Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods


tetrodotoxin, marine bivalves, marine gastropods, human health risk
First published in the EFSA Journal
20 April 2017
15 March 2017
Opinion of the Scientific Committee/Scientific Panel

Tetrodotoxin (TTX) and its analogues are produced by marine bacteria and have been detected in marine bivalves and gastropods from European waters. The European Commission asked EFSA for a scientific opinion on the risks to public health related to the presence of TTX and TTX analogues in marine bivalves and gastropods. The Panel on Contaminants in the Food Chain reviewed the available literature but did not find support for the minimum lethal dose for humans of 2 mg, mentioned in various reviews. Some human case reports describe serious effects at a dose of 0.2 mg, corresponding to 4 μg/kg body weight (bw). However, the uncertainties on the actual exposure in the studies preclude their use for derivation of an acute reference dose (ARfD). Instead, a group ARfD of 0.25 μg/kg bw, applying to TTX and its analogues, was derived based on a TTX dose of 25 μg/kg bw at which no apathy was observed in an acute oral study with mice, applying a standard uncertainty factor of 100. Estimated relative potencies for analogues are lower than that of TTX but are associated with a high degree of uncertainty. Based on the occurrence data submitted to EFSA and reported consumption days only, average and P95 exposures of 0.00–0.09 and 0.00–0.03 μg/kg bw, respectively, were calculated. Using a large portion size of 400 g bivalves and P95 occurrence levels of TTX, with exception of oysters, the exposure was below the group ARfD in all consumer groups. A concentration below 44 μg TTX equivalents/kg shellfish meat, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. Liquid chromatography with tandem mass spectroscopy (LC–MS/MS) methods are the most suitable for identification and quantification of TTX and its analogues, with LOQs between 0.1 and 25 μg/kg.

Panel members at the time of adoption
Jan Alexander, Lars Barregård, Margherita Bignami, Beat Brüschweiler (from 23 June 2016), Sandra Ceccatelli, Bruce Cottrill, Michael Dinovi, Lutz Edler, Bettina Grasl-Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Helle Katrine Knutsen, Carlo Stefano Nebbia, Isabelle P. Oswald, Annette Petersen, Vera Maria Rogiers (until 9 May 2016), Martin Rose, Alain-Claude Roudot, Tanja Schwerdtle, Christiane Vleminckx, Günter Vollmer and Heather Wallace.
Panel on Contaminants in the Food Chain
EFSA Journal 2017;15(4):4752 [65 pp.].
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