Mixtures of Lipophilic Phycotoxins: Exposure Data and Toxicological Assessment

Abstract

Lipophilic phycotoxins are secondary metabolites produced by phytoplanktonic species. They accumulate in filter-feeding shellfish and can cause human intoxication. Regulatory limits have been set for individual toxins, and the toxicological features are well characterized for some of them. However, phycotoxin contamination is often a co-exposure phenomenon, and toxicological data regarding mixtures effects are very scarce. Moreover, the type and occurrence of phycotoxins can greatly vary from one region to another. This review aims at summarizing the knowledge on (i) multi-toxin occurrence by a comprehensive literature review and (ii) the toxicological assessment of mixture effects. A total of 79 publications was selected for co-exposure evaluation, and 44 of them were suitable for toxin ratio calculations. The main toxin mixtures featured okadaic acid in combination with pectenotoxin-2 or yessotoxin. Only a few toxicity studies dealing with co-exposure were published. In vivo studies did not report particular mixture effects, whereas in vitro studies showed synergistic or antagonistic effects. Based on the combinations that are the most reported, further investigations on mixture effects must be carried out.

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

“…Thus, for a 60 kg adult to avoid exceeding the ARfD of 0.8 μg PTX eq/kg b.w., a 400 g portion of shellfish should not contain more than 48 μg PTX eq corresponding to 120 μg PTX-2 eq/kg shellfish meat [ 43 ]. In Asian molluscs, several combinations of lipophilic marine toxins were reported, including OA/YTX, OA/PTX-2, YTX/OA, PTX-2/OA, PTX-2/GYM, GYM/PTX-2 [ 44 ], and also AZA-2/PTX-2 [ 45 ]. It appears that OA is the most often recorded lipophilic toxin in mixtures, as well as the predominant toxin in the mixture [ 44 ].…”

“…In Asian molluscs, several combinations of lipophilic marine toxins were reported, including OA/YTX, OA/PTX-2, YTX/OA, PTX-2/OA, PTX-2/GYM, GYM/PTX-2 [ 44 ], and also AZA-2/PTX-2 [ 45 ]. It appears that OA is the most often recorded lipophilic toxin in mixtures, as well as the predominant toxin in the mixture [ 44 ]. Toxicological studies reporting the effects of the co-association AZA-2/PTX-2 were not found in the literature.…”

Current Trends and New Challenges in Marine Phycotoxins

“…This further enlarges the resources needed to evaluate potential toxicity of these toxins, which may be reduced by knowledge of VGSC structure in combination with bioinformatic tools, though experimental data are essential to confirm computational predictions. Aside from analogues affinity and toxicity data, a growing concern arises from additive effects of co-occurring toxins [ 87 ].…”

Monitoring Lipophilic Toxins in Seawater Using Dispersive Liquid—Liquid Microextraction and Liquid Chromatography with Triple Quadrupole Mass Spectrometry

“…Depending on their polarity, marine toxins can be classified as hydrophilic, lipophilic, or amphiphilic [ 9 ]. The main compounds included in the lipophilic group are okadaic acid (OA) and dinophysitoxins (DTXs), pectenotoxins, yessotoxins, azaspiracids (AZAs), and cyclic imines, the last mentioned including spirolides (SPXs), pinnatoxins, pteriatoxins, and gymnodimins.…”