Abstract |
A range-finding evaluation (T.P.S. Study 380B) was conducted on 7 groups (2/sex/group) of CD-1 mice to determine dose levels for the acute intraperitoneal toxicity evaluation (T.P.S. Study 380D). Following this, TPPA was administered in a dimethyl sulfoxide (DMSO) vehicle by interparitoneal injection at dose levels range from 4.5 to 8.0 g/kg body weight to 5 male and 5 female mice per group that were fasted overnight prior to dosing. The animals were observed for at least 4 hours after dosing and twice daily for 14 days for signs of toxicity or mortality. Body weights were recorded prior to dosing, weekly thereafter, and at the time of death. All mice (T.P.S. Study 380D), whether dying during the test or by terminal sacrifice, were subjected to gross necropsy examination to determine, if possible, any organs or systems affected. Clinical signs following acute dosing included unkempt appearance, soft stool, hyperactivity, yellow staining of the perineum and sunken sides while walking. All surviving mice gained or maintained weight during the study. Gross necropsy findings were limited to one mouse with red, friable small intestines and a hard white material in the abdominal cavity of many of the TPPA treated mice. This white material was presumed to be undissolved test material accompanied by an inflammatory reaction. The LD50 value was calculated to be 6.9 g/kg with 95% confidence limits of 5.0 to 9.6 g/kg. |