Brevetoxins emergent toxins in France: Evaluation of BTX-3 mouse acute toxicity by oral gavage

Brevetoxins (BTXs) constitute a family of lipophilic marine phycotoxins produced by the dinoflagellate Karenia brevis, but other dinoflagellates are likewise assumed synthesizing BTX-like analogs. BTXs can accumulate in shellfish, fish and diverse marine organisms. Exposure to BTXs in humans may occur mainly by inhalation through aerosolized marine water and potentially by seafood ingestion. BTXs produce the so-called neurotoxic shellfish poisoning (NSP), characterized by neurological, gastrointestinal and/or cardiovascular symptoms. In 2018, BTXs were first detected in mussels from a Mediterranean lagoon in Corsica Island (France). To prevent health risks associated to the consumption of contaminated shellfish, ANSES recommended a guidance level of 180 µg BTX-3 eq/kg shellfish meat, and recommended assessing the BTXs acute oral toxicity in rodents. This study provides information on the acute oral toxicity of BTX-3, the main BTX analog found in shellfish, in male and female mice administered with increasing doses of BTX-3 over a 48-hour observation period. Through our experimental approach, we identified potential starting points that could be used to establish an acute oral reference dose (ARfD) including reductions in body weight, body temperature, and muscle activity.