Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD50) and No-observed-adverse-effect level (NOAEL)

Andrea Boente-Juncal; Carmen Vale; Mercedes Camiña; J Manuel Cifuentes; Mercedes R Vieytes; Luis M Botana

doi:10.1016/j.toxicon.2020.01.010

Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD₅₀) and No-observed-adverse-effect level (NOAEL)

Toxicon. 2020 Apr 15:177:16-24. doi: 10.1016/j.toxicon.2020.01.010. Epub 2020 Jan 24.

Authors

Andrea Boente-Juncal¹, Carmen Vale², Mercedes Camiña³, J Manuel Cifuentes⁴, Mercedes R Vieytes⁵, Luis M Botana⁶

Affiliations

¹ Departamento de Farmacoloxía, Farmacia e Tecnología Farmacéutica, Facultade de Veterinaria, Universidade de Santiago de Compostela, Lugo, 27002, Spain. Electronic address: andrea.boente.juncal@usc.es.
² Departamento de Farmacoloxía, Farmacia e Tecnología Farmacéutica, Facultade de Veterinaria, Universidade de Santiago de Compostela, Lugo, 27002, Spain. Electronic address: mdelcarmen.vale@usc.es.
³ Departamento de Fisioloxía, Facultade de Veterinaria, Universidade de Santiago de Compostela, Lugo, 27002, Spain. Electronic address: merchi.camina@usc.es.
⁴ Departamento de Anatomía, Producción Animal y Ciencias Clínicas Veterinarias, Facultad de Veterinaria, Universidade de Santiago de Compostela, Lugo, 27002, Spain. Electronic address: m.cifuentes@usc.es.
⁵ Departamento de Fisioloxía, Facultade de Veterinaria, Universidade de Santiago de Compostela, Lugo, 27002, Spain. Electronic address: mmercedes.rodriguez@usc.es.
⁶ Departamento de Farmacoloxía, Farmacia e Tecnología Farmacéutica, Facultade de Veterinaria, Universidade de Santiago de Compostela, Lugo, 27002, Spain. Electronic address: luis.botana@usc.es.

PMID: 32056831
DOI: 10.1016/j.toxicon.2020.01.010

Abstract

Palytoxin is an emergent toxin in Europe and one of the most toxic substances know to date. The toxin disrupts the physiological functioning of the Na⁺/K⁺-ATPase converting the enzyme in a permeant cation channel. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Several reports have previously investigated the oral and intraperitoneal toxicity of PLTX in mice. However, in all cases short observation periods (24 and 48 h) after toxin administration were evaluated. In this work, single oral or intraperitoneal doses of PLTX were administered to healthy mice and surviving animals were followed up for 96 h. The data obtained here allowed us to calculate the oral and intraperitoneal lethal doses 50 (LD₅₀) which were in the range of the values previously described. Surprisingly, the oral NOAEL for PLTX was more than 10 times lower than that previously described, a fact that indicates the need for the reevaluation of the levels of the toxin in edible fishery products.

Keywords: EFSA; Fishery products; Na(+)/K(+)-ATPase; Palytoxin; Risk assessment.

MeSH terms

Acrylamides / toxicity*
Animals
Cnidarian Venoms / toxicity*
Humans
Lethal Dose 50
Mice
No-Observed-Adverse-Effect Level
Sodium-Potassium-Exchanging ATPase / metabolism
Toxicity Tests, Acute*

Substances

Acrylamides
Cnidarian Venoms
Sodium-Potassium-Exchanging ATPase
palytoxin