In France, four groups of lipophilic toxins are currently regulated: okadaic acid/dinophysistoxins, pectenotoxins, yessotoxins and azaspiracids. However, many other families of toxins exist, which can be emerging toxins. Emerging toxins include both toxins recently detected in a specific area of France but not regulated yet (e.g., cyclic imines, ovatoxins) or toxins only detected outside of France (e.g., brevetoxins). To anticipate the introduction to France of these emerging toxins, a monitoring program called EMERGTOX was set up along the French coasts in 2018. The single-laboratory validation of this approach was performed according to the NF V03-110 guidelines by building an accuracy profile. Our specific, reliable and sensitive approach allowed us to detect brevetoxins (BTX-2 and/or BTX-3) in addition to the lipophilic toxins already regulated in France. Brevetoxins were detected for the first time in French Mediterranean mussels (Diana Lagoon, Corsica) in autumn 2018, and regularly every year since during the same seasons (autumn, winter). The maximum content found was 345 µg (BTX-2 + BTX-3)/kg in mussel digestive glands in November 2020. None were detected in oysters sampled at the same site. In addition, a retroactive analysis of preserved mussels demonstrated the presence of BTX-3 in mussels from the same site sampled in November 2015. The detection of BTX could be related to the presence in situ at the same period of four Karenia species and two raphidophytes, which all could be potential producers of these toxins. Further investigations are necessary to understand the origin of these toxins.

Shellfish accumulate microalgal toxins, which can make them unsafe for human consumption. In France, in accordance with EU regulations, three groups of marine toxins are currently under official monitoring: lipophilic toxins, saxitoxins, and domoic acid. Other unregulated toxin groups are also present in European shellfish, including emerging lipophilic and hydrophilic marine toxins (e.g., pinnatoxins, brevetoxins) and the neurotoxin β-N-methylamino-L-alanine (BMAA). To acquire data on emerging toxins in France, the monitoring program EMERGTOX was set up along the French coasts in 2018. Three new broad-spectrum LC-MS/MS methods were developed to quantify regulated and unregulated lipophilic and hydrophilic toxins and the BMAA group in shellfish (bivalve mollusks and gastropods). A single-laboratory validation of each of these methods was performed. Additionally, these specific, reliable, and sensitive operating procedures allowed the detection of groups of EU unregulated toxins in shellfish samples from French coasts: spirolides (SPX-13-DesMeC, SPX-DesMeD), pinnatoxins (PnTX-G, PnTX-A), gymnodimines (GYM-A), brevetoxins (BTX-2, BTX-3), microcystins (dmMC-RR, MC-RR), anatoxin, cylindrospermopsin and BMAA/DAB. Here, we present essentially the results of the unregulated toxins obtained from the French EMERGTOX monitoring plan during the past five years (2018–2022). Based on our findings, we outline future needs for monitoring to protect consumers from emerging unregulated toxins.

In 2020–2021, a “mysterious illness” struck Senegalese fishermen, causing severe acute dermatitis in over one thousand individuals following exposure through drift-net fishing activity. Here, by performing deep analysis of the environmental samples we reveal the presence of the marine dinoflagellate Vulcanodinium rugosum and its associated cyclic imine toxins. Specifically, we show that the toxin PortimineA, strongly enriched in environmental samples, impedes ribosome function in human keratinocytes, which subsequently activates the stress kinases ZAKα and P38 and promotes the nucleation of the human NLRP1 inflammasome, leading to the release of IL-1β/IL-18 pro-inflammatory cytokines and cell death. Furthermore, cell-based models highlight that naturally occurring mutations in the P38-targeted sites of human NLRP1 are unable to respond to PortimineA exposure. Finally, the development and use of human organotypic skins and zebrafish models of PortimineA exposure demonstrate that the ZAKα-NLRP1 axis drives skin necrosis and inflammation. Our results exemplify the threats to human health caused by emerging environmental toxins and identify ZAKα and NRLP1 as important pharmacological targets to mitigate PortimineA toxicity.