The rapidly accelerating rate of growth of modern technology has been accompanied by a proliferation of a wide variety of new toxic chemicals such as styrene, polyesters, polythene, etc. Recent studies1-3 show that nearly 50% of the global pollution isolated from natural products or synthesized which enter the atmosphere are generated by man. The pervasiveness of toxic chemical agents is well documented. In 1987, American industry poured 22 billion lb. of toxic chemicals into the air, food and water. Overall, Texas, ranking first in air and land releases,4 dumped the most pollutants. Every day several million gallons of chemicals are emptied into Lake Erie, which is the source of drinking and bathing water for most cities from Toledo to Cleveland, OH, to Buffalo, NY.
Inorganic pollutants include ozone, carbon monoxide, nitrous oxides, sulphur dioxides, heavy metals,5-10 and other metals (e.g., Al, Cu, etc.).11,12 Organic pollutants include pesticides, formaldehyde,13 solvents (e.g., toluene and xylene), drugs,14 terpenes, cleaning chemicals, cigarette smoke, combustion products, consumer products (e.g., clothing, building materials, hygiene products, etc.),15-17 and biological compounds (mold toxins).18,19 The most toxic organic pollutants are those classified as halogenated aromatic and aliphatic hydrocarbons.20
According to the EPA,21 more than four million chemical compounds are currently recognised. Over 60,000 of these are produced commercially, and about 3 new compounds are introduced each day. The rampant widespread presence of hazardous chemicals in our environment has become critical. Unfortunately, the link between chemical sensitivity and our individual wellbeing described by Randolph22 over 35 years ago has been ignored until now. While celebrated instances of gross contamination through industrial waste 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. Throughout this book, we will emphasize understanding and interpreting the effects of this environmental load on individual malfunction.
In our opinion, the major stumbling block in recognising the etiology of chemical sensitivity and many instances of resultant fixed-named diseases has been the general failure of the medical profession to appreciate the massive increase in and adverse effects of exposure to environmental pollution. Nonetheless, ten environmental centres and thousands of physicians and scientists on four continents acknowledge the effects of environmental pollution on human health and have contributed to the scientific and clinical evidence for the existence of chemical sensitivity.
Chemical sensitivity is one of the major manifestations of environmentally triggered disease and is the main focus of this book. It is an adverse reaction(s) to ambient levels of toxic chemical(s) contained in air, food, and water. The nature of these adverse reactions depends upon the tissue(s) or organ(s) involved, the chemical and pharmcologic nature of the substance(s) involved (i.e., duration of time, concentration, and virulence of exposure), the individual susceptibility of the exposed person (i.e., nutritional state, genetic makeup, and toxic load at the time of exposure), and the length of time and amount and variety of other body stressors (i.e., total load), and synergism at the time of reaction(s).
Chemical allergies are a small but significant part of the overall spectrum of chemical sensitivity. They may involve both allergic (immunologically mediated mechanisms including all of the four types of hypersensitivity reactions) and toxic (nonimmune mechanisms) responses. They involve the mechanisms of the 1gE class of immunoglobulins. An example of chemical allergy is the 1gE-mediated toluene diisocyanate antigen/antibody reaction which frequently manifests itself as asthma or some other form of respiratory or vascular dysfunction. Other immune mechanisms such as 1gG, cytotoxic response, immune complex (1gG + complement), or T and B cell abnormalities are often involved in chemical sensitivity, although these reactions are frequently secondary responses following an initial enzyme detoxification response. Failure of enzyme detoxification appears to be the prime mechanism in chemical sensitivity. Regardless of the mechanisms involved, clinical manifestations of chemical sensitivity may be the same. For example, rhinitis may occur either as an 1gE response to toluene diisocyanate, or it may be an enzyme detoxification system response to formaldehyde.
Chemical sensitivities may arise in several ways. Individuals who survive near-fatal exposures to toxic substances often experience lowered resistance to disease as a result of the depletion of their nutrient pool brought on by exposure. They may then develop chronic symptoms of ill health. If these people are later exposed to ambient doses of toxic chemicals, they may experience additional and/or enhanced symptoms. "Spreading," which can involve both new organ systems and increased sensitivities to additional substances, may occur. For example, an individual working in a chemical plant may be exposed to high doses of xylene after an explosion. He immediately develops headaches and flu-like symptoms that become chronic. Weeks later, after ongoing ambient exposures in the workplace and at home, this person develops asthma and sensitivity to ambient doses of various toxic and nontoxic (e.g., perfume) substances. Of the chemically sensitive patients seen at the EHC-Dallas, 13% relate the onset of their sensitivity to a severe acute exposure.
Three major incidents have occurred in the 20th century which graphically illustrate that chemical sensitivity may be caused by a significant, acute exposure to toxic substances. The first occurred during World War 1 when many of the troops were gassed with mustard gas.23,24 The clinical aftermath for many of the survivors was the development of chemical sensitivity. The second incident involved military personnel who were sprayed with defoliants while serving in Vietnam. The "agent orange" syndrome, as symptoms from this exposure where later dubbed, persisted for years after their initial contact. The third incident occurred in Bhopol, India, where an accidental atmospheric exposure to large quantities of cyanate left an estimated 86,000 people injured.25 Several months later, many remained afflicted with recurrent symptoms that are today believed to be manifestations of chemical sensitivity.
Chemical sensitivity can occur subsequent to severe bacterial, viral, or parasitic infliction. Of the patients treated for chemical sensitivity at the EHC-Dallas, 1% have traced the origin of their illness to such an event.
The onset of chemical sensitivity has also been attributed to exposure to ambient doses of toxic chemicals following massive trauma, childbirth, surgery, or immunizations. At the EHC-Dallas, 12% of our patients associated massive trauma with the start of their illness; 9% identified childbirth as the triggering event; 2% traced onset to surgery; and linked their illness to other causes.
In contrast to those who develop chemical sensitivity as a result of acute exposure to toxic substances, there exists another group for whom a specific cause of illness is often difficult to discern. This group includes individuals who have become chemically sensitive following accumulative subacute toxic exposures over time. Of our patients at the EHC-Dallas, 60% fit into this category.
Only 2% of our chemically sensitive patients are unable to account for the specific events that precipitated onset of their illness. Because we can link only 28% of our patients' illnesses to employment that involved exposure to high levels of toxic chemicals, such as work in pesticide plants or refineries or work involving pesticide spraying, we speculate that some cases of chemical sensitivity may evolve as a result of a series of events that occur with the passage of time. These events may include an individual's long-term exposure to ever-present, subtle levels of pollutants of which he is unaware. We believe that as these toxic, environmental exposures occur, an insidious breakdown in resistance mechanisms takes place. An individual's vulnerability increases and eventually chemical sensitivity ensues.
Chapter 3. Principles, details how this phenomenon can occur. The development of chemical sensitivity may be chronic and, therefore, insidious. Individuals are often unaware of their developing sensitivity until their chemical intolerance is such that only minuscule concentrations of chemicals are needed to trigger symptoms of illness. At this point, reactions to lower levels of toxic chemicals commonly occur. "Spreading," which involves both single-organ susceptibility to increasing numbers of toxic chemicals and increasing susceptibility of new organ systems to one or many toxic chemicals, may then follow. Fixed-named or end-stage disease may occur, and eventually its course may proceed autonomously. For example, an individual may develop arthralgia due to a sensitivity to formaldehyde. Symptoms may fluctuate from many months to years. Then the individual may develop sensitivities to more toxic chemicals, and arthritis may result. Eventually, if left environmentally untreated, this individual may develop fixed intractable arthritis that appears to be self-perpetuating.
"Low levels" of toxic chemicals have been implicated in the insidious onset of some chemical sensitivities. Because of this connection, use of the term "low level" itself needs to be reconsidered. We believe the term should not be used because it implies that such levels are harmless when, in fact, many chemicals are potentially lethal at low levels. The herbicide 2,4,5-T, for example, has been found to be harmful in the parts-per-trillion or even less. Furthermore, the levels of chemicals considered to be "low" by today's standards are based on levels found in the average population or environment and then termed "normal" and, hence, "low level." Unless a toxic chemical such as formaldehyde or pentane is generated by the body, the control levels usually be nondetectable and not "low level." For example, mathematical calculations of a toxic substance reveal that the number of chlordane molecules per cell is between 700 and 1500 when serum levels are measured at one part per billion.
Too often, "safe" levels of toxic chemicals are assigned based on inferences from an unhealthy control population who are assumed healthy because they are able to function with a minimum of short-term illnesses such as flu or symptom-masking medications. More commonly, levels are assigned from animal studies. We believe the control population from which "safe" levels of toxic chemicals ought to be derived should be those who are totally well and medication free. This population in western society, however, is hard to find. Until such a population can be isolated and appropriate "safe" levels of toxic chemicals determined from their examination, we advocate a reference point for blood and tissue levels of toxic chemicals that is nondetectable.
Because modern medical practitioners accept occasional illness or medicated wellness as part of general good health, we often fail to detect what may be symptoms of the early stages of chemical sensitivity, and because we fail to recognize these stages for what they are, we miss the opportunity to intervene in time to reverse any ongoing damage or prevent the development of serious, fixed-named illnesses. Instead, we misdiagnose and mistreat symptoms, and as a result of our present attitudes and practices, we probably grossly underestimate the incidence of chemical sensitivity.
Symptoms of chemical sensitivity typically are multiple in nature. Usually, one main organ is affected with secondary symptoms occurring in others. End-organ responses are often in the smooth muscles of the cardiovascular, gastrointestinal, urogenital, respiratory systems, or in the nervous system. Also, common early responses may occur in the skin (such as nonjaundice yellowing or edema) or other body organs. At their onset, symptoms of chemical sensitivity are almost always reversible. As end-organ involvement increases, however, responses are more difficult to decipher and reverse.
Pollutant damage can occur at the main site of pollutant entry or in the detoxifying organ or it can be random, affecting any end-organ. Usually, however, the weakest end-organ, that which has been genetically damaged or previously harmed by trauma or exposure, is the first affected.
The sicker the patient with chemical sensitivity, the more diverse and multiple are his responses to a large number of individual incitants, suggesting primary and secondary organ involvement. For example, a patient develops rhinitis on exposure to formaldehyde. Later in the course of his illness, symptoms and signs of cystitis and colitis develop in addition to the rhinitis. Although these various illnesses involve multiple systems and organs, only one end-organ may ultimately be damaged as the result of repeated insults to the same resistance mechanism. After this damage occurs, however, end-organ failure follows and extreme fixed-named illness results. For example, a mechanic constantly exposed to car exhaust could develop general symptoms such as aches, pains, malaise, headaches, and fatigue. These symptoms might then continue for several months until finally renal failure or some other specific end-organ disease develops.
Onset of chemical sensitivity is influenced by multiple factors including total body load (burden), total toxic load, nutritional state, synergisms, competition for storage, bioaccumulation, and biological half-life of the chemicals themselves.
Total Toxic (Body) Load (Burden)
Total toxic (body) load is the sum of all pollutants in
the body at one time. When this accumulation overloads the system, chemical
sensitivity can occur.
The nutritional state needed to maintain good health is
depleted by toxic exposure. Overload of pollutants can increasingly tax the
detoxification systems, eventually resulting in depletion of nutrients,
system/organ malfunctions, and susceptibility to illness.
Synergisms may be additive if the effects of the
pollutants equal the sum of the individual pollutants involved. For example, a
patient whose sensitivity to mold results in a runny nose and whose sensitivity
to formaldehyde yields burning eyes might react to exposure to both with runny
nose and burning eyes. Synergisms may also be potentiative where the effects of
the potentially harmful substances exceed the sum of the individual substances
involved. For example, mold toxin and formaldehyde combined may together give
swollen eyes along with a swollen face and extremities in addition to or
substituting for the burning eyes and runny nose. Occasionally, individual
pollutants may have antagonistic effects. If introduced simultaneously,these
substances may cancel each other's usual effects. For example, salicylic acid
and acetophenomen introduced simultaneously reduce each others effects so that
an individual exposed to these might exhibit slight or no symptoms.
Competition for Storage and Removal
Some chemicals may be competitive for both storage and removal. DDT, for example, increases and dieldrin decreases when they are introduced simultaneously. Both compete for the same enzyme sites for detoxification and metabolic function for detoxification, thus, one may circulate and even be deposited in a lipid membrane while the other is metabolized and used or cleared from the body. In our clearing studies, we have observed that certain toxic chemicals cannot be removed until others are mobilized and removed.
Bioaccumulation of Toxic Substances
The accumulation of a single agent in the body is dependent upon the dose level, interval and duration of exposure, and half-life and lipophilic nature of a chemical. Accumulation of a toxic substance also depends on an individual's quantity and quality of immune and enzyme detoxication responses along with his age and overall health. Accumulation may also occur with constant exposures that allow no time for clearing.
The factors influencing chemical accumulation are solubility quotient, the storage of chemicals in poorly perfused tissues, poor glomerular filtration, intensive tubular reabsorption, and slow biotransformation. This bioaccumulation may be likened to a layered sponge. Each layer fills due to the excess pollutants that are absorbed yet unable to be immediately metabolized.
With each new contact, more layers fill with excess pollutants until the maximum load is exceeded and the disease process begun.
Biological Half-Life of Toxic Substances
The biological half-life of a chemical is one half the time a chemical takes to disintegrate. It is usually calculated from animal exposures. It is also based on inadvertent acute exposures of healthy people to toxic substances. The half-life may have little relationship to the detoxification mechanisms available. Metabolism may be high for initial high-dose exposures, but very slow for low doses.26 This latter response will leave residue in blood and tissues and may explain why low dose exposures can be a significant cause of disease. (See Chapter 4. Nonimmune Mechanisms). Various investigators 27-29 have shown a relationship between the presence and the bioaccumulation of foreign chemicals in human tissue and the incidence of cancer. This correlation appears to exist for nonmalignant diseases as well. This finding should cause even greater concern because apparently some environmentally persistent halogenated hydrocarbons such as DDT or chlordane may have a significant negative effect on the human immune system.30
1. National Research Council, Safe Drinking Water Committee. "Drinking
Water and Health" (Washington. DC: National Academy of Sciences, 1977).
2. National research Council. "Indoor Pollutants"(Washington, DC: National Academy Press, 1981), pp. 16-27.
3. Winslow, S.G. "The Effects of Environmental Chemicals on the Immune
System: A Selected Bibliography with Abstracts" (Oak Ridge, TN:
Toxicology Information Response Centre, Oak Ridge National Laboratory,
4. "Is Your Drinking Water Safe?" (Washington, DC: U.S. Environmental
Protection Agency, Office of Public Affairs, March 1977).
5. National Research Council, Safe Drinking Water Committee. "Drinking
Water and Health" Washington, DC: National Academy of Sciences, 1977).
6. Dooms-Goossens. A., A. Ceuterick, N. Vanmaete, and H. Degreef. "Follow-
up study of patients with contact dermatitis caused by chromates, nickel,
and cobalt," Dermatologica 160(4): 249-260 (1980).
7. Freedman, B. J. "Sulphur dioxide in food and beverages: its use as a
preservative and its effect on asthma," Br. J. Dis. Chest 74(2):128-134
8. Mustafa. M. G., and D. F. Tierney. "Biochemical and metabolic changes
in the lung with oxygen, ozone, and nitrogen dioxide toxicity," Am. Rev.
Respir. Dis. 118(6):1061-90 (1978).
9. Vermeiden. I., A. P. Oranje, V. D. Vuzevski, and E. Stolz. "Mercury
exanthum as occupational dermatitis." Contact Dermatitis 6(2): 88-90
10.Whittemore, A. S., and E. L. Korn. " Asthma and air pollution in the
L., A. area," Am. J. Public Health 70(7): 687-696 (1980).
11.National Research Council, Safe Drinking Water Committee. "Drinking
Water and Health" (Washington DC: National Academy of Sciences, 1977).
12.Clemmenson, O., and H. E. Knudsen. "Contact sensitivity to aluminium
in a patient hyposensitized with aluminium precipitated grass pollen,"
Contact Dermatitis 6(2): 305-308 (1980).
13.Fisher, A. A. "Dermatitis due to the presence of formaldehyde in
certain sodium lauryl sulphate (SLS) solutions," Cutis 27(4): 360-366
14.Dahl, R. "Sodium salicylate and aspirin disease," Allergy 35(2): 155-
15.Frigas, E., W. V. Filley, and C. E. Reed. "asthma induced by dust from
urea formaldehyde foam insulating material," Chest 79(6): 706-707 (1981).
16.Imbeau, S. A., and C. E. Reed. "Nylon stocking dermatitis. An unusual
case," Contact Dermatitis 5(3): 163-164 (1979).
17.Larson, W. G. "Sanitary napkin dermatitis due to the perfume," Arch.
Dermatol. 115(3): 363 (1979).
18.Olson, K. R., S. M. Pond, J. Seward, K. Healey, O. F. Woo, and C. E.
Becker, "Amanita phalloides-type mushroom poisoning," West J. Med. 37:
19.Wilson, C. W. M. "Hypersensitivity to Maine tap water in children: Its
clinical features and treatment," Nutr. Health 2: 51-63 (1983).
20.Laseter, J. L., I. R. DeLeon, W. J. Rea, and J. R. Butler.
"Chlorinated hydrocarbon pesticides in enviromentally sensitive patients"
Arch. Clin. Ecol. 2(1):6 (1983). 21.Schnare, D. W., D. B. Katzin, and D.
E. Root," Diagnosis and Treatment of Patients Presenting Subclinical
Signs and Symptoms of Exposure to Chemicals which Bioaccumulate in Human
Tissue," P-150, Proceedings of the National Conference on Hazardous
Wastes and Environmental Emergencies. Cincinnati, OH. May 14-16, 1985.
22.Randolph, T. G. "Sensitivity to petroleum: Including its derivatives
and antecedents" J. Lab. Clin. Med. 40: 931-932 (1952).
23.Lefebure, V. The Riddle of the Rhine: Chemical Strategy in Peace and
War (New York: E. P. Dutton and Co., 1923).
24.Heller, C. E. "Chemical warfare in World War 1: The American
experience 1917-1918," Leavenworth papers, No 10, Combat Studies
Institute, Library of Congress Cataloging in Publication Data, Forth
Leavenworth, KA(1984),pp. 24-25.
25.Shrivastava, P. Bhopal: Anatomy of a Crisis (Cambridge, MA: Ballinger
Publishing Company, 1987).
26.Balazs, T. "Hepatic reactions to chemicals," in Toxicology: Principles
and Practices,Vol.1,A.L.Reeves, Ed.(New York:John Wiley & Sons, Inc.,
27.Williams, G. M.,and J. H. Weisburger. "Chemical carcinogens," in
Caserett and Doull's Toxicology: The Basic Science of Poisons,3rd ed., C.
D. Klassen, M. O. Amdur, and John Doull, Eds. (New York: Macmillan
Publishing Co., Inc. 1986), pp. 124 and 153.
28.Unger, M., and V. Olsen,"Organochlorine compounds in the adipose
tissue of deceased people with and without cancer," Environ. Res. 23: 257-
29.Wasserman, N. M., D. P. Nogueira, S. Cucos, A. P. Mirra, H. Shibata,
g. Arie, H. Miller and D. Wasserman. "Organochlorine compounds in
neoplastic and apparently normal gastric mucosa," Bull. Environ. Contam.
toxicol. 20: 544-553 (1978).
30.Klotz, V. I., R. A. Bahayantz, V. G. Brysin, and A. Safarova," Effects
of pesticides on the immunological reactivity of the body of animals and
man," Gig. Sanit. 9: 35-36 (1978).
AN EXTRACT FROM: CHEMICAL SENSITIVITY VOLUME 1 BY PROFESSOR WILLIAM J. REA. PUBLISHED 1992.