title: Characterization of the dinophysistoxin-2 acute oral toxicity in mice to define the Toxicity Equivalency Factor.
abstract: Ingestion of shellfish with dinophysistoxin-2 (DTX2) can lead to diarrheic shellfish poisoning (DSP). The official control method of DSP toxins in seafood is the liquid chromatography-mass spectrometry analysis (LC-MS). However in order to calculate the total toxicity of shellfish, the concentration of each compound must be multiplied by individual Toxicity Equivalency Factor (TEF). Considering that TEFs caused some controversy and the scarce information about DTX2 toxicity, the aim of this study was to characterize the oral toxicity of DTX2 in mice. A 4-Level Up and Down Procedure allowed the characterization of DTX2 effects and the estimation of DTX2 oral TEF based on determination of the lethal dose 50 (LD50). DTX2 passed the gastrointestinal barrier and was detected in urine and feces. Acute toxicity symptoms include diarrhea and motionless, however anatomopathology study and ultrastructural images restricted the toxin effects to the gastrointestinal tract. Nevertheless enterocytes microvilli and tight junctions were not altered, disconnecting DTX2 diarrheic effects from paracellular epithelial permeability. This is the first report of DTX2 oral LD50(2262 μg/kg BW) indicating that its TEF is about 0.4. This result suggests reevaluation of the present TEFs for the DSP toxins to better determine the actual risk to seafood consumers.
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Abal
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain. Electronic address: mcarmen.louzao@usc.es.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Louzao
authors.affiliation: Departamento de Anatomía, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Cifuentes
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Vilariño
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain.
authors.forename: Ines
authors.initials: I
authors.lastname: Rodriguez
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Alfonso
authors.affiliation: Departamento de Fisiología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain.
authors.forename: Mercedes R
authors.initials: MR
authors.lastname: Vieytes
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain. Electronic address: luis.botana@usc.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002853:Chromatography, Liquid / Q000379:methods; D004435:Eating / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D005260:Female; D007422:Intestines / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008387:Marine Toxins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D019319:Okadaic Acid / Q000031:analogs & derivatives; D011714:Pyrans / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D053719:Tandem Mass Spectrometry / Q000379:methods; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D008387:Marine Toxins; D011714:Pyrans; D019319:Okadaic Acid; C076221:dinophysistoxin 2
keywords: Dinophysistoxin-2; Intestinal tight junctions; Oral toxicity; Toxicity Equivalency Factor; Ultrastructural effects