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CARR; GDDDSDN & LEE. P E. DISEASE PROFILE PSYCHOLOGICAL AMD BEHAVIORAL DISTURBANCES I. DEFINITION A. Diet ionary The terms psychological and behavioral disturbances refer, respectively, to various mental disorders (e.g., depression, or hypochondria), and changes in conduct of an individual (e.g., fatigue, irritability, or lack of concentration) that may be caused by genetic and/or environmental factors. B. Synptoms The clinical hallmarks include: fatigue or lethargy, depression, loss of appetite, memory loss, loss of concentration, irritability, hypochondria, sleep disturbances, loss of libido, alcohol intolerance, apathy-, and dulled emotional response. C. Durt ion Duration is highly variable depending on the type of symptom, its cause, and treatment. D. Treatment Drug treatment includes the use of tranquilizers and mood elevating drugs. Other treatments include psychiatric therapy, psychological therapy and dietary regimes. E. Diagnostic Criteria Because of the many different types of psychological and behaviorial disturbances, diagnostic criteria and protocol are variable. Medical history questionnaires are generally given along with clinical CONFIDENT! AT SUBJECT TO PROTECTIVE ORDER. C2397< Ca r r ,G o d d s o n & Le e .P C. Psychological and Behavioral Disturbances Page 2 examinations to identify any organic causes. Patients may also be referred to specialists such as psychiatrists or psychologists for more specialized difagnostic testing (e.g., Weehsler test, a general intelligence and coordination test involving both verbal and performance skills; Rorschach test, sensitive to disorders of thought and emotion; and the Minnesota Multiphasic Personality Inventory (MV1PI), a clinical test used to assess personality traits and diseases). II. EVIDENCE RELATING DISEASE TO 2.4,5-T, TCDD, or 2,4-D EXPOSURE A. Human Studies 1. Industrial Accidents An explosion at a plant in Nitro, West Virginia in 1949 resulted in exposure of enployeess and clean-up crews to TCDD contaminated material. Fatigue, nervousness and irritability, and decrease in libido followed chloracne and peripheral neuropathy in order of relative frequency of clinical synptoms. A follow-up examination of workers three years later revealed a general regression of these synptoms. Some nervousness and excess fatigue continued. No clinical explanation could be made based on results of physical examination. The exposure level of TCDD was not reported in the study (1980, E). Singer reported on a 1971 German study by Kleu and Goltz that looked at ten workers acutely exposed to TCDD fifteen years earlier. The study found that the workers still reported fatigue, decreased lioido, alcohol intolerance, and memory loss. The exposure level of TCDD was not reported in the study (1982, C). CONFIDENTIAL SUBJECT TO PROTECTIVE ORDER. C23973 Carr.Gdod s d n & Lee.PC. Psychological and Behavioral Disturbances Page 3 An explosion at a BASF chemical plant in West Germany in 1953 !ofresulted in a total of 53 ill workers soon after the explosion. the 14 workers suffering from chloracne, three also reported increased fatigue (1973, I). A follow-up study in 1976 reported that of the 53 workers, two committed suicide. However, the suicides were attributed by psychiatric and neurological specialists to psychoses rather than dioxin exposure. (1976, G). Workers exposed to TCDD as a result of an explosion at a 2,4,5-TCP production facility of the Coalite company in England in 1968 resulted in no cases of reported psychological or behavioral disturbances even though 79 cases of chloracne were reported. Levels of TCDD were not described (1973, H). 2. Occupational Exposure Poland et^ al_. studied the chronic industrial exposure of 73 male employees involved from 1964 to 1970 in the production of 2,4-D, 2,4,5-TCP and 2,4,5-T at a Newark, New Jersey plant of the Diamond Alkali Company. In addition to medical histories and physical examinations, the Minnesota Multiphasic Personality Inventory (MVPI) was administered to administrative staff ana production workers. Wien scores of both groups of enployees were compared with the normal values given for the MVPI test scales, administrative staff and production workers varied significantly from the norms on a total of six and nine scales respectively. Of particular interest were high values of the employees in the depression, hysteria, and manic scales. Furthermore, there was a high correlation between those employees with severe chloracne and a high manic scale score (a state characterized by an expansive emotional state, including elation, hyperirritability, or flight of ideas) (1971, M). However, beyond test score changes, the study did not identify any observable psychological or behavioral disturbances. CONFIDENTI A I. SUBJECT TO PROTECTIVE ORDER. C23974 Carr. Gdddson & L e e . P C. Psychological and Behavioral Disturbances Page 4 A Czechoslovakian study looked at dioxin poisoning during ft 1965 to 1968 among workers involved in the production of 2,4,5-TJ Of the 400 workers enployed in the plant, 80 became ill. Fifty-five of those persons were studied over a ten year period. Thirty-five workers were characterized as neurasthenic (characterized by chronic abnormal fatigability, lack of energy, feelings of inadequacy, moderate depression, inability to concentrate, loss of appetite, and insomnia) or depressive. The authors observed that during the ten year follow-up study the psychiatric conditions improved. The depressive and anxiety components of neurasthenic disorders had completely disappeared and the number of patients who showed no sign of mental disorders had increased (1981, D). Baaaer and Bauer studied workers at a West German plant that produced pentachlorophenol for six months during 1948-1949. Of 17 workers suffering from chloracne, four also experienced disturbances of libido (1951, O). Bauer et a K also studied 31 workers in a 2,4,5-T plant in Hamburg, Germany. Exposure levels and duration of exposure were not reported. There were reports of fatigue, a sense of insecurity, sullenness, and irritation. The authors observed that not infrequently., a mood component of fear and unease was present. Changes in affeetivity were reported by patients in the form of increased emotional reactions, tendency to fits of temper, and in some cases a certain dullness. There were also reports of decreased libido, decreased appetite, and in some instances, abnormal and constantly changing eating habits with cravings for varied types of food. Six of the employees were studied over a two year period and given psychological examinations. The Hamburg-Wechsler test (German version of the Wechsler test) was adninistered for the discovery of intellectual performance shortcomings. CONFIDENTI AL SUBJECT TO PROTECTIVE ORDER. In the majority of C23975 Carr. G d d d s o n X Le e .P C. Psychological and Behavioral Disturbances Page 5 those tested, there mbs a significantly raised percentage of degeneration, f. providing a certain indication of an acquired decrease in mental capacity. The Rorschach psychogram was administered with results demonstrating signs of f weakened emotional reactivity, poor concentration, reduction in tempo, and a sluggishness of mental processes (1961, N). 3. Veteran Studies A recent study by Korgeski et al_. examined the relationship between 100 Vietnam veterans' self-reported and objectively determined exposure to Agent Orange ana the relationship between self-reported or objective ratings and self-reported psychological and medical problems. Comparison of the subjects' VMPI scores grouped according to self-reported levels of herbicide exposure indicated a consistent trend. Persons believing that they had been exposed to herbicides reported significantly more psychological problems. The authors observed that these findings suggest a tendency for belief in exposure to herbicides to be correlated with self-reports of an extremely wide variety of psychological conplaints, such as depression, anxiety, somatic conplaints, and interpersonal difficulties. The study noted that a pattern of this type is not typical in persons suffering from most specific psychiatric disorders. The M^fl results were different when subjects were grouped according to objective ratings of herbicide exposure (based on where the subjects had been stationed in Vietnam and Defense Department records of herbicide spray missions). There were essentially no significant differences on the VMPI clinical scales between those classified as exposed and those classified as not exposed. The study also looked at "success at living" variables since normally, persons experiencing significant emotional problems typically show poor levels of functioning in areas of life such as employment, income, SUBJECT TO PROTECTIVE ORDER. G23976  Ca r r .G o o d s o n S Le e .R C. Psychological and Behavioral Disturbances Page 6 educational attainment, social and coomunity involvement. The results * demonstrated that regardless of whether the subjects were classified according to self-reported or objective ratings of herbicide exposure, ttfey did not differ on the indices of "success at living." Another series of tests found that there were no significant differences between the suojects on the indices of neuropsychological functioning, (e.g., delayed recall testing) whether they were grouped according to self-reported or objective ratings of herbicide exposure. The authors concluded that this study did not seem to support the hypothesis that exposure to Agent Orange caused psychological problems in veterans, nor did there seem to be a link between herbicide exposure and neuropsychological problems in veterans (1983, A). A three_month Australian study of 58 Vietnam veterans suggested that neuropsychiatrie disturbances experienced by Vietnam veterans were linked to dioxin as well as organophosphate insecticides. Synptoms noted in the study included loss of drive, concentration and memory, irritability, insomnia, depression, and attempted suicide. All of these synptoms were aggravated by small amounts of alcohol to which most veterans were hypersensitive (1982, B). 4. Other The accidental spraying of TCDD contaminated salvage oil in three horse arenas in Missouri resulted in TCDD concentrations of about 30 ppm in the arena soil. Human health impacts studied have been limited to six individuals exposed to the soil. One of the individuals experienced, among other things, lethargy (1977, F). A questionnaire and interview of 98 Vietnam refugees who had claimed exposure to chemical sprays in South Vietnam found that 92% CONFIDENTIAL SUBJECT TO PROTECTIVE ORDER. C2397 Ca r r .G o o d s o n s Le e .R C. Psychological and Behavioral Disturbances Page 7 reported fatigue, weariness, or dizziness after the spraying. Most of the respondents claimed to have inhaled the spray and to have been wetted by it. The study did not address whether the reported injuries ware verified by physicians (1972, L). B. Animal Studies 1. Manuals Dogs orally fed 7CDD at doses of 9.1 to 3.0 mg/kg experienced, among other things, anorexia and depression (1973, K). The Missouri horse arena incident (previously discussed) also resulted in injury to livestock. Of 85 horses ridden in the arena, 58 became ill. Of those 58, 24 horses suffered anorexia (1977, F). 2. Rodents Rats receiving 100 ug/kg of TCDD demonstrated syrrptoms of ruffled hair coat, hunched posture, and depression (1973, J). III. PRINCIPAL DOCUMENTS A. 1983. B. 1982. Correlates of Self-Reported and Objectively Determined Exposure to Agent Orange Korgeski, Gregory P . ; Leon, Gloria R. Carr Document No. - A-2765 Copy attached Neuropsychiatrie Effects of Herbicides Barr, Malcolm Copy attached n 1982. Nerve Conduction Velocity Studies of Workers Enployed in the Manufacture of Phenoxy Herbicides Singer, Raymond; Moses, Marion; Valciukas, Jose'; Lilis, Ruth; Selikoff, Irving J. Copy attached D. 1981. The Development and Prognosis of Chronic Intoxication bv TCDD in Men Vejlupkova-Pazderova, Jana; Jirasek, Lubor; Nemcova, Marcela; Pickova, Jane Carr Document No. - A-2520 C23973 SUBJECT TO PROTECTIVE ORDER. Ca r r ,G d d d s d n & Le e ,R C. Psychological and Behavioral Disturbances Page 8 E. 1980. The Mortality Experience of Workers Exposed t o j Tetrachlorodibenzodioxin in a Trichlorophenol Process Accident Zack, J.A.; Suskind, R.R Carr Document No. - A-198 Microfiche No. - A78 C04-C08 F. 1977. Epidemiology and Pathology of a Tetrachlorodibenzodioxin Poisoning Episode Kimbrough, Renate, D. ; Carter, Coleman, D.; Liddle, John A. ; Cline, Richard E. Carr Document No. - A-219 Microfiche No. - A82 B14-C10 G. 1975. H. 1973. I. 1973. J. 1973. K. 1973. L. 1972. M. 1971. Follow-up Report on the TrichlorophenolDioxin Accident at BASF P C on 13, November 1953 Thiess, A.M.; Goldnan, P. Carr Document No. - A-887 Microfiche No. - A262 B13-C04 Chloracne From the Accidental Production of Tetrachlorodibenzodioxin . May, George Carr Document No. - B-277 Microfiche No. - B123 B03-B12 Severe Acute Chloracne: A Mass Intoxication by 2,3t6,7Tetrachlorobenzodioxin Goldman, Paul J. Carr Document No. - A-885 Microfiche No. - A262 A08-B04 General Biological Effects of TCDD in Laboratory Animals Harris, M.W. ; Moore, J.A. ; Vos, J.G. ; Gupta, B.N. Carr Document No. - B-1212 Microfiche No. - B274 F03-F14 Toxicology of Chlorinated Dibenzo-p-dioxins Schwetz, B.A.; Norris, J.M. ; Sparchu, G.L.; Rowe, V.K.; Gehring, P.J.; Emerson, J.L.; Gerbig, C.G. Carr Document No. - A-944 Microfiche No. - A280 B06-C11 Chemical Spraying as Reported by Refugees from South Vietnam Rose, Hilary A; Rose, Steven P.R. Carr Document No. - B-1422 Microfiche No. - B351 E14-F04 A Health Survey of Vtorkers in a 2,4-D and 2,4,5-T Plant Poland, Alan P; Smith, Donald; Metter, Gerald; Possick, Paul Carr Document No. - B-958 Microfiche No. ~ B253 D03-E03 CONFIDENTIAL C23979 SUBJECT TO PROTECTIVE ORDER. Ca r r ,G o o d s o n & Le e ,R C. Psychological and Behavioral Disturbances Page 9 N. 1961. t O. 1951. Occupational Intoxication Occurring in the Production of Chlorophenol Compounds i Bauer, H; Shulz, K.H.; Spiegel berg, U. Carr Document No. - B-482 Microfiche No. - B163 D08-E01 Industrial Intoxication Due to Pentachlorophenol Baader, E.W. ; Bauer , H.J. Carr Document No. - B-414 Microfiche No. - B149 A13-B05 ** CONFIDENTIAL SUBJECT TO PROTECTIVE ORDER. 023980 Ca r r .G o o d s o n X Le e .P C. Psychological and Behavioral Disturbances Page 10 V . OONFOUNDERS ' A. Because of the variability and subjective nature of many of the synptoms related to psychological and behaviorial disturbances, there are a host of other genetic, physiological and environmental factors that should be considered on a patient specific basis (e.g., general health and family history, medication and recreational drugs, or occupation). B. Post Traumatic Stress Disorder as experienced by Vietnam veterans, and others exposed to traumatic situations, manifests disturbances similar to those described by the plaintiffs. See. Stress Disorders Among Vietnam Veterans, edited by Charles R. Figley; (Brunnery Mazel, 1978). SUBJECT TO PROTECTIVE ORDER C23981