TESIS FICOTOXINAS MARINAS EVA FONFRIA

Introduction
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Publicaciones
Gymnodimines (GYM) and spirolides belong to an emerging, heterogeneous group
of lipophilic marine toxins called cyclic imines [1] . Since their discovery in the early
1990s in New Zealand [2] and Canada [3] respectively, gymnodimines and
spirolides have been demonstrated to have a global distribution. GYM have been also
detected in Tunisia [4] and Australia [5] and spirolides have been detected in
Norway, Adriatic Sea, Denmark, France and Spain, among other places [6-10] .
Worldwide, gymnodimines or/and spirolides have been found as contaminants in
clams, oysters, pipis, mussels, cockles and scallops [2, 4-6, 9-14] .
Cyclic imines are easily recognizable by expert laboratory personnel due to their
“fast acting toxicity” and their acute threshold response (“all or nothing”) in
mammalian bioassays. Rapid death is observed after intraperitoneal administration to
rodents of these toxins at lethal doses, but animals recover fully and quickly at
sublethal doses [3] . The oral and intraperitoneal toxicities of gymnodimines and
spirolides were determined by toxicological studies in mice. The intraperitoneal LD50
of GYM-A is in the range of 80-96 µg/Kg [15, 16] , while recent studies suggest that
the LD50 of pure 13-desmethyl C spirolide is 5-8 µg/Kg [17] . Orally, GYM has an
estimated LD50 of 755 µg/Kg when administered by gavage [16] and pure 13-
desmethyl C spirolide has an estimated LD50 of approximately 150 µg/Kg by the
same administration route [17] .
At present, gymnodimines and spirolides have not been categorically linked to any
human intoxication and there is still no legal regulation regarding their presence in
shellfish. However, their high intraperitoneal toxicity is an important source of false
positives in lipophilic toxin detection by mouse bioassay [11] and the current
opinion of the scientific community is in favor of regulating the levels of spirolides
given their high oral toxicity in laboratory animals. Developments of fast, specific
and reliable detection methods for gymnodimines and spirolides that can be used in
shellfish extracts are thus essential to guarantee adequate closure of aquaculture
areas, and for human health protection. Currently the only detection methods for
GYM and spirolides are the mouse bioassay, and liquid chromatography-mass
spectrometry (LC-MS)-based detection techniques [6, 8, 11, 13, 18, 19] . The mouse
bioassay is not a specific technique and it entails technical, ethical and legal