Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Red-backed salamanders (Plethodon cinereus) were exposed to four different concentrations of 1,3,5-trinitrohexahydro-1,3,5-triazine (RDX) in soil under controlled laboratory conditions for 28 days. Wild-caught P. cinereus (N = 20/treatment) were exposed to target concentrations of 5,000, 1000, 100, 10, and 0 mg RDX/kg soil (dry wt) using a microcosm design. Animals were fed 5 to 10 uncontaminated mutant Drosophila flies every 3 days and monitored daily. Animals were weighed 1 day before being placed in treatment and weekly thereafter. RDX concentrations in soil were analytically determined after the compound was added and mixed at the beginning, the midpoint, and the end of exposure. RDX soil concentrations were relatively stable throughout the exposure period. Signs of overt toxicity were observed primarily in the highest exposure group. Salamanders exposed to 5,000 mg RDX/kg soil exhibited signs of neuromuscular effects (lethargy, gaping, hypersensitivity, tremors) and exhibited significant weight loss. A single moribund animal from this group lost >20% of its original body weight and was killed. Animals in this exposure group also lost weight relative to animals in other treatments. Histopathologic evaluations, including an evaluation of melanomacrophage parameters, indicated no strong treatment-related findings. This study provided information regarding the effects from subchronic dermal exposure of a terrestrial amphibian species to RDX in soil and provides a microcosm approach to the evaluation of toxicity of contaminants in soil to a terrestrial vertebrate.
 ...
PMID:Toxicologic and histopathologic response of the terrestrial salamander Plethodon cinereus to soil exposures of 1,3,5-trinitrohexahydro-1,3,5-triazine. 1549

Hexahydro-1,3,5-trinitro-1,3,5-triazine, a cyclonitramine commonly known as RDX, is used in the production of military munitions. Contamination of soil, sediment, and ground and surface waters with RDX has been reported in different places around the world. Acute and subacute toxicities of RDX have been relatively well documented in terrestrial vertebrates, but among aquatic vertebrates the information available is limited. The objective of this study was to characterize the acute toxicity of RDX to larval zebrafish. Mortality (LC50) and incidence of vertebral column deformities (EC50) were two of the end points measured in this study. The 96-h LC50 was estimated at 22.98 and 25.64 mgl(-1) in two different tests. The estimated no-observed-effective-concentration (NOEC) values of RDX on lethality were 13.27+/-0.05 and 15.32+/-0.30 mgl(-1); and the lowest-observed-effective-concentration (LOEC) values were 16.52+/-0.05 and 19.09+/-0.23 mgl(-1) in these two tests, respectively. The 96-h EC50 for vertebral deformities on survivors from one of the acute lethality tests was estimated at 20.84 mgl(-1), with NOEC and LOEC of 9.75+/-0.34 and 12.84+/-0.34 mgl(-1), respectively. Behavioral aberrations were also noted in this acute toxicity study, including the occurrence of whirling movement and lethargic behavior. The acute effects of RDX on survival, incidence of deformities, and behavior of larval zebrafish occurred at the high end of the most frequently reported concentrations of RDX in aquatic environments. The chronic effects of RDX in aquatic vertebrates need to be determined for an adequate assessment of the ecological risk of environmental RDX.
 ...
PMID:Toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine to larval zebrafish (Danio rerio). 1616 40

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.
 ...
PMID:Toxic effects of oral hexahydro-1,3,5-trinitro-1,3,5-triazine in the western fence lizard (Sceloporus occidentalis). 1910 80

Munitions constituents (MCs) including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), and TNT derivatives are recognized to elicit aberrant neuromuscular responses in many species. The onset of seizures resulting in death was observed in the avian model Northern bobwhite after oral dosing with RDX beginning at 8 mg/kg/day in subacute (14 days) exposures, whereas affective doses of the TNT derivative, 2,6-dinitrotoluene (2,6-DNT), caused gastrointestinal impacts, lethargy, and emaciation in subacute and subchronic (60 days) exposures. To assess and contrast the potential neurotoxicogenomic effects of these MCs, a Northern bobwhite microarray was developed consisting of 4119 complementary DNA (cDNA) features enriched for differentially-expressed brain transcripts from exposures to RDX and 2,6-DNT. RDX affected hundreds of genes in brain tissue, whereas 2,6-DNT affected few (<or= 17), indicating that 2,6-DNT exposure had relatively little impact on the brain in comparison to RDX. Birds exhibiting RDX-induced seizures accumulated over 20x more RDX in brain tissues in comparison to non-seizing birds even within a common dose. In parallel, expression patterns were unrelated among seizing and non-seizing birds exposed to equivalent RDX doses. In birds experiencing seizures, genes related to neuronal electrophysiology and signal transduction were significantly affected. Comparative toxicology revealed strong similarity in acute exposure effects between RDX and the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) regarding both molecular mechanisms and putative mode of action. In a manner similar to DDT, we hypothesize that RDX elicits seizures by inhibition of neuronal cell repolarization postaction potential leading to heightened neuronal excitability and seizures facilitated by multiple molecular mechanisms.
 ...
PMID:Neurotoxicogenomic investigations to assess mechanisms of action of the munitions constituents RDX and 2,6-DNT in Northern bobwhite (Colinus virginianus). 1941 77