Pesticides & brain-function changes in a controlled environment

William J. Rea, MD, FACSCDirector Environmental Health Center-Dallas, Dallas, TX

Joel R. Butler, PhDCNorth Texas State University, Denton, TX

John L. Laseter, PhDCCenter for Bio-Organic Studies of the University of New Orleans, where this work was done

Iildefonso R. DeLeon, BSCEnviro-Health Systems, Inc., New Orleans, LA

Address all correspondence to: WJ Rea, MD, 8345 Walnut Hill Ln, Suite 205, Dallas, TX 75231

Source: Rpt. from Clinical Ecology, Vol. II, No. 3, Summer 1984, pp. 145-150.

Key words: pesticides

chlorinated hydrocarbons

MMPI

Bender-Gestalt

WAIS-R

neurotoxicity

psychological/brain-function

environmental sensitivity

environmental control

Abstract: The purpose of the present study was to determine (1) the extent to which chlorinated hydrocarbon pesticides in environmentally sensitive patients would be reduced by Environmental Control Unit (ECU) treatment programs and (2) the correlation of brain-function/psychological test results with treatment effect. Before and after therapy studies were performed on 40 ECU patients with proven levels of blood pesticides. There was a significant decrease in magnitude of blood pesticides and a significant increase in performance on brain-function/psychological tests after ECU treatment. There was also a corresponding decrease in symptoms overall. It was concluded that rigid environmental controls in treatment strongly contributed to the decrease in blood pesticide levels. Further, a more serious psychological profile was associated with these patients who showed improvement consistent with treatment.
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INTRODUCTION

There is clinical evidence that environmentally sensitive patients clear chemicals from their body under less-polluted controlled conditions. Previous reports1-3 from the Environmental Health Center-Dallas (EHC-Dallas) have shown that some chemically sensitive patients do clear their symptoms while under rigid environmental control. Furthermore, studies4 have shown a positive correlation of their chemical sensitivity with levels and numbers of chlorinated pesticide and volatile organic hydrocarbons in their blood. A prospective study was designed to determine if brain function correlated with the levels of pesticide change in the blood of 40 chemically sensitive patients.
 
  METHODS AND MATERIALS

Patients

Studies were performed on 40 consecutive chemically sensitive patients (proven by double-blind challenge) under rigid environmental controls. All patients demonstrated brain dysfunction on observation and clinical impression by several physicians. All had known exposure to environmental toxic organohalidesCeither by acute repeated exposure or chronic long-term, low-level exposure. There were 30 females (ages 20-70) and 10 males (ages 16-65). Brain-function Tests The following brain-function tests (perceptual, cognitive, psychological) were administered to all patients.

The Minnesota Multiphasic Inventory (MMPI) is an empirically derived objective measure of psychological pathology containing nine clinical scales and three validity scales. The reliability is 0.77 over all scales.5 The Wechsler Adult Intelligence Scale-Revised (WAIS-R)6 is an individually administered, standardized, objective measure of intelligence and cognitive function. It is divided into the two major sectionsCverbal and performance. Test reliability of the WAIS-R is 0.97.

The Bender-Gestalt7 consists of nine geometric designs which the patient is asked to reproduce. The Bender is objectively scored by the Embree/Butler8 method to serve as a nuerological screen (reliability, 0.91).

 Procedure Patients were placed in a specially designed pesticide-free and chemically reduced environment within a hospital.9 All water, air, and foods were controlled to assure a significant reduction of organic chemicals and chlorinated pesticides in the individuals= total intake. This theoretically allowed for an increased possibility of removing of the organohalides out of the body into the air, urine, feces, and through the skin.

The patients were administered psychological/brain-function tests (MMPI, WAIS-R, and Bender-Gestalt) at the beginning of treatment and retested at the end of the treatment phase. All tests were scored by standardized techniques, by qualified examiners.

Blood pesticide levels were measured before and after treatment. Sign and symptom scores were obtained before and after treatment.

Chlorinated pesticides measured were:

 Hepatchlor Dieldrin

Endosulfan I Aldrin

gamma-Chlordane gamma-BHC

DDT delta-BHC

Hexachlorobenzene DDD

Heptachlor Epoxide DDE

beta-BHC Endrin

Mirex

The analysis of blood levels was done in a sophisticated environmentally controlled biochemical laboratory in order to avoid cross-contamination with other organic pollutants.

Pesticides were measured in serum using high resolution glass capillary gas chromatographic methods following extraction with residue analysis grade hexane. Detection was by elecron capture. Confirmatory gas chromatography-mass spectrometry analyses were performed in 10% of the extracts. Glassware and solvent blanks were analyzed to insure proper quality control. An internal standard method was employed for quantitation of identified pesticides by Laseter et al.4
 
 

 RESULTS All patients showed at least 0.05/ppb level of 1 to 8 pesticides. The number of pesticides averaged 3.6 per patient. A 79% reduction was found in blood serum levels of the original blood pesticides following EHC treatment. The t-test analysis of this data was significant (p<0.001) as shown in Table I. Originally occurring pesticide data were subjected to chi square analysis to evaluate change in occurrence for each pesticide pre- and post-treatment. Differences were significant on gamma-Chlordane (p<0.05), Endosulfan I (p<0.02), DDT (p<0.05), and heptachlor (p<0.001).

Table 1

Blood Pesticide Decrease with ECU Treatment Measured Individually (by Chi-Square) and Overall (by t-test)
Chlorinated Pesticides
Magnitude of Change after Treatment
Heptachlor
7.54***
Endosulfan I
5.84**
gamma-Chlordane
4.00*
DDT
3.01*
Hexachlorobenzene
1.90
Heptachlor Epoxide
1.02
beta-BHC
1.02
Dieldrin
1.15
Aldrin
1.02
gamma-BHC
2.93
delta-BHC
1.02
DDD
1.02
DDE
3.14
Endrin 
1.02
Mirex
3.14
Notes:

N=40

t<0.001 overall change

*p<0.05

**p<0.01

***p<0.001

All other figures not statistically significant even though decreased, due to small total sample size.
The brain-function/blood pesticides pre- and post-treatment data of the CPST (Chlorinated Pesticide Screening Test) were subjected to t-test analysis for differences in number of pesticides found among patients. There was a significant difference (p<0.001) between the number of pesticides found in the blood in the pretreatment, and immediate-post-treatment, periods. The data were subjected to the t-test analysis over an 11-month period after treatment, and a significant difference (p<0.01) was found between pesticide levels. At the end of the 11 months, 55% of the patients showed different pesticides in the blood. Further, there was a reduction in frequency of occurrence, as well as reduction in quantity, of all pesticides from pre- to post-testing. Brain function testing data inversely varied consistently with the decrease in number of pesticides from pre-to post-testing. The MMPI showed an average of four clinical scale scores above T-score=70 (pathology index) before, and 0.7 T-score=70 after, treatment. Data were subjected to a t-test analysis and a significant difference (p<0.001) was found. Composite brain-function scores on the Bender showed a 33% reduction of errors from 18 to 12. The Bender scores before and immediately after showed a significant difference (p<0.001) from above the pathological index score of 15 to 12. The Wechsler showed improvement (IQ=X 5-point increase) at p<0.01 level.

Symptoms and sign scores were reduced 80% over admission. The various body systems affected by pesticides may be seen in Table II. All 40 patients demonstrated brain/neurological effects, and more than half showed cardiovascular disturbances.

Table II

Systems Affected by Pesticides
System Affected
Number of Patients
Brain/Neurological
40
Cardiovascular
22
Respiratory
9
Genitourinary
4
Gastrointestinal 
10
Skin
3

 

DISCUSSION

Airborne chlorinated pesticides are ubiquitous, resulting in a broad public exposure to potentially hazardous materials.4 Th e uptake and tissue storage of chlorinated pesticides have achieved increased attention in the last several years.10-12 By 1980, over 400 synthetic chemicals had been identified in human tissue. The main involvements were blood, breast milk, liver, and nervous tissue.12 The present study confirms the clinical impression that patients not only improve symptomatically, but also by objective measurement, under rigid environmentally controlled conditions. Various attempts have been made to reduce organohalide body burdens.13-18 Patients may lose some of their body burden in several ways. Evidence suggests that significant clinical improvment requires strict avoidance in intake of chlorinated hydrocarbons in food, air, and water.3,19 Additionally, mobilization of the tissue stores by fasting3,19,20 and neutralization of free radicals by vitamin intake apparently occur.21 Both DDE and PCBs can be altered with lipid mobilization under these conditions.20 The exact mechanism for mobilization of chemicals from adipose tissue is unknown. Apparently, some chemicals mobilize at the same rate as lipid. However, DDT has not shown this characteristic, but stays much longer. The loss of chlorinated pesticides from the body was thought to be a long-term, if not impossible, propostion in that early half-life studies showed some lasting for years. A recent study by Schnare22 suggested that a regime of vitamin ingestion combined with external hyperthermia could usually remove pesticides from the body faster than formerly stated. His therapy (in addition to the previous modalities discussed) may help lipid moblization of chlorinated pesticides and be a valuable adjunctive treatment. His study supports Randolph19 and our clinical observations over the last several years that toxic chemicals must be coming out of the body in order to explain the patients= improvement under environmental control.1-3 Reduction of intake not only assures less stress in the body=s immune and detoxification systems, but it also might allow them to function much better in clearing the body burden of pesticides as well as other organic chemicals. Indeed, such appeared to be the case in this group of patients. A regime of 5 to 15 grams of intravenous vitamin C daily was used since some reports suggested an organohalide depression in the activities of the enzymes L-gluconolactone oxidase and dehydroascorbitase along with an increased urinary excretion of ascorbic acid.21 While the significant decrease in the number of pesticides in the patient group and improved health are clearly related, the exact influence of pesticides on the individual cannot yet be determined. Environmental Control Unit (ECU) treatment programs also impact on health of the patient by decrease of other toxins from the blood. The compound effect of pesticides with other toxins can be assumed to magnify the clinical picture, but the precise interaction effect is not yet known. Some evidence exists that organohalides mobilized into the blood stream go to the liver. Though this may be partially true, in these patients the clearing of symptoms and lack of long-term liver changes suggest that the pesticides are eliminated from the body by the urine and feces as well as other orifices. Unfortunately, their levels in excrements were not measured in this study. Alternatively, some shift may occur into the liver, then into the fat, rather than the gut.

The clearing of pesticides from the blood under environmentally controlled conditions may be used as an indicator with a high degree of accuracy of levels of pesticides in other tissue resulting in improvement of the patient. Not shown in the present study (due to too few numbers) was the observation that blood pesticide levels would frequently increase after institution of enivronmental control. The patients= clinical condition appeared to worsen during this period suggesting at least in part that they were adversely responding to the increase in chemical load in their blood stream. This again would suggest that blood pesticide levels would influence clinical symptoms. There appeared to be a varied rate of clearing of some pesticides. Several pesiticides seemed to be removed more eaily from the body. For example, heptachlor (X2=7.54) was removed much faster than ß-BHC (X2=1.02). The reasons for this are unclear. However, animal data would suggest that microsomal enzyme induction varies with the type of chlorinated pesticides ingested, thus theoretically changing clearing rates.

One puzzling fact occurred: 55% of the patients showed different pesticides in the blood after treatment over a period of 11 months. This could be due either to new pesticides from external exposure or more likely due to sequestered pesticides coming out of the tissue. The latter conclusion is more likely in humans, since the patients were taking care to minimize re-exposure by taking less contaminated food, water, and airCand also were continually improving symptomatically. There are some animal data to support this last concept. For example, the body will preferentially store dieldrin over DDT, while DDT will suppress heptachlor storage in rats.23

In the present study, chlorinated hydrocarbon pesticides are strongly correlated with a changed psychological/brain-function condition. A previous study from this group (and others)4 has shown that these pesticides affect the central nervous system, maintaining a body burden. In terms of psychological/brain-function behavior associated with pesticide poisoning, the clinical factors are somewhat worse that those of environmental patients who may seem to (but do not) represent a neuroticsomatoform disorder. Chlorinated pesticides appear to be associated with a more serious psychological profile in which the patient shows more indications of major variance of behavior such as depression with obsessive-compulsive patterns of coping, and of symptoms such as emotional sensitivity (an apparent overreaction to emotional stimuli), often with feelings of being rather overwhelmend by adversityCsometimes to the point of having persecutory thoughts that lead to unreasonably angry responses. Further, this patient profile suggests feelings of alienationCof not understanding one=s own attitude or behavior (Athis is not true of me@) and of distancing one=s self from others (even significant others). There are also indications of some tendency toward diminished ego control in dealing with reality along with a sense of strangeness in bodily reactions.

While the clinical patterns of these patients were usually similar, not all of the patients showed all of the symptoms. They exhibited central and peripheral nervous system (cognitive, perceptual, motor) symptoms and signs including recent-memory deficits, paresthesias, headache, dizziness, and motor instability. There was consistent and significant improvement in these parameters as the patients cleared pesticides from the blood. These reactive profiles are consistent with (but not totally inclusive of) what is known about accidental poisoning by the pesticides, with the highest frequency of detection being BHC, DDT, heptachlor epoxide, hexachlorobenzene, and dieldrin.

 Weiss24 has noted that almost every major pesticide acts by inducing neurotoxicity, but it has proven very difficult to detect the subtle progression of often vague and varied symptomatology. One thing sems clear, however: more than indirect chemical or biological measures are necessary, and the insidious nature of the effects require baseline data before any real meaning can be attached to a changed condition. For example, it would appear useful to have test data pre-treatment or pre-employment (in potentially hazardous chemical exposure areas of work). Also, any measurement or definition of Aenviornmental health@ must include some assessment of (and recognized way of assessing) how people feel and function. These measurements will broaden the clinician=s information scope beyond the disease model.

Fein25 and her associates have concluded that evidence of poisoning may appear in subtle behavioral alterations and in emotional or sensorimotor difficulties discernable only when the individual is observed systematically over time in carefully designed assessment situations. At low levels of exposure, the effects may differ in different individuals due to genetic deficits, heavy stress, or other variables. Behavioral changes could promote interpersonal difficulties because of the affected individual=s depression, irritability, activity rate, etc. There may be a long latency of reaction (weeks to years) for those persons exposed to chemicals, and reactions may take different forms in different systems. These range from emotional lability to impaired learning ability and can affect the unborn child.

The incidence of blood pesticide levels is associated with a more serious psychological pattern of brain function variance, which may be reflective of the general response to chemical contamination. The effects of chemical-toxic reaction in the validity of objective standardized test patterns will require systematic observation of repetitive design to ensure predictive accuracy in the interpretation of behavior. Chemical/pesticide effects on emotions and intellect are apparent, but precision in determining the multiple interactions remain to be discovered.
 
 

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The authors wish to express their appreciation for the assistance of Sharon G. Wright, MS, and Melody J. Milam, PhD, of North Texas State University.