Toxic effects of oral hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine in the western fence lizard (Sceloporus occidentalis)

Abstract

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been widely used as an explosive in munition formulations, resulting in contamination of wildlife habitat on military installations. To estimate health effects for reptilian species, acute, subacute, and subchronic oral toxicity studies were conducted using the Western fence lizard (Sceloporus occidentalis). Estimated oral median lethal doses were 72 (95% confidence interval [CI], 49-106) mg/kg body weight (slope, 3.754) for males and 88 (95% CI, 65-119) mg/kg (slope, 4.525) for females. Toxicity from RDX suggested the neurological system as the critical target tissue. A 14-d subacute study followed with males dosed orally with RDX (corn oil) at 0, 10, 20, 25, 30, 45, and 60 mg/kg/d. Signs of toxicity frequently included a characteristic body posture. A significant dose-survival relationship was seen over the range of doses, with a significant decrease in survival at 20 mg/kg/d. Males in the 60-d subchronic study were dosed at 0, 1, 2.5, 5, 8, and 11 mg/kg/d, and signs of toxicity included lethargy, cachexia, and anorexia. Survival was decreased at 8 and 11 mg/kg/d. Reduced growth rate and food consumption occurred at 5 mg/kg/d. Brain tissue was assayed for RDX when seizures were observed at a residue concentration of at least 18 microg/g. No abnormalities were observed in the hematologic indices, whereas plasma proteins were reduced. Hepatic enlargement and decreased testes mass occurred at 8 and 11 mg/kg/d. Plasma testosterone concentrations, sperm counts, and motility measures were variable for all treatment levels. Based on survival, growth rate, food intake, and testes to brain weight ratios, these data suggest a lowest-observed-adverse effect level of 5 mg/kg/d and a no-observed-adverse effect level of 2.5 mg/kg/d.