Pharmacokinetic and toxicological data of spirolides after oral and intraperitoneal administration

Spirolides are a kind of marine toxins included in the cyclic imine toxin group and produced by the dinoflagellate Alexandrium ostenfeldii. This study shows for the first time a complete and detailed description about the symptoms observed in mice when these toxins were intraperitoneal (i.p.) administered. It is also compared the i.p. toxicity of 13-desmethyl spirolide C (13-desMeC), 13,19-didesMeC (13,19-didesMeC) and 20-methyl spirolide G (20-Me-G) in experiments performed with highly purified toxins. The bioassay indicates that 13-desMeC and 13,19-didesMeC are extremely toxic compounds which have a LD50 of 27.9 μg/kg and 32.2 μg/kg, respectively. However, when 20-MeG was i.p administrated with dose up 63.5 μg/kg, no deaths were recorded.In order to evaluate the oral toxicity, spirolides were administered by gastric intubation into mice. Then, samples of blood, urine and faeces were collected and analyzed by liquid chromatography-mass spectrometry tandem (LC-MS/MS) technique. Spirolides appear in blood at 15 min and in urine after 1 h of being toxin administered. In summary, in this paper, it is provided new data about the toxicity, absorption, and excretion of spirolides in mouse. So far, little information is available on this item but necessary for spirolide regulation in the European Union (EU).

► The symptoms observed in mice when spirolides were intraperitoneal administered are described. ► 13-desMeC is slightly more toxic than 13,19-didesMeC. ► 13-desMeC and 13,19-didesMeC are considerably more toxic than 20-MeG. ► Spirolides are absorbed by via oral administration. ► The availability in blood is greater for 13-desMeC than 13,19-didesMeC.