Effect of mouse strain and gender on LD50 of yessotoxin

The aim of the present study was to determine whether the intraperitoneal LD50 for yessotoxin (YTX) in mice varies with strain or gender. Thirty-six male and 36 female mice, of body weight 16-20 g, from each of the strains ICR (CD-1), Swiss (CFW-1) and NMRI were employed. They were not fasted before YTX treatment. At each dose, nine mice were injected with YTX solutions at 1.0 mL/20 g body weight, and observed for 24 h. Symptoms and time to death were recorded. Within each mouse strain and gender arm, the study was performed as a basic four level Response Surface Pathway designed trial with nine mice at each dose level. YTX was isolated from a culture of Protoceratium reticulatum. The LD50 values for female and male mice, respectively, were estimated as 380 and 462 mu g/kg for the ICR, 269 and 328 mu g/kg for the Swiss, and 314 and 412 mu g/kg for the NMRI strains. The increases in LD50 from female to male mice were found to be 22% for ICR, 22% for Swiss and 31% for NMRI. The largest difference in LD50 among mouse strains was detected between the ICR and Swiss strains, where the deviation was 41% in both females and males. The difference between mouse strains was found significant (p = 0.03). For all three strains, females were more susceptible than males, with a difference in LD50 Of 1.2-1.3-fold. The largest difference between the least- and most-susceptible strain was 1.4-fold for both females and males. The largest difference in LD50, 1.7-fold, was observed between female Swiss and male ICR mice. The difference between genders was not significant (p = 0.12). These results indicate that other factors, like handling of the animals, and the source and handling of the toxin, may significantly influence the outcome of studies on acute toxicity since the reported differences in LD50 vary by a factor of about seven. (c) 2008 Elsevier Ltd. All rights reserved.