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Although the toxicities of major TTX analogues have been investigated, the acute toxicity and biological distribution of 6-deoxyTTX remain poorly understood because of limited availability of purified or synthetic 6-deoxyTTX. In this study, acute toxicity of 6-deoxyTTX was evaluated based on mouse bioassay. The toxicity of 6-deoxyTTX was estimated to be 1 MU = 570 ng, with an LD99 value of 28 \u03bcg\/kg. Based on comparison with the LD99 value of TTX (10 \u03bcg\/kg), the relative potency of 6-deoxyTTX was estimated to be 0.36, indicating higher toxicity than other deoxy analogues. In addition, high-resolution LC\u2013MS analysis revealed the occurrence of 6-deoxyTTX in toxic pufferfish species in the genera Takifugu, Arothron, and Lagocephalus. Although 6-deoxyTTX was generally present at much lower concentrations than TTX, 6-deoxyTTX should be considered a toxicologically relevant analogue because of its relatively high acute toxicity. These results demonstrate that 6-deoxyTTX is a low-abundance TTX analogue with relatively high toxicity, providing new information relevant to food safety assessment and the distribution of TTX analogues in pufferfish.<\/jats:p>","DOI":"10.3390\/md24070250","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:32:08Z","timestamp":1784514728000},"page":"250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicity Assessment of 6-Deoxytetrodotoxin by Mouse Bioassay and Its Distribution in Pufferfish"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1586-2004","authenticated-orcid":false,"given":"Yuta","family":"Kudo","sequence":"first","affiliation":[{"name":"Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai 980-8578, Japan"},{"name":"Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki-Aza-Aoba, Aoba-ku, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-0409","authenticated-orcid":false,"given":"Mari","family":"Yotsu-Yamashita","sequence":"additional","affiliation":[{"name":"Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki-Aza-Aoba, Aoba-ku, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","first-page":"587","article-title":"Studies on Pufferfish Toxin","volume":"29","author":"Tahara","year":"1909","journal-title":"J. Pharm. Soc. Jpn."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1126\/science.144.3622.1100","article-title":"Tarichatoxin-Tetrodotoxin: A Potent Neurotoxin","volume":"144","author":"Mosher","year":"1964","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1126\/science.1138374","article-title":"Tetrodotoxin: Occurrence in Atelopid Frogs of Costa Rica","volume":"189","author":"Kim","year":"1975","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1126\/science.619451","article-title":"Maculotoxin: A Neurotoxin from the Venom Glands of the Octopus Hapalochlaena maculosa Identified as Tetrodotoxin","volume":"199","author":"Sheumack","year":"1978","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1073\/pnas.0506093103","article-title":"Ecological Functions of Tetrodotoxin in a Deadly Polyclad Flatworm","volume":"103","author":"Paul","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"220","DOI":"10.3390\/md6020220","article-title":"Tetrodotoxin\u2014Distribution and Accumulation in Aquatic Organisms, and Cases of Human Intoxication","volume":"6","author":"Noguchi","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"577","DOI":"10.3390\/md8030577","article-title":"The Chemical and Evolutionary Ecology of Tetrodotoxin (TTX) Toxicity in Terrestrial Vertebrates","volume":"8","author":"Hanifin","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.toxicon.2010.04.017","article-title":"Detection of Tetrodotoxin from the Grey Side-Gilled Sea Slug\u2014Pleurobranchaea maculata, and Associated Dog Neurotoxicosis on Beaches Adjacent to the Hauraki Gulf, Auckland, New Zealand","volume":"56","author":"McNabb","year":"2010","journal-title":"Toxicon"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nakazawa, Y., Shimano, S., Miyasaka, T., Adachi, M., Nishikawa, T., Yoshitake, K., Amano, M., Sato, S., and Takada, K. (2026). Oribatid Mites Supply Tetrodotoxin to Poisonous Newts. J. Nat. Prod.","DOI":"10.64898\/2026.03.03.709434"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.2331\/suisan.48.253","article-title":"Comparison of Toxicity of the Cultured and Wild Puffer Fish Fugu niphobles","volume":"48","author":"Matsui","year":"1982","journal-title":"Bull. Jpn. Soc. Sci. Fish."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.toxicon.2008.10.018","article-title":"Transfer Profile of Intramuscularly Administered Tetrodotoxin to Non-Toxic Cultured Specimens of the Pufferfish Takifugu rubripes","volume":"53","author":"Ikeda","year":"2009","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.toxicon.2015.05.008","article-title":"Confirmation of the Absence of Tetrodotoxin and its Analogues in the Juveniles of the Japanese Fire-Bellied Newt, Cynops pyrrhogaster, Captive-Reared from Eggs in the Laboratory Using HILIC-LC-MS","volume":"101","author":"Kudo","year":"2015","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.toxicon.2017.07.016","article-title":"Dietary Administration of Tetrodotoxin and its Putative Biosynthetic Intermediates to the Captive-Reared Non-Toxic Japanese Fire-Bellied Newt, Cynops pyrrhogaster","volume":"137","author":"Kudo","year":"2017","journal-title":"Toxicon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.toxicon.2017.03.001","article-title":"Profile Differences in Tetrodotoxin Transfer to Skin and Liver in the Pufferfish Takifugu rubripes","volume":"130","author":"Tatsuno","year":"2017","journal-title":"Toxicon"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.2331\/suisan.48.1173","article-title":"Tetrodotoxin in the Starfish Astropecten Polyacanthus, in Association with Toxification of a Trumpet Shell, \u201cBoshubora\u201d Charnia sauliae","volume":"48","author":"Noguchi","year":"1982","journal-title":"Nippon Suisan Gakkai Shi"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.toxicon.2015.10.009","article-title":"Toxic Takifugu pardalis Eggs Found in Takifugu niphobles Gut: Implications for TTX Accumulation in the Pufferfish","volume":"108","author":"Itoi","year":"2015","journal-title":"Toxicon"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.toxicon.2014.12.006","article-title":"First Identification of Tetrodotoxin (TTX) in the Flatworm Stylochoplana sp.; A Source of TTX for the Sea Slug Pleurobranchaea maculata","volume":"95","author":"Salvitti","year":"2015","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00027-016-0500-5","article-title":"In Situ Accumulation of Tetrodotoxin in Non-Toxic Pleurobranchaea maculata (Opisthobranchia)","volume":"79","author":"Salvitti","year":"2016","journal-title":"Aquat. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12302","DOI":"10.1038\/s41598-018-30696-z","article-title":"Including Planocerid Flatworms in the Diet Effectively Toxifies the Pufferfish, Takifugu niphobles","volume":"8","author":"Itoi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"126217","DOI":"10.1016\/j.chemosphere.2020.126217","article-title":"The Planocerid Flatworm Is a Main Supplier of Toxin to Tetrodotoxin-Bearing Fish Juveniles","volume":"249","author":"Itoi","year":"2020","journal-title":"Chemosphere"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Suo, R., Kashitani, M., Oyama, H., Adachi, M., Nakahigashi, R., Sakakibara, R., Nishikawa, T., Sugita, H., and Itoi, S. (2021). First Detection of Tetrodotoxins in the Cotylean Flatworm Prosthiostomum trilineatum. Mar. Drugs, 19.","DOI":"10.3390\/md19010040"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s12562-024-01754-5","article-title":"Distribution of Tetrodotoxin and its Analogs in the Toxic Flatworm Planocera multitentaculata from Honshu Island, Japan","volume":"90","author":"Suo","year":"2024","journal-title":"Fish. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s10126-025-10560-8","article-title":"Trophic Role of the Tetrodotoxin-Bearing Flatworm Plancera multitentaculata in the Marine Food Web","volume":"28","author":"Shirai","year":"2026","journal-title":"Mar. Biotechnol."},{"key":"ref_24","first-page":"793","article-title":"Bacterial Production of Tetrodotoxin and Anhydrotetrodotoxin","volume":"50","author":"Yasumoto","year":"1986","journal-title":"Agric. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/oxfordjournals.jbchem.a135476","article-title":"Occurrence of Tetrodotoxin and Anhydrotetrodotoxin in Vibrio sp. Isolated from the Intestines of a Xanthid Crab, Atergatis floridus","volume":"99","author":"Noguchi","year":"1986","journal-title":"J. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.3390\/md11082695","article-title":"Diversity and Biosynthetic Potential of Culturable Microbes Associated with Toxic Marine Animals","volume":"11","author":"Chau","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Magarlamov, T.Y., Melnikova, D.I., and Chernyshev, A.V. (2017). Tetrodotoxin-Producing Bacteria: Detection, Distribution and Migration of the Toxin in Aquatic Systems. Toxins, 9.","DOI":"10.3390\/toxins9050166"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"276939","DOI":"10.5402\/2011\/276939","article-title":"Tetrodotoxin Poisoning Due to Pufferfish and Gastropods, and Their Intoxication Mechanism","volume":"2011","author":"Noguchi","year":"2011","journal-title":"ISRN Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.trstmh.2010.10.002","article-title":"Puffer Fish Poisoning in Bangladesh: Clinical and Toxicological Results from Large Outbreaks in 2008","volume":"105","author":"Islam","year":"2011","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Al-Sulaimani, S., Titelbaum, N.V., Ward, R.E., Zahran, T.E., Chalhoub, S., and Kazzi, Z. (2022). Case Report of Tetrodotoxin Poisoning from Lagocephalus sceleratus in Lebanon. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192214648"},{"key":"ref_31","first-page":"e33627","article-title":"Tetrodotoxin Poisoning Due to Pufferfish Ingestion in the United Arab Emirates","volume":"15","author":"Zarzour","year":"2023","journal-title":"Cureus"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tamele, I.J., Silva, M., and Vasconcelos, V. (2019). The Incidence of Tetrodotoxin and its Analogs in the Indian Ocean and the Red Sea. Mar. Drugs, 17.","DOI":"10.3390\/md17010028"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"ii21011","DOI":"10.2807\/1560-7917.ES2015.20.2.21009","article-title":"Detection of the Pufferfish Toxin Tetrodotoxin in European Bivalves, England, 2013 to 2014","volume":"20","author":"Turner","year":"2015","journal-title":"Eurosurveillance"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Turner, A.D., Dhanji-Rapkova, M., Coates, L., Bickerstaff, L., Milligan, S., O\u2019Neill, A., Faulkner, D., McEneny, H., Baker-Austin, C., and Lees, D.N. (2017). Detection of Tetrodotoxin Shellfish Poisoning (TSP) Toxins and Causative Factors in Bivalve Molluscs from the UK. Mar. Drugs, 15.","DOI":"10.3390\/md15090277"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Numano, S., Kudo, Y., Cho, Y., Konoki, K., and Yotsu-Yamashita, M. (2019). Temporal Variation of the Profile and Concentrations of Paralytic Shellfish Toxins and Tetrodotoxin in the Scallop, Patinopecten yessoensis, Cultured in a Bay of East Japan. Mar. Drugs, 17.","DOI":"10.3390\/md17120653"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.chemosphere.2018.10.081","article-title":"First Detection of Tetrodotoxin and High Levels of Paralytic Shellfish Poisoning Toxins in Shellfish from Sicily (Italy) by Three Different Analytical Methods","volume":"215","author":"Tartaglione","year":"2019","journal-title":"Chemosphere"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"124404","DOI":"10.1016\/j.chemosphere.2019.124404","article-title":"Tetrodotoxin in Marine Bivalves and Edible Gastropods: A Mini-Review","volume":"236","author":"Biessy","year":"2019","journal-title":"Chemosphere"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105908","DOI":"10.1016\/j.aquatox.2021.105908","article-title":"The Role of Toxic Planocerid Flatworm Larvae on Tetrodotoxin Accumulation in Marine Bivalves","volume":"237","author":"Okabe","year":"2021","journal-title":"Aquat. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1007\/s10126-023-10199-3","article-title":"Tetrodotoxin Detection in Japanese Bivalves: Toxification Status of Scallops","volume":"25","author":"Yasukawa","year":"2023","journal-title":"Mar. Biotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107710","DOI":"10.1016\/j.toxicon.2024.107710","article-title":"Temporal Variation in the Concentrations and Profiles of Paralytic Shellfish Toxins and Tetrodotoxin in Scallop (Mizuhopecten yessoensis) and Bloody Clam (Anadara broughtonii) Collected from the Coast of Miyagi Prefecture, Japan","volume":"243","author":"Shingai","year":"2024","journal-title":"Toxicon"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3358\/shokueishi.65.129","article-title":"Validation Study of LC-MS\/MS for Paralytic Shellfish Toxins and Tetrodotoxin in Scallops","volume":"65","author":"Numano","year":"2024","journal-title":"Shokuhin Eiseigaku Zasshi"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Turner, A.D., Dean, K.J., Lewis, A.M., Hartnell, D.M., Jenkins, Z., Bear, B., Mace, A., Almeida, N., van Ree, R., and Etchells, K. (2025). ScillyHAB: A Multi-Disciplinary Survey of Harmful Marine Phytoplankton and Shellfish Toxins in the Isles of Scilly: Combining Citizen Science with State-of-the-Art Monitoring in an Isolated UK Island Territory. Mar. Drugs, 23.","DOI":"10.3390\/md23120478"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s12562-025-01864-8","article-title":"Compositions of Tetrodotoxins in Seven Japanese Bivalve Species\/Subspecies","volume":"91","author":"Shirai","year":"2025","journal-title":"Fish. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Matsui, R., Cho, Y., Kudo, Y., Konoki, K., Nagasawa, K., and Yotsu-Yamashita, M. (2026). Hemolymph-Mediated Dynamics of Paralytic Shellfish Toxins and Tetrodotoxin in Scallops. Mar. Drugs, 24.","DOI":"10.3390\/md24060200"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Contaminants in the Food Chain (CONTAM), Knutsen, H.K., Alexander, J., Barreg\u00e5rd, L., Bignami, M., Br\u00fcschweiler, B., Ceccatelli, S., Cottrill, B., Dinovi, M., and Edler, L. (2017). Risks for Public Health Related to the Presence of Tetrodotoxin (TTX) and TTX Analogues in Marine Bivalves and Gastropods. EFSA J., 15, e04752.","DOI":"10.2903\/j.efsa.2017.4752"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2131\/jts.9.SupplementI_1","article-title":"Toxicological Studies on Puffer Fishes: Comparison of Toxicities in the Various Species","volume":"9","author":"Endo","year":"1984","journal-title":"J. Toxicol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3390\/md10010163","article-title":"Tetrodotoxin Concentrations in Pleurobranchaea maculata: Temporal, Spatial and Individual Variability from New Zealand Populations","volume":"10","author":"Wood","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"145799","DOI":"10.1016\/j.foodchem.2025.145799","article-title":"Seasonal Variation of Tetrodotoxin and Analogues in Korean Pufferfish (Takifugu pardalis) and Risk Assessment of Dietary Exposure in Korean Population","volume":"493","author":"Park","year":"2025","journal-title":"Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.toxicon.2011.08.019","article-title":"Transfer Profile of Intramuscularly Administered Tetrodotoxin to Artificial Hybrid Specimens of Pufferfish, Takifugu rubripes and Takifugu niphobles","volume":"58","author":"Wang","year":"2011","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s12562-018-1265-7","article-title":"Tetrodotoxin Distribution in Natural Hybrids between the Pufferfish Species Takifugu rubripes and Takifugu porphyreus","volume":"85","author":"Tatsuno","year":"2019","journal-title":"Fish. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"109189","DOI":"10.1016\/j.toxicon.2026.109189","article-title":"Species Identification and Tetrodotoxin Distribution in Natural Hybrid Pufferfish Collected from Japanese Coastal Waters","volume":"281","author":"Ota","year":"2026","journal-title":"Toxicon"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"78","DOI":"10.14252\/foodsafetyfscj.D-25-00021","article-title":"Occurrence of Natural Interspecific Hybrids in the Pufferfish, Genus Takifugu, and Their Tetrodotoxin-Accumulating Tissues","volume":"14","author":"Tatsuno","year":"2026","journal-title":"Food Saf."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.toxicon.2013.01.011","article-title":"Change in the Transfer Profile of Orally Administered Tetrodotoxin to Non-Toxic Cultured Pufferfish Takifugu rubripes Depending of its Development Stage","volume":"65","author":"Tatsuno","year":"2013","journal-title":"Toxicon"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"109087","DOI":"10.1016\/j.toxicon.2026.109087","article-title":"Organ-Specific Proteomic Responses to Tetrodotoxin Administration in the Liver and Skin of Takifugu rubripes","volume":"276","author":"Ono","year":"2026","journal-title":"Toxicon"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.toxicon.2007.10.002","article-title":"Occurrence of Paralytic Shellfish Toxins in Cambodian Mekong Pufferfish Tetraodon turgidus: Selective Toxin Accumulation in the Skin","volume":"51","author":"Ngy","year":"2008","journal-title":"Toxicon"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.toxicon.2006.07.034","article-title":"Distribution of Tetrodotoxin, Saxitoxin, and Their Analogs among Tissues of the Puffer Fish Fugu pardalis","volume":"48","author":"Jang","year":"2006","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"109127","DOI":"10.1016\/j.toxicon.2026.109127","article-title":"Tetrodotoxin and Saxitoxins in Sharpnose Pufferfish Canthigaster rivulata from Nagasaki, Japan","volume":"279","author":"Zhu","year":"2026","journal-title":"Toxicon"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Nocchi, N., Santana-Mayor, \u00c1., Conde-D\u00edaz, A., Hern\u00e1ndez-Lopez, V., Rodr\u00edguez Hern\u00e1ndez, A., Brito, A., D\u00edaz-Marrero, A.R., and Fern\u00e1ndez, J.J. (2026). Toxicity Profile of the Oceanic Pufferfish Lagocephalus lagocephalus in the Eastern Atlantic Area. Mar. Drugs, 24.","DOI":"10.3390\/md24060195"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1749-6632.1986.tb15560.x","article-title":"Interspecies Distribution and Possible Origin of Tetrodotoxin","volume":"479","author":"Yasumoto","year":"1986","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1006\/abio.2000.4953","article-title":"Electrospray Ionization Mass Spectrometry of Tetrodotoxin and its Analogs: Liquid Chromatography\/Mass Spectrometry, Tandem Mass Spectrometry, and Liquid Chromatography\/Tandem Mass Spectrometry","volume":"290","author":"Shoji","year":"2001","journal-title":"Anal. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"107081","DOI":"10.1016\/j.toxicon.2023.107081","article-title":"The Quite Low Cross-Reactivity of Kawatsu\u2019s Anti-Tetrodotoxin Monoclonal Antibody to 5,6,11-Trideoxytetrodotoxin, 11-Nortetrodotoxin-6(S)-Ol, and 11-Oxotetrodotoxin, the Major Tetrodotoxin Analogues in Pufferfish","volume":"226","author":"Yamaki","year":"2023","journal-title":"Toxicon"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"133","DOI":"10.7883\/yoken1952.50.133","article-title":"Rapid and Highly Sensitive Enzyme Immunoassay for Quantitative Determination of Tetrodotoxin","volume":"50","author":"Kawatsu","year":"1997","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Sato, S., Takaishi, S., Yasumoto, K., and Watabe, S. (2019). Novel Polyclonal Antibody Raised against Tetrodotoxin Using its Haptenic Antigen Prepared from 4,9-Anhydrotetrodotoxin Reacted with 1,2-Ethaneditiol and Further Reacted with Keyhole Limpet Hemocyanin. Toxins, 11.","DOI":"10.3390\/toxins11100551"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ab.2006.02.010","article-title":"Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Mass Spectrometry of Tetrodotoxin and its Analogs","volume":"352","author":"Nakagawa","year":"2006","journal-title":"Anal. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3390\/md8041049","article-title":"LC\/MS Analysis of Tetrodotoxin and its Deoxy Analogs in the Marine Puffer Fish Fugu niphobles from the Southern Coast of Korea, and in the Brackishwater Puffer Fishes Tetraodon nigroviridis and Tetraodon biocellatus from Southeast Asia","volume":"8","author":"Jang","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11419-010-0106-x","article-title":"Optimization of Simultaneous Analysis of Tetrodotoxin, 4-epiTetrodotoxin, 4,9-Anhydrotetrodotoxin, and 5,6,11-Trideoxytetrodotoxin by Hydrophilic Interaction Liquid Chromatography-Tandem Mass Spectrometry","volume":"29","author":"Jang","year":"2011","journal-title":"Forensic Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.3390\/md11082799","article-title":"First Identification of 5,11-Dideoxytetrodotoxin in Marine Animals, and Characterization of Major Fragment Ions of Tetrodotoxin and its Analogs by High Resolution ESI-MS\/MS","volume":"11","author":"Abe","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.3390\/toxins7093436","article-title":"Tetrodotoxin and its Analogues in the Pufferfish Arothron hispidus and A. nigropunctatus from the Solomon Islands: A Comparison of Their Toxin Profiles with the Same Species from Okinawa, Japan","volume":"7","author":"Puilingi","year":"2015","journal-title":"Toxins"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/0041-0101(92)90857-2","article-title":"Actions of 6-epiTetrodotoxin and 11-Deoxytetrodotoxin on the Frog Skeletal Muscle Fiber","volume":"30","author":"Yang","year":"1992","journal-title":"Toxicon"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/S0022-3565(24)38322-3","article-title":"Effects of Specific Modifications of Several Hydroxyls of Tetrodotoxin on its Affinity to Rat Brain Membrane","volume":"289","author":"Sugimoto","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0006-3495(03)74849-8","article-title":"Interactions of the C-11 Hydroxyl of Tetrodotoxin with the Sodium Channel Outer Vestibule","volume":"84","author":"Choudhary","year":"2003","journal-title":"Biophys. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"984","DOI":"10.3390\/md13020984","article-title":"Selective Blocking Effects of 4,9-Anhydrotetrodotoxin, Purified from a Crude Mixture of Tetrodotoxin Analogues, on NaV1.6 Channels and its Chemical Aspects","volume":"13","author":"Teramoto","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1021\/acs.jnatprod.9b00178","article-title":"Isolation and Biological Activity of 8-epiTetrodotoxin and the Structure of a Possible Biosynthetic Shunt Product of Tetrodotoxin, Cep-226A, from the Newt Cynops ensicauda popei","volume":"82","author":"Kudo","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"aau2596","DOI":"10.1126\/science.aau2596","article-title":"Structural Basis for the Modulation of Voltage-Gated Sodium Channels by Animal Toxins","volume":"362","author":"Shen","year":"2018","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1126\/science.aaw2493","article-title":"Structures of Human Nav1.7 Channel in Complex with Auxiliary Subunits and Animal Toxins","volume":"363","author":"Shen","year":"2019","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3390\/md10030655","article-title":"Isolation and Structural Determination of the First 8-epi-Type Tetrodotoxin Analogs from the Newt, Cynops ensicauda popei, and Comparison of Tetrodotoxin Analogs Profiles of This Newt and the Puffer Fish, Fugu poecilonotus","volume":"10","author":"Kudo","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1021\/acs.jnatprod.5c01546","article-title":"Identification of Deoxy- and epi-Tetrodotoxin Analogues from the Newt Cynops ensicauda popei Suggests Stepwise Oxidation in Terrestrial Tetrodotoxin Biosynthesis","volume":"89","author":"Horie","year":"2026","journal-title":"J. Nat. Prod."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2183\/pjab.101.033","article-title":"Chemical Properties and Biological Activities of Three Highly Purified Major Tetrodotoxin Analogues","volume":"101","author":"Kudo","year":"2025","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1016\/S0040-4039(00)99369-9","article-title":"Isolation of 11-Oxotetrodotoxin from the Puffer, Arothron nigropunctatus","volume":"30","author":"Khora","year":"1989","journal-title":"Tetrahedron Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0041-0101(03)00068-0","article-title":"Occurrence of 11-Oxotetrodotoxin in the Red-Spotted Newt, Notophthalmus viridescens, and Further Studies on the Levels of Tetrodotoxin and its Analogues in the Newt\u2019s Efts","volume":"41","author":"Mebs","year":"2003","journal-title":"Toxicon"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0041-0101(03)00235-6","article-title":"The Occurrence of 11-Oxotetrodotoxin, a Rare Tetrodotoxin Analogue, in the Brachycephalidae Frog Brachycephalus ephippium","volume":"42","author":"Pires","year":"2003","journal-title":"Toxicon"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.toxicon.2016.05.012","article-title":"The Voltage-Gated Sodium Ion Channel Inhibitory Activities of a New Tetrodotoxin Analogue, 4,4a-Anhydrotetrodotoxin, and Three other Analogues Evaluated by Colorimetric Cell-Based Assay","volume":"119","author":"Saruhashi","year":"2016","journal-title":"Toxicon"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9329","DOI":"10.1016\/0040-4039(95)02020-P","article-title":"5,6,11-Trideoxytetrodotoxin From the Puffer Fish, Fugu poecilonotus","volume":"36","author":"Yamagishi","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1271\/bbb.63.961","article-title":"Isolation and Structural Assignment of 5-Deoxytetrodotoxin from the Puffer Fish Fugu poecilonotus","volume":"63","author":"Schimmele","year":"1999","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.toxicon.2007.06.026","article-title":"6,11-Dideoxytetrodotoxin from the Puffer Fish, Fugu pardalis","volume":"50","author":"Jang","year":"2007","journal-title":"Toxicon"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1021\/np401097n","article-title":"Isolation of 6-Deoxytetrodotoxin from the Pufferfish, Takifugu pardalis, and a Comparison of the Effects of the C-6 and C-11 Hydroxy Groups of Tetrodotoxin on its Activity","volume":"77","author":"Kudo","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1021\/ja00215a078","article-title":"New Tetrodotoxin Analogues from the Newt Cynops ensicauda","volume":"110","author":"Yasumoto","year":"1988","journal-title":"J. Am. Chem. Soc."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Kudo, Y. (2026). Structural Elucidation of Micro-Scale Natural Products through Analytical and Synthetic Approaches. Biosci. Biotechnol. Biochem., zbag099.","DOI":"10.1093\/bbb\/zbag099"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"15087","DOI":"10.1038\/s41598-022-19355-6","article-title":"An Almost Nontoxic Tetrodotoxin Analog, 5,6,11-Trideoxytetrodotoxin, as an Odorant for the Grass Puffer","volume":"12","author":"Noguchi","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"bjac011","DOI":"10.1093\/chemse\/bjac011","article-title":"Green Spotted Puffers Detect a Nontoxic TTX Analog Odor Using Crypt Olfactory Sensory Neurons","volume":"47","author":"Suzuki","year":"2022","journal-title":"Chem. Senses"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1021\/acs.jnatprod.2c00588","article-title":"Isolation and Biological Activity of 9-epiTetrodotoxin and Isolation of Tb-242B, Possible Biosynthetic Shunt Products of Tetrodotoxin from Pufferfish","volume":"85","author":"Yaegashi","year":"2022","journal-title":"J. Nat. Prod."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.toxicon.2003.08.002","article-title":"Biological Activity of 8,11-Dideoxytetrodotoxin: Lethality to Mice and the Inhibitory Activity to Cytotoxicity of Ouabain and Veratridine in Mouse Neuroblastoma Cells, Neuro-2a","volume":"42","author":"Urabe","year":"2003","journal-title":"Toxicon"},{"key":"ref_93","unstructured":"Japan Food Hygienic Association (2015). Pufferfish Toxin. The Manual for the Methods of Food Sanitation Tests (Ed. Bureau of Environmental Health. Ministry of Health and Welfare, Japan), Japan Food Hygienic Association."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"108474","DOI":"10.1016\/j.toxicon.2025.108474","article-title":"Necessity of Redefinition and Revision of Mouse Unit for Tetrodotoxin: Relationship between Lethal Time and Mouse Unit of Tetrodotoxin in Mouse Bioassay","volume":"265","author":"Suzuki","year":"2025","journal-title":"Toxicon"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0022-3565(25)26513-2","article-title":"Pharmacological Studies on Tarichatoxin, a Potent Neurotoxin","volume":"140","author":"Kao","year":"1963","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3358\/shokueishi.54.277","article-title":"Distribution of toxicity in liver of wild pufferfish Takifugu rubripes","volume":"54","author":"Taniguchi","year":"2013","journal-title":"Shokuhin Eiseigaku Zasshi"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0041-0101(85)90149-7","article-title":"Tetrodotoxin Derivatives in Puffer Fish","volume":"23","author":"Nakamura","year":"1985","journal-title":"Toxicon"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1271\/bbb.56.370","article-title":"Isolation and Structural Assignment of 11-Nortetrodotoxin-6(S)-ol from the Puffer Arothron nigropunctatus","volume":"56","author":"Yotsu","year":"1992","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1529\/biophysj.104.048173","article-title":"Modeling P-Loops Domain of Sodium Channel: Homology with Potassium Channels and Interaction with Ligands","volume":"88","author":"Tikhonov","year":"2005","journal-title":"Biophys. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0014-5793(91)81159-6","article-title":"Mapping the Site of Block by Tetrodotoxin and Saxitoxin of Sodium Channel II","volume":"293","author":"Terlau","year":"1991","journal-title":"FEBS Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/356441a0","article-title":"Calcium Channel Characteristics Conferred on the Sodium Channel by Single Mutations","volume":"356","author":"Heinemann","year":"1992","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0896-6273(00)81133-2","article-title":"From Ionic Currents to Molecular Mechanisms: The Structure and Function of Voltage-Gated Sodium Channels","volume":"26","author":"Catterall","year":"2000","journal-title":"Neuron"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1006\/bbrc.1999.1974","article-title":"Binding Properties of 3H-PbTx-3 and 3H-Saxitoxin to Brain Membranes and to Skeletal Muscle Membranes of Puffer Fish Fugu pardalis and the Primary Structure of a Voltage-Gated Na+ Channel \u03b1-Subunit (fMNa1) from Skeletal Muscle of F. pardalis","volume":"267","author":"Nishimori","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nature03444","article-title":"Evolutionary Diversification of TTX-Resistant Sodium Channels in a Predator\u2013Prey Interaction","volume":"434","author":"Geffeney","year":"2005","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1159\/000435905","article-title":"Predictably Convergent Evolution of Sodium Channels in the Arms Race between Predators and Prey","volume":"86","author":"Brodie","year":"2015","journal-title":"Brain Behav. Evol."},{"key":"ref_106","first-page":"101","article-title":"Chemical Ecology of the North American Newt Genera Taricha and Notophthalmus","volume":"118","author":"Hanifin","year":"2022","journal-title":"Prog. Chem. Org. Nat. Prod."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"109126","DOI":"10.1016\/j.toxicon.2026.109126","article-title":"Tetrodotoxin-Resistant Skeletal Muscle Sodium Channel Nav1.4 of German Newts with Low Toxin Levels","volume":"278","author":"Kudo","year":"2026","journal-title":"Toxicon"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: Tools for Structure Building and Analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/7\/250\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:19:18Z","timestamp":1784521158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/7\/250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,18]]},"references-count":108,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["md24070250"],"URL":"https:\/\/doi.org\/10.3390\/md24070250","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,18]]}}}