title: Peri-pubertal administration of 3-nitro-1,2,4-triazol-5-one (NTO) affects reproductive organ development in male but not female Sprague Dawley rats.
abstract: Nitrotriazolone (3-nitro-1,2,4-triazol-5-one; NTO) is an insensitive munition that has demonstrated effects on reproductive organs in adult male rats. NTO was administered to male (0, 250, and 500milligrams per kilogram per day (mg/kg-day)) and female (0, 500, and 1000mg/kg-day) Sprague-Dawley rats (15/sex/group) via oral gavage from weaning through post-natal day 53/54 and 42/43, respectively. Age and body mass at vaginal opening (VO) and preputial separation (PPS), as well as all measures of estrous cyclicity were not affected by treatment with NTO. Males treated with NTO exhibited reductions in testis mass associated with tubular degeneration/atrophy. Less pronounced reductions in accessory sex organ masses were also observed in the 500mg/kg-day group. Treatment with NTO did not affect thyroid hormone or testosterone levels. These findings suggest that NTO is not acting as an estrogen or thyroid active compound, but may indicate effects on steroidogenesis and/or direct testicular toxicity.
authors.affiliation: Army Institute of Public Health, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010, USA. Electronic address: emily.m.lent.civ@mail.mil.
authors.forename: Emily May
authors.initials: EM
authors.lastname: Lent
authors.affiliation: Army Institute of Public Health, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010, USA. Electronic address: lee.crouse.civ@mail.mil.
authors.forename: Lee C B
authors.initials: LC
authors.lastname: Crouse
authors.affiliation: Army Institute of Public Health, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010, USA. Electronic address: shannon.m.wallace.mil@mail.mil.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallace
authors.affiliation: Army Institute of Public Health, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010, USA. Electronic address: erica.e.carroll.mil@mail.mil.
authors.forename: Erica E
authors.initials: EE
authors.lastname: Carroll
mesh_terms: D000818:Animals; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005837:Genitalia, Male / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000254:growth & development; D008297:Male; D009574:Nitro Compounds / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012098:Reproduction; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood; D014230:Triazoles / Q000633:toxicity*; D014621:Vagina / Q000187:drug effects / Q000254:growth & development
chemical_list: C505897:3-nitro-1,2,4-triazol-5-one; D009574:Nitro Compounds; D013963:Thyroid Hormones; D014230:Triazoles; D013739:Testosterone
keywords: Endocrine disruption; NTO; Nitrotriazolone; Reproductive development; Steroidogenesis; Testicular toxicity; Testosterone; Toxicology