Acute Toxicity Assessment: Macroscopic and Ultrastructural Effects in Mice Treated with Oral Tetrodotoxin

Abal, Paula; Louzao, M. Carmen; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luís M.

doi:10.3390/toxins11060305

Cited by 11 publications

(11 citation statements)

References 40 publications

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“…However, animals treated orally with a single TTX dose from 125 to 500 µg/kg b.w. showed liquid and gas accumulation in the stomach while ultrastructural changes were observed in the spleen, liver and intestine two hours after oral administration of TTX to mice at doses of 500 µg/kg [22]. Recently, the first report on the chronic toxicity of TTX after exposure of mice to low oral doses of toxin following the internationally adopted guidelines of the Organisation for Economic Co-operation and Development (OECD) has been released [23].…”

Section: Introductionmentioning

confidence: 99%

Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin

Boente-Juncal

Otero

Rodríguez³

et al. 2020

Toxins

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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.

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Section: Introductionmentioning

confidence: 99%

Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin

Boente-Juncal

Otero

Rodríguez³

et al. 2020

Toxins

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“…Stomach samples preparation for transmission electron microscopy was performed according to previously described procedures [ 35 , 57 , 58 ]. Concisely, organ samples (1 mm 3 ) were fixed by immersion (2.5% glutaraldehyde in phosphate buffered saline (PBS) containing in mM: 137 NaCl, 8.2 Na 2 HPO 4 , 1.5 KH 2 PO 4 and 3.2 KCl) for 2 h at 4 °C and rinsed three times with PBS.…”

Section: Methodsmentioning

confidence: 99%

In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin

Boente-Juncal

Raposo-García

Vale

et al. 2020

Toxins

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Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products.

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“…However, EFSA also highlighted the need to re-evaluate the seafood safety risk to consumers since recently reported results pointed to potential harmful effects of chronic low oral doses of TTX. This requires further and detailed studies, especially considering the possible synergies between different marine biotoxins with the same mechanism of action [ 43 , 45 , 56 ].…”

Section: Lack Of Traceability Of Toxicity Valuesmentioning

confidence: 99%

Current Trends and New Challenges in Marine Phycotoxins

et al. 2022

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Marine phycotoxins are a multiplicity of bioactive compounds which are produced by microalgae and bioaccumulate in the marine food web. Phycotoxins affect the ecosystem, pose a threat to human health, and have important economic effects on aquaculture and tourism worldwide. However, human health and food safety have been the primary concerns when considering the impacts of phycotoxins. Phycotoxins toxicity information, often used to set regulatory limits for these toxins in shellfish, lacks traceability of toxicity values highlighting the need for predefined toxicological criteria. Toxicity data together with adequate detection methods for monitoring procedures are crucial to protect human health. However, despite technological advances, there are still methodological uncertainties and high demand for universal phycotoxin detectors. This review focuses on these topics, including uncertainties of climate change, providing an overview of the current information as well as future perspectives.

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Acute Toxicity Assessment: Macroscopic and Ultrastructural Effects in Mice Treated with Oral Tetrodotoxin

Cited by 11 publications

References 40 publications

Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin

Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin

In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin

Current Trends and New Challenges in Marine Phycotoxins

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