Health risk assessment related to pinnatoxins in French shellfish

Abstract

Pinnatoxins (PnTXs) are a group of emerging marine biotoxins produced by the benthic dinoflagellate Vulcanodinium rugosum, currently not regulated in Europe or in any other country in the world. In France, PnTXs were detected for the first time in 2011, in mussels from the Ingril lagoon (South of France, Mediterranean coast). Since then, analyses carried out in mussels from this lagoon have shown high concentrations of PnTXs for several months each year. PnTXs have also been detected, to a lesser extent, in mussels from other Mediterranean lagoons and on the Atlantic and Corsican coasts. In the French data, the main analog is PnTX G (low levels of PnTX A are also present in some samples). No cases of PnTXs poisoning in humans have been reported so far in France or anywhere else in the world. In mice, PnTXs induce acute neurotoxic effects, within a few minutes after oral administration. Clinical signs of toxicity include decreased mobility, paralysis of the hind legs, tremors, jumps and breathing difficulties leading to death by respiratory arrest at high doses. The French agency for food safety (ANSES) recently conducted a review of the state of knowledge related to PnTXs and V. rugosum. Based on (i) the clinical signs of toxicity in mice, (ii) the mode of action of PnTXs as nicotinic acetylcholine receptor competitive antagonists and (iii) knowledge on drugs and natural toxins with PnTX-related pharmacology, potential human symptoms have been extrapolated and proposed. In this work, a provisional acute benchmark value for PnTX G of 0.13 μg/kg bw per day has been derived from an oral Please note that this is an author-produced PDF of an article accepted for publication following peer review. The definitive publisher-authenticated version is available on the publisher Web site.acute toxicity study in mice. Based on this value and a large shellfish meat portion size of 400g, a concentration lower than 23 μg PnTX G/kg shellfish meat is not expected to result in adverse effects in humans. ANSES recommends taking into account PnTXs in the French official monitoring program for shellfish production and identified data gaps to refine health risk assessment. Highlights► A state of knowledge of PnTXs and Vulcanodinium rugosum is proposed. ► A provisional acute healthbased guidance value for PnTX G of 0.13 μg/kg bw per day has been derived. ► PnTXs in shellfish should not exceed 23 μg PnTX G/kg. ► PnTXs should be included in national official monitoring programs for shellfish production. ► This work is a major step forward in taking into account this emerging hazard.

Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis

“…Lamas et al (2019) found that the maximum PnTX-G levels in the South of Europe are during winter [ 11 ]. However, Arnich et al (2020) showed that PnTX-G peaks were observed between June and September from molluscs collected from the French Mediterranean coast between 2013 and 2017 [ 14 ]. Last year, because of the occurrence of PnTXs in France, the French Agency for Food, Environmental and Occupational Health and Safety has developed a scientific opinion regarding the presence of PnTXs in shellfish, setting an acceptable contamination value of 23 μg PnTX-G/kg (total meat).…”

“…Last year, because of the occurrence of PnTXs in France, the French Agency for Food, Environmental and Occupational Health and Safety has developed a scientific opinion regarding the presence of PnTXs in shellfish, setting an acceptable contamination value of 23 μg PnTX-G/kg (total meat). Thus, a possible risk for human consumers occurs when bivalves accumulate toxins higher than this value as a result of ingesting the toxic microalgae [ 14 ]. In the present study, PnTX-G reached a maximum of 5.25 µg/kg ( M. chilensis ), much lower than the proposed level.…”

“…In the past decade, evidence has grown for the occurrence of non-regulated toxins, spirolides (SPXs) and pinnatoxins (PnTXs), in mollusc from EU waters [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. These compounds belong to the cyclic imine (CIs) group and chemistry, they are macrocyclic molecules with imine and spiro-linked ether moieties [ 15 , 16 ].…”

Summer bloom of Vulcanodinium rugosum in Cienfuegos Bay (Cuba) associated to dermatitis in swimmers

“…Vulcanodinium rugosum is the only known producer of pinnatoxins and portimine, cyclic imine toxins considered as emergent threats to human health and challenges to the shellfish industry (Arnich et al, 2020). Pinnatoxins are neurotoxic compounds while portimine has demonstrated cytotoxic activity to mammalian cells; however no human illnesses associated with these toxinsor with any other emerging J o u r n a l P r e -p r o o f algal toxinhave been described so far (Delcourt et al, 2019;Molgó et al, 2016).…”

“…In mice, symptoms following lethal dose include decrease of activity or immobility preceded of hyperactivity (except for PnTX-H), piloerection, prostration, tremors, hypothermia, jumping, hind leg extension/paralysis, abdominal breathing abruptly progressing to decrease in respiratory rate, cyanosis, exophthalmia and death (Munday et al, 2012;Selwood et al, 2010;Sosa et al, 2020). Acute toxicity, both via oral intake and i.p route, varies substantially among different pinnatoxins, being higher in PnTX-F (reviewed in Arnich et al, 2020), the dominant form in the J o u r n a l P r e -p r o o f Journal Pre-proof Cuban bloom sample. In humans, possible symptoms of PnTX intoxication via oral intake, as derived from pharmacologically similar compounds, would include the anticholinergic syndrome, pyramidal syndrome, muscle weakness, dyspnea, dysautonomia and seizures (Delcourt et al, 2019).…”