title: Combined oral toxicity of azaspiracid-1 and yessotoxin in female NMRI mice.
abstract: For many years, the presence of yessotoxins (YTXs) in shellfish has contributed to the outcome of the traditional mouse bioassay and has on many occasions caused closure of shellfisheries. Since YTXs do not appear to cause diarrhoea in man and exert low oral toxicity in animal experiments, it has been suggested that they should be removed from regulation. Before doing so, it is important to determine whether the oral toxicity of YTXs is enhanced when present together with shellfish toxins known to cause damage to the gastrointestinal tract. Consequently, mice were given high doses of YTX, at 1 or 5 mg/kg body weight, either alone or together with azaspiracid-1 (AZA1) at 200 μg/kg. The latter has been shown to induce damage to the small intestine at this level. The combined exposure caused no clinical effects, and no pathological changes were observed in internal organs. These results correspond well with the very low levels of YTX detected in internal organs by means of LC-MS/MS and ELISA after dosing. Indeed, the very low absorption of YTX when given alone remained largely unchanged when YTX was administered in combination with AZA1. Thus, the oral toxicity of YTX is not enhanced in the presence of sub-lethal levels of AZA1.
authors.affiliation: Norwegian School of Veterinary Science, Department of Food Safety and Infection Biology, P.O. Box 8146 Dep., 0033 Oslo, Norway. john.aasen@nvh.no
authors.forename: John A B
authors.initials: JA
authors.lastname: Aasen
authors.forename: Arild
authors.initials: A
authors.lastname: Espenes
authors.forename: Christopher O
authors.initials: CO
authors.lastname: Miles
authors.forename: Ingunn A
authors.initials: IA
authors.lastname: Samdal
authors.forename: Philipp
authors.initials: P
authors.lastname: Hess
authors.forename: Tore
authors.initials: T
authors.lastname: Aune
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008817:Mice, Mutant Strains; D008978:Mollusk Venoms; D035964:Oxocins / Q000008:administration & dosage / Q000633:toxicity*; D013141:Spiro Compounds / Q000008:administration & dosage / Q000633:toxicity*; D053719:Tandem Mass Spectrometry; D000095702:Polyether Toxins
chemical_list: D004338:Drug Combinations; D008387:Marine Toxins; D008978:Mollusk Venoms; D035964:Oxocins; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins; C066632:yessotoxin