title: Assessment of 3-nitro-1,2,4-triazol-5-one as a potential endocrine disrupting chemical in rats using the Hershberger and uterotrophic bioassays.
abstract: 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.
authors.affiliation: US Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, Aberdeen, MD, USA michael.james.quinn@us.army.mil.
authors.forename: M J
authors.initials: MJ
authors.lastname: Quinn
authors.affiliation: US Army Public Health Command, Aberdeen Proving Ground, Aberdeen, MD, USA.
authors.forename: D I
authors.initials: DI
authors.lastname: Bannon
authors.affiliation: US Army Public Health Command, Aberdeen Proving Ground, Aberdeen, MD, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Jackovitz
authors.affiliation: US Army Public Health Command, Aberdeen Proving Ground, Aberdeen, MD, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Hanna
authors.affiliation: US Army Public Health Command, Aberdeen Proving Ground, Aberdeen, MD, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Shiflett
authors.affiliation: US Army Public Health Command, Aberdeen Proving Ground, Aberdeen, MD, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Johnson
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000494:pharmacology; D053834:Explosive Agents / Q000633:toxicity*; D005260:Female; D005835:Genitalia / Q000187:drug effects / Q000254:growth & development; D008297:Male; D009574:Nitro Compounds / Q000633:toxicity*; D009919:Orchiectomy; D009929:Organ Size; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects*; D014230:Triazoles / Q000633:toxicity*; D014599:Uterus / Q000187:drug effects*
chemical_list: C505897:3-nitro-1,2,4-triazol-5-one; D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D004965:Estrogen Antagonists; D053834:Explosive Agents; D009574:Nitro Compounds; D014230:Triazoles
keywords: 3-nitro-1,2,4-triazol-5-one; 932-64-9; Hershberger; endocrine disruption; uterotrophic