Tetramethylenedisulfotetramine: Old Agent and New Terror

Whitlow, K. Scott; Belson, Martin; Barrueto, Fermin; Nelson, Lewis S.; Henderson, Alden

doi:10.1016/j.annemergmed.2004.09.009

Cited by 60 publications

(85 citation statements)

References 11 publications

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“…3A) was considerably more potent than three of its analogs assayed with either radioligand. The TETS-type compounds (1-5) and several insecticides or cage convulsants (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) (Fig. 5) illustrate that EBOB and TBPO overlap the proposed TETS binding site (located around the 1′2′ region of the pore).…”

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confidence: 99%

“…However, it is still available illegally and responsible for accidental or intentional poisonings in China and other countries. The estimated lethal dose of 7-10 mg in adult humans coupled with its ease of synthesis and stability serve as the basis for the chemical threat concern (10)(11)(12)(13)(14)(15). Neurotoxicity is sometimes alleviated or antidoted by compounds modulating the target site to reduce disruption by the toxicant.…”

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confidence: 99%

“…Baclofen at 1 μM and ethanol at 300 mM had apparently somewhat different effects with the two radioligands (SI Appendix, section S3). However, TETS poisoning cases in humans have been treated with diazepam, allopregnanolone, and NaDMPS with little or no benefit (9)(10)(11)(12)(13)(14)(15). The GABA A R is the target of many toxicants for mammals (TETS) and insects (insecticides) and exists in a multiplicity of subunit and interface combinations (43,44), allowing high toxicity that reaches its extreme for mammals with TETS and some other small-cage convulsants.…”

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confidence: 99%

“…After a half century of search, there are still no adequate antidotes for TETSinduced poisoning, either accidental or intentional. The candidates have come from anticonvulsants used to counteract convulsant action, trials in rats and mice, and mechanism studies in animals, cells, and in vitro systems (SI Appendix, section S1 (30) and alleviating TETS toxicity (11,27,28). NaDMPS, a chelating agent normally used for treating heavy metal poisoning, is effective as a TETS antidote in rodent models and human poisonings proposed to be due to elevating GABA levels rather than as a chelator (SI Appendix, section S1).…”

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confidence: 99%

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GABA _A receptor target of tetramethylenedisulfotetramine

Zhao

Hwang

Buchholz³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Tetramethylenedisulfotetramine (TETS) is a feared chemical threat agent because of its high convulsant toxicity, ease of synthesis, and availability even though it is banned as a rodenticide. Earlier physiological evidence indicating action as a GABA receptor antagonist and inhibitor of [ 35 S]TBPS and [ 3 H]EBOB binding is confirmed here by radiosynthesis of [ 14 C]TETS and defining its binding site in rat brain membranes by accelerator mass spectrometry and toxicant specificity studies on inhibition of [ 14 C]TETS and [ 3 H]EBOB binding. TETS undergoes specific and unique polar interactions inside the 1′2′ ring pore region instead of the 2′,6′, and 9′ site for insecticides. This study helps define GABA A R sites for potential antidotes acting to prevent TETS binding or displace it from its binding site.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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GABA _A receptor target of tetramethylenedisulfotetramine

Zhao

Hwang

Buchholz³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Especially in mass poisonings, forensic issues are a concern. Also there have been some publications on intentional organophosphate poisoning in animals (10)(11)(12), but very less in humans (13). It was reported that food contamination by organophosphates in humans mostly occurs in farmers and agriculture workers (14,15).…”

Section: Organophosphate (Op) Compounds Are Possibly the Most Widely-mentioning

confidence: 99%

Organophosphate Poisoning Due to a Wheat Bagel

Kavalcı¹,

Durukan

Özer³

et al. 2009

Intern. Med.

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Rodenticides

Semino

2023

Patty's Toxicology

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Rodenticides are chemicals used for the control of mammal pests, particularly commensal rats and mice but also a variety of field rodents. There are many different active ingredient s ( AI s) used as rodenticides and they vary widely in the hazard they present. They are mainly used in baits and to limited extent applied as fumigant. Rodenticides used in baits are broadly classified into two categories: anticoagulants and nonanticoagulant acute poisons. Rodent pest control worldwide relies largely on the use of anti‐vitamin K (AVK) anticoagulants. They interfere with the activation of vitamin K, a critical component in the production of blood clotting factors in the liver. The anticoagulants are themselves separated into first‐generation (much more toxic when feeding occurs on several successive days rather than on 1 day only) and second‐generation chemicals (which can kill after a single night feeding and tend to remain in animal tissues longer than do first‐generation ones). Nonanticoagulant rodenticides act through various mechanism of action. Bromethalin poisons the central nervous system (CNS) and ultimately causes respiratory distress following ingestion of a single dose. Cholecalciferol, the biologically active form of vitamin D, induces hypercalcemia (elevated blood calcium levels), which ultimately results in heart problems and kidney failure. Zinc phosphide liberates toxic phosphine gas upon interaction with stomach acid, leading to rodent mortality within few hours from ingestion. Except for Alphachloralose for mice control, the other rodenticides, formally referred to as the acute toxicants (e.g., arsenic, red squill, and phosphorus) are either no longer registered or of little importance in commensal rodent control. Products containing substances applied by fumigation (like carbon dioxide, hydrogen cyanide, and aluminum phosphide) are strictly reserved for rodent control professionals. As rodenticides are generally nonselective animal poisons, they carry a few serious risks to other vertebrate species and are frequently the cause of unintended consequences, from the stench of rodents decomposing in the walls to poisonings of nontarget organisms. Primary poisoning can result from wild birds and pets, while secondary poisoning of birds and mammals (including dogs and cats) can accompany the ingestion of poisoned rodents. Human incident data sources report numerous incidents, especially involving children less than 6 years old, so that human exposure to rodenticides may result in severe outcomes and/or medical care. Therefore in the last two decades, risk mitigation measures ( RMM ) and integrated pest management ( IPM ) strategies have been adopted worldwide. These measures require rodenticide products used in homes and marketed to general residential consumers to be sold only with bait stations that contain and/or are packaged with a rodenticide bait that is in block or paste form and accredited training programs are carried out for professional use rodenticides. Moreover, regulatory authorities conduct periodical re‐evaluations of registered rodenticides to ensure they meet modern health and safety standards to remain in the market.

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Tetramethylenedisulfotetramine: Old Agent and New Terror

Cited by 60 publications

References 11 publications

GABA _A receptor target of tetramethylenedisulfotetramine

GABA _A receptor target of tetramethylenedisulfotetramine

Organophosphate Poisoning Due to a Wheat Bagel

Rodenticides

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Tetramethylenedisulfotetramine: Old Agent and New Terror

Cited by 60 publications

References 11 publications

GABA A receptor target of tetramethylenedisulfotetramine

GABA A receptor target of tetramethylenedisulfotetramine

Organophosphate Poisoning Due to a Wheat Bagel

Rodenticides

Contact Info

Product

Resources

About

GABA _A receptor target of tetramethylenedisulfotetramine

GABA _A receptor target of tetramethylenedisulfotetramine