title: Investigations into the toxicology of spirolides, a group of marine phycotoxins.
abstract: Spirolides are marine phycotoxins produced by the dinoflagellates Alexandrium ostenfeldii and A. peruvianum. Here we report that 13-desmethyl spirolide C shows little cytotoxicity when incubated with various cultured mammalian cell lines. When administered to mice by intraperitoneal (ip) injection, however, this substance was highly toxic, with an LD(50) value of 6.9 µg/kg body weight (BW), showing that such in vitro cytotoxicity tests are not appropriate for predicting the in vivo toxicity of this toxin. Four other spirolides, A, B, C, and 20-methyl spirolide G, were also toxic to mice by ip injection, with LD(50) values of 37, 99, 8.0 and 8.0 µg/kg BW respectively. However, the acute toxicities of these compounds were lower by at least an order of magnitude when administration by gavage and their toxic effects were further diminished when administered with food. These results have implications for future studies of the toxicology of these marine toxins and the risk assessment of human exposure.
authors.affiliation: AgResearch, Ruakura Research Centre, Private Bag, Hamilton 3123, New Zealand. rex.munday@agresearch.co.nz
authors.forename: Rex
authors.initials: R
authors.lastname: Munday
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quilliam
authors.forename: Patricia
authors.initials: P
authors.lastname: LeBlanc
authors.forename: Nancy
authors.initials: N
authors.lastname: Lewis
authors.forename: Pamela
authors.initials: P
authors.lastname: Gallant
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Sperker
authors.forename: H Stephen
authors.initials: HS
authors.lastname: Ewart
authors.forename: Shawna L
authors.initials: SL
authors.lastname: MacKinnon
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008387:Marine Toxins / Q000633:toxicity*; D051379:Mice; D018570:Risk Assessment; D013141:Spiro Compounds / Q000633:toxicity*
chemical_list: C517170:13-desmethylspirolide C; D008387:Marine Toxins; D013141:Spiro Compounds; C429215:spirolide A; C467770:spirolide B