DDT Poisoning - Biskind and Bieber, 1949

From American Journal Of Psychotherapy (1949) p261:{This manuscript was received on March 27, 1949 for publication. - Ed}

DDT Poisoning
A New Syndrome With
Neuropsychiatric Manifestations

Morton S. Biskind, M.D. and Irving Bieber, M.D.
New York, NY

(with thanks to Jim West who made this document available on his website)

DDT (dichloro-diphenyl-trichloroethane), an organic compound, first synthesized in 1874 and resurrected from decent interment in chemical archives in 1938, has since attained world renown as the “miracle” insecticide. Beyond question, no other substance known to man was ever before developed so rapidly and spread indiscriminately over so large a portion of the earth in so short a time.
In previous reports (3, 4, 5) one of us (M. S. B.) has pointed out the similarity between the known indications of DDT poisoning and the new and highly debilitating syndrome in the human being commonly attributed to a hypothetical “virus X.” An identical relationship has also been found to exist between the new and highly fatal “X disease” (1, 6, 29, 84) of cattle and intoxication with this pesticide (3).
Although DDT produces serious functional and morphologic changes in virtually every organ of the body (2, 7, 9, 11, 14, 16, 18-22, 24, 28, 30-33, 38-40, 42, 44-49, 51-61), among its most disturbing and debilitating manifestations are those of the nervous system.
In a previous report (5), already mentioned, the disorder which now appears to have reached pandemic proportions throughout the United States, has been described as follows:
"...A group of or all the following: Acute gastro-enteritis occurs, with nausea, vomiting, abdominal pain, and diarrhea usually associated with extreme tenesmus. Coryza, cough and persistent sore throat are common, often followed by a persistent or recurrent feeling of constriction or of a 'lump' in the throat; occasionally the sensation of constriction extends substernally and to the back and may be associated with severe pain in either arm. In some cases the hyoid bone becomes acutely painful to pressure for a few days. Pain in the joints, generalized muscle weakness and exhausting fatigue are usual; the latter are often so severe in the acute stage as to be described by some patients as 'paralysis.' Pain and stiffness in the back of the neck is a frequent complaint. Sometimes the initial attack is ushered in by vertigo and syncope. Intractable headache and giddiness are not uncommon. Occasionally herpes zoster appears. Paresthesias of various kinds occur in most of the cases; areas of skin become exquisitely hypersensitive1 and after a few days this hyperesthesia disappears only to recur elsewhere, or irregular numbness, tingling sensation is, pruritus or formication may occur. Erratic fibrillary twitching of voluntary muscles is common. Usually there is diminution of vibratory sense in the extremities."
“After subsidence of the acute attack, irregular spasm of smooth muscle throughout the gastrointestinal tract often persists for weeks or months, associated with increased fatigability, which only gradually regresses. Febrile reactions occur occasionally during the initial stages but are not the rule. Except for a tendency to anemia, and in some cases a relative lymphocytosis, no constant changes are observable in the blood. Many of the patients have an acute bout of apprehension associated with the foregoing symp-tom complex and rarely is this relieved by reassurance as to the absence of physical findings sufficient to account for the severity of the disturbance.”
Thus far several hundred cases of this syndrome from various parts of the United States have been investigated.
Certain of the disturbances relating to the nervous system were observed in early investigations on the toxicology of DDT, both in animals (7, 38, 57) and in man (9, 22, 58), and were well known to those versed in this field before DDT was introduced for indiscriminate use as an insecticide. But because of the bizarre nature of the syndrome now prevalent, it is often confused with a variety of known disturbances, infectious, organic or psychogenic, when it is not attributed to some mysterious new infectious agent.
This is especially true because exposure to DDT is virtually universal, through its widespread occurrence in milk (53, 56, 60)2 and milk derivatives, meat (8)3, fats and oils, vegetables and fruits (43, 59)4, as well as from direct exposure by inhalation, ingestion and absorption through the skin, of DDT in the form of aerosols, solutions, emulsions, and dusts.
The 0.5 per cent concentration originally suggested as the upper limit for reasonable safety (7) rapidly increased to 3, 5, 10, 25 and now even to 100 per cent preparations. The incredible carelessness with which this lethal compound is now used by the public has no known precedents.
The relationship would undoubtedly have been detected much earlier, however, were it not for the tremendously wide variation in sensitivity to DDT in the general population; Certain individuais appear to be able to tolerate large cumulative doses without apparent ill effect; others are so sensitive that mere traces of DDT can set off an almost immediate reaction of the type described. In addition, sensitization phenomena appear to occur in many previously nonreactive persons after repeated exposure to DDT. Although it is known that detoxication processes both in animals and man involve conversion of DDT to the less toxic acetate (35, 46, 47), little is as yet known about variations from person to person in these detoxication mechanisms, and even less about the intermediary metabolism concerned. Regardless of detoxicatiou, DDT is stored cumulatively in body fat and excretion of the sub-stance is extremely slow even after intake ceases. For this reason, and also because actual morphologic damage may occur, recovery is often very slow, requiring weeks, months and even years.
The purpose of this article is to call attention to the necessity for consideration of DDT poisoning is the differential diagnosis of neuropsychiatric disorders, and to report our further observations on the neurologic and subjective manifestations.
By far the most disturbing of all the manifestations are the subjec.tive reactions and the extreme muscular weakness. In the severe acute poisonings, patient after patient has used identical words, “I felt like I was going to die.” The mental effect is difficult to comprehend unless it has been experienced.
Wigglesworth (58), following brief application to the skin of a solution of DDT in acetone, reported “extreme nervous tension” and “anxiety” among numerous other changes. There was complete disability for ten weeks and recovery was not yet complete at the end of a year. Case (9) and a colleague likewise exposed themselves to skin absorption of DDT. Case described their experience as follows: “The tiredness, heaviness, and aching of the limbs were very real things, and the mental state also was most distressing. Not only was a state of extreme irritability present, but also both subjects had a great distaste for work of any sort and a feeling of mental incompetence in tackling the simplest mental... The joint pains were quite violent at times... subject A. I. was so prostrated he had to take to his bed for a day.”
Other findings were increase in erythrocyte destruction, decrease in mean corpuscular hemoglobin, increase in reticulocytes, diminution in granulocytes accompanied by appearance of immature leukocytes, appearance of indican in the urine, diminution of some reflexes, and in one of the subjects, patchy anesthesia of the skin, slight impairment of hearing and transitory yellow vision, and muscular fibrillation. Recovery required from 4 to 5 weeks.
In our experience, the sensation can perhaps best be described as one of unbearable emotional turbulence. There are at various times excitement, hyperirritability, anxiety, confusion, inability to concentrate, inattentiveness, forgetfulness and depression. Perhaps the one common phenomenon is extreme apprehensiveness. These episodes can easily be confused with anxiety attacks. The feeling of tension essentially involved the extremities, particularly the legs and the forearms. This differs from the usual distribution of psychic tension ‘in skeletal muscles where the nuchal and lumbosacral musculature is predominantly affected. The feeling the patients complain of is that they cannot keep their arms and legs still; they seem to “want to jump,” and these phenomena are usually accompanied by widespread fine fibrillary twitchings. Disturbances of equilibrium may occur. Intractable headache and insomnia are frequent. Disturbances of the autonomic nervous system are likewise common: there may be attacks of tacbycardia associated with dermal ischemia, sweating of the palms and a sense of impending syncope, followed by bradycardia, flushing of the skin, relaxation and cessation of palmar perspiration. (Whether or not disturbances of adrenal medullary function are associated with this phenomenon is a subject requiring further investigation.)
A characteristic of diagnostic importance, is the recurrence of the subjective reactions in “waves,” as numerous patients have’ described it. Some have actually been able to clock the reaction with considerable precision from day to day. The reactions appear most likely to occur during periods of low blood sugar. Additionally, consumption of alcoholic beverages or acute emotional stress may provoke a severe exacerbation.
Often, patients with this disorder complain of a “hollow feeling” in the epigastrinm which bears no constant chronologic relation to the ingestion of food, and in fact may occur immediately after a full meal. Attempts to eat further may provoke sharp repugnance for food and occasionally may lead to an attack of hiccups, or nausea. In other patients, actual overeating indistinguishable from the compulsive types seen in certain psychogenic disturbances may result.
Hardly a single sensory nerve appears to be immune to involvement in this disorder: Paresthesias of every known variety, in cluding disorders of vision, smell, taste, and hearing, may occur. Pain of varying intensity and duration may involve any area of the skin, may localize in a joint or even a tooth. Severe peripheral neuritis involving intense, protracted pain in one or more of the extremities is frequent. Pain in the inguinal region, usually bilateral, is a frequent complaint; occasionally this may be referred to the genitalia. ‘Virtually all these patients have striking diminution of vibratory sensation in the extremities. (This has repeatedly been observed in patients in whom readings had been taken on several occasions with the Collens vibrometer, prior to known exposure to DDT.) As already indicated, recurrent extreme fatigability is common. In acute exacerbations, mild clonic convulsions involving mainly the legs, have been observed. Several young children exposed to DDT developed a limp lasting from 2-3 days to a week or more.
Patients with this syndrome rarely show objective changes on physical examination sufficient to account for the severity of the subjective disorder and the actual amount of disability present. In addition to the change in vibratory sensation mentioned, enlargement and tenderness of the liver5 and palpable spasticity of the colon are the only findings which occur with any degree of constancy. There may be a relative lymphocytosis, and somewhat more often, diminution in hemoglobin.
A characteristic history is that of a person (and in a number of cases, an entire family simultaneously involved) who, previously well and able to make a satisfactory emotional adjustment to his environment, suddenly is affected with the syndrome described and remains partially disabled for many months. In innumerable such cases it was possible to trace the onset of the illness to known exposure to DDT, usually from its use in the home.
Psychotherapy is often resorted to in an effort to trace, and alleviate, possible etiologic psychogenic factors. Additionally, patients may develop this syndrome while under analysis and fruitless months may be spent assessing emotional conflict as a basis such cases have occurred in our experience. for the acute disturbance. Actually, such cases have occurred in our experience.
One of these patients, in her second pregnancy, developed peculiar feelings of muscle tension in all extremities associated with multiple fibrillations, restlessness, marked fatigability and insomnia. The patient has never before suffered these symptoms, nor was there anything discernable in the psychiatric picture to account for these changes. A second patient in analysis for 24 months developed marked fatigability and difficulty in concentration very shortly after copious spraying of her house with DDT for roaches. After two months these symptoms were unchanged. They were never present before and cannot be accounted for psychiatrically.
In these cases, recovery occurs slowly only when exposure to DDT is reduced to a minimum. Sprayed clothing, textiles and bedding must be cleaned with lipoid solvents, the particles of DDT must be removed from the room dust in places that have been treated with DDT aerosol, preferably by lacquering, painting or waxing affected surfaces. (Wall paper impregnated with DDT has caused severe symptoms in a number of the cases investigated.)
Persons sensitive to DDT must avoid as much as possible visiting places known to have been treated with this agent. Foods or portions of foods in which DDT is now known to occur must be avoided or restricted, especially the fatty portion of milk andy products containing it (cream, butter, cheeses made from whole milk). The cream cannot be separated from homogenized milk and homogenization enhances absorption of the fat, hence this form should be avoided, as should beef, and the outer layers of fruits and vegetables that may contain DDT residues. These necessary dietary restrictions pose difficulties, as some of these patients lose weight even while on a full diet, no doubt owing to the fact that DDT stimulates oxidative metabolism similarly to dinitrophenol (24, 44).
Administration of small doses (30 to 45 mg.) of the short-acting barbiturates (e.g., pentobarbital sodium) appears to be a useful, but limited, method of controlling the reactions when they appear. Frequently, instead of the usual hypnotic effect, patients notice an unusual clearheadedness as soon as the emotional turbulence is suppressed. Except for this palliative therapy, other remedies tried appear to be of little use.

Footnotes:
1) For instance, localized facial hyperesthesia on shaving.
2) ‘Though it was originally observed in 1945 (53, 60) that DDT is absorbed through the skin, accumulates In the body fat and appears in the milk of animals, It has recently become almost universal practice to spray cattle with DDT. According to the U. S. Department of Agriculture (56), milk from cattle sprayed with the minimum concentration of DDT in use (0.5 per cent) contained from 0.1 to 2 parts of DDT per million. (As a concentration of 0.5 per cent is often exceeded in actual dairy practice, higher values would not be surprising.) Analysis of butter purchased on the open market in New York City revealed in one sample 8 parts per million and in another 13 p.p.m. When calculated to 4 per cent butterfat of the original milk, these figures fall within the range found by the government investigators. Although young animals are much more susceptible to the effects of DDT than adults, so far as the available literature is concerned, it does not appear that the effects of such concentrations on infants and children have even been considered.
3) In addition to accumulation of DDT in the meat from skin absorption, certain feeds have been found to contain as high as 20 p.p.m. (50).
4) Vegetables and fruits are also widely sprayed with DDT. Residues as high as 7 parts per million are considered acceptable (43). In view of the fact that DDT is a cumulative poison, that it is impossible to remove it by ordinary washing, and that it is not affected by cooking (8), such residues of so stable a. compound can hardly be considered negligible.
5) Domeniel (13) has reported four cases in young nurses, all occurring about the same time, characterized by hepatitis without hepatomegaly, in which “the protracted course, marked by exacerbations and remissions, was associated with marked psycliologic turmoil.” The syndrome was presumed infectious but bears a remarkable resemblance to DDT poisoning.
6) C satisfied with the lethal properties of DDT for insects, related chlorinated cyclic hydrocarbons have now appeared in widespread use. Chlordane (“1068”) (23, 42). now also commonly used by exterminators in households and institutions, and hexacbloro-cyclohexane (“benzene hexachloride,” “BHC,” “666,” usually a mixture of isomers the most active of which is called “gammexane”) (25), like DDT, produce severe functional disturbances of the nervous system. In some respects these compounds are even more toxic than DDT. In animals poisoned with chlordane or hexachlorocyclohexane, those that develop symptoms related to the nervous system rarely recover (25, 42).
Another preparation, parathion (O,O.diethyl O-paranitrophenyl thiophosphate), used on certain fruits, vastly exceeds even these compounds in toxicity.

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ADDENDUM
Since this manuscript was submitted for publication, the pregnant patient (p. 266) was delivered. An analysis of her colostrum and four samples of her milk taken on consecutive days for total organic chlorides (DDT and allied compounds revealed the following amounts reported in terms of DDT: Colostrum 116 ppm, 18 ppm, 2 ppm, 5 ppm, 5 ppm. (7) [see ddt138.htm]
M. B. and I. B.

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