• This record comes from PubMed

Tetramethylenedisulfotetramine: A Health Risk Compound and a Potential Chemical Warfare Agent

. 2018 Aug 22 ; 6 (3) : . [epub] 20180822

Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic

Document type Journal Article, Review

Tetramethylenedisulfotetramine (TETS, tetramine) is a toxic organic compound that is used as an effective rodenticide. However, this neurotoxin is not only toxic to rodents, it also causes poisoning in humans. Due to its high level of toxicity for humans, the use of TETS as a rodenticide has been banned and its production has been discontinued. Despite this, human poisoning by this substance is unfortunately still very common. The largest number of poisonings are reported in China, but in the United States, dozens of poisonings still happen annually. TETS is one of the most hazardous pesticides and also a possible chemical warfare agent with no known antidote. In this article, we aim to summarize the biochemical and toxicological data of TETS and hope to cast some light on the toxicological risk to human health.

See more in PubMed

Banks C.N., Yang D., Lein P.J., Rogawski M.A. Tetramethylenedisulfotetramine. In: Wexler P., editor. Encyclopedia of Toxicology. 3rd ed. Elsevier Inc.; Davis, CA, USA: 2014.

Centers for Disease Control and Prevention (CDC) Poisoning by an Illegally Imported Chinese Rodenticide Containing Tetramethylenedisulfotetramine-New York City, 2002. Morb. Mortal. Wkly. Rep. 2003;52:199–201. PubMed

Shakarjian M.P., Velíšková J., Stanton P.K., Velíšek L. Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABA(A) receptors. Toxicol. Appl. Pharmacol. 2012;265:113–121. doi: 10.1016/j.taap.2012.08.037. PubMed DOI PMC

Whitlow K.S., Belson M., Barrueto F., Nelson L., Henderson A.K. Tetramethylenedisulfotetramine: Old Agent and New Terror. Ann. Emerg. Med. 2005;45:609–613. doi: 10.1016/j.annemergmed.2004.09.009. PubMed DOI

Flannery B.M., Silverman J.L., Bruun D.A., Puhger K.R., McCoy M.R., Hammock B.D., Crawley J.N., Lein P.J. Behavioral assessment of NIH Swiss mice acutely intoxicated with tetramethylenedisulfotetramine. Neurotoxicol. Teratol. 2015;47:36–45. doi: 10.1016/j.ntt.2014.10.008. PubMed DOI PMC

Li J.M., Gan J., Zeng T.F., Sander J.W., Zhou D. Tetramethylenedisulfotetramine intoxication presenting with de novo Status Epilepticus: A case series. Neurotoxicology. 2012;33:207–211. doi: 10.1016/j.neuro.2011.10.008. PubMed DOI

Smith K.J., Skelton H. Chemical warfare agents: Their past and continuing threat and evolving therapies part I of II. Skinmed. 2003;2:215–221. doi: 10.1111/j.1540-9740.2003.03021.x. PubMed DOI

Shakarjian M.P., Ali M.S., Velíšková J., Stanton P.K., Heck D.E., Velíšek L. Combined diazepam and MK-801 therapy provides synergistic protection from tetramethylenedisulfotetramine-induced tonic-clonic seizures and lethality in mice. Neurotoxicology. 2015;48:100–108. doi: 10.1016/j.neuro.2015.03.007. PubMed DOI PMC

Esser T., Karu A.E., Toia R.F., Casida J.E. Recognition of tetramethylenedisulfotetramine and related sulfamides by the brain GABA-gated chloride channel and a cyclodiene-sensitive monoclonal antibody. Chem. Res. Toxicol. 1991;4:162–167. doi: 10.1021/tx00020a007. PubMed DOI

Barrueto F., Furdyna P.M., Jr., Hoffman R.S., Hoffman R.J., Nelson L.S. Status epilepticus from an illegally imported Chinese rodenticide: “Tetramine”. J. Toxicol. Clin. Toxicol. 2003;41:991–994. doi: 10.1081/CLT-120026523. PubMed DOI

Mayer B.P., Albo R.L.F., Hok S., Valdez C.A. NMR spectroscopic investigation of inclusion complexes between cyclodextrins and the neurotoxin tetramethylenedisulfotetramine. Magn. Reson. Chem. 2012;50:229–235. doi: 10.1002/mrc.3803. PubMed DOI

Ning P., He Q., Yu F., Feng Z., Deng P., Jia T. Fifty two cases of acute tetramine poisoning. Chin. J. Ind. Hyg. Occup. Dis. 1997;15:108–109.

Ge X., Li X., Guan L., Ma P., Wang H. Study on the effect using haemoperfusion to treat tetramine poisoned patients. Chin. J. Ind. Hyg. Occup. Dis. 2002;20:403–404. PubMed

Zhang C., Zhu T., Chen X., Hu G., Liu D. The convulsive effects and mechanism of tetramethylenedisulfotetramine. J. Health Toxicol. 2001;15:5–7.

Pressly B., Nguyen H.M., Wulff H. GABAA receptor subtype selectivity of the proconvulsant rodenticide TETS. Arch. Toxicol. 2018;92:833–844. doi: 10.1007/s00204-017-2089-4. PubMed DOI PMC

Liu T., Fan C., Wu G. Determination of tetramethylenedisulfotetramine in blood by gas chromatography. Clin. Chem. 1993;39:173–174. PubMed

Zhu C.H., Liu Y., Deng L.B. Detecting DNA damage of cell in rats using comet assay after tetramine poisoned. Fa Yi Xue Za Zhi. 2005;21:27–29. PubMed

Wang Y., Shen L.H., Chen W.J., Liu M., Li F., Liao Z.G. Expressions of Bcl-2 and Caspase-3 in the internal organs of rats when tetramine was administered. Fa Yi Xue Za Zhi. 2006;22:241–244. PubMed

Zhi C.H., Liu L., Liu Y. Study on ultra-structural pathological changes of rats poisoned by tetramine. Fa Yi Xue Za Zhi. 2005;21:107–109. PubMed

Cao Z., Hammock B.D., McCoy M., Ein P.J., Rogawski M.A., Pessah I.N. Tetramethylenedisulfotetramine alters Ca2+ dynamics in cultured hippocampal neurons: Mitigation by NMDA receptor blockade and GABAA receptor positive modulation. Toxicol. Sci. 2012;130:362–372. doi: 10.1093/toxsci/kfs244. PubMed DOI PMC

Bruun D.A., Cao Z., Inceoglu B., Vito S.T., Austin A.T., Hulsizer S., Hammock B.D., Tancredi D.J., Rogawski M.A., Pessah I.N., et al. Combined treatment with diazepam and allopregnanolone reverses tetramethylenedisulfotetramine (TETS)-induced calcium dysregulation in cultured neurons and protects TETS-intoxicated mice against lethal seizures. Neuropharmacology. 2015;95:332–342. doi: 10.1016/j.neuropharm.2015.03.035. PubMed DOI PMC

Xiang P., Shen M., Bu J., Huang Z. The stability of tetramine, morphine and meperidine in formalin solution. Forensic Sci. Int. 2001;122:159–162. doi: 10.1016/S0379-0738(01)00491-1. PubMed DOI

Rice N.C., Rauscher N.A., Langston J.L., Myers T.M. Behavioral intoxication following voluntary oral ingestion of tetramethylenedisulfotetramine: Dose-dependent onset, severity, survival, and recovery. Neurotoxicology. 2017;63:21–32. doi: 10.1016/j.neuro.2017.08.009. PubMed DOI PMC

Lauková M., Velíšková J., Velíšek L., Shakarjian M.P. Developmental and sex differences in tetramethylenedisulfotetramine (TMDT)-induced syndrome in rats. Dev. Neurobiol. 2018;78:403–416. doi: 10.1002/dneu.22582. PubMed DOI PMC

Wu G.H., Huang M.Y. Determination of the concentration of tetramethylenedisulfotetramine in human blood by GC FPD. J. Foren. Sci. 1992;37:1213–1215. PubMed

Kim J.H., Lee K.J., Suzuki T., Kim C.M., Lee J.Y., Mok J.S., Lee T.S. Identification of tetramine, a toxin in whelks, as the cause of a poisoning incident in Korea and the distribution of tetramine in fresh and boiled whelk (Neptunea intersculpta) J. Food Protect. 2009;72:1935–1940. doi: 10.4315/0362-028X-72.9.1935. PubMed DOI

Takasaki S., Konta T., Shiomi K., Kubota I. Tetramine poisoning. Neurologic symptoms in a dialysis patient after ingesting seafood. Am. J. Kidney Dis. 2009;54:A37–A39. PubMed

Deng X., Li G., Mei R., Sun S. Long term effects of tetramine poisoning: An observational study. Clin. Toxicol. 2012;50:172–175. doi: 10.3109/15563650.2012.657758. PubMed DOI

Zhang Y., Su M., Tian D.P. Tetramine poisoning: A case report and review of the literature. Forensic Sci. Int. 2011;204:e24–e27. doi: 10.1016/j.forsciint.2010.06.025. PubMed DOI

Desneux N., Decourtye A., Delpuech J. The sublethal effects of pesticides on beneficial arthropods. Annu. Rev. Entomol. 2007;52:81–106. doi: 10.1146/annurev.ento.52.110405.091440. PubMed DOI

Voss E., Haskell A.R., Gartenberg L. Reduction of tetramine toxicity by sedatives and anticonvulsants. J. Pharm. Sci. 1961;50:858–860. doi: 10.1002/jps.2600501014. PubMed DOI

Hager J. Schwere Vergiftungen in einer Polstermöbelfabrik durch einen neuartigen hochtoxischen Giftstoff (Tetramethylendisulfotetramin) Dtsch. Med. Wochenschr. 1950;75:183–184.

Li Y., Gao Y., Yu X., Peng J., Ma F., Nelson L. Tetramine poisoning in China: Changes over a decade viewed through the media’s eye. BMC Public Health. 2014;14:842. doi: 10.1186/1471-2458-14-842. PubMed DOI PMC

Guan F.Y., Liu Y.T., Luo Y., Hu X.Y., Liu F., Li Q.Y., Kang Z.W. GC/MS identification of tetramine in samples from human alimentary intoxication and evaluation of artificial carbonic kidneys for the treatment of the victims. J. Anal. Toxicol. 1993;17:199–201. doi: 10.1093/jat/17.4.199. PubMed DOI

Zolkowska D., Banks C.N., Dhir A., Inceoglu B., Sanborn J.R., McCoy M.R., Bruun D.A., Hammock B.D., Lein P.J., Rogawski M.A. Characterization of seizures induced by acute and repeated exposure to tetramethylenedisulfotetramine. J. Pharmacol. Exp. Ther. 2012;341:435–446. doi: 10.1124/jpet.111.190579. PubMed DOI PMC

Fraga C.G., Wahl J.H., Nunez S.P. Profiling of volatile impurities in tetramethylenedisulfotetramine (TETS) for synthetic-route determination. Forensic Sci. Int. 2011;210:164–169. doi: 10.1016/j.forsciint.2011.02.025. PubMed DOI

Shakarjian M.P., Laukova M., Velíšková J., Stanton P.K., Heck D.E., Velíšek L. Tetramethylenedisulfotetramine: pest control gone awry. Ann. N. Y. Acad. Sci. 2016;1378:68–79. doi: 10.1111/nyas.13120. PubMed DOI PMC

Barnych B., Vasylieva N., Joseph T., Hulsizer S., Nguyen H.M., Cajka T., Pessah I., Wulff H., Gee S.J., Hammock B.D. Development of Tetramethylenedisulfotetramine (TETS) hapten library: Synthesis, electrophysiological studies, and immune response in rabbits. Chem.-Eur. J. 2017;23:8466–8472. doi: 10.1002/chem.201700783. PubMed DOI PMC

Zolkowska D. Characterization of rodent model of tetramethylenedisulfotetramine (TETS)-induced seizures and potential treatment options. Pharmacol. Rep. 2013;65:258–260. doi: 10.1016/S1734-1140(13)70999-X. DOI

Wang Y., Zhao J. Survey and development on determination of tetramine poisoning. Pesticides. 2001;8:4.

Wu Q., Zhang M.S., Lan Z.R. Simultaneous determination of fluoroacetamide and tetramine by gas chromatography. Chin. J. Chromatogr. 2002;20:381–382. PubMed

Bolognesi C. Genotoxicity of pesticides: A review of human biomonitoring studies. Mutat. Res. 2003;543:251–272. doi: 10.1016/S1383-5742(03)00015-2. PubMed DOI

Zeng D., Chen B., Yao S., Ying J. Determination of tetramethylenedisulfotetramine in human urine with gas chromatograph-flame thermionic detection coupling with direct immersed solid-phase micro-extraction. Forensic Sci. Int. 2006;159:168–174. doi: 10.1016/j.forsciint.2005.07.013. PubMed DOI

Owens J., Hok S., Alcaraz A., Koester C. Quantitative analysis of tetramethylenedisulfotetramine (tetramine) spiked into beverages by liquid chromatography-tandem mass spectrometry with validation by gas chromatography-mass spectrometry. J. Agric. Food Chem. 2009;57:4058–4067. doi: 10.1021/jf900271z. PubMed DOI

Luan T., Li G., Zhao M., Zhang Z. Rapid detection of tetramethylenedisulfotetramine in human blood by solid-phase microextraction/gas chromatography. Anal. Chim. Acta. 2000;404:329–334. doi: 10.1016/S0003-2670(99)00725-4. DOI

Shen M., Xiang P. Rapid determination of tetramine in urine of rodenticide-poisoned person with SPME and GC/NPD. Chin. Pharm. J. 2000;35:341–343.

Cao Y., Wei Y. Analysis of tetramine in biological samples by GC-MS. Chem. Anal. Meas. 2001;3:8.

Liang G., Wu F. Simultaneous GC/MS determination of several organic poisons. Phys. Test. Chem. Anal. Part B Chem. Anal. 2001;4:15.

Vasylieva N., Barnych B., Rand A., Inceoglu B., Gee S.J., Hammock B.D. Sensitive immunoassay for detection and quantification of the neurotoxin, tetramethylenedisulfotetramine. Anal. Chem. 2017;89:5612–5619. doi: 10.1021/acs.analchem.7b00846. PubMed DOI PMC

Li Z.J., Zeng J.Y. Clinical analysis of 15 cases with tetramethylenedisulfotetramine. Bull. Hunan Med. Univ. 2001;26:65–66. PubMed

Zhao C., Hwang S.H., Buchholz B.A., Carpenter T.S., Lightstone F.C., Yang J., Hammock B.D., Casida J.E. GABAA receptor target of tetramethylenedisulfotetramine. Proc. Natl. Acad. Sci. USA. 2014;111:8607–8612. doi: 10.1073/pnas.1407379111. PubMed DOI PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...