{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:22:51Z","timestamp":1789690971589,"version":"4.0.1"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T00:00:00Z","timestamp":1427241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Economy and Competitiveness of Spain","award":["AGL2012-40185-C02-02 (ToxEmRisk project)"],"award-info":[{"award-number":["AGL2012-40185-C02-02 (ToxEmRisk project)"]}]},{"name":"FEDER INNTERCONECTA Galicia 2013","award":["SinTox project"],"award-info":[{"award-number":["SinTox project"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Lipophilic marine toxins pose a serious threat for consumers and an enormous economic problem for shellfish producers. Synergistic interaction among toxins may play an important role in the toxicity of shellfish and consequently in human intoxications.  In order to study the toxic profile of molluscs, sampled during toxic episodes occurring in different locations in Galicia in 2014, shellfish were analyzed by liquid chromatography tandem mass spectrometry (LC\u2013MS\/MS), the official method for the detection of lipophilic toxins. The performance of this procedure was demonstrated to be fit for purpose and was validated in house following European guidelines. The vast majority of toxins present in shellfish belonged to the okadaic acid (OA) group and some samples from a particular area contained yessotoxin (YTX). Since these toxins occur very often with other lipophilic toxins, we evaluated the potential interactions among them. A human neuroblastoma cell line was used to study the possible synergies of OA with other lipophilic toxins. Results show that combination of OA with dinophysistoxin 2 (DTX2) or YTX enhances the toxicity triggered by OA, decreasing cell viability and cell proliferation, depending on the toxin concentration and incubation time. The effects of other lipophilic toxins as 13-desmethyl Spirolide C were also evaluated in vitro.<\/jats:p>","DOI":"10.3390\/md13041666","type":"journal-article","created":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T11:53:17Z","timestamp":1427284397000},"page":"1666-1687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Occurrence of Lipophilic Marine Toxins in Shellfish from Galicia (NW of Spain) and Synergies among Them"],"prefix":"10.3390","volume":"13","author":[{"given":"Laura","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u00edbal","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Paz","sequence":"additional","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-0293","authenticated-orcid":false,"given":"Jorge","family":"Lago","sequence":"additional","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Blanco","sequence":"additional","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Vieites","sequence":"additional","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Cabado","sequence":"additional","affiliation":[{"name":"ANFACO-CECOPESCA, Carretera del Colegio Universitario 16, 36310 Vigo PO, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,25]]},"reference":[{"key":"ref_1","unstructured":"FAO Fisheries and Aquaculture Department. Statistical Collections. Available online:http:\/\/www.fao.org\/fishery\/statistics\/en."},{"key":"ref_2","unstructured":"Blanco, J. Evaluaci\u00f3n del impacto de los m\u00e9todos y niveles utilizados para el control de toxinas en el mejill\u00f3n. Available online:http:\/\/www.magrama.gob.es\/app\/jacumar\/planes_nacionales\/documentos\/97_if_culmites_anexo_galicia.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Botana, L.M. (2014). Seafood and Freshwater Toxins. Pharmacology, Physiology and Detection, CRC Press. [3rd ed.].","DOI":"10.1201\/b16662"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Botana, L.M. (2014). Seafood and Freshwater Toxins. Pharmacology, Physiology and Detection, CRC Press. [3rd ed.].","DOI":"10.1201\/b16662"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.hal.2008.04.007","article-title":"Renewal time and the impact of harmful algal blooms on the extensive mussel raft culture of the Iberian coastal upwelling system (SW Europe)","volume":"7","author":"Labarta","year":"2008","journal-title":"Harmful Algae"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6778","DOI":"10.1007\/s11356-012-1295-0","article-title":"Microarray testing for the presence of toxic algae monitoring programme in Galicia (NW Spain)","volume":"20","author":"Dittami","year":"2013","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_7","unstructured":"Galicia, X.D. Anuario de pesca 2009. Available online:http:\/\/www.pescadegalicia.com\/Publicaciones\/AnuarioPesca2009\/index.htm."},{"key":"ref_8","first-page":"269","article-title":"Accumulation and transformation of DSP toxins in mussels Mytilus galloprovincialis during a toxic episode caused by Dinophysis acuminata","volume":"26","author":"Maneiro","year":"2003","journal-title":"Aquat. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.foodchem.2011.04.054","article-title":"Automated on-line solid-phase extraction coupled to liquid chromatography tandem mass spectrometry for determination of lipophilic marine toxins in shellfish","volume":"129","author":"Regueiro","year":"2011","journal-title":"Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.toxicon.2007.09.002","article-title":"Anatomical distribution of diarrhetic shellfish poisoning (DSP) toxins in the mussel Mytilus galloprovincialis","volume":"50","author":"Blanco","year":"2007","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.toxicon.2007.02.002","article-title":"Lipophilic toxin profile in Galicia (Spain): 2005 toxic episode","volume":"49","author":"Botana","year":"2007","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.toxicon.2008.09.001","article-title":"First detection of pectenotoxin-11 and confirmation of OA-D8 diol-ester in Dinophysis acuta from European waters by LC-MS\/MS","volume":"52","author":"Pizarro","year":"2008","journal-title":"Toxicon"},{"key":"ref_13","unstructured":"Henshilwood, K., Deegan, B., McMahon, T., Cusak, C., Keaveney, S., Silke, J.O., Cinneide, M., Lyons, D., and Hess, P. (2006). Fifth International Conference on Molluscan Shellfish Safety, Marine Institute."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0041-0101(03)00105-3","article-title":"The first identification of azaspiracids in shellfish from France and Spain","volume":"42","author":"Magdalena","year":"2003","journal-title":"Toxicon"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.toxicon.2006.09.001","article-title":"First evidence of spirolides in Spanish shellfish","volume":"48","author":"Botana","year":"2006","journal-title":"Toxicon"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/j.marpolbul.2006.07.007","article-title":"Joint FAO\/WHO\/IOC activities to provide scientific advice on marine biotoxins (research report)","volume":"52","author":"Toyofuku","year":"2006","journal-title":"Mar. Pollut. Bull."},{"key":"ref_17","unstructured":"FAO Food and nutrition paper 80: Marine biotoxins. Available online:http:\/\/www.fao.org\/docrep\/007\/y5486e\/y5486e00.HTM."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0040-4020(01)96469-5","article-title":"Diarrethic shellfish toxins","volume":"41","author":"Yasumoto","year":"1985","journal-title":"Tetrahedron Lett."},{"key":"ref_19","unstructured":"EFSA (2008). Scientific opinion of the panel on contaminants in the food chain. Marine biotoxins in shellfish-okadaic acid and analogues. EFSA J., 589, 1\u201362."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1021\/ja00399a082","article-title":"Okadaic acid, a cytotoxic polyether from two marine sponges of the genus Halichondria","volume":"103","author":"Tachibana","year":"1981","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0041-0101(90)90074-H","article-title":"Identification of okadaic acid from a caribbean dinoflagellate, Prorocentrum concavum","volume":"28","author":"Dickey","year":"1990","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/S0041-0101(01)00126-X","article-title":"Toxin composition of the toxic dinoflagellate Prorocentrum lima isolated from different locations along the Galician coast (NW Spain)","volume":"39","author":"Bravo","year":"2001","journal-title":"Toxicon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.toxicon.2006.05.016","article-title":"Pectenotoxin-2 in single-cell isolates of Dinophysis caudata and Dinophysis acuta from the Galician R\u00edas (NW Spain)","volume":"48","author":"Reguera","year":"2006","journal-title":"Toxicon"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.hal.2009.12.002","article-title":"Bloom dynamics of Dinophysis acuta in an upwelling system: In situ growth versus transport","volume":"9","author":"Escalera","year":"2010","journal-title":"Harmful Algae"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/BF00003877","article-title":"Determination of diarrhetic shellfish toxins in various dinoflagellate species","volume":"1","author":"Lee","year":"1989","journal-title":"J. Appl. Phycol."},{"key":"ref_26","unstructured":"Smayda, T., and Shimuzu, Y. (1993). Toxic Phytoplankton Blooms in the Sea, Elsevier."},{"key":"ref_27","unstructured":"Taylor, D., and Seliger, H. (1979). Toxic Dinoflagellates Blooms, Elsevier."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hu, T., Doyle, J., Jackson, D., Marr, J., Nixon, E., Pleasance, S., Quilliam, M.A., Walter, J.A., and Wright, J.L.C. (1992). Isolation of a new diarrhetic shellfish poison from Irish mussels. J. Chem. Soc. Chem. Commun., 39\u201341.","DOI":"10.1039\/c39920000039"},{"key":"ref_29","unstructured":"Lassus, P., Arzul, G., Erard, E., Gentien, P., and Marcaillou, C. (1995). Harmful Marine Algal Blooms, Lavoisier Science Publishers."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1016\/S0041-0101(00)00079-9","article-title":"Dinophysistoxin-2: A rare diarrhoeic toxin associated with Dinophysis acuta","volume":"38","author":"Vale","year":"2000","journal-title":"Toxicon"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S0041-0101(98)00247-5","article-title":"Esters of okadaic acid and dinophysistoxin-2 in Portuguese bivalves related to human poisonings","volume":"37","author":"Vale","year":"1999","journal-title":"Toxicon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0041-0101(01)00183-0","article-title":"Esterification of DSP toxins by portuguese bivalves from the northwest coast determined by LC\u2013MS\u2014A widespread phenomenon","volume":"40","author":"Vale","year":"2002","journal-title":"Toxicon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.5740\/jaoacint.11-465","article-title":"Quantitative determination of the okadaic acid toxins group by a colorimetric phosphatase inhibition assay: Interlaboratory study","volume":"96","author":"Smienk","year":"2013","journal-title":"J. AOAC Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1016\/S0040-4039(01)81076-5","article-title":"Isolation and structure of yessotoxin, a novel polyether compound implicated in diarrhetic shellfish poisoning","volume":"28","author":"Murata","year":"1987","journal-title":"Tetrahedron Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/19970504NT7","article-title":"Identification of Protoceratium reticulatum as the biogenetic origin of yessotoxin","volume":"5","author":"Satake","year":"1997","journal-title":"Nat. Toxins"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/S0041-0101(98)00254-2","article-title":"High levels of yessotoxin in mussels and presence of yessotoxin and homoyessotoxin in dinoflagellates of the Adriatic Sea","volume":"37","author":"Draisci","year":"1999","journal-title":"Toxicon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.hal.2005.06.008","article-title":"Yessotoxin production by Gonyaulax spinifera","volume":"5","author":"Rhodes","year":"2006","journal-title":"Harmful Algae"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.toxicon.2004.05.021","article-title":"Production and release of yessotoxins by the dinoflagellates Protoceratium reticulatum and Lingulodinium polyedrum in culture","volume":"44","author":"Paz","year":"2004","journal-title":"Toxicon"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.hal.2012.11.002","article-title":"Yessotoxins production during the culture of Protoceratium reticulatum strains isolated from Galician Rias Baixas (NW Spain)","volume":"21\u201322","author":"Paz","year":"2013","journal-title":"Harmful Algae"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.toxicon.2009.11.005","article-title":"Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications","volume":"56","author":"Paz","year":"2010","journal-title":"Toxicon"},{"key":"#cr-split#-ref_41.1","unstructured":"European Commission (2004). Regulation"},{"key":"#cr-split#-ref_41.2","unstructured":"(EC) No 853\/2004 of the European Parliament and of the Council of April 29, 2004 laying down specific hygiene rules for food of animal origin. Off. J. Eur., L139, 55-205."},{"key":"ref_42","unstructured":"European Commission (2013). Comission regulation (EU) No 786\/2013 of 16 August 2013 amending Annex III to regulation (EC) No 854\/2204 of the European Parliament and of the Council as regards the permitted limits of yessotoxins in live bivalve molluscs. Off. J. Eur. Communities., L220, 14."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/(SICI)1522-7189(1997)5:6<255::AID-NT6>3.0.CO;2-P","article-title":"Toxicologic evaluation of yessotoxin","volume":"5","author":"Ogino","year":"1997","journal-title":"Nat. Toxins"},{"key":"ref_44","first-page":"269","article-title":"First evidence on occurrence of gymnodimine in clams from Tunisia","volume":"11","author":"Krys","year":"2002","journal-title":"J. Nat. Toxins"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Botana, L.M. (2007). Phycotoxins: Chemistry and Biochemistry, Blackwell Publishing.","DOI":"10.1002\/9780470277874"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1016\/S0040-4039(01)00480-4","article-title":"Pinnatoxins B and C, the most toxic components in the pinnatoxin series from the Okinawan bivalve Pinna muricata","volume":"42","author":"Takada","year":"2001","journal-title":"Tetrahedron Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1016\/S0040-4039(01)00478-6","article-title":"Structural determination of pteriatoxins A, B and C, extremely potent toxins from the bivalve Pteria penguin","volume":"42","author":"Takada","year":"2001","journal-title":"Tetrahedron Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7876","DOI":"10.1021\/ja00231a048","article-title":"Prorocentrolide, a toxic nitrogenous macrocycle from a marine dinoflagellate, Prorocentrum lima","volume":"110","author":"Torigoe","year":"1988","journal-title":"J. Am. Chem. Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1021\/ja00108a043","article-title":"Pinnatoxin A: A toxic amphoteric macrocycle from the Okinawan bivalve Pinna muricata","volume":"117","author":"Uemura","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1039\/c39950002159","article-title":"Spirolides B and D, two novel macrocycles isolated from the digestive glands of shellfish","volume":"20","author":"Hu","year":"1995","journal-title":"J. Chem. Soc. Chem. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/1522-7189(200009\/10)7:5<197::AID-NT62>3.0.CO;2-H","article-title":"Spirolide composition of micro-extracted pooled cells isolated from natural plankton assemblages and from cultures of the dinoflagellate Alexandrium ostenfeldii","volume":"7","author":"Cembella","year":"1999","journal-title":"Nat. Toxins"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2216\/i0031-8884-39-1-67.1","article-title":"The marine dinoflagellate Alexandrium ostenfeldii (Dinophyceae) as the causative organism of spirolide shellfish toxins","volume":"39","author":"Cembella","year":"2000","journal-title":"Phycologia"},{"key":"ref_53","first-page":"782","article-title":"Morphogenetic diversity and biotoxin composition of Alexandrium (Dinophyceae) in Irish coastal waters","volume":"7","author":"Touzet","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"EFSA (2010). Scientific opinion on marine biotoxins in shellfish\u2014Cyclic imines (spirolides, gymnodimines, pinnatoxins and pteriatoxins). EFSA J., 8, 1\u201339.","DOI":"10.2903\/j.efsa.2010.1628"},{"key":"ref_55","unstructured":"Norte, M., and Fern\u00e1ndez, J.J. (2003, January 3\u20135). Floraciones algales nocivas y condiciones oceanogr\u00e1ficas en las r\u00edas gallegas durante 2001 y 2002. VIII Reuni\u00f3n Ib\u00e9rica sobre fitoplancton t\u00f3xico y biotoxinas, Proceedings of the VIII Reuni\u00f3n Ib\u00e9rica sobre fitoplancton t\u00f3xico y biotoxinas, La Laguna, Spain."},{"key":"ref_56","unstructured":"Gilabert, J. (2007, January 7\u201310). Microplancton t\u00f3xico y nocivo en las r\u00edas gallegas en los a\u00f1os 2003 a 2006. Avances y tendencias en fitoplancton t\u00f3xico y biotoxinas, Proceedings of the IX Reuni\u00f3n Ib\u00e9rica sobre Fitoplancton T\u00f3xico y Biotoxinas, Cartagena, Spain."},{"key":"ref_57","unstructured":"Villalba, A., Reguera, B., Romalde, J.R., and Beiras, R. (2002, January 4\u20138). First report of pectenotoxin-2 in phytoplankton net-hauls and mussels from the Galician Rias Bajas during proliferations of Dinophysisacuta and Dinophysis caudata. Proceedings of Forth International Conference on Molluscan Shellfish Safety, Santiago de Compostela, Spain."},{"key":"ref_58","first-page":"1","article-title":"Comparison between cytotoxic effects induced by PTX-2 in vitro in two human cell lines","volume":"3","author":"Lamas","year":"2006","journal-title":"Egypt. J. Nat. Toxins"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0887-2333(01)00095-9","article-title":"Characterization of distinct apoptotic changes induced by okadaic acid and yessotoxin in the BE(2)-M17 neuroblastoma cell line","volume":"16","author":"Leira","year":"2002","journal-title":"Toxicol. In Vitro"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1007\/s00204-005-0679-z","article-title":"Effect of okadaic acid on integrins and structural proteins in BE(2)-M17 cells","volume":"79","author":"Santaclara","year":"2005","journal-title":"Arch. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.tiv.2008.04.012","article-title":"Characteristics of palytoxin-induced cytotoxicity in neuroblastoma cells","volume":"22","author":"Valverde","year":"2008","journal-title":"Toxicol. In Vitro"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Fernandes, J.A. (2007). Focus on Neuroblastoma Research, Nova Science Publishers, Inc.","DOI":"10.1016\/S1351-4180(06)72048-7"},{"key":"ref_63","unstructured":"Cabado, A.G., and Vieites, J.M. (2013). New Trends in Marine and Freshwater Toxins, Nova Science."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3390\/toxins4050339","article-title":"Single laboratory validation of ready-to-use phosphatase inhibition assay for detection of okadaic acid toxins","volume":"4","author":"Smienk","year":"2012","journal-title":"Toxins"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6076","DOI":"10.1073\/pnas.0912372107","article-title":"Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism","volume":"107","author":"Bourne","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/toxins4010001","article-title":"Investigations into the toxicology of spirolides, a group of marine phycotoxins","volume":"4","author":"Munday","year":"2012","journal-title":"Toxins"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s00204-003-0505-4","article-title":"Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells","volume":"78","author":"Cabado","year":"2004","journal-title":"Arch. Toxicol."},{"key":"ref_68","unstructured":"EFSA (2008). Scientific opinion of the panel on contaminants in the food chain. Marine biotoxins in shellfish-yessotoxin group. EFSA J., 907, 1\u201362."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Botana, L.M. (2008). Seafood and Freshwater Toxins. Pharmacology, Physiology and Detection, CRC Press, Taylor & Francis Group.","DOI":"10.1201\/9781420007541"},{"key":"ref_70","unstructured":"INTECMAR Instituto Tecnol\u00f3xico para o Control do Medio Mari\u00f1o de Galicia. Technological Institute for the Control of the Marine Environmet in Galicia. Available online:http:\/\/www.intecmar.org\/."},{"key":"ref_71","unstructured":"(EU-RL-MB) EU-Harmonised Standard Operation Procedure for Determination of Lipophilic Marine Biotoxins in Molluscs by LC-MS\/MS. Available online:http:\/\/aesan.msssi.gob.es\/en\/CRLMB\/web\/procedimientos_crlmb\/crlmb_standard_operating_procedures.shtml."},{"key":"ref_72","unstructured":"EFSA (2009). Scientific opinion of the panel on contaminants in the food chain on a request from the European Commission on marine biotoxins in shellfish-Summary on regulated marine biotoxins. EFSA J., 1306, 1\u201323."},{"key":"ref_73","unstructured":"European Commission (2002). 2002\/657\/EC: Commission decision 2002\/657\/EC implementing Council directive 96\/23\/EC concerning the performance of analytical methods and the interpretation of results. Off. J. Eur. Communities, L221, 8\u201336."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/jaoac\/89.4.1095","article-title":"The Horwitz ratio (Horrat): A useful index of method performance with respect to precision","volume":"89","author":"Horwitz","year":"2006","journal-title":"J. AOAC Int."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/13\/4\/1666\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:43:55Z","timestamp":1760215435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/13\/4\/1666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,25]]},"references-count":75,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4]]}},"alternative-id":["md13041666"],"URL":"https:\/\/doi.org\/10.3390\/md13041666","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,25]]}}}