"GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

MAXIMUM DOSE VOLUME APPLIED: 1.19 mL/kg. The dose volume was determined by dividing each dose level, expressed as g/kg, by the density (1.6813 g/mL) (dose volumes of 0.0297, 0.178 and 1.19 mL/kg bw for the 50, 300 and 2000 mg/kg bw groups, respectively).

DOSAGE PREPARATION: Prior to use, the bulk test substance container was inverted and/or swirled. On each day of dosing, a sufficient volume of test substance was transferred into an amber glass vial. A stir bar was added, and the contents stirred throughout use. The container was purged with nitrogen and capped immediately. The pH was measured using litmus paper for the first dispensation and was found to be 5.

CLASS METHOD

- Rationale for the selection of the starting dose:

The test substance was administered once to 3 fasted male and 3 fasted female albino mice at a dose level of 2000 mg/kg bw. Mortality was observed for 1 male and 1 female, and 3 additional males and 3 additional females were subsequently dosed at 2000 mg/kg bw. All 3 additional males and all 3 additional females at 2000 mg/kg bw died or were euthanized in extremis. Therefore, 3 males and 3 females were dosed at 300 mg/kg bw. Only 1 male at 300 mg/kg bw was euthanized in extremis, and as called for in the guidelines, 3 additional males were dosed at 300 mg/kg bw. No more unscheduled deaths occurred in the 300 mg/kg bw group males, and therefore, no additional males were dosed. All 3 females dosed at 300 mg/kg bw died or were euthanized in extremis. Therefore, 3 females were dosed at 50 mg/kg bw. No mortality was observed for these females, and 3 additional females were dosed at 50 mg/kg bw. Again, no mortality was observed, and therefore, no additional females were dosed."

Male Crl:CD-1 Rats