New insensitive munitions are being developed to minimize the acute hazards associated with non-intentional detonation of warheads. Two components often used in munition formulations have limited toxicity data, i.e., 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4-dinitroanisole (DNAN). Oral acute, subacute, and subchronic studies have recently been completed. The primary adverse effect from subchronic oral NTO exposure was hypospermia, which followed a dose-dependent trend. Effects from DNAN exposure include reduced body weight, anemia, and neurotoxicity. Occupational exposure levels (OEL) have recently been developed for NTO and DNAN. However, other concerns regarding environmental issues have been raised. Herein we present the latest toxicity data and interpretations for NTO and DNAN as well as the third component of IMX-101, nitroguanidine (NQ), and describe a process to assist with holistic environmental, safety, and occupational health assessment for sustained production and use.