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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.
Andrea Boente-Juncal; Paz Otero; Inés Rodríguez; Mercedes Camiña; Mercedes Rodriguez-Vieytes; Carmen Vale; Luis M. Botana. 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 .
AMA StyleAndrea Boente-Juncal, Paz Otero, Inés Rodríguez, Mercedes Camiña, Mercedes Rodriguez-Vieytes, Carmen Vale, Luis M. Botana. Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin. Toxins. 2020; 12 (5):312.
Chicago/Turabian StyleAndrea Boente-Juncal; Paz Otero; Inés Rodríguez; Mercedes Camiña; Mercedes Rodriguez-Vieytes; Carmen Vale; Luis M. Botana. 2020. "Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin." Toxins 12, no. 5: 312.
Palytoxin is an emergent toxin in Europe and one of the most toxic substances know to date. The toxin disrupts the physiological functioning of the Na+/K+-ATPase converting the enzyme in a permeant cation channel. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Several reports have previously investigated the oral and intraperitoneal toxicity of PLTX in mice. However, in all cases short observation periods (24 and 48 h) after toxin administration were evaluated. In this work, single oral or intraperitoneal doses of PLTX were administered to healthy mice and surviving animals were followed up for 96 h. The data obtained here allowed us to calculate the oral and intraperitoneal lethal doses 50 (LD50) which were in the range of the values previously described. Surprisingly, the oral NOAEL for PLTX was more than 10 times lower than that previously described, a fact that indicates the need for the reevaluation of the levels of the toxin in edible fishery products.
Andrea Boente-Juncal; Carmen Vale; Mercedes Camiña; J. Manuel Cifuentes; Mercedes R. Vieytes; Luis M. Botana. Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD50) and No-observed-adverse-effect level (NOAEL). Toxicon 2020, 177, 16 -24.
AMA StyleAndrea Boente-Juncal, Carmen Vale, Mercedes Camiña, J. Manuel Cifuentes, Mercedes R. Vieytes, Luis M. Botana. Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD50) and No-observed-adverse-effect level (NOAEL). Toxicon. 2020; 177 ():16-24.
Chicago/Turabian StyleAndrea Boente-Juncal; Carmen Vale; Mercedes Camiña; J. Manuel Cifuentes; Mercedes R. Vieytes; Luis M. Botana. 2020. "Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD50) and No-observed-adverse-effect level (NOAEL)." Toxicon 177, no. : 16-24.
Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. InitiallyTTX was associated with human food intoxications in Japan, but nowadays, concerns about thehuman health risks posed by TTX have increased in Europe after the identification of the toxin infish, marine gastropods, and bivalves captured in European waters. Even when TTX monitoring isnot currently performed in Europe, an acute oral no observable effect level (NOAEL) of 75 μg/kghas been recently established but, to date, no studies evaluating the chronic oral toxicity of TTXhave been released, even when EFSA has highlighted the need for them. Thus, in this work, thechronic effects of low oral TTX doses (below the acute lethal dose 50) were evaluated followinginternationally adopted guidelines. The results presented here demonstrate that low oral doses ofTTX have deleterious effects on renal and cardiac tissues. Moreover, alterations in bloodbiochemistry parameters, urine production, and urinalysis data were already detected at the oraldose of 75 μg/kg after the 28 days exposure. Thus, the data presented here constitute an initialapproach for the chronic evaluation of the in vivo toxicity of tetrodotoxin after its ingestion throughcontaminated fishery products.
Andrea Boente-Juncal; Carmen Vale; Manuel Cifuentes; Paz Otero; Mercedes Camiña; Mercedes Rodriguez-Vieytes; Luis Miguel Botana. Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity. Toxins 2019, 11, 96 .
AMA StyleAndrea Boente-Juncal, Carmen Vale, Manuel Cifuentes, Paz Otero, Mercedes Camiña, Mercedes Rodriguez-Vieytes, Luis Miguel Botana. Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity. Toxins. 2019; 11 (2):96.
Chicago/Turabian StyleAndrea Boente-Juncal; Carmen Vale; Manuel Cifuentes; Paz Otero; Mercedes Camiña; Mercedes Rodriguez-Vieytes; Luis Miguel Botana. 2019. "Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity." Toxins 11, no. 2: 96.
Ciguatoxins are polyether marine toxins that act as sodium channel activators. These toxins cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents several symptoms in humans including long-term neurological alterations. Earlier work has shown that both acute and chronic exposure of primary cortical neurons to synthetic ciguatoxin CTX3C have profound impacts on neuronal function. Thus, the present work aimed to identify relevant neuronal genes and metabolic pathways that could be altered by ciguatoxin exposure. To study the effect of ciguatoxins in primary neurons in culture, we performed a transcriptomic analysis using whole mouse genome microarrays, for primary cortical neurons exposed during 6, 24, or 72 h in culture to CTX3C. Here, we have shown that the effects of the toxin on gene expression differ with the exposure time. The results presented here have identified several relevant genes and pathways related to the effect of ciguatoxins on neurons and may assist in future research or even treatment of ciguatera. Moreover, we demonstrated that the effects of the toxin on gene expression were exclusively consequential of its action as a voltage-gated sodium channel activator, since all the effects of CTX3C were avoided by preincubation of the neurons with the sodium channel blocker tetrodotoxin.
Juan Andrés Rubiolo; Carmen Vale; Andrea Boente-Juncal; Masahiro Hirama; Shuji Yamashita; Mercedes Camiña; Mercedes R. Vieytes; Luis M. Botana. Transcriptomic Analysis of Ciguatoxin-Induced Changes in Gene Expression in Primary Cultures of Mice Cortical Neurons. Toxins 2018, 10, 192 .
AMA StyleJuan Andrés Rubiolo, Carmen Vale, Andrea Boente-Juncal, Masahiro Hirama, Shuji Yamashita, Mercedes Camiña, Mercedes R. Vieytes, Luis M. Botana. Transcriptomic Analysis of Ciguatoxin-Induced Changes in Gene Expression in Primary Cultures of Mice Cortical Neurons. Toxins. 2018; 10 (5):192.
Chicago/Turabian StyleJuan Andrés Rubiolo; Carmen Vale; Andrea Boente-Juncal; Masahiro Hirama; Shuji Yamashita; Mercedes Camiña; Mercedes R. Vieytes; Luis M. Botana. 2018. "Transcriptomic Analysis of Ciguatoxin-Induced Changes in Gene Expression in Primary Cultures of Mice Cortical Neurons." Toxins 10, no. 5: 192.