An Update of Tetrodotoxins Toxicity and Risk Assessment Associated to Contaminated Seafood Consumption in Europe: A Systematic Review

Following the occurrence of Tetrodotoxins (TTXs) in Europe-a group of neurotoxins identified in Asia, where fatalities occurred after the ingestion of contaminated pufferfish-the EFSA proposed a limit of 44 µg of TTX/kg of shellfish meat in mollusks in 2017, to protect heavy consumers. The limit was based on an acute reference dose (ARfD) derived from the few available data on TTX toxicity. TTX is expected to increase with sea-surface warming; indeed, it has been found in spring/summer in mollusks in Europe, with concentrations often exceeding this limit. Due to the numerous uncertainties of the EFSA's ARfD, we conducted a systematic review to provide an update on TTX toxicity. Out of 12,741 articles retrieved from PubMed, Science Direct, and Scopus since 2017, only 17 were eligible for data extraction. Our results show that they are not sufficient to modify the EFSA's conclusions. Furthermore, our analysis of occurrence data in European seafood, to assess the current risk of exposure to TTX, reveals several gaps, such as different LODs/LOQs and seasonal monitoring not allowing comparisons between areas and too few analyzed sites. However, the presence of positive samples exceeding the EFSA limit indicates a potential risk even for general consumers, highlighting the urgency to address these knowledge gaps.