DEVELOPMENTAL TOXICITY OF SARIN IN RATS AND RABBITS

Sarin (Agent GB, isopropyl methylphosphonofluoridate) is an organophos phate cholinesterase inhibitor. Sarin (Type I or Type II) was administ ered by gavage to CD rats on d 6-15 of gestation at dose levels of 0, 100, 240, or 380 mu g/kg/d and to New Zealand White (NZW) rabbits on d 6-19 of gestation at dose levels of 0, 5, 10, or 15 mu g/kg/d. Female s were weighed on gestational days (GD) 0, 6-16 for rats and 6-20 for rabbits, and immediately prior to termination (GD 20 for rats and GD 2 9 for rabbits). All animals were monitored daily for clinical signs of toxicity throughout dosing and until sacrifice. At necropsy, gravid u teri were weighed and examined for the number and status of implants ( live, resorbed, or dead). Individual fetal body weight, malformations, and variations (external, visceral, and skeletal) were recorded. Rat and rabbit dams in the high-dose groups exhibited significant signs of maternal toxicity and increased maternal mortality. Examination of gr avid uteri revealed no statistical differences among treatment groups in the incidence of resorptions or of dead or malformed fetuses, or in average body weight of live fetuses per litter. These results show no evidence of developmental toxicity in the CD rat or NZW rabbit follow ing exposure to either Type I or Type II sarin during embryonic differ entiation and major organogenesis, even at a dose that produced matern al toxicity.