TOXICOLOGICAL EVALUATION OF SAXITOXIN, NEOSAXITOXIN, GONYAUTOXIN-II, GONYAUTOXIN-II-PLUS-III AND DECARBAMOYLSAXITOXIN WITH THE MOUSE NEUROBLASTOMA CELL BIOASSAY

Four major paralytic shellfish poisoning (PSP) toxins in pure form-sax itoxin (STX), neosaxitoxin (NEO), gonyautoxin II (GTX II), and decarba moylsaxitoxin (dcSTX), and mixed gonyautoxin II plus III (GTX II/III)- were toxicologically evaluated in the neuroblastoma cell bioassay and compared with the United States Food and Drug Administration standard reference saxitoxin (FDA STX). Mean relative toxicities of these exper imental preparations were 99.5 (STX), 128.0 (NEO), 48.4 (GTX II) and 4 2.6 (dcSTX) when compared with FDA STX set arbitrarily at 100. Two mix tures of GTX II/III with relative concentrations of 1:2.5 and 4:1 had percentage relative toxicities of 52.4 and 54.5, respectively. Except for GTX II/III, which increased in toxicity, the toxicities of the exp erimental toxin preparations were not affected by boiling for 5 min in equal volumes of either 0.1 or 1.0 N HCl. Detailed examinations of do se-responses of each individual toxin preparation in the cell bioassay revealed some differences in response profiles. The toxicological dat a presented here support and extend previous information collected wit h the mouse bioassay and HPLC. The EC(50) values of STX and GTX II/III obtained under different conditions of matrix (acetic acid v. ethanol ), filtration (filtered 0.22 mu m or unfiltered) and time in storage a t 5 degrees C after opening of the sealed ampoules were largely unaffe cted by any of the experimental treatments.