William J. Rea, Alfred R. Johnson, Gerald H. Ross, Joel
R. Butler, Ervin J. Fenyves, Bertie Griffiths, John Laseter
Over the last 16 years, physicians and scientists at the Environmental Health Center in 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 were double-blind. Blood chemical levels and fat biopsies for organic hydrocarbons number over 2,000, while the measurement of immune parameters are 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 National Academy of Sciences Committee for the study of chemical sensitivity.
To demonstrate cause-and-effect proof of environmental influence 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, and biochemical individuality. Each principle will be discussed separately.
We have differing quantities and interactions of carbohydrates, fats, proteins, enzymes, vitamins, minerals, and immune parameters with which to respond to environmental factors. One simple example is the noted relationship between low serum magnesium levels and the HLA B35 genotype.40 This biochemical individuality allows us to either clear the body of noxious substances, or to collect them and contribute to the body burden. Biochemical individuality is dependent on at least three factors: genetic endowment, the state of the fetus=s nutritional health and toxic body burden during pregnancy, and the individual=s present toxic body burden and nutritional state at the time of exposure.
Some individuals, for example, are born with significantly lower quantities of specific enzymes (it may be 75%, 50%, or even 25% of the norms). Their response to environmental stimuli if 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
Spreading may occur for many reasons. It may be due to a failure of the detoxification mechanismsCoxidation, reduction, degradation and conjugationCbrought about by toxic overloading, or it may occur because of depletion of the enzyme or coenzyme=s nutrient fuels, such as zinc, magnesium, all B vitamins, amino acid, or fatty acid. This depletion may account for an increasing inability to detoxify and respond appropriately. The blood brain barrier or peripheral cellular membranes of the skin, lung, nasal mucosa, gastrointestinal or genitourinary systems may be damaged allowing previously excluded toxic and nontoxic substances to penetrate to areas that increase the risk of harm. Immune or pharmacological releasing mechanisms may become so damaged that they are triggered by many substances toxic, then non-toxic (such as food) in addition to the specific one to which they were intended to respond. 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 sensitivity.
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.
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 (e.g., 24-hour) reaction. Often we have seen, for example, transient brain dysfunction followed by arthralgia, followed by diarrhea, followed by arrhythmia.
This life-long progression of disease does not have to
occur if the switch phenomenon is recognized during initial evaluation.
To prevent it, individuals and physicians need simply to be cognizant of
seemingly unrelated events. For example, statements are often made to the
effect that a child will outgrow a problem when, in reality, one symptom
complex dissipates only to be replaced by a new set of symptoms. For example,
a child may have recurrent ear infections. Eventually, these may stop,
but bed wetting may ensue. Over time the bed wetting may cease, but the
child may then develop asthma. These changes in health may appear to be
totally unrelated; in this instance, however, they are switch phenomena.
The situation of an adult who sprays pesticides in his home, and then visits
a neurologist with complaints of headaches and a rheumatologist with symptoms
of arthritis is similar. Both the physician and the patient frequently
fail to recognize the relevancy of these seemingly disparate symptoms as
being part of a larger pattern needing further investigation.
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 Randolph almost 40 years ago.43 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.1,7,8,36 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 which 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 benzyl peroxide, carbon tetrachloride,61
sulfates,62 dithiocarbamates,63 and diisocyanates.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 Alow@ levels of synthetic pollutants is Anormal.@ 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 exist and have been documented, including Times Beach, Missouri, with winter floods flushing dioxin-contaminated oil used twenty years ago, Niagara=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 their burial sites, these leftovers directly contaminate our ground water. Polluted ground water exists at 347 of the nation=s 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 trichloroethylene 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 13 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 byproducts, oil, grease, radioactive waste, and heat. Other sources of contamination are drinking water disinfectants and byproducts;68 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, ultra-violent 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 which 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 biphenyls, just to name a few.
A recently completed study found that skin absorption contributed from 29 to 91% of the total body dose of pollutants (from water), with an average of about 64%.76 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 radio nuclide that seeps from rocks and may be concentrated in airtight homes, especially the basements. At this stage, more information is needed to assess fully 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 may contain 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
The literature abounds with reports of chemical sensitivities to many additives.80,81 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 in the air and water as well. Bell has reported urticarial reactions and immunological changes to exposures to a number of food additives.82 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 Lindemayer has associated urticarial reactions with several additives such as p-hydroxy benzoic acid propyl ester, benzoic acid, sodium benzoate, ponceau rouge, and indigo carmine.90 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 reactions,92 while aspirin-like food contaminants and dyes may trigger urticaria, angioedema, bronchoconstriction, and purpura.93 An even wider variety of symptoms, including severe gastro-intestinal disorders, has been associated with sensitivities to aniline, commonly found in rapeseed oil.94
Reports of sensitivities to chemicals in textiles, including synthetic acrylic fibers,114 polyester spin finishes,115 the epoxy resins, and synthetic clothing are widespread.116 Products such as fabric spray starch may also be considered toxic for the chemically sensitive individual117 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 produce 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 used to clean and polish furniture.119
The very construction of many homes may prove dangerous for the chemically sensitive patient. Data suggests that chemicals contained in wood preservatives (e.g., pentachlorphenols) are environmental incitants capable of triggering a variety of symptoms.121-123 Others report problems with reactions to formaldehyde-containing pressboard, 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 plants132,133 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.
Natural gas heat and stoves and routine insecticiding
or termite proofing of homes can be prime offenders in chemical sensitivity.
One must consider these potential source of contaminants when developing
studies on chemical sensitivity. In our experience, failure to evaluate
building and home environments before challenge testing will often make
challenge studies invalid 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 Minimata, Japan, developed neurological disease from eating fish exposed to toxic methyl mercury chloride. Mercurial pesticides fall into this category. Of the patients with immunological involvement seen at the EHC-Dallas, 20% seem to fall into this Type II category.
Type III shows immune complexes of complement and gamma globulin damaging the vessel wall. A clinical example of this is lupus vasculitis. Numerous chemicals, including procainamide and chlorothaizide, 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 microaneurysms 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 angiitis, Henoch-Schonlein purpura,
and Wegener=s granulomatosis.1,139
A recent study done at the EHC-Dallas on 104 proven chemically sensitive
individuals (70 vascular, 27 asthmatic, and 7 rheumatoid), comparing them
with 60 normal controls, showed that those manifesting a chemical sensitivity
through their vascular tree had suppression of the suppressor T-cells (>4
SD).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 system=s liver and respiratory mucosa, plays an important role in clearing of 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 microsomal (redox reactions involving alcohols, aldehydes, and ketones). There are basically four biotransformation categoriesCoxidation, reduction, degradation, and conjugation.
There are generally five major categories of foreign-compound
conjugative processes.140 These are (1) acetylation through
co-enzyme A, for detoxifying aromatic amines and sulfur amides; (2) peptide
conjugation with glycine and aromatic carboxylic acids to hippuric
acid; (3) sulfonation with glutathione (containing cysteine) or
PAPS, and microsomal enzyme conjugation for multi-ring systems such as
naphthalene, anthracene, and pheno-anthracene, which eventually results
in benign mercaptic acids or alternatively benign sulfate esters; (4) alkylations
by methionine of amines, phenols, thiols, noradrenalin, histamine, serotonin,
pyridine, pyrogallol, ethylmucaptin sulfites, selenites and tellurites;
(5) Glucuronation. Glucuronides detoxify pesticides, alcohols, phenols,
enols, carboxylic acid, amino hydroxamines, carbamides, sulfonamide, and
thiol.140,141 All of these process 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 measurable and have been accomplished in over 2,000 chemically sensitive
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 chemically less contaminated, charcoal-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.
Pesticide in Blood
% Distribution in 200 Patients
|DDT and DDE||
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 than fat such as seen with such substances as 2-methyl pentane and 3-methyl pentane.
Skin biopsies of bruising and petechiae reveal perivascular lymphocyte infiltrates around the vessel wall in chemically sensitive patients.
Over 200,000 intradermal challenges of chemicals have been done 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 placebo 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 a hospitalized, environmentally controlled setting. Some studies done in our center, under strictly controlled conditions in an environmental unit, showed significant findings (4 SD) 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
completely evaluate the chemically sensitive individual. In our Center,
analysis of over 300 chemically sensitive patients showed the following
vitamin deficiencies: B6C64%;
folic acidC27%; vitamin DC24%;
B3C19%; vitamin CC6%;
B12C3%; Out of 190
chemically sensitive patients with mineral deficiencies, 88% had chromium
deficiency, 12% selenium, 8% zinc, 40% magnesium, and 35% sulfur. Many
had mineral excess in their blood cells.
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 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.
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