Reproductive Toxicity Screen of Ammonium Dinitramide Administered in the Drinking Water of Sprague-Dawley Rats

The Department of Defense is currently considering replacing ammonium perchlorate with ammonium dinitramide (ADN), a class 1.1 explosive oxidizer to be used in solid rocket propellant mixtures and explosives. This study was intended to evaluate the potential of ADN to produce alterations in paternal fertility, maternal pregnancy and lactation, and growth and development of offspring. Male and female rats received drinking water containing 0.0, 0.2, 1.0, or 2.0 g ADN/liter throughout the study. Mating occurred following 14 days of treatment. All dams, one-half the males, and representative pups were maintained for a total of 90 days of treatment. No mortality occurred in parental animals during the study. Treatment with ADN resulted in no adverse effects on mating; 92-100% of the animals mated. No treatment-related effects were seen in parental animals clinically or histopathologically. Adverse treatment-related effects were noted in maternal and paternal fertility indices, gestational indices, and live birth indices in both the mid- and high-dose groups. Litter sizes in themid- and high-dose groups were significantly smaller than those of the low-dose and control groups. Mean pup weights showed no statistically significant differences between ADN-treated pups and controls. Gross and histopathological examination of the animals failed to identify the cause for the decrease in litter production in the mid- and high-dose dams. This study indicates that ADN is a reproductive toxicant. The no-observable-effect level (NOEL) is 29 mg/kg/day, the median dose of the low-level female rats.

[1]  C. Miller,et al.  General Toxicity and Reproductive Screen of Liquid Propellant Xm46 Administered in the Drinking Water of Sprague-Dawley Rats , 1995, Toxicology and industrial health.

[2]  C. Miller,et al.  Reproductive Toxicity Screen of 1,3,5-Trinitrobenzene Administered in the Diet of Sprague-Dawley Rats , 1994, Toxicology and industrial health.

[3]  E. Kinkead,et al.  Reproductive Toxicity Screen of Liquid Propellant XM46 Administered in the Drinking Water of Sprague-Dawley Rats. , 1994 .

[4]  E. Kinkead,et al.  Range-Finding Study for a Reproductive Assessment of 1,3,5- Trinitrobenzene Administered in the Diet of Sprague-Dawley Rats. , 1994 .

[5]  V. Valli,et al.  CHAPTER 2 – The Hematopoietic System , 1993 .

[6]  C. Sibley,et al.  Effect of maternal hypokalaemia on unidirectional maternofetal and net potassium fluxes across the placenta of the anaesthetized rat. , 1992, Placenta.

[7]  E. Kinkead,et al.  Effects of a 13-Week Chloropentafluorobenzene Inhalation Exposure of Fischer 344 Rats and B6C3F1 Mice , 1991, Toxicology and industrial health.

[8]  L. Strader,et al.  Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats. , 1990, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[9]  T. A. Connors,et al.  Preliminary investigations into the involvement of the intestinal microflora in CNS toxicity induced by 1,3-dinitrobenzene in male F-344 rats. , 1987, Toxicology letters.

[10]  P. M. Lish,et al.  Determination of the Chronic Mammalian Toxicological Effects of TNT (twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Trinitrotoluene (TNT) in the B6C3F1 Hybrid Mouse). Volume 1 , 1984 .

[11]  P. M. Lish,et al.  Subchronic toxicity of trinitrotoluene in Fischer 344 rats. , 1984, Toxicology.

[12]  Robert S. Barcikowski,et al.  Computer Packages and Research Design: With Annotations of Input and Output from the BMDP, SAS, SPSS, and SPSSX Statistical Packages , 1983 .

[13]  J. M. Burns,et al.  Determination of the Chronic Mammalian Toxicological Effects of TNT. Twenty-Six Week Subchronic Oral Toxicity Study of Trinitrotoluene (TNT) in the Beagle Dog. , 1983 .

[14]  E. Baráth,et al.  Fundamentals of Biostatistics. , 1992 .

[15]  Roger L. Black,et al.  Goodman and Gilman's The Pharmacological Basis of Therapeutics , 1991 .

[16]  L. Hastings,et al.  1,3-dinitrobenzene: toxic effects in vivo and in vitro. , 1981, Journal of toxicology and environmental health.

[17]  J. A. Hathaway Trinitrotoluene: a review of reported dose-related effects providing documentation for a workplace standard. , 1977, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[18]  J. A. Hathaway,et al.  Biological effects of trinitrotoluene from exposure below the threshold limit value. , 1976, American Industrial Hygiene Association journal.

[19]  L. Witts,et al.  Some Early Effects of Exposure to Trinitrotoluene. * , 1945 .