Oral chronic toxicity of the marine toxin tetrodotoxin

Tetrodotoxin (TTX) is a very toxic compound responsible for human intoxications after ingestion of contaminated fishery products. Although TTX was initially associated mainly with human fatalities occurring in Asiatic countries[1], nowadays has expanded to other regions including European countries. In Europe, the first non-fatal human intoxications by TTX was reported more than 10 years ago after the ingestion of a Charonia lampas trumpet shell captured in the Portuguese coast and commercialized in Spain[2]. Since then, during the last decade, the presence of the TTX-containing pufferfish Lagocephalus sceleratus has been reported in European coasts, mainly in the Mediterranean Sea[3,4] with some fish tissues containing TTXs amounts as high as 2 mg/kg[5]. Moreover, an increasing concern regarding food safety has been raised after the detection of TTX in mussels, oysters and clams harvested in UK, Greece, the Netherlands[6-8] and Spain. The current European legislation in marine toxins did not yet regulated the levels of TTX in fishery products, and nowadays the presence of the toxin is only regularly monitored in the Netherlands although the European Food Safety Authority (EFSA) has recommended the level of 44 µg/kg TTXs for routine monitoring since, at this dose, no adverse effects were observed in humans. Considering initial data on the acute oral toxicity of TTX and in view of the EFSA opinion remarking the need for additional chronic toxicity studies to further reduce the uncertainty of the likely future toxin regulation. In this work, the oral chronic toxicity of TTX using doses of 25, 44, 75 and 125 µg/kg and an observation period of 28 days was explored in female mice using protocols internationally validated to test the toxicity of chemicals. The data presented here indicated that 25 and 44 µg/kg of TTX did not cause neither blood biochemical nor behavioral alterations in mice, while at the dose of 125 µg/kg kidney and heart alterations were observed under electron microscopy analysis. Therefore, the data presented here indicate that the safety TTX dose proposed by EFSA is low enough to prevent human adverse effects, while caution should be taken in the presence of higher TTX doses.

References:

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