The explosive 3-nitro-1,2,4-triazol-5-one (NTO) is an insensitive formulation developed to replace high energetics that are susceptible to accidental detonation from heat, shock, and impact. Although studies have shown NTO to be nontoxic at acute exposures, recent subacute and subchronic tests have demonstrated effects on testes and subsequent sperm production in rats. This study assessed endocrine disruption as a potential mechanism for these reproductive effects via the Hershberger and uterotrophic bioassays. These assays are 2 of the US Environmental Protection Agency's tier 1 in vivo screens for the Endocrine Disruptor Screening Program that measure differences in androgen- and estrogen-sensitive tissue weights in castrated and ovariectomized rats. The gonadectomized rats were orally exposed to NTO in a corn oil vehicle at doses of 250, 500, or 1000 mg/kg body weight (bw)/d for 10 and 3 days for the Hershberger and uterotrophic assays, respectively, according to standard protocols. Male rats also received testosterone (0.2 mg/kg/d, subcutaneous) and antiandrogenic flutamide (3mg/kg/d, oral) as negative and positive controls, and females received 17 α-ethynyl estradiol (0.3 µg/d, subcutaneous) as positive controls. 3-Nitro-1,2,4-triazol-5-one caused neither a decrease in androgen-sensitive male reproductive selected tissue (seminal vesicles with fluid/without fluid, glans penis, Cowper gland, ventral prostrate, and levator ani-bulbocavernosus) weights nor a change in uterine weights. The results of this study provide no evidence to suggest that NTO acts like an estrogenic or antiandrogenic endocrine disruptor in rats at these doses.

The purpose of this study was to assess the toxicological effects of two munition compounds, 4-amino-2,6-dinitrotoluene (4A-DNT) and 1,3,5-trinitro-1,3,5-triazine (RDX), on three different bird species: two common toxicological model species-the Northern Bobwhite (Colinus virginianus) and the Japanese Quail (Coturnix japonica), and a representative passerine-the Zebra Finch (Taeniopygia guttata). Bobwhite were exposed to 4A-DNT at 0, 8, 15, 30, 60, or 150 mg/kg body weight (bw) d by oral gavage for seven days; because the high dose of 4A-DNT was lethal to bobwhite, the maximum dose was changed to 100 mg/kg bw d for Japanese quail and finches to ensure tissue could be used for future toxicogenomic work. RDX was similarly administered at 0, 0.5, 1.5, 3, 6, or 12 mg/kg bw d. Blood was drawn prior to euthanasia for blood cellularity and chemistry analyses. Finches were clearly least affected by 4A-DNT as evidenced by a lack of observable effects. Bobwhite appeared to be the most sensitive species to 4A-DNT as observed through changes in blood cellularity and plasma chemistry effects. Bobwhite appeared to be more sensitive to RDX than Japanese Quail due to increased effects on measures of plasma chemistries. Finches exhibited the greatest sensitivity to RDX through increased mortality and seizure activity. This study suggests that sensitivity among species is chemical-specific and provides data that could be used to refine current avian sensitivity models used in ecological risk assessments.