D.D.T. POISONING IN MAN
1
1178 overlooked by omitting radiological examination of ottier parts of the skeleton. e REFERENCES Burke, F. G. (1948) J. Pediat. 32, 441. Caffey, J. (1946) Ibid, 29, 541. Silverman, W. A. (1945) Amer. J. Roentgenol. 54, 1. Dickson, D. D., Luckey, C. A., Logan, N. H. (1947) J. Bone Jt Surg. 29, 224. Ellis, R. W. B. (1939) Proc. R. Soc. Med. 32, 139. Fisk, C. (1947) J. Iowa St. med. Soc. 37, 529. Gipson, A. C., Clark, B. P. (1948) Pediatrics, 1, 221. O’Reilly, J. N. (1949) Arch. Dis. Childh. 24, 67. Shuman, H. H. (1948) J. Pediat. 32, 195. Smyth, F. S., Potter, A., Silverman, W. (1946) Amer. J. Dis. Child. 71, 333. van Zeben, W. (1948) Acta pœdiat. 35, 10. Whipple, R. K. (1947) New Engl. J. Med. 236, 239. D.D.T. POISONING IN MAN A SUSPECTED CASE A. M. G. CAMPBELL M.A., D.M. Oxfd, M.R.C.P. PHYSICIAN, BRISTOL ROYAL HOSPITAL THE use of 2, 2 bis (p-chlorphenyl) 1, 1, 1, trichlorethane (D.D.T.) as an insecticide has become so general, and toxic symptoms in man have been recorded so rarely, that it is thought worth recording another possible case. In poisoning by D.D.T. in animals the main toxic effects seem to fall on the liver and sometimes produce hepatic necrosis. The kidneys are also affected. There are loss of weight and ill-defined damage of the nervous system, accompanied by convulsions and sometimes damage to the anterior-horn cells (Draize et al. 1944, Woodard et al.1944).. Wigglesworth (1945) recorded the first case of D.D.T. poisoning in man. The victim had been exposed to a high concentration of D.D.T. in acetone and had obviously absorbed much through the skin. He complained of heaviness and aching in the limbs, sleeplessness, spasms of great nervous tension, extreme fatigue, prostration, and twitching of the muscles over the whole body. For a long time his symptoms were thought to be due to a neurosis, until it was recognised that he had run the risk of absorbing a great deal of D.D.T. and this might be their cause. Case (1945) found that Service personnel exposed to a high concentration of D.D.T. were liable to have fatigue, aching of the limbs, irritability, emotional instability, and violent cramp in the limbs. This finding suggests that the symptoms in Wigglesworth’s (1945) cases were genuinely due to D.D.T. despite their resem- blance to an anxiety state. Case mentions that one person, who was not hypochondriacal, was so prostrated that he had to take to his bed. Among other symptoms noted by Case were " yellow vision " in one person and diminution in auditory acuity in another. The most striking feature in man has been the mental symptoms, and the following case is no exception. CASE-RECORD A man, aged 32, who had been a demonstrator of D.D.T. powder for the Ministry of Agriculture for six years, had handled and inhaled the powder, but not to the extent of what is generally thought to be a toxic hazard. His previous history was perfectly normal and, so far as can be ascertained, he had been free from any nervous breakdown or tempera- mental difficulty. About three months before consulting a doctor he had noticed periods of extreme fatigue and prostration while walking. He often felt an intense desire to sit down and an inability to take any exercise without a rest. He had noticed a tendency to emotional instability and weeping, and at the same time was getting cramping pains in his limbs varying from day to day and from limb to limb. The pain lasted twenty minutes on one occasion and three or four hours on another. 0 examination no abnormality in his central nervous system was found except a slight tremor of the outstretched hands, and his performance of mental tests was good. Three lipomata were found on the left thigh ; these the patient had not previously noticed. Polyps were found in the maxillary antrum. Investigations.-The blood picture was normal. A blood- count gave red cells 5,000,000 per c.mm., Hb 107%, white cells 9,200 per c.mm. (differential count and platelets normal). The erythrocyte-sedimentation rate (E.s.R.) was 24 mm. in 1 hr. (Wintrobe). A urea-clearance test and straight radio- graphy of the kidneys were normal. The urine contained albumin, red cells, and granular casts. The blood-urea was 38 mg. per 100 ml. Lumbar puncture produced normal cerebrospinal fluid under a pressure of 120 mm. H20, con- taining 2 lymphocytes per c.mm. and 30 mg. of protein per 100 ml. The Wassermann reaction was negative. The fasting venous blood-sugar was 90 mg. per 100 ml. The blood- lead was normal, serum-sodium 335 mg. per 100 ml., serum- potassium 17 mg. per 100 ml., serum-calcium 9-7 mg. per 100 ml., plasma-chloride 626 mg. per 100 ml. (as sodium chloride), plasma-bicarbonate 56 vols. % (as CO2.combining power). plasma inorganic phosphorus 3-7 mg. per 100 ml., and plasma, protein 6-7 g. per 100 ml. All these figures are within normal limits. All liver-function tests were normal, as likewise were an electro-encephalogram, an electrocardiogram, and a radiogram of the skull. Treatment and Progress.-The lipomata were removed from the thigh. The patient made a complete recovery from cramps and weakness, and after a fortnight in hospital was discharged with slight feelings of nervous tension, albuminuria (the red cells and casts had disappeared), and an E.s.R. of 12 mm. in 1 hr. DISCUSSION Extreme mental fatigue and anxiety, cramps, and tremor have been reported in all human cases of D.D.T. poisoning so far published. Weakness and nervous tension have also been observed in D.D.T. poisoning in some animals (Woodard et al. 1944). Since D.D.T. has been thought to produce hypoglycsemia in animals and to decrease liver glycogen, the fatigue may possibly be related to a lowering of blood-sugar (Judah 1949). This was not shown in the present case. The mental symptoms may be due to the direct effects of D.D.T. on the brain. Philips and Gilman (1946} showed that curarised animals injected with lethal doses of D.D.T. had convulsive seizures, as shown by electro-encephalography. Whether this action is due to an upset of enzyme activity connected with tissue respiration is not known. Pathological and biochemical investigations in this case were strikingly normal, except for the finding of casts and red cells in the urine. It is impossible to say whether this renal damage and the raised E.S.R. were caused by D.D.T. poisoning. In animals, especially rabbits, renal damage and nephritis have been reported. A lowered blood-calcium level has been reported in some cases of D.D.T. poisoning in animals, but in the present patient the blood-calcium level was normal. Though it is impossible to ascribe the present patient’s symptoms with certainty to D.D.T., the facts that he had worked with D.D.T. fairly intimately for six years and that his symptoms agreed so closely with those previously observed in D.D.T. poisoning make this the most likely diagnosis. A periodical medical examination of all persons working regularly with D.D.T. is advisable. Judah (1949) has confirmed experimentally that calcium gluconate affords partial protection against D.D.T. intoxication. REFERENCES Case, R. A. M. (1945) Brit. med. J. ii, 842. Draize, J. H., Nelson, A. A., Calvery, H. O. (1944) J. Pharmacol. 82, 159. Judah, J. D. (1949) Brit. J. Pharmacol. 4, 120, 842. Nelson, A. A., et al. (1944) Publ. Hlth Rep. Wash. 59, 1009. Philips, F. S., Gilman, A. (1946) J. Pharmacol. 86, 213. Wigglesworth, V. B. (1945) Brit. med. J. i, 517. Woodard, G., Nelson, A. A., Calvery, H. O. (1944) J. Pharmacol. 82, 152.
Transcript of D.D.T. POISONING IN MAN
1178
overlooked by omitting radiological examination of ottierparts of the skeleton. e
REFERENCES
Burke, F. G. (1948) J. Pediat. 32, 441. Caffey, J. (1946) Ibid, 29, 541.
— Silverman, W. A. (1945) Amer. J. Roentgenol. 54, 1.Dickson, D. D., Luckey, C. A., Logan, N. H. (1947) J. Bone Jt Surg.
29, 224.Ellis, R. W. B. (1939) Proc. R. Soc. Med. 32, 139.Fisk, C. (1947) J. Iowa St. med. Soc. 37, 529.Gipson, A. C., Clark, B. P. (1948) Pediatrics, 1, 221.O’Reilly, J. N. (1949) Arch. Dis. Childh. 24, 67.Shuman, H. H. (1948) J. Pediat. 32, 195.Smyth, F. S., Potter, A., Silverman, W. (1946) Amer. J. Dis. Child.
71, 333.van Zeben, W. (1948) Acta pœdiat. 35, 10.Whipple, R. K. (1947) New Engl. J. Med. 236, 239.
D.D.T. POISONING IN MANA SUSPECTED CASE
A. M. G. CAMPBELLM.A., D.M. Oxfd, M.R.C.P.
PHYSICIAN, BRISTOL ROYAL HOSPITAL
THE use of 2, 2 bis (p-chlorphenyl) 1, 1, 1, trichlorethane(D.D.T.) as an insecticide has become so general, andtoxic symptoms in man have been recorded so rarely,that it is thought worth recording another possible case.
In poisoning by D.D.T. in animals the main toxiceffects seem to fall on the liver and sometimes producehepatic necrosis. The kidneys are also affected. Thereare loss of weight and ill-defined damage of the nervoussystem, accompanied by convulsions and sometimes
damage to the anterior-horn cells (Draize et al. 1944,Woodard et al.1944)..Wigglesworth (1945) recorded the first case of D.D.T.
poisoning in man. The victim had been exposed to ahigh concentration of D.D.T. in acetone and had obviouslyabsorbed much through the skin. He complained ofheaviness and aching in the limbs, sleeplessness, spasmsof great nervous tension, extreme fatigue, prostration,and twitching of the muscles over the whole body.For a long time his symptoms were thought to be dueto a neurosis, until it was recognised that he had run therisk of absorbing a great deal of D.D.T. and this mightbe their cause.
Case (1945) found that Service personnel exposed toa high concentration of D.D.T. were liable to have
fatigue, aching of the limbs, irritability, emotional
instability, and violent cramp in the limbs. This findingsuggests that the symptoms in Wigglesworth’s (1945)cases were genuinely due to D.D.T. despite their resem-blance to an anxiety state. Case mentions that one
person, who was not hypochondriacal, was so prostratedthat he had to take to his bed. Among other symptomsnoted by Case were " yellow vision " in one person anddiminution in auditory acuity in another.The most striking feature in man has been the mental
symptoms, and the following case is no exception.
CASE-RECORD
A man, aged 32, who had been a demonstrator of D.D.T.powder for the Ministry of Agriculture for six years, hadhandled and inhaled the powder, but not to the extent ofwhat is generally thought to be a toxic hazard. His previoushistory was perfectly normal and, so far as can be ascertained,he had been free from any nervous breakdown or tempera-mental difficulty. About three months before consultinga doctor he had noticed periods of extreme fatigueand prostration while walking. He often felt an intensedesire to sit down and an inability to take any exercisewithout a rest. He had noticed a tendency to emotional
instability and weeping, and at the same time was gettingcramping pains in his limbs varying from day to dayand from limb to limb. The pain lasted twenty minutes on oneoccasion and three or four hours on another.
0 examination no abnormality in his central nervous
system was found except a slight tremor of the outstretched
hands, and his performance of mental tests was good. Three
lipomata were found on the left thigh ; these the patienthad not previously noticed. Polyps were found in the
maxillary antrum.Investigations.-The blood picture was normal. A blood-
count gave red cells 5,000,000 per c.mm., Hb 107%, whitecells 9,200 per c.mm. (differential count and platelets normal).The erythrocyte-sedimentation rate (E.s.R.) was 24 mm. in1 hr. (Wintrobe). A urea-clearance test and straight radio-graphy of the kidneys were normal. The urine containedalbumin, red cells, and granular casts. The blood-ureawas 38 mg. per 100 ml. Lumbar puncture produced normalcerebrospinal fluid under a pressure of 120 mm. H20, con-taining 2 lymphocytes per c.mm. and 30 mg. of protein per100 ml. The Wassermann reaction was negative. The
fasting venous blood-sugar was 90 mg. per 100 ml. The blood-lead was normal, serum-sodium 335 mg. per 100 ml., serum-potassium 17 mg. per 100 ml., serum-calcium 9-7 mg. per 100ml., plasma-chloride 626 mg. per 100 ml. (as sodium chloride),plasma-bicarbonate 56 vols. % (as CO2.combining power).plasma inorganic phosphorus 3-7 mg. per 100 ml., and plasma,protein 6-7 g. per 100 ml. All these figures are within normallimits. All liver-function tests were normal, as likewisewere an electro-encephalogram, an electrocardiogram, and aradiogram of the skull.
Treatment and Progress.-The lipomata were removed fromthe thigh. The patient made a complete recovery from
cramps and weakness, and after a fortnight in hospital wasdischarged with slight feelings of nervous tension, albuminuria(the red cells and casts had disappeared), and an E.s.R. of12 mm. in 1 hr.
DISCUSSION
Extreme mental fatigue and anxiety, cramps, andtremor have been reported in all human cases of D.D.T.poisoning so far published. Weakness and nervous
tension have also been observed in D.D.T. poisoning insome animals (Woodard et al. 1944). Since D.D.T. hasbeen thought to produce hypoglycsemia in animals andto decrease liver glycogen, the fatigue may possibly berelated to a lowering of blood-sugar (Judah 1949). Thiswas not shown in the present case.The mental symptoms may be due to the direct
effects of D.D.T. on the brain. Philips and Gilman (1946}showed that curarised animals injected with lethaldoses of D.D.T. had convulsive seizures, as shown byelectro-encephalography. Whether this action is due toan upset of enzyme activity connected with tissue
respiration is not known.Pathological and biochemical investigations in this
case were strikingly normal, except for the finding ofcasts and red cells in the urine. It is impossible to saywhether this renal damage and the raised E.S.R. werecaused by D.D.T. poisoning. In animals, especiallyrabbits, renal damage and nephritis have been
reported.A lowered blood-calcium level has been reported in
some cases of D.D.T. poisoning in animals, but in thepresent patient the blood-calcium level was normal.Though it is impossible to ascribe the present patient’s
symptoms with certainty to D.D.T., the facts that hehad worked with D.D.T. fairly intimately for six yearsand that his symptoms agreed so closely with thosepreviously observed in D.D.T. poisoning make this themost likely diagnosis.A periodical medical examination of all persons working
regularly with D.D.T. is advisable. Judah (1949) hasconfirmed experimentally that calcium gluconate affordspartial protection against D.D.T. intoxication.
REFERENCES
Case, R. A. M. (1945) Brit. med. J. ii, 842.Draize, J. H., Nelson, A. A., Calvery, H. O. (1944) J. Pharmacol.
82, 159.Judah, J. D. (1949) Brit. J. Pharmacol. 4, 120, 842.Nelson, A. A., et al. (1944) Publ. Hlth Rep. Wash. 59, 1009.Philips, F. S., Gilman, A. (1946) J. Pharmacol. 86, 213.Wigglesworth, V. B. (1945) Brit. med. J. i, 517.Woodard, G., Nelson, A. A., Calvery, H. O. (1944) J. Pharmacol.
82, 152.
