Toxicity of palytoxin after repeated oral exposure in mice and in vitro effects on cardiomyocytes

Ostreospis cf. ovata blooms in coastal water: Italian guidelines to assess and manage the risk associated to bathing waters and recreational activities

“…Moreover, histological analysis showed severe inflammation, locally associated with necrosis in the lung, as well as hyper-eosinophilia and separation of muscular fibres in the myocardium. From this study it was possible to calculate a provisional NOAEL of 3 mg/kg bw/day (Del Favero et al, 2013), with a rather steep dose response relationship. The NOAEL has been termed 'provisional' by the authors because of the limited number of animals used and the high interindividual variability with some mice apparently 'resilient' to the action of the toxin, independently on the treatment group.…”

“…The new available data related to an oral NOAEL obtained administering PLTX by gavage equal to 300 mg/kg bw (Sosa et al, 2009) and the provisional NOAEL related to short term repeated oral exposure of 3 mg/kg bw per day (Del Favero et al, 2013), which are likely the most representative human exposure scenarios, could be the basis for an update of the evaluation described above. While the EFSA derived ARfD can be considered conservative for protecting consumers following acute exposures, lower values should be used for short-term repeated exposure scenarios.…”

A roadmap for hazard monitoring and risk assessment of marine biotoxins on the basis of chemical and biological test systems

“…Higher Pltx doses provoke macroscopic alterations at the gastrointestinal level (gastric ulcers and intestinal fluid accumulation) in mice, while histological analysis highlighted severe inflammation, locally associated with necrosis, at pulmonary level, as well as hyper-eosinophilia and fiber separation in myocardium (Tubaro et al, 2011b). The Pltx induced cardiac pathology was further studied in vitro on cardiomyocytes, indicating a severe and irreversible impairment of their electrical properties (Del Favero et al, 2013). As the reference point for establishment of the ARfD, the lOAel for oral toxicity (gavage) in mice 200 μg PlTX/kg b.w.…”

Cardiovascular Toxicity from Marine Envenomation

“…18 More recent studies have focused on acute and repeated oral administration and have yielded interesting results. Del Favero et al 19 found that the minimum lethal dose over 7 days was 30 μg/kg per day (previous oral LD50 studies found a median of 510À767 μg/kg), that death occurred on earlier days in animals subjected to higher dosages, and that death also occurred during the recovery period following palytoxin administration. This suggested that irreversible change resulted from repeated exposure and/or that the lipophilic portion of the toxin allows accumulation in tissues.…”

“…This suggested that irreversible change resulted from repeated exposure and/or that the lipophilic portion of the toxin allows accumulation in tissues. 19 Case studies of oral human intoxication are limited and few have been able to definitively identify palytoxin as the causative agent; this is generally due to the lack of available analysis equipment and trained staff, the physiological activity of the toxin at extremely low quantities, and the lack of a toxin source (e.g., leftover food). Intoxication has also been reported following inhalation of coral vapors after applying boiling water to Palythoa spp.…”