RT Journal Article T1 Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin A1 Boente Juncal, Andrea A1 Otero Fuertes, María Paz A1 Rodríguez Filgueiras, Inés A1 Camiña García, María Mercedes A1 Rodríguez Vieytes, Mercedes A1 Vale González, María del Carmen A1 Botana López, Luis Miguel K1 Tetrodotoxin K1 Saxitoxin K1 Risk assessment K1 Oral chronic toxicity K1 Mollusk AB Tetrodotoxin (TTX) is a potent natural toxin causative of human food intoxications that shares its mechanism of action with the paralytic shellfish toxin saxitoxin (STX). Both toxins act as potent blockers of voltage-gated sodium channels. Although human intoxications by TTX were initially described in Japan, nowadays increasing concern about the regulation of this toxin in Europe has emerged due to its detection in fish and mollusks captured in European waters. Currently, TTX is only regularly monitored in Dutch fishery products. However, the European Food Safety Authority (EFSA) has established a safety level of 44 µg/kg TTX as the amount of toxin that did not cause adverse effects in humans. This level was extrapolated considering initial data on its acute oral toxicity and EFSA remarked the need for chronic toxicity studies to further reduce the uncertainty of future toxin regulations. Thus, in this work, we evaluated the oral chronic toxicity of TTX using the safety levels initially recommended by EFSA in order to exclude potential human health risks associated with the worldwide expanding presence of TTX. Using internationally recommended guidelines for the assessment of oral chronic toxicity, the data provided here support the proposed safety level for TTX as low enough to prevent human adverse effects of TTX even after chronic daily exposure to the toxin. However, the combination of TTX with STX at doses above the maximal exposure level of 5.3 µg/kg body weight derived by EFSA increased the lethality of TTX, thus confirming that both TTX and paralytic shellfish toxins should be taken into account to assess human health risks PB MDPI YR 2020 FD 2020 LK http://hdl.handle.net/10347/23584 UL http://hdl.handle.net/10347/23584 LA eng NO Boente-Juncal, A.; Otero, P.; Rodríguez, I.; Camiña, M.; Rodriguez-Vieytes, M.; Vale, C.; Botana, L.M. Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin. Toxins 2020, 12, 312 NO The research leading to these results has received funding from the following European Regional Development Fund (FEDER) cofunded grants. From Conselleria de Cultura, Educacion e Ordenación Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01). From the Centre for the Development of Industrial Technology (CDTI) and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, (AEI/FEDER, UE), ISCIII/PI16/01830 and RTC-2016-5507-2, ITC-20161072 DS Minerva RD 25 abr 2026