Tetramethylenedisulfotetramine
80-12-6O=S1(=O)N2CN3CN1CN(C2)S3(=O)=OAGGKEGLBGGJEBZ-UHFFFAOYSA-NTetramethylenedisulfotetramine is a neurotoxic synthetic polyhedral organic compound and type A gamma-aminobutyric acid receptor (GABAAR) antagonist that was banned worldwide for use as a pesticide in 1991. It is characterized as a colorless and odorless solid, and exposure occurs by inhalation, ingestion, or contact.
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Danger
H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]
P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 39 reports by companies from 1 notifications to the ECHA C&L Inventory.
2,6-Dithia-1,3,5,7-tetraazatricyclo3.3.1.13,7decane, 2,2,6,6-tetraoxide: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.
A 2020 publication details the serendipitous discovery of the neurotoxicity of TETS through the investigation of a mysterious occupational exposure in 1949 at a German uphostery factory. Also, it provides a what have we learned in the past 70 years discussion about the neurotoxicity of TETS, e.g., after being promoted as a rodenticide, it was banned worldwide due to its danger to human health. However, despite the ban, the clandestine manufacture of TETS has continued and there have been large numbers of inadvertent, intentional, and mass poisonings with no known antidote or targeted treatment. A 2017 publication about TETS states that over 14,000 accidental and intentional poisonings have occurred worldwide, with the vast majority of TETS poisonings involving tainted food or drink.
개요Tetramethylenedisulfotetramine (2,6-dithia-1,3,5,7-tetraazadamantane, 2,2,6,6-tetraoxide, TETS) is a highly toxic heteroadamantane rodenticide. It is an odorless, tasteless, white crystalline powder that is slightly soluble in water (0.25 mg ml-1), dimethyl sulfoxide and acetone. It was originally synthesized in 1933 as a resinous condensation product of sulfamide and formaldehyde and used commercially in pillows and upholstery as an impregnating stiffening and antimold agent. However, in 1950, a massive poisoning of German workers in the furniture manufacturing industry was linked to ‘Crinex’ wool, which contained TETS as a byproduct of processing. Early experimental studies in rodents revealed that TETS was an extremely toxic convulsant agent. It was also discovered at this time that TETS is a highly effective rodent repellent, which resulted in its use during reforestation projects to prevent seed predation by rodents. However, because of its high toxicity in mammals, including humans, and its persistence in the environment, many countries banned its production and use in 1984. This ban became worldwide when China issued similar restrictions in 1991. However, due to its relative ease of synthesis and low cost, TETS remains available on the black market, particularly in many rural areas of China and in regions outside of China that have large Asian populations.
용도Despite the worldwide ban on its production and use, TETS continues to be used illicitly as a rodenticide in various regions of the world. In China, TETS is known as ‘Dushuqiang’, ‘Meishuming,’ or ‘Shanbudao.’ In 2000, the National Poison Control Center of China revealed that 74% of commercial rodenticides contained illegal chemicals, with TETS found in nearly 50% of these pesticides. From 1977 to 2002, it was estimated that there were thousands of cases of TETS poisoning in China, resulting in hundreds of deaths. A more recent analysis indicates that between 1991 and 2010, there were over 14 000 cases of TETS intoxication in China, of which 932 resulted in death. In 2003, the first case of TETS intoxication in the United States was reported: a healthy 15-month-old girl was poisoned following accidental ingestion of a rodenticide imported from China that contained TETS. While many cases are thought to be due to accidental poisonings, there have been numerous reports of TETS being used to intentionally poison humans.
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80-12-6DTXSID8040307Acute intoxication with TETS or picrotoxin can cause seizures that rapidly progress to status epilepticus and death. Both inhibit γ-aminobutyric acid type-A (GABAA) receptors with similar potency; however, TETS is approximately 100-fold more lethal than picrotoxin. TETS is also 100 times more toxic than potassium cyanide.
A 2011 publication includes a case report of a 28-year-old female who died of multi-organ failure after exposure to TETS. The authors also performed a retrospective study of 40 cases of poisoning from the 1996 to 2010 literature. They summarized the pathological changes related to TETS poisoning in all cases as includng signs of asphyxia, along with edema and congestion of organs (in particular,the brain). Also, subarachnoid and cerebral hemorrhaging were common. They concluded that TETS poisoning should be considered when there are signs of abnormal excitation of the central nervous system, convulsions, hyperspasmia, and cerebral hemorrhage.
A 2016 publication includes two case reports , one for TETS and one for fluoroacetamide (FAA). Both patients were initially misdiagnosed and they died. The authors suggest that physicians should consider TETS and FAA poisoning when seeing patients with generalized seizures, especially for cases without a clear cause and diagnosis of disease.