Effects of Ammonium Dinitramide on Preimplantation Embryos in Sprague- Dawley Rats and B6C3Fl Mice

摘要

The Department of Defense is considering replacing ammonium perchlorate (AP) with ammonium dinitramide (ADN) in rocket propellants and explosives. Previous studies performed at the Toxicology Division have shown that ADN is a female reproductive toxicant, causing implantation failure in Sprague-Dawley rats when administered during the preimplantation period of gestation. The purpose of this follow-up study was to identify the mechanism(s) associated with implantation failure following exposure to ADN. In Phase I, mated female rats were treated with 2.0 grams/liter (g/L) ADN in their drinking water for 24, 48, 72, or 96 hours before preimplantation embryos were harvested from the oviducts or uterine horns. On gestation day (GD) 1, comparable numbers of morphologically normal 2-cell embryos were harvested from the oviducts of the treatment and control groups. On GD-2, the development of the embryos harvested from the treated animals was either slowed or halted when compared to the control embryos. By GD-4, 98% of the embryos harvested from the control group had developed to the morula or blastocyst stage; these were collected from the uterine horns. On GD-4 in the treated group, 41 % of the harvested embryos remained at the 2- to 6-cell stage and 59% were degenerate; 82% of these embryos were collected from the oviducts. In Phase II, 2-cell embryos were harvested from the oviducts of superovulated mated B6C3Fl mice. The embryos were cultured for 72 hours in medium supplemented with 0 mM, 1 mM, 4 mM, 6 mM, 10 mM, or 20 mM ADN. The development of embryos in vitro was affected by ADN in all dose groups when compared to the control group. Culture in medium containing > 1 mM ADN either slowed or arrested development of the embryos.