Azaspiracid toxins: toxicological profile

Azaspiracids (AZAs) are a toxin group that originate from marine dinoflagellates of the genera Azadinium and Amphidoma. After accumulation of these toxins in edible marine organisms and their subsequent consumption, humans develop a gastrointestinal syndrome referred to as azaspiracid shellfish poisoning (AZP). This syndrome is very similar to diarrheic shellfish poisoning (DSP), with main symptoms appearing after a few hours from consumption and including diarrhea, vomiting, and stomach cramps. Due to extensive metabolism in shellfish, more than 30 analogues have been reported to date, and purified compounds for selected analogues have recently been made available for toxicological studies. Currently, only AZA1, AZA2, and AZA3 are regulated in Europe and internationally; however, more recent evidence suggests that AZA6, AZA17, and AZA19 may also be analogues of importance for estimating the full risk of seafood. Even though animal studies have pointed out target organs (digestive tract, liver, heart, and lung), mechanism of action studies at cellular level are not yet conclusive. While a number of common targets have been excluded (protein phosphatases, kinases, actin depolymerization, G protein-coupled receptors), some evidence points toward ion channel activity of AZAs. Still, in vitro studies do not correlate well with symptoms observed in humans. Also, while some animal studies point toward longer-term effects, no such evidence has been reported from human poisoning events. However, it should be noted that in-depth epidemiological studies are still lacking. Even though all risk assessments have based their evaluation on a single, relatively early poisoning event in 1997, in Arranmore Island, Ireland, producing organisms and toxin occurrences have been reported worldwide, and further occurrence studies should provide a better base for such epidemiological studies.