Toxicity Studies on Agents GB and GD (Phase 2): 90-Day Subchronic Study of GB(Sarin, Type I) in CD-Rats

摘要

A two-phase Dose Range finding study and a 90-Day Subchronic study were conductedin CD rats using the organophosphate ester Sarin (Agent GB, Type I, CAS Number 107-44-8). The highest dose level without lethality in the second phase of the range finding study was designated the maximum tolerated dose (MTD). The doses selected for the subchronic study were the MTD (300 micron GBI/Kg/day), MTD/2 (150, micron GBI/Kg/day), MTD/4 (75 micron GBI/Kg/day), and a vehicle control (O micron /Kg/day). Forty-eight male and forty-eight female CD rats were randomly allocated at 11-12 weeks of age into four treatment groups (12 per sex per group). The animals were gavaged Monday through Friday for 13 weeks and euthanized with carbon dioxide at the beginning of the fourteenth week. Animals were observed daily for clinical signs of toxicity and were weighed weekly. The rats were bled (6 rats/sex/dose) during weeks -1, 1, 3, 7, and at necropsy. Necropsy examination was performed on all animals. Microscopic evaluation was performed on all high-dose and control animals, and on those tissues of lower dose animals that were abnormal at necropsy. All gross lesions and all animals dying or removed early received histological examination. A cause of death or morbidity for animals removed before the end of the study, determined from histopathological examination, was established in four of the eight cases. There were several statistically significant effects in the clinical chemistry and hematology data. These effects were scattered among the treatment groups and were not numerous enough to develop a pattern of organ toxicity.