2,4-Dinitroanisole (DNAN) (2014)

2,4-dinitroanisole (DNAN) is a warhead explosive currently under investigation as a replacement for TNT in melt-cast insensitive munitions. In animal studies, DNAN is a mild ocular and skin irritant with a significant potential for dermal absorption. It is not a dermal sensitizer. Acute and subacute rat inhalation studies demonstrated minimal toxicity with LC50 and LOAEL endpoints of 2.9 and 150 mg/m(3), respectively. In rat oral toxicity studies (14 and 90 days) organ weight and clinical chemistry changes suggested hepatocellular injury and anemia, particularly in females. In males there was evidence of testicular injury at the high-dose level (80 mg/kg/day). The NOAELs for the 14- and 90-day studies were 25 and 5 mg/kg/day, respectively, with a calculated BMDL10 value of 0.93 mg/kg/day. No chronic, carcinogenicity or reproductive/developmental toxicity data were available for DNAN, but a maternal and fetal NOAEL of 5.1 mg/kg/day was inferred. DNAN is considered non-mutagenic and non-genotoxic. It is metabolized in vivo to 2,4-dinitrophenol (DNP), but other details of its metabolism or pharmacokinetics are unknown. There are considerable toxicity data for DNP, a known un-coupler of oxidative phosphorylation among other things, and these data may further inform regarding the safety of DNAN. In humans, DNAN was a component of louse powder (prior to DDT) with no reported safety concerns. However, its handling and use as a munition component presents a potential occupational hazard by both inhalation and dermal routes of exposure. Considering both DNAN and DNP toxicity endpoints, the recommended Workplace Environmental Exposure limit for DNAN is 0.1 mg/m(2) (8-h time weighted average).