J Occup Health 2007; 49: 305–310 Case Study 4th day after the cessation of 4 days’ exposure to DMT. Clinical Features and Laboratory Findings A Case of Acute Organotin Poisoning The patient showed blood pressure of 110/70 mmHg, Cheol In YOO1, Yangho KIM1, Kyoung Sook JEONG1, pulse rate of 85 per min, respiratory rate of 19 per min, Chang Sun SIM1, Nari CHOY1, Jongchul KIM2, Jun Bum EUM3, and body temperature of 36.3°C with drowsy Yoshiaki NAKAJIMA4, Yoko ENDO4 and Yu Jung KIM1 consciousness in the emergency room. The pupils were symmetric with a pupil size of approximately 3 mm. The 1Department of Occupational and Environmental Medicine, light reflex, corneal reflex, and muscle power were within 2Department of Neurology, 3Department of Internal Medicine, the normal range. The past medical history and family Ulsan University Hospital, University of Ulsan College of history were non-contributable. Posterior anterior chest Medicine, South Korea and 4Research Center for Occupational X-rays showed normal findings. All the clinical Poisoning, Tokyo Rosai Hospital, Japan procedures were performed with the patient’s/patient’s family’s informed consent. The serum level of aspartate Key words: Dimethyl tin, Trimethyl tin, Neurotoxicity, aminotransferase (AST) and alanine aminotransferase Leukoencephalopathy (ALT) were 81 and 46 IU/l, respectively. The result of spinal tapping was negative on the 4th day of admission. Alkyl compounds of tin chlorides are widely used for On the fourth day of hospital admission, the patient the production of plastics in the chemical industry. They deteriorated into a state of coma, and he was placed on inhibit the dissociation of hydrochloric acid from mechanical ventilation. He also showed metabolic polyvinyl chloride (PVC) and in combination with PVC acidosis in arterial blood gas analysis (ABGA) (pH 7.178, they are not toxic. However, as free molecules, organic pO2 71.5 mmHg, pCO2 25.1 mmHg, HCO3 9.1 mmol/l, tin compounds are highly toxic in contrast to inorganic + SaO2 93.2%) along with severe hypokalemia (K 1.6 tin compounds1). The toxic components are dimethyltin mmol/l), and difficulty in respiration. Electrocardiogram chloride and trimethyltin chloride. Previous studies have showed ST depression and T-wave flattening due to reported that dimethyltin chloride is toxic to the liver hypokalemia. The patient showed signs of acute renal and kidneys, whereas trimethyltin chloride damages the failure (from BUN 58.3 mg/dl and Cr 1.32 mg/dl, to BUN central nervous system2–4). The neurotoxicity of dialkyltin 67.6 mg/dl and Cr 2.35 mg/dl) the next day. or trialkyltin compounds has been recognized in animal On day 7, the patient’s blood test showed WBC count studies, but only a few descriptions of their human toxicity of 9,360 per mm3, hemoglobin of 11.2 g/dl, platelet count have been reported1, 5–14). Especially, reports of human of 185,000 per mm3, AST of 351 IU/l, ALT of 119 IU/l, dimethyltin intoxication are very rare15). We report here BUN of 78.3 mg/dl, Cr of 3.07 mg/dl, LDH of 1,030 IU/ a case with neurological manifestations similar to l, CPK of 9,686 IU/l, CK-MB of 38.29 IU/l, compatible trialkyltin encephalopathy from the exposure to with acute renal failure and rhabdomyolysis. From dimethyltin compounds. hospital day 7, British-anti-Lewisite (BAL) was injected intramuscularly at a dose of 2.5 mg/kg four times daily Case Presentation for two days, and twice a day for the two next days, and A 43-yr-old male with disorientation and behavioral then once a day for four consecutive days. On day 9, change was admitted to our hospital. He had been liver function improved, and hypokalemia was corrected working as a tank cleaner for several different companies (K+ 4.2 mmol/l) with the conservative treatment, however, in the previous 8 yr, and a week before admission he had metabolic acidosis persisted. cleaned a tank which had contained dimethyltin (DMT) The fluid-attenuated inversion recovery (FLAIR) brain for 4 d. A day after finishing the job, he suffered from MR imaging taken on day 12, showed extensive, dizziness, disorientation, hallucination, irritability and symmetric high signal lesions of white matter in the decreased memory. The behavioral changes did not subcortical and deep white matter of bilateral cerebral improve and mental deterioration progressed. Brain hemispheres, posterior rim of the internal capsule, corpus magnetic resonance image (MRI) taken at another clinic callosum, cerebral peduncle, corticospinal track, and did not explain his condition, and he was transferred to middle cerebellar peduncle (Fig. 1A–D). Therapeutically, the emergency room of Ulsan University Hospital on the dexamethasone was administered in attempt to treat the cerebral edema. Metabolic acidosis was corrected on Received Feb 22, 2007; Accepted Apr 12, 2007 day 14. An electroencephalogram test suggested a Correspondence to: Y. Kim, Department of Occupational and moderate diffuse cerebral dysfunction. From day 20, the Environmental Medicine, Ulsan University Hospital, University patient’s consciousness gradually improved and he of Ulsan College of Medicine, #290-3 Cheonha-Dong, Dong-Gu, responded to verbal commands. However, he continued Ulsan 682-060, South Korea (e-mail:[email protected].) to show disorientation, retrograde amnesia, and severe 306 J Occup Health, Vol. 49, 2007 Fig. 1. Axial fluid-attenuated inversion recovery brain MRI at the hospital on day 12 of hospitalization showed extensive, symmetric high signal lesions in the subcortical and deep white matter of bilateral cerebral hemispheres (A), posterior rim of the internal capsule and corpus callosum (B), cerebral peduncle (C), middle cerebellar peduncle (D). MRI on day 90 (E through H) showed no parenchymal lesion. Table 1. Clinical course and laboratory findings HD Laboratory findings + Clinical course Treatment K BUN Cr AST ALT LDH CPK HCO3 (mmol/l) (mg/dl) (mg/dl) (IU/l) (IU/l) (IU/l) (IU/l) (mmol/l) 1 Drowsy Conservative Tx 3.5 21.5 1.14 81 46 355 298 4 Comatous, intubation Conservative Tx 1.6 58.3 1.32 61 36 418 110 9.5 7 Ventilator care Chelation started 4.1 78.3 3.07 351 119 1,030 9,686 10.0 9 Fever, ventilator care Chelation 4.2 44.5 2.19 218 94 1,170 4,576 8.9 12 Ventilator care Chelation 3.7 32.0 1.37 117 74 1,162 1,879 13.7 14 Ventilator weaning Chelation stopped 4.8 35.0 1.23 104 69 1,126 1,573 15.4 20 Drowsy Conservative Tx 3.9 28.9 1.07 54 118 626 198 21.4 23 Alert Conservative Tx 3.7 24.7 1.02 32 80 538 118 26.9 163 Discharged 3.9 19.5 0.99 23 23 255 75 HD: hospital days, HD 1 is the 4th day after the cessation of 4 days’ exposure to DMT. Tx: treatment. BUN: blood urea nitrogen. Cr: serum creatinine. AST: aspartate aminotransferase. ALT: alanine aminotransferase. LDH: lactic dehydrogenase. CPK: creatinine phosphokinase. motor ataxia. MRI on day 90 (Fig. 1E–H) showed no moderate motor ataxia, memory loss, disorientation, and parenchymal lesion on FLAIR imaging. Nerve speech difficulty (Table 1). conduction velocity test showed that the sensory potentials of both superficial peroneal nerves and the Occupational History compound muscle action potential (CAMP) of the deep The patient’s had been an office worker at an insurance peroneal nerve were not evoked. The test suggested both company until 8 yr ago. He had then worked as a tank peroneal neuropathy of axonal type. The patient was cleaner for several different companies in the previous 8 discharged on the day 163 from the hospital, still showing yr, and also performed the same cleaning job for 8 d last Cheol In YOO, et al.: Acute Organotin Poisoning 307 Fig. 2. Chromatogram of inorganic tin (In-Sn), monomethyltin (MMT), dimethyltin (DMT), trimethyltin (TMT) in urine, blood and standard samples. Blood and urine samples were obtained on days 6 and 9 of hospitalization, respectively. year without any problem. One week before admission, the mobile phase (5.0 mM HNO3, 6.0 mM NH4NO3, 1.5 he had cleaned a tank used in the manufacture of mM pyridine dicarbonic acid) at a flow rate of 1 ml/min. dimethyltin dichloride (DMTC) for 4 d. The size of the ICP-MS was used for the determination of tin and 1 mg/ tank was 2.25 m × 2.25 m × 3.4 m. The DMTC was l of germanium solution was used as the internal standard. made from inorganic tin and methyl chloride under 4.5 The ICP-MS detection mass was set to m/z 118 (118Tin+) atmospheric pressure at 170°C. An engineer at the and m/z 72 (72Ge+). Detection limits for In-Sn, MMT, company said that less than 0.3% of trimethyltin chloride DMT and TMT were 0.1, 0.1, 0.05, and 0.5 µg Sn/l, (TMTC) was produced as a by-product in the reaction. respectively. The chromatograms of tin compounds in The patient had worked inside the tank, while three other standard solution, urine and blood of the patient are shown workers assisted him outside the tank. Before the tank in Fig. 2. was opened, it was washed with methanol and water DMT and TMT concentrations in blood and urine several times for several weeks. He had to remove the collected during hospitalization are shown in Table 2. remainder of the inorganic tin accumulated at the bottom TMT concentrations were higher than DMT of the tank with an air drill. He wore personal protective concentrations in all blood samples.