Bioaccumulation Diagnosis and Treatment

Diagnosis and Treatment of Patients Presenting Subclinical Signs and Symptoms of Exposure to Chemicals Which Bioaccumulate in Human Tissue

Abstract

This Conference is dedicated to examining all facets of "hazardous wastes and environmental emergencies." At the national, state and local levels, a tremendous nationwide effort is being exerted to clean up air, water and ground pollution. However, as the eminent environmental scientist Rene Dubos noted over 15 years ago, "The greatest danger of pollution may well be that we shall tolerate levels of it so low as to have no acute nuisance value, but sufficiently high, nevertheless, to cause delayed pathological effects and despoil the quality of life." This paper examines some of the problems in attempting to diagnose and treat low-level body burdens of toxic chemicals and discusses a review of 120 patients who were prescribed detoxification treatment as developed by Hubbard to eliminate fat-stored foreign compounds.

Introduction

Four million distinct chemical compounds have been reported in the literature since 1965, with approximately 6000 new compounds being added to the list each week. Of these, as many as 70,000 chemicals are in current commercial production.' Human exposure to them is both direct and indirect: more than 3000 chemicals are deliberately added to food and over 700 have been identified in drinking water. Along with pharmaceuticals and recreational street drugs, the direct exposure to humans is considerable.

A significant number of these toxic chemicals are lipid or fat soluble and tend to bioaccumulate, particularly in the fatty tissues throughout the body. Over 400 chemicals have been identified in human tissues, with 48 found in adipose tissue, at least 40 in milk, 73 in the liver and over 250 in blood plasma.' Examples of these types of lipid-soluble chemicals which tend to bioaccumulate are polychlorinated biphenyls, polybrominated biphenyls, PCP and THC. Evidence regarding the persistence of these fat-soluble chemicals in humans has accumulated, especially with respect to the organohalides.

Several studies 4,5,6 have shown that fat biopsy samples taken as many as 18 months apart have shown no significant reduction in levels of PBBs and PCBs. This is a point of some significance; once these types of chemicals enter the body's fat stores, they are not easily removed from the body by natural mechanisms and, therefore, tend to bioaccumulate in the human body. By 1975, studies on adipose tissue levels of organohalides had shown that over 90% (and in some cases 100%) of the samples collected had detectable levels of DDT/DDE, Dieldrin, heptachlor, epoxide and PCB.7,8

There have been several large-scale human exposures to these lipophilic toxic chemicals; one example is the 1973 PBB exposure in Michigan. Most of you will recall the episode in which PBB, a fire retardant, was substituted for a cattle feed supplement, thereby contaminating a large portion of the meat and milk in the state of Michigan. By 1978, 97% of individuals tested in Michigan had detectable PBBs in their adipose tissue.' Several studies have estimated that these residents may bear this toxic burden throughout their lives. 10, 11, 12 Unfortunately, the effects of such long term burdens have yet to be determined.

Diagnosis

Diagnosis of chemical intoxification has traditionally required a history of exposure to a known chemical and the finding of appropriate symptoms and clinical signs. Threshold limit values are based on the known effects of exposure to one chemical at a time over a known or limited time period. The "no-effect level", "safety factor" and "acceptable daily intake" have been considered sacrosanct for so long that the weakness of the rationale on which they are based may come as a shock." Most of these levels are based on pathological or tissue findings where possible."

However, we are concerned with the more subtle findings which may occur in neurological and other organ systems before permanent tissue damage has occurred. These more subtle changes take the form of symptoms common to all of us which can be related to other types of medical and emotional problems: increased fatigue, malaise, slowing of motor reactions, impaired regulation of appetite, reduced visual discrimination capacities under low levels of illumination, headache, irritability, tiredness, etc. These functional changes are seldom reflected in pathologic signs or findings. However, these behavioral changes may be more sensitive indicators of general organ system toxicity." Attempts at trying to recognize these "subclinical" or "subliminal" signs and symptoms of toxic exposure are not new: Goldberg in 1972 noted:

"Subliminal toxicology seeks to study levels of exposure that elicit no overt clinical effect on man or animal. The subliminal approach aims at discovering indicators of exposure and of effect that are so sensitive as to provide the required information at dose levels comparable with those to which the human population is actually being exposed."

There are several problems which arise when attempting to provide health care to chemically exposed patients.

Problems in Diagnosing Low-Level Toxic Exposure

Disease Progression

The chronic effects of low-level exposure to toxic chemicals have been studied in only a very few chemicals. Table 1 shows the progression of disease associated with bioaccumulation of PBBs and PCBS. Disease syndromes progress very slowly, and it may take many years of exposure before overt signs are present which provide pathologic diagnosis. Unfortunately, by this time many of the changes (carcinogenesis, peripheral nerve damage, central nervous system damage, etc.) are permanent and irreversible. It is essential, therefore, that early diagnosis of low-level bioaccumulations of toxic chemicals be made.

*Fat concentration measured on a per lipid weight basis

Nonspecificity of Symptoms

Many chemicals can cause identical symptoms. A review of the literature over the past 10 years for 46 selected chemicals shows many instances of wide overlap of symptomatology to exposure to these chemicals (Table 2). It is important to note that the symptoms related to lipophilic chemicals are not significantly different from those related to hydrophilic chemicals. Many of the symptoms may relate to psychiatric or psychological symptomatology. However, several studies 16, 17, 18 have shown that the existing differences between exposed groups and control groups could not be otherwise explained without considering an etiologic role for exposure to the toxic substances.

Chemical Cocktail Dilemma

Patients, and indeed all of us, are exposed to low levels of many different toxic compounds on a daily basis. Even with known drug interactions, the physician, nevertheless, has a difficult time keeping track of the interactions of the many different medications he may prescribe to a single individual. The literature of pharmacology and toxicology is replete with examples in which one agent enhances the effects of others, either directly or indirectly." Reiter notes, Although one might prefer to know more about the potential effects of toxicants when administered alone before we tackle the problem of mixtures, the 'real world' situation demands the development of a strategy for the evaluation of mixtures."

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