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

•Endocrine disruptor screening studies (OPPTS 890.1450/1500) were conducted.•NTO did not affect age or body mass at puberty for male or female rats.•NTO did not affect any measures of estrous cyclicity in female rats.•NTO treated males had reduced testis mass and tubular degeneration/atrophy.•NTO did not affect serum thyroid hormone or serum testosterone levels.

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 500 milligrams per kilogram per day (mg/kg-day)) and female (0, 500, and 1000 mg/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 500 mg/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.