title: Toxicologic characterization of a novel explosive, guanidinium 3,4-dinitropyrazolate (GDNP), in female rats and Ames mutagenicity assay.
abstract: Sustainable use of military training ranges requires the development of compounds that have a minimal impact to the environment when used in a weapon system. Guanidinium 3,4-dinitropyrazolate (GDNP) is a novel explosive compound of interest for application in some weapon systems. Little is known of its toxicologic properties. To ensure the health of potentially exposed personnel and the environment, initial toxicity investigations were conducted and the results were compared with another widely used energetic (hexahydro-1,3,5-trinitro-1,3,5-triazine [RDX]). In a microplate Ames assay, GDNP was not cytotoxic to bacterial tester strains at concentrations less than 100 μg/mL. However, GDNP was mutagenic to 4 of 5 bacterial strains with and without S9 metabolic incubation at concentrations as low as 0.7 μg/mL. Unlike RDX, GDNP did not have an affinity for the γ-aminobutyric acid(A) receptor convulsant site and was predicted to not induce seizure. After acute oral dosing in female rats, the median lethal dose in female rats of GDNP in tap water solution was determined to be 720 mg/kg. Daily oral exposure to 500 mg/kg per d of GDNP for 14 days caused weight loss, increased liver and spleen weights, and adverse histopathologic events in kidney and spleen. These adverse events were not observed in animals receiving lower doses of GDNP. In this study, the lowest-observed-adverse-effect-level from oral exposure to GDNP for 14 days was 500 mg/kg per d and the no-observable-adverse-effect-level was 152 mg/kg per d.
authors.affiliation: Army Institute of Public Health, US Army Public Health Command, Portfolio of Toxicology, Health Effects Research Program (MCHB-IP-THE), 5158 Blackhawk Rd., Aberdeen Proving Ground, MD 21010-5403, USA. USAPHCTOXINFO@amedd.army.mil
authors.forename: Larry R
authors.initials: LR
authors.lastname: Williams
authors.forename: Valerie H
authors.initials: VH
authors.lastname: Adams
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallace
authors.forename: Mark S
authors.initials: MS
authors.lastname: Johnson
mesh_terms: D000818:Animals; D053834:Explosive Agents / Q000633:toxicity*; D005260:Female; D006146:Guanidines / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011720:Pyrazoles / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013154:Spleen / Q000187:drug effects / Q000473:pathology
chemical_list: D053834:Explosive Agents; D006146:Guanidines; D009153:Mutagens; D011720:Pyrazoles; C578598:guanidinium 3,4-dinitropyrazolate