Dose- (and time-) dependent blockade of pregnancy in Sprague-Dawley rats administered ammonium dinitramide in drinking water.
Ammonium dinitramide (ADN) is a class 1.1 explosive oxidizer that can be used in solid rocket propellant mixtures and explosives. A 90-day general toxicity/ reproductive screen performed on this compound at doses of 162, 103, 29, and 0.0 mg ADN/kg/day resulted in a treatment-related adverse effect on litter production. Incidences of animals producing litters (1/11, 3/12, 12/12, and 11/12, respectively) and mean numbers of pups per litter (7, 7, 16, and 15, respectively) both were statistically significantly less than controls. In a follow-up study, mated dams treated with ADN at the same doses and examined at gestation days (GDs) 10 and 20 showed an effect in fetus loss similar to that seen in the reproductive screen. A pre- versus postimplantation dosing regimen indicated that implantation is vulnerable to ADN effects during the preimplantation period (GDs 1-3). No implantation sites were found in the rats treated with 2000 mg ADN/L drinking water (target dose of 160 mg ADN/kg/day) during GDs 1-3. Numbers of implantation sites found in the rats treated during GDs 4-8 were similar to those found in the control group. The pituitary was not identified specifically in this study as the site of primary action, but serum progesterone was reduced by 27%, which may have resulted in reduced fertility.
Kinkead
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Man Tech Environmental Technology, Inc., Dayton, OH 45437-0009, USA.
Wolfe
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Feldmann
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D000284:Administration, Oral; D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D015386:Hazardous Substances / Q000633:toxicity*; D008297:Male; D009573:Nitrites / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015386:Hazardous Substances; D009573:Nitrites; D000644:Quaternary Ammonium Compounds; C098609:ammonium dinitramide