title: Age dependent acute oral toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and two anaerobic N-nitroso metabolites in deer mice (Peromyscus maniculatus).
abstract: Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) transforms anaerobically into N-nitroso compounds: hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX). Exposure to these N-nitroso metabolites may occur in areas contaminated with explosives, as anaerobic degradation occurs via some bacteria and is one remediation strategy used for RDX. Few papers report acute oral toxicity and none have evaluated age dependent toxicity of RDX or its N-nitroso metabolites. Median lethal dose (LD50) was determined in deer mice (Peromyscus maniculatus) of three age classifications 21 d, 50 d, and 200 d for RDX, MNX, and TNX using the US EPA up-and-down procedure (UDP). Hexahydro-1,3,5-trinitro-1,3,5-triazine and N-nitroso metabolites caused similar overt signs of toxicity. Median lethal dose for 21 d deer mice were 136, 181, and 338 mg/kg for RDX, MNX, and TNX, respectively. Median lethal dose for 50 d deer mice were 319, 575, and 338 mg/kg for RDX, MNX, and TNX, respectively. Median lethal dose for 200 d deer mice were 158, 542, and 999 mg/kg for RDX, MNX, and TNX, respectively. These data suggest that RDX is the most potent compound tested, and age dependent toxicity may exist for all compounds and could play a role in RDX and RDX N-nitroso metabolite ecological risk evaluation of terrestrial wildlife at RDX contaminated sites.
authors.affiliation: The Institute of Environmental and Human Health, The Department of Environmental Toxicology, Texas Tech University, Lubbock, TX 79409, USA. jordan.smith@tiehh.ttu.edu
authors.forename: Jordan N
authors.initials: JN
authors.lastname: Smith
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Marina A
authors.initials: MA
authors.lastname: Espino
authors.forename: George P
authors.initials: GP
authors.lastname: Cobb
mesh_terms: D000375:Aging / Q000502:physiology*; D000693:Anaerobiosis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053834:Explosive Agents / Q000633:toxicity*; D006801:Humans; D007928:Lethal Dose 50; D016014:Linear Models; D008297:Male; D009603:Nitroso Compounds / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010542:Peromyscus / Q000502:physiology*; D018570:Risk Assessment; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D014227:Triazines / Q000633:toxicity*
chemical_list: D053834:Explosive Agents; D009603:Nitroso Compounds; D014227:Triazines; C009160:cyclonite