe, A. H. (1930). Allergic toxemia and migraine due to food allergy. Calif West Med, 33, 785-792.

39. Williams, R. J. (1963). Biochemical individuality. New York:Wiley.

40. Noordhout, B., et al. (1987). Latent tetany, magnesium and HLA tissue antigens. Magnesium-Bulletin 3 (Offizielles Organ Gesellshaft fur Magnesium Forschung), 9, 3.

41. Stanbury, J. B., et al. (1983). The metabolic basis of inherited disease. New York: McGraw-Hill Book Co.

42. Nadal, A., & Lee, L. Y. (1977). Airway hyperirritability induced ozone. In S. D. Lee (Ed.), Biochemical Effects of Environmental Pollutants. Anarbor, MI: Anarbor Science Publishers.

43. Randolph, T. G. (1952, Dec.). Sensitivity to petroleum. Including the derivatives and antecedents. J Lab Clin Med, 40, 931 -932.

44. Fisher, S. A. (1981, Apr.). Dermatitis due to the presence of formaldehyde in certain sodium lauryl sulfate (SLS) solutions. Curtis, 27(4), 360-2, 366.

45. Fregernt, S. (1980, Dec.). Irritant dermatitis from phenol-formaldehyde resin powder. Contact Dermatitis 6(7), 493.

46. U. S. Environmental Protection Agency. Unfinished business: A comparative assessment of environmental problems.

47. Rea, W. J., Johnson, A. R., Youdim, S., Fenyves, E. J., & Samadi, N. (1989). T & B lymphocytes parameters measured in chemically sensitive patients and controls. Clin Ec, 4(1), 11-14.

48. Møhave, L., & Moller, J. (1978). The atmospheric environment in modern Danish dwellings— Measurements in 39 flats. Insitute of Hygiene, University of Aarhus, Denmark. Paper presented at International Indoor Climate Symposium. Copenhagen.

49. Suhonen, (1980, June). Contact allergy to dodecyl-di-(aminoethyl) glycine (Dedsimex I). Contact Dermatitis, 6 (4), 290-1.

50. McMillian, initials? (1979, Nov. 30). Environmentally-induced thrombocytopenic purpura. JAMA, 242 (22), 2434-5.

51. Rea, W. J., Bell, I. R., & Smiley, R. E. (1975). Environmentally triggered large-vessel vasculitis. In F. Johnson & J. T. Spence (Eds.), Allergy: Immunology and medical treatment (pages?). Chicago: Symposia Specialist.

52. Rea, W. J. (1979-80). Review of cardiovascular disease in allergy. In C. A. Frazier (Ed.), Biannual Review of Allergy (pages?), Springfield, IL.

53. Peacock, A. I. (1981, Apr. 4). Case reports, hydralazine-induced necrotizing vasculitis. Br Med J, 282(6270), 1121-2.

54. Dooms-Goossens, A., Ceuterick, A., Vanmaele, N., & Degreef, H. (1980). Follow-up study of patients with contact dermatitis caused by chromates, nickel, and cobalt. Dermatologica, 160(4), 249-60.

55. Clemmensen, 0., & Knudsen, H. E. (1980, Aug.). Contact sensitivity to aluminum in a patient hyposensitized with aluminum precipitated grass pollen. Contact Dermatitis,6(2), 305-308.

56. Vermeiden, ?, Oranje, A. P., Vuzevski, V. O., & Stolz, E. (1980, Jan.). Mercury exanthem as occupational dermatitis. Contact Dermatitis, 6 (2), 88-90.

57. Hughes, E. G. (1980, Jan.). Medical surveillance of platinum refinery workers. J Soc Occup Med, 30(1), 27-30.

58. Bell, I., & King, D. (1982). Psychological and physiological research relevant to clinical ecology: An overview of the recent literature. Clin Ecol.

59. Bjorkner, B., Dahlquist, I., & Fregert, S. (1980, Oct.). Allergic contact dermatitis from acrylates in ultraviolet curing inks. Contact Dermatitis, 6(6), 405-9.

60. Bjorkner, B. (1981). Sensitization capacity of acrylated prepolymers in ultraviolet curing inks tested in the guinea pig. Acta DermVenercol (Stockh), 61(1), 7-10.

61. Romaguera, Gimalt. (1980, Oct.). Sensitization to benzoyl peroxide, retinoic acid and carbon tetrachloride. Contact Dermatitis, 6(6), 442.

62. Satish, J. (1980, Sept.). Importance and measurement of sulfates in floating dust. Soz Praeventivmed, 25 (4), 201-2.

63. Kleibl, K., Rackova, M. (1980, Sept.). Cutaneous allergic reactions to dithiocarbamates. Contact Dermatitis, 6(5), 348-9.

64. Gallagher, J. S., Tse, C. S., Brooks, S. M., & Bernsten, I. I. (1981, Sept.). Diverse profiles of immunoreactivity in toluene diisocyanate (TOI) asthma. JOM, 23(9), 610-6.

65. Wilson C. W. M. (1983). Hyperactivity to Maine tap water in children:its clinical features and treatment. Nutri and Health, 2, 5163.

66. Glaze, W. E. (Date?). North Texas State University, Environmental Division, Denton, Texas. Personal communication.

67. Cherry, R., & Cherry, F. (1974, Dec. 8). What's in the water we drink? The New York Times Magazine.

68. Environmental Protection Agency (EPA). Is your drinking water safe? (Booklet).

69. Trimble, J. (1984, Feb. 28). There should be an article title here. U.S. News and World Report, Vol #?, 2732.

70. Spalding, R. F., Junk, G. A., & Richard, J.J. (1980). Water: Pesticides in ground water beneath irrigated farmland in Nebraska. Pesticides Monitoring Journal, 1(2), 70-3.

71. Junk, G. A., Spalding, R. F., & Richard, J. J. (1983). Areal, vertical, and temporal differences in ground water chemistry. II. Organic constituents.

72. Corwin, A. H. (1976). Heavy metals in air, water, and our habitat. In L. D. Dickey (Ed.), Clinical Ecology (pp. 292-305). Springfield, IL:Charles C. Thomas.

73. Moran, J. M., Morgan, M. 0., & Wiersma, J.N. (1986). Introduction to environmental science (2nd ed.), (pp.177-209). New York: W. H. Freeman.

74. Skiba, N. S. (1963). Role of river discharge of solids in migration of mercury. Zao Kirqizsk Otd Vses Mineralog Obschchestva, 4, 31; (1964) Chem Abs, 61, 5357e.

75. Takeuchi, T., Morikawa, N., Matsumoto, H., & Shiraishi, Y. (1962). A pathological study of Minamata disease in Japan. Acta Neuropathol, 2, 40.

76. Brown, H. S., Bishop, D. R., & Rowan, C. A. (1984). The role of skin absorption as a route of exposure for volatile organic compounds in drinking water. Am J Pub Health, 74, 479-484.

77. Randolph, T. G. (1965). Ecologic orientation in medicine:Comprehensive environmental control in diagnosis and therapy. Ann Allergy, 23, 7-22.

78. Randolpn, T. G. (1965). The ecologic unit. Hospital management, Part I , 97, 45; Part II, 97, 46.

79. Wilson, C. W. M. (1983). Hypersensitivity to Maine tap water in children: Its clinical features and treatment. Nutrition and Health, 2, 51-63.

80. Juhlin, L. (1980, Dec.). Incidence of intolerance to food additives. Int J Dermatol, 19(10), 548-51.

81. Fries, J. H. (1981, May). Food allergy: Current concerns. Ann Allergy, 46(5), 260-3.

82. Bell; I., & King, D. (1982). Psychological and physiological research relevant to clinical ecology: An overview of the recent literature. Clin Ecol.

83. Condemi, J. J. (1981, Sept.). Aspirin and food dye reactions. Bull NY Acad Med, 57(7), 600-7.

84. Rea, W. J. (1977). Environmentally triggered small vessel vasculitis. Annals of Allergy, 38, 245-51.

85. Potkin, S. G.,Weinberger, D., Kleinman, J., et al. (1981). Wheat gluten challenge in schizophrenic patients. Amer J Psychiat, 138, 1208-11.

86. Hanninen, H., Eskelinen, L., Husman, K., & Numinen, M. (1976). Behavioral effects of long-term exposure to a mixture of organic solvents. Scand J Work Environ Health, 4, 240-55.

87. Randolph, T. G. (1974). The history of ecologic mental illness. In C. A. Frazier (Ed.), Annual Rev Allergy. Flushing, NY: Med Exam Pub Co.

88. Savage, G. H. (1884). Insanity and allied neuroses. Philadelphia: Lea and Febiger.

89. Rea, W. J., Butler, J. R., Laseter, J. L., & DeLeon, I. R. (1984). Pesticides and brain function changes in a controlled environment. Clin Ecol, 2 (3), 145-50.

90. Lindemayr, H., & Schmidt, ?. (1979, Dec. 21). Intolerance to acetylsalicylic acid and food additives in patients suffering from recurrent urticaria (author's transl.). Wien Kiln Wochenschr, 91(24), 817-22.

91. Hanington, E. (1980). Diet and migraine. J Hum Nutr, 34:175-80.

92. Dahl, R. (1980, Mar.). Sodium salicylate and aspirin disease. Allergy, 35(2), 5-6.

93. Wuthrich, F. (1981, Sept. 26). Acetylsalicylic acid and food additive intolerance in urticaria, bronchial asthma and rhinopathy. Schweiz. Med. Wochenchr, 111(39),1445-50.

94. Tabuenca, J. M. (1981, Sept.). Toxic-allergic syndrome caused by ingestion of rapeseed oil denatured with aniline. Lancet, 12(2), 567-8.

95. Cullen, M. (Ed.). (1987). Workers with multiple chemical sensitivities. Occup. Med. State of the Art Reviews. 2 (4).

96. Thune, P. (1981, Jan.). Photosensitivity and allergy to cosmetics. Contact Dermatitis, 7(1), 54-5.

97. Zaynoun, S. T., Aftimos, B. A., Tenekjian, K. K., & Kurban, A. K. (1981, Mar.). Berloque dermatitis a continuing cosmetic problem. Contact Dermatitis, 7 (2), 111-6.

98. Fisher, A. A. (1980, Sept.). Reactions to popular cosmetic humectants, Part III. Glycerin, propylene glycol, and butylene glycol. Curtis, 26(3), 243-4.

99. Guin, J. D., & Berry, V. K. (1980, Sept.). Perfume sensitivity in adult females. J Am Acad Dermatol, 3(3), 299-302.

100. Foussereau, J., Reuter, G., & Petitjean, J. (1980, Jan.). Is hair dyed with PPD—like dyes allergenic? Contact Dermatitis, 6(2), 143.

101. Klein, A. D., 3d, & Rodman, 0. G. (1981, Jan.). Allergic contact dermatitis to paraphenylenediamine in hair dye. Milit Med 146 (1), 46-7.

102. Ramsay, C. A. (1979, Feb.). Skin responses to ultraviolet radiation in contact photodermatitis due to fenticlor. J Invest Dermatol, 72(2), 99-102.

103. Schlueter, L. E., Soto, R. J., Baretta, E. D., Herrmann, A. A., Ostrander, L. E., & Stewart, R. D. (1979, May). Airway response to air spray in normal subjects and subjects with hyperreactive airways. Chest 75(5), 544-8.

104. Stoll, D., & King, L. E., Jr. (1980, Nov.). Disulfiram-alcohol skin reaction to beer-containing shampoo. JAMA, 244(18), 2045.

105. Hindson (1980, Apr.). Phenyl salicylate (Salol) in a lip salve. Contact Dermatitis, 6(3), 216. 106)

106. Fisher, A. A. (1980, Jan.). Permanent loss of finger nails from sensitization and reaction to acrylic in a preparation designed to make artificial nails. J Dermatol Surg Oncol, 6(1), 70-1.

107. Jordan, W. P., Jr. (1981, May). Contact dermatitis from D & C yellow 11 dye in a toilet bar soap. J Am Acad Dermatol, 45(5), 613-4.

l08. Larson, W. G. (1981, Mar.). Sanitary napkin dermatitis due to the perfume. Arch Dermatol, 115(3), 363.

109. Mathias, C. G., Chappler, R. R., & Maibach, H. I. (1980, Jan.). Contact urticaria from cinnamic aldehyde. Arch Dermatol, 116(1), 746.

110. Aust, L. B., & Maibach, H. (1980, June). Incidence of human skin sensitization to isostearyl alcohol in two separate groups of panelists. Contact Dermatitis, 6(4), 269-71.

111. Sertoli, ?, Di Fonzo, E., Spallanzani, P., & Panconesi, E. (1980, June). Allergic contact dermatitis from thimerosal in a soft contact lens wearer. Contact Dermatitis, 6(4), 2923.

l12. Zeigen, S. R., Jacobs, I. H., & Weinberger, G. I. (1981, May). Delayed hypersensitivity to thimerosal in contact lens solutions. J Med Soc NJ, 78(5), 362-4.

113. Jackson, R. T., Nexbitt, L. T., Jr., & DeLeo, V. A. (1980, Feb.). 6-Methylcoumarin photocontact dermatitis. J Am Acad Dermatol, 2(2), 124-7.

114. ElSaad EI-Rifaie, M. (1980). Periorai dermatitis with epitheboid cell granulomas in a woman: A possible new etiology. Acta Derm Venereal (Stockn), 60(4), 359-60.

115. Burrows, D., & Campbell, H. S. (1980, Aug.). Contact dermatitis to polyesters in finishes. Contact Dermatitis, 6(5), 362-3.

116. Imbeau, S. A., & Reed, C. E. (1979, May). Nylon stocking dermatitis. An unusual example. Contact Dermatitis, 5(3), 163-4,

117. McDaniel, W. H., & Marks, J. G., Jr. (1979, May). Contact urticaria due to sensitivity to spray starch. Arch Dermatol, 115(5), 628.

118. Larson, F. S., & Brandrup, F. (1980, June). Nickel release from metallic buttons in blue jeans. Contact Dermatitis, 6(4), 298.

119. Rudzki, E., & Kozlowska, A. (1980, Apr.). Causes of chromate dermatitis in Poland. Contact Dermatitis 63, 191-6.

120. Kleinhans, Days. (1980). Formaldehyde contact allergy. Derm Beruf Umwelt, 28(4), 101-3.

121. Klascnka, F., von Nieding, F., & Walter, R. (1979, June). Skin sensitization to wood preservatives containing pentachiorophenol (PGP). Zentralbl Arbeitsmed Arbeitsschutz Proohv, l29(6), 150-4.

122. Bach, B., & Pedersen, N. B. (1980, Jan.). Contact dermatitis from a wood preservative containing tetrachloroisophthalonitriles. Contact Dermatitis, 6(2), 142.

123. Spindeldreier, A., & Deichmann, B. (1980). Contact dermatitis against a wood preservative with a new fungicidal agent. Derm Beruf Umwelt, 28(3), 88-90.

124. Frigas, E., Filley, W. V., & Reed, C. E. (1981, June). Asthma induced by dust from urea-formaldehyde foam insulating material. Chest, 79(6), 706-7.

125. Matsushita, T., Nomura, S., & Wakatsuki, T. (1980, June). Epidemiology of contact dermatitis from pesticides in Japan. Contact Dermatitis, 6(4), 255-9.

126. Rudzki, M. (1980, June). Dermatitis caused by the Polish fungicide Sadoplon 75. Contact Dermatitis 6(4) :300-1.

127. Weinstein, L. H., & Fellner, M. J. (1979, Sept.). Rubber band dermatitis. Int J Dermatol, 18(7), 558.

128. Conde-Salazar, L., Romero, L., & Guimaraens, D. (1981, May). Metal content in Spanish coins. Contact Dermatitis, 7(3), 166.

129. Fregert, S. (1981, Sept.). Epoxy dermatitis from the nonworking environment. Br J Dermatol, 105 (Suppl. 21), 63-4.

130. Gum, 3. D. (1981, June). Contact dermatitis to perfume in paper products [Letter]. J Am Acad Dermatol, 4(6), 733-4.

131. Marks, J. G., Jr. (1981, June 12). Allergic contact dermatitis from carbonless copy paper. JAMA, 245 (22), 2331-2,

132. Calnan, C. D. (1981, Mar.). Dermatitis from ivy (Hederacanariensis variegata). Contact Dermatitis, 7(2), 124-5.

133. Sugai, T., Takahashi., Y., & Okuno, F. (1981, Jan.). Chrysanthemum dermatis. Japan Contact Dermatitis, 6(2), 155.

134. Fuchs, E. (1979, May-June). Insects as inhalant allergens. Allergol Immunopathol (Madr) 7 (3), 227-30.

135. Levine, S., & Kidd, ?. (1985). Antioxidants Adaptations. San Leando, CA:Bio Division, Allergy Research Group.

136. Theorell, ?, Blambock, M., & Kockum, C. (1976). Demonstration of reactivity to airborne and food antigen in cutaneous vasculitis by variation in fibrinopeptide and others, blood coagulation, fibrinolysis, and complement parameters. Thrombo Haemo Sts (Stattz), 36, 593.

137. Gaworoki, C. L., & Sharma, R. P. (1978). The effects of heavy metals on (3H) thymidine uptake in lymphocytes. Toxicol Appl Pharmacol, 46(2), 305-13.

138. Winslow, S. G. (1981). The effects of environmental chemicals on the immune system: A selected bibliography with abstracts (pp. 1-36). Oak Ridge, TN:Toxicology information Response Center, Oak Ridge National Laboratory.

139. Rea, W. J., & Suits, C. W. (1980). Cardiovascular disease triggered by foods and chemicals. In J. W. Gerrard (Ed.), Food allergy: New perspectives (pages?) . Springfield, IL: Charles C. Thomas.

140. Jakoby, W. B. (Ed.). (1983). Enzymatic Basis of Detoxication (Vol. 1). New York: Academic Press.

141. Reeves, A. L. (Ed.). (1981). Toxicology: Principles and practice. New York: John Wiley & Sons.

142. O’Shea, J., & Porter, A. (1981). Double-blind study of children with hyperkinetic syndrome treated with multi-allergen extract sublingually. J Learning Disabil, 14, 189 -91.

143. Forman, R. A. (1981). Critiques of evaluation studies of sublingual and intracutaneous provocation tests for food allergy. Med Hypotheses, 7, 1019-27.

144. Miller, J. B. (1977). A double-blind study of food extract injection therapy. Ann Allergy, 38(3), 185-91.

145. Boris, M., Shiff, M., & Weindorf, S. (1983). Bronchoprovocation blocked by neutralization therapy. J Allergy Clin Immunol, 7, 92.

146. Rea, W. J., Pan, Y., & Johnson, A. R. (1987/88). Clearing of toxic volatile organic hydrocarbons from humans. Clin Ecol, 5(4), 166-170.

147. Boris, M., Schiff, M., & Weindorf, S. (1985). Antigen-induced asthma attenuated by neutralization therapy. Clin Ecol, 3, 59-62.

148. Boris, M., Schiff, M., & Weindorf, S. (1988). Injection of low-dose antigen attenuates the response to subsequent bronchoprovocative challenge. Otolaryngol—Head Neck-Surg, 98, 538-545.

149. Miller, J. B. (1987). Intradermal provocative/neutralizing food testing and subcutaneous food extract injection therapy. In J. Brostoff & S. Challacombe (Eds.), Food allergy and intolerance (pp. 932-946). London, Bailliere Tindall Publishers.

150. Rea, W. J., et al. (1984). Elimination of oral food challenge reaction by injection of food extracts. Arch Otolaryngol, 110, 248-252.

151. Scadding G., & Brostoff, J. (1986). Low-dose sublingual therapy in patients with allergic rhinitis due to house dust mite. Clin Allergy, 16, 483-491.

152. Rea, W. J. (1992). Chemical sensitivity:Vol. 1 (pp. 33-35). Boca Raton, FL: Lewis Publishers.

153. Simon, T. R., Hickey, D. C., Rea, W. J., Johnson, A. R., & Ross, G. H. (1992, Nov. 29-Dec.4). Breast implants and organic solvent exposure can be associated with abnormal cerebral SPECT studies in clinically impaired patients. Radiological Society of North America, 78th Scientific Assembly and Annual Meeting, Chicago, lllinois (subsequently published in (1992). Radiology, 185, 234.)