Toxicity Studies on Agents GB and GD (Phase 2): Delayed Neuropathy Study ofSarin, Type I, in SPF White Leghorn Chickens. Appendices I-X

摘要

A two-phase range finding study and a 90-Day Subchronic study were conducted inCD rats using the organophosphate ester Soman (Agent GB). 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 (70 micrograms GD/kg/day), MTD/2 (35 micrograms GD/kg/day), MTD/4 (17.5 microgram GD/kg/day), and a vehicle control (O micrograms GD/kg/day). Forty-eight male and forty-eight female CD rats were randomly allocated at 1-12 weeks of age into four treatment groups (1 2/sex/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 rats were bled (6 rats/sex/dose) during weeks -1, 1, 3, 7, and at necropsy. Necropsy examination was performed of 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.