Estimation of the toxicity equivalence factors (TEFs) for okadaic acid and dinophysistoxins based on oral toxicity

Okadaic acid (OA) and the dinophysistoxin-1 and 2 (DTX1, DTX2) are molecules produced by dinoflagellates that can accumulate in filter-feeding bivalves and cause Diarrhetic Shellfish Poisoning (DSP) upon human consumption with... [ view full abstract ]

Okadaic acid (OA) and the dinophysistoxin-1 and 2 (DTX1, DTX2) are molecules produced by dinoflagellates that can accumulate in filter-feeding bivalves and cause Diarrhetic Shellfish Poisoning (DSP) upon human consumption with symptoms such as diarrhea, nausea, vomiting and abdominal pain. These toxins represent a health risk; therefore European legislation has set a limit of 160 µg OA equivalents/Kg shellfish meat. Liquid chromatography-mass spectrometry (LC-MS) is the official reference method for monitoring DSP toxins in seafood. In this method the use of Toxicity equivalence factors (TEFs) is necessary to allow a better estimation of the shellfish toxicity. TEF recommended by the European Food Safety Authority (EFSA) are based on the lethal dose 50 (LD50) by intraperitoneal (i.p.) injection and protein phosphatase 2A (PP2A) inhibition. However, since TEF are used to protect human consumers, they should be based on data from exposure via the oral route.

The aim of this study is to estimate the relative oral toxicity of DTX1 and DTX2 compared with OA. Toxins were administrated by gavage to Swiss female mice according to an optimized 4-level Up and Down Procedure to evaluate symptoms and establish the oral LD50. Results indicate that DTX1 is almost twice as toxic as OA while DTX2 is about three times less potent than OA. Our results may help regulatory agencies better assess human health risks associated with DSP toxin-contaminated seafood and suggest a reevaluation of TEFs established by EFSA for DSP toxins.