Acute Oral Toxicity of Pinnatoxin G in Mice

Abstract

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8–450 µg kg−1). At the dose of 220 µg kg−1 and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 µg kg−1, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD50 for PnTx-G equal to 208 μg kg−1 (95% confidence limits: 155–281 µg kg−1) and to estimate a provisional NOEL of 120 µg kg−1.

Epibenthic Harmful Marine Dinoflagellates from Fuerteventura (Canary Islands), with Special Reference to the Ciguatoxin-Producing Gambierdiscus

“…Its high abundance in the present study is a remarkable new interesting finding given the high concentrations observed in Playitas station. Vulcanodinium rugosum, the only one species described so far from the genus, was described in 2011 from a French Mediterranean Lagoon and is responsible for producing neurotoxic pinnatoxins (PnTXs) which have been recurrently detected in the shellfish from that region [64,65]. The morphology of Vulcanodinium cells in the samples coincide with those described by Rhodes et al and Zeng et al [64,66] as motile cells, however their benthic/planktonic character should be studied.…”

“…This type of cysts has been called division cysts which have been described in species considered planktonic but with an intense relationship with the benthos [67,68]. No human poisonings by PnTXs are known, however because of their high toxic potential, European Food Safety Authority (EFSA) have pointed out the need for more information on the oral toxicity of these compounds for risk assessment as seafood contaminant [65]. Therefore, future taxonomic, life cycle, and toxin studies are required from the organism found in the Canary Islands.…”

Health risk assessment related to pinnatoxins in French shellfish

“…Orally, only three studies are available and focused on PnTX E, F, G and H (Munday et al, 2012;Selwood et al, 2014; ANSES-University of Trieste-CNRS report, 2014 also published in Sosa et al, 2020). We did not find any information on the toxicity by the oral route for PtTXs (metabolites of certain PnTXs) and portimine (a toxin also produced by V. rugosum).…”

“…The second point relies on neurotoxic symptoms, quickly leading to the mouse's death by respiratory arrest. Clinical signs of toxicity, regardless of the route of administration and the PnTX analogue, include decreased mobility (sometimes preceded by an initial phase of hyperactivity immediately following administration), paralysis of the hind legs and breathing difficulties (Munday et al, 2012), with tremors and jumps also being reported (ANSES-University of Trieste-CNRS Report, 2014;Sosa et al, 2020). In the study by Munday et al (2012), the authors reported that at sublethal doses (without specifying which ones), some mice recovered completely after exhibiting symptoms.…”

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

“…In the present study, PnTX-G reached a maximum of 5.25 µg/kg ( M. chilensis ), much lower than the proposed level. A very recent study has allowed to stablish an oral LD 50 for PnTx-G of 208 μg/kg and a provisional No Observed Effect Level (NOEL) of 120 μg/kg [ 35 ].…”