Acute Trimethyltin Poisoning Caused by Exposure to Polyvinyl Chloride Production: 8 Cases.

This manuscript aimed to describe and analyze acute trimethyltin poisoning caused by exposure to polyvinyl chloride production and review the literature. Combined with an analysis of occupational hygiene survey data, the clinical data of 8 cases of acute trimethyltin poisoning were analyzed retrospectively. The clinical manifestations of acute trimethyltin poisoning are mainly related to central nervous system damage, hypokalemia and metabolic acidosis in patients with severe poisoning. Early positive potassium supplementation and symptomatic treatment are beneficial to the improvement of the condition. The early recognition of central nervous system manifestations and hypokalemia is beneficial for early diagnosis and correct treatment.

[Clinical analysis of sequelae of acute trimethyltin oxide poisoning].

Objective: Clinical analysis of sequelae of 16 patients with trimethyltin chloride (TMT) poisoning after 2 years. Methods: Sixteen patients with TMT poisoning from a waste recycling company in Ganzhou City in August 2016 were enrolled. They were investigated by questionnaires and assessed by various scales after two years. 6 cases of severe poisoning were examined by head MRI. The scale includes Hamilton Anxiety Scale (HAMA) , Depression Scale (HAMD) , Simple Mental State Examination Scale (MMSE) , Activity of Daily Living (ADL) , International Cooperative Ataxia Rating Scale (ICARS) . Results: 16 cases of TMT poisoning still have headache, dizziness and other symptoms. Instability of walking in 4 patients with severe poisoning, and the brain MRI manifestations included obvious atrophy of temporal lobe, hippocampus, insula lobe, cerebellum and ventricle enlargement. Two patients were rated as severe mixed anxiety and depression, one as moderate mixed anxiety and depression, and one as mild anxiety. 3 cases were diagnosed as dementia and 1 case as mild cognitive impairment. Two cases were totally dependent on living ability. ICARS scores were 66 points and 63 points respectively. Two cases were mildly dependent on living ability. ICARS scores were 28 points and 6 points respectively. There were 2 cases of mild mixed anxiety and depression in mild and moderate poisoning patients, and 1 case of mild cognitive impairment in each patient. They could live independently. ICARS scores were 0. Conclusion: After 2 years of TMT poisoning, some patients still have general clinical symptoms such as dizziness, headache and so on. There are also mental and intellectual symptoms such as anxiety, depression and cognitive impairment. Some of patients with severe poisoning presented with dementia and cerebellar ataxia, and even lost independent living ability.

[Characteristics of clinical, Magnetic Resonance Imaging and electroencephalogram after trimethyltin chloride poisoning].

Objective: Characteristics of clinical, MRI and electroencephalogram after trimethyltin chloride (TMT) poisoning. Methods: The clinical manifestations, MRI, EEG, treatment and prognosis of 16 patients with TMT poisoning were analyzed retrospectively. Results: Among the 16 cases of TMT poisoning, 6 cases were severe poisoning, 4 cases were moderate poisoning, and 6 cases were mild poisoning. All patients had dizziness, headache, general fatigue, loss of appetite, nausea, vomiting and other general clinical symptoms. Six patients with severe poisoning had psychobehavioral abnormalities, including 4 patients with mania, delirium, ataxia, epileptic seizures. Glasgow was 15 points in mild and moderate poisoning. Of the 6 cases of severe poisoning, 4 cases of Glasgow were 9~11 points, and 2 cases of Glasgow were 13 points. 2 patients with severe poisoning had abnormal MRI in head, and the total abnormal rate was 12.50%. Toxic encephalopathy was considered in 1 case with abnormal signal of corpus callosum pressure, and patchy ischemic foci of left cerebral foot and mild cerebral atrophy in 1 case. The total abnormal rate of EEG was 56.25%. The abnormal rate of electroencephalogram in severe poisoning was 83.33%. There were 2 cases of severe abnormal electroencephalogram, 2 cases of moderate abnormal electroencephalogram and 1 case of slight abnormal electroencephalogram. Twelve patients were recovered and discharged from hospital. 4 cases of severe poisoning are still getting better, and there are still cerebellar ataxia symptoms such as dizziness and unstable walking. Conclusion: In clinical work, attention should be paid to the identification of patients with mild and moderate TMT poisoning, and attention should be paid to the patients with severe TMT poisoning manifested by disturbance of consciousness. The positive rate of MRI test in TMT poisoning is low, and the lesion is nonspecific. Electroencephalogram test has a high positive rate in TMT poisoning, which can well reflect the degree of illness. Attention should be paid to the prevention and treatment of neurodegeneration caused by TMT poisoning.

[Electromyography analysis in 13 patients with acute trimethyltin chloride poisoning].

Objective: To investigate the electromyography (EMG) characteristics and clinical significance in patients with acute trimethyltin chloride (TMT) poisoning. Methods: Retrospectively analyze the EMG results of major limb nerves and muscles of 13 patients with acute TMT poisoning. Results: Among the 13 patients, 10 cases had abnormal and the abnormal rate was 76.9%. The same degree of involvement of upper and lower limbs is the most common. And distal peripheral nerve damage is the most common, mainly manifested as sensory damage or mixed sensory and motor damage, with axonal injury and demyelinating lesions to almost the same degree. The peroneal nerve and median nerve were the most vulnerable, with an abnormal rate of 39.1% and 35.9%, respectively. The peroneal nerve and median nerve were damaged first but recovered slowly.The ulnar nerve first appeared damaged and recovered quickly. The sural nerve was damaged later. Conclusion: Acute TMT poisoning can cause limb peripheral nerve damage. This damage is a slow, gradual process, and its recovery is also a slow process.

The sequential magnetic resonance images of tri-methyl tin leukoencephalopathy.

Organotin compounds are commonly used in industrial and agriculture. It causes toxic effects on skin, eyes, respiratory system, gastrointestinal system, and nervous system. After cleaning a di-methyl tin tank, 43-year-old man showed a dizziness, disorientation, visual hallucination, and agitation. Through a measurement by liquid chromatography and inductively coupled plasma-mass spectrometry, di-methyl tin and tri-methyl tin was detected. Although magnetic resonance (MR) image 3 days after exposure showed no abnormal signal intensity, follow-up MR images 15 days after exposure revealed abnormal extensive signal intensities in the white matter that was not ever coincident with previous reports. It was hardly explainable that previous abnormal signal intensities of MR image nearly disappeared 4 months later. We present a case of a patient who developed acute toxic leukoencephalopathy from an acute inhalational exposure to methyl tin with sequential MR images showing an involvement of white matter that was not ever reported.

[Biological monitoring of workers exposed to trimethyltin chloride].

OBJECTIVE: To investigate suitable biomarkers for workers exposure to trimethyltin chloride (TMT-cl). METHODS: Urinary samples of 44 male workers from five TMT-cl occupational poisoning incidents were collected. Methyltin mercaptide stabilizers and waste plastics used in the incidents were also collected. The levels of TMT-cl in all the samples were determined by gas chromatography. The concentration of blood potassium for each poisonings was determined compared to control group (50 male workers of a food company), and the correlation between blood potassium and urinary TMT-cl were also determined. RESULTS: TMT-cl was detected in urine of all the poisonings. The results were (0.869 +/- 0.392) microg/L (severe poisoning), (0.963 +/- 0.482) microg/L (moderate poisoning), (0.716 +/- 0.384) microg/L (mild poisoning) respectively and the difference was statistically significant (P < 0.01). But the severity of the clinical status did not seem to be closely correlated to the level of urinary TMT-cl (F = 1.88, P > 0.05). In the severe poisonings, there were no differences in urinary TMT-cl on day 4 after poisoning from day 1 (P > 0.05). In contrast, urinary TMT-cl was decreased significantly on day 4 than on day 1 in mild and moderate poisonings (P < 0.01). On day 21, levels of urinary TMT-cl of all the poisonings were higher than those of the workers exposed to TMT-cl who had no clinical status (P < 0.01). Blood potassium levels of exposed group was 77.3% which was significantly lower than normal value (P < 0.01). The concentration of blood potassium was lower than normal value (3.5 mmol/L) and was correlated with the severity of the clinical status (F = 4.45, P < 0.05). Level of urinary TMT-cl of exposed group was negatively correlated with blood potassium (r = -0.4456, P < 0.01). CONCLUSION: Level of urinary TMT-cl can be used as exposure biomarker of TMT-cl poisoning. Blood potassium is an early biomarker of effect for TMT-cl poisoning so as to find poisoning population early.

Studies on hypokalemia induced by trimethyltin chloride.

OBJECTIVES: To determine the possible relationship between plasma potassium concentration and severity of acute trimethyltin chloride (TMT) poisoning and to assess the mechanism of TMT induced hypokalemia. METHODS: SD rats were treated with various dosages of TMT (i.p.). All the indices were measured and analysed for determining their possible relations with plasma K+. RESULTS: With increase of dosage, the plasma K+ level dropped rapidly, and deaths appeared more quickly. The LD50 of TMT (i.p.) was 14.7 mg/kgbw. In the low dosage group (10 mg/kgbw), the plasma K+ level dropped slowly with the lowest dosage on day 6 (4.85 mmol/L). It rose again on day 11 (5.06 mmol/L), and recovered on day 28. The poisoning signs corresponded with decline of the span of K+ level. The plasma Na+ level dropped half an hour after TMT treatment, but recovered 24 h later. In the high dosage group (46.4 mg/kgbw), the levels of plasma K+ and Na+ fell rapidly within half an hour (P < 0.05), the intracellular potassium concentration of RBC did not decrease obviously (P > 0.05), the activities of Na(+)-K(+)-ATPase and Mg(2+)-ATPase in RBC membrane were depressed remarkably (P < 0.01, P < 0.05, respectively), the plasma aldosterone concentrations rose as high as tenfold (P < 0.01), the arterial blood pH fell from 7.434 to 7.258 (P < 0.01), pCO2 was raised from 29.62 to 45.33 mmHg (P < 0.01). In the 24 h urine test, when rats were treated with TMT (21.5 mg/kgbw, i.p.), urine volume, urinary potassium, sodium and chloride increased significantly in comparison with those in the controls (P < 0.01). CONCLUSION: TMT could induce hypokalemia in SD rats. The available evidence suggests that TMT can induce acute renal leakage of potassium. At the same time, a significant rise of plasma aldosterone may play an important role in promoting potassium leakage from kidney to result in severe hypokalemia with inhaling acid-base abnormalities produced, which aggravate the poisoning symptoms. In the end the rats would die of respiratory failure.

Temporal change of hippocampal enkephalin and dynorphin mRNA following trimethyltin intoxication in rats: effect of anticonvulsant.

Trimethyltin (TMT), an organic metal, has been known to induce behavioral abnormalities including seizures and aggression. We administered TMT to rats, then, behavioral changes as well as the changes of dynorphin and Met-enkephalin mRNA were observed with or without phenobarbital treatment in order to reveal the role of neuropeptides in seizure-generating mechanisms. Met-enkephalin mRNA was significantly increased at the 2nd to 6th day after TMT administration when seizure was frequently observed. Meanwhile, dynorphin mRNA was decreased significantly from the 2nd day to 16th day during aggression score remained high. Phenobarbital abolished not only seizures and aggression, but also the changes of neuropeptide expressions. These results suggest that the changes of dynorphin mRNA are more strongly associated with aggression than seizures, while Met-enkephalin changes correlate more with seizures.

Trimethyltin intoxication induces marked changes in neuropeptide expression in the rat hippocampus.

In situ hybridization and immunocytochemistry were applied to investigate changes in the expression of somatostatin, neuropeptide Y, neurokinin B, cholecystokinin, dynorphin, and Met-enkephalin in the rat hippocampus after administration of a single peroral dose of trimethyltin hydroxide (9 mg/kg). Two time intervals were investigated: 5 days after trimethyltin treatment, when CA3 damage becomes manifest and is associated with increased aggression, seizure susceptibility, and memory deficit, and 16 days after trimethyltin, when neuronal damage is almost maximal and seizure susceptibility is declining. Robust but transient increases of neuropeptide Y, neurokinin B, and Met-enkephalin mRNA levels were revealed in the granule cell layer of the dentate gyrus and increased neuropeptide Y and neurokinin B immunoreactivities were found in mossy fibers. In reverse, dynorphin mRNA and immunoreactivity were decreased transiently in the dentate gyrus and mossy fibers, respectively. Strong over-expression of NPY mRNA was also observed in hilar interneurons and in CA1 and CA3 pyramidal cells as well as in the cortex at 5 days postdosing. Cholecystokinin- or neurokinin B-containing basket cells were preserved, while somatostatin-bearing interneurons were damaged by trimethyltin exposure. These neurochemical changes induced by trimethyltin intoxication strikingly parallel to those observed in animal models of temporal lobe epilepsy and may reflect activation of endogenous protective mechanisms. It is also suggested that hilar interneurons respond differently to trimethyltin exposure, for which neuropeptides are valuable markers.

Nitric oxide synthase-containing neurons in the hippocampus are preserved in trimethyltin intoxication.

We studied the effects of trimethyltin (TMT) (9 mg/kg, p.o.) on the nitric oxide synthase (NOS)-containing neurons in the rat hippocampus by NADPH-diaphorase histochemistry and a biochemical assay of NOS activity. TMT exposure caused the typical behavioral changes and a loss of the CA3/4 pyramidal cells, which were NADPH diaphorase-negative. The scattered interneurons and the CA1 pyramidal cells, which were NADPH diaphorase-positive, were spared. Hippocampal NOS activity showed no reduction in the TMT-treated rats compared with the controls. These results provide evidence of the preservation of the NOS-containing neurons in TMT intoxication.

Changes in muscarinic (M1 and M2 subtypes) and phencyclidine receptor density in the rat brain following trimethyltin intoxication.

The main purpose of this study was to determine whether one or both of the muscarinic receptor subtypes (M1 and M2) contributed to the total cholinergic receptor loss found in trimethyltin (TMT) treated rats and to assess the effect of TMT on phencyclidine (PCP) receptor density in several regions of the rat brain. The distribution and changes in muscarinic (M1 and M2) receptor and PCP receptor sites were analysed by means of quantitative autoradiography using [3H]quinuclidinyl benzilate (QNB) and [3H] N-(1-(2-thienyl) cyclohexyl) 3,4-piperidine (TCP) respectively. The results demonstrate a TMT induced decrease in [3H]QNB binding in a large number of brain regions particularly the hippocampal formation, for both M1 and M2 muscarinic receptor subtypes. There is also a decrease in [3H]TCP binding in several brain regions. The effects of TMT on PCP receptors suggest that TMT induced damage is not restricted to the cholinergic system and that N-methyl-D-aspartate (NMDA) receptors are also affected.

Trimethyltin poisoning: report of a case with postmortem examination.

A 48-year old woman died six days after intake of an unknown amount of trimethyltin (TMT). Early clinical features were tinnitus, lightheadedness, aggression and episodes of unresponsiveness. She gradually developed coma and died of multiorgan failure. The main pathologic findings were confined to the nervous system which revealed generalized chromatolysis of the neurons in the brain, spinal cord and spinal ganglia. Recent neuronal necrosis, which probably was caused by toxic effect of TMT, was present in the fascia dentata of the hippocampus and in the spinal ganglia. Recent necrosis was also present in the pyramidal cell layer of the hippocampus, cerebral cortex, basal ganglia and Purkinje cell layer of the cerebellum, but some of these changes could have been caused by an anoxic episode shortly before death. Electron microscopy revealed marked accumulation of lysosomal dense bodies and disorganization of the granular endoplasmic reticulum in the neurons. The findings were similar to those described in experimental TMT intoxications. Cytoplasmic zebra bodies, which were described in a previous human case of TMT intoxication, were not observed in the present case.

Acute short-term memory loss from trimethyltin exposure.

We report a case of organic tin exposure in a graduate chemistry student. The inhalational and transcutaneous exposure occurred following a laboratory explosion. The patient initially presented with first and second degree burns of the face and chest, and developed an acute loss of short-term memory 72 hours after exposure. The memory loss gradually improved over the course of several months.

Dose-specific effects of trimethyltin poisoning on learning and hippocampal corticosterone binding.

The organometal neurotoxin trimethyltin (TMT) damages limbic forebrain, and impairs acquisition of lever-directed behaviors in an autoshaping task, in which a lever is presented according to a random time schedule, and rats learn to associate its presentation/retraction with food delivery (Cohen et al., 1987). This impairment is evident only if a sufficiently long delay of reinforcement is interposed between lever retraction (which occurs either automatically after 15 sec, or immediately upon a touch response) and food pellet delivery. Paradoxically, rats given a higher (7.5 mg/kg) dose show a smaller acquisition impairment, perhaps because they are generally more reactive to the lever than controls. These rats sustain a larger hippocampal lesion (measured by wet weight of the structure). The experiment reported here was done to investigate (1) an autoshaping deficit related to hippocampal weight loss, and (2) biochemical changes in hippocampus which might be related to behavioral impairments. Rats were treated with water vehicle or TMT four weeks before autoshaping using a 6 sec reinforcement delay. In addition to lever touching, touches of the food trough were measured. The timing of trough-touching behaviors within a trial was used as an indication of the strength of the association formed between the lever and the site of food delivery. Following autoshaping rats were adrenalectomized and killed for measurement of cytosolic [3H]corticosterone binding in hippocampus. As before, rats treated with 6.0 mg TMT/kg showed a deficit in acquisition of lever-directed behaviors. Also, as hypothesized, the proportion of total trough-directed behaviors made during the 6 sec reinforcement delay intervals (when reinforcement probability was high) diverged significantly from control values as learning progressed. These rats also showed a reduction in hippocampal weight compared with controls, but significant decreases in hippocampal steroid binding were observed only in groups given the low and median dose of TMT. Further, steroid binding was correlated with lever-directed behaviors. It thus appears that lever and trough behaviors can be used to simultaneously assess different aspects of impairment in associative learning which are accompanied by differential cell loss and biochemical deficit.

Neuropathology of trimethyltin intoxication. IV. Changes in the spinal cord.

Young C57BL/6N mice were injected (ip) with trimethyltin chloride at a dosage of 3.0 mg/kg body wt. Animals were sacrificed between 48 to 72 hr postinjection by means of intracardial perfusion of saline solution followed by 2.5% buffered glutaraldehyde. For light microscopy, the cords were further fixed in 10% buffered formalin and embedded in Paraplast. For electron microscopy, tissue samples were obtained from the cord levels at L1-L4, further fixed in glutaraldehyde and osmium tetroxide, and embedded in Epon. Chromatolytic and vacuolar changes involving neurons mainly in the medial and lateral motor nuclei of the anterior horns were observed. Electron microscopy revealed lysosomal accumulation and extensive dilatation of the cytoplasmic membrane systems (endoplasmic reticulum, Golgi complex). Large intraneuronal vacuoles were formed as a result of extensive intraneuronal edema. Progressive distention of the cytoplasmic membranes resulted in severe vacuolation, disintegration, and total breakdown of the neurons.