Thirteen week toxicity study of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in fischer 344 rats

Levine, Barry; Furedi, E M; Gordon, Donovan E.; Burns, John; Lish, Paul M.

doi:10.1016/0378-4274(81)90108-9

Cited by 31 publications

(20 citation statements)

References 7 publications

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“…It has been well known for some time that RDX exposure causes adverse central nervous system (CNS) syndromes, including convulsion, epileptic seizure, and loss of reflexes in human and experimental animals (Burdette et al 1988; Goldberg et al 1992; Levine et al 1981; Pan et al 2007; Testud et al 1996). However, the molecular mechanism of RDX-induced neurotoxicity is unknown.…”

Section: Discussionmentioning

confidence: 99%

RDX Induces Aberrant Expression of MicroRNAs in Mouse Brain and Liver

Zhang

Pan

2009

Environ Health Perspect

132

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BackgroundAlthough microRNAs (miRNAs) have been found to play an important role in many biological and metabolic processes, their functions in animal response to environmental toxicant exposure are largely unknown.ObjectivesWe used hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a common environmental contaminant, as a toxicant stressor to investigate toxicant-induced changes in miRNA expression in B6C3F1 mice and the potential mechanism of RDX-induced toxic action.MethodsB6C3F1 mice were fed diets with or without 5 mg/kg RDX for 28 days. After the feeding trials, we isolated RNAs from both brain and liver tissues and analyzed the expression profiles of 567 known mouse miRNAs using microarray and quantitative real-time polymerase chain reaction technologies.ResultsRDX exposure induced significant changes in miRNA expression profiles. A total of 113 miRNAs, belonging to 75 families, showed significantly altered expression patterns after RDX exposure. Of the 113 miRNAs, 10 were significantly up-regulated and 3 were significantly down-regulated (p < 0.01) in both mouse brain and liver. Many miRNAs had tissue-specific responses to RDX exposure. Specifically, expression of seven miRNAs was up-regulated in the brain but down-regulated in the liver or up-regulated in the liver but down-regulated in the brain (p < 0.01). Many aberrantly expressed miRNAs were related to various cancers, toxicant-metabolizing enzymes, and neurotoxicity. We found a significant up-regulation of oncogenic miRNAs and a significant down-regulation of tumor-suppressing miRNAs, which included let-7, miR-17-92, miR-10b, miR-15, miR-16, miR-26, and miR-181.ConclusionsEnvironmental toxicant exposure alters the expression of a suite of miRNAs.

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Section: Discussionmentioning

confidence: 99%

RDX Induces Aberrant Expression of MicroRNAs in Mouse Brain and Liver

Zhang

Pan

2009

Environ Health Perspect

132

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“…The toxic effects of RDX exposure in laboratory mammals via the oral route have been well documented [9][10][11][12][13][14]. Reported acute toxic effects range from central nervous system-related clonic/tonic convulsions and hyperactivity to congestion of the liver, lung, and kidney.…”

Section: Introductionmentioning

confidence: 99%

“…Reported acute toxic effects range from central nervous system-related clonic/tonic convulsions and hyperactivity to congestion of the liver, lung, and kidney. Levine et al [11,12] exposed F344 rats to oral RDX exposures of up to 600 mg/kg/d for 90 d. Hyperactivity and convulsions followed by death were reported in some rats exposed to 600 mg/kg/d. Levine et al [11,12] exposed F344 rats to oral RDX exposures of up to 600 mg/kg/d for 90 d. Hyperactivity and convulsions followed by death were reported in some rats exposed to 600 mg/kg/d.…”

Section: Introductionmentioning

confidence: 99%

Dietary oral exposure to 1,3,5‐trinitro‐1,3,5‐triazine in the northern bobwhite (Colinus virginianus)

Gogal

Johnson

Larsen

et al. 2003

Enviro Toxic and Chemistry

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The potential risk to wildlife from exposure to explosives, including 1,3,5-trinitro-1,3,5-triazine (RDX), has been an issue at numerous U.S. military installations where these substances are found in soil and water. Presently, no data describing the effects of RDX exposure in avian species exist. Therefore, an acute lethal dose (ALD) and 14- and 90-d subchronic dietary exposures to RDX were evaluated in a species potentially present at many contaminated sites, i.e., the northern bobwhite (Colinus virginianus). The ALDs for females and males were 187 and 280 mg/kg, respectively. Data from the 14-d dietary trial suggested that RDX exposure inhibited food consumption, weight gain, and egg production. Dietary RDX exposure for 90-d produced a dose-dependant decreasing trend in total feed consumption, total egg production, and hen-housed production parameters. These collective data suggest that quail may respond differently to oral RDX exposure compared with mammals.

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“…In fact, RDX occasionally has been used as a rat poison [11]. Subchronic toxicity studies using Fischer 344 rats receiving daily doses of 100 mg RDX/kg body weight for 90 d showed that RDX can cause lethality, specific organ toxicities, and neurological effects [12]. Acute oral toxicity studies showed that the RDX metabolite hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) caused 100% lethality at 400 mg/kg in gavaged Sprague-Dawley rats [13].…”

Section: Introductionmentioning

confidence: 99%

Accumulation of hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine by the earthworm Eisenia andrei in a sandy loam soil

Sarrazin

Dodard

Savard

et al. 2009

Enviro Toxic and Chemistry

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The heterocyclic polynitramine hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (RDX) is a highly energetic compound found as a soil contaminant at some defense installations. Although RDX is not lethal to soil invertebrates at concentrations up to 10,000 mg/kg, it decreases earthworm cocoon formation and juvenile production at environmentally relevant concentrations found at contaminated sites. Very little is known about the uptake of RDX in earthworms and the potential risks for food‐chain transfer of RDX in the environment. Toxicokinetic studies were conducted to quantify the bioaccumulation factors (BAFs) using adult earthworms (Eisenia andrei) exposed for up to 14 d to sublethal concentrations of nonlabeled RDX or [14C]RDX in a Sassafras sandy loam soil. High‐performance liquid chromatography of acetonitrile extracts of tissue and soil samples indicated that nonlabeled RDX can be accumulated by the earthworm in a concentration‐ and time‐dependent manner. The BAF, expressed as the earthworm tissue to soil concentration ratio, decreased from 6.7 to 0.1 when the nominal soil RDX concentrations were increased from 1 to 10,000 mg/kg. Tissue concentrations were comparable in earthworms exposed to nonlabeled RDX or [14C]RDX. The RDX bioaccumulation also was estimated using the kinetically derived model (BAFK), based on the ratio of the uptake to elimination rate constants. The established BAFK of 3.6 for [14C]RDX uptake was consistent with the results for nonlabeled RDX. Radioactivity also was present in the tissue residues of [14C]RDX‐exposed earthworms following acetonitrile extraction, suggesting the formation of nonextractable [14C]RDX metabolites associated with tissue macromolecules. These findings demonstrated a net accumulation of RDX in the earthworm and the potential for food‐chain transfer of RDX to higher‐trophic‐level receptors.

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Thirteen week toxicity study of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in fischer 344 rats

Cited by 31 publications

References 7 publications

RDX Induces Aberrant Expression of MicroRNAs in Mouse Brain and Liver

RDX Induces Aberrant Expression of MicroRNAs in Mouse Brain and Liver

Dietary oral exposure to 1,3,5‐trinitro‐1,3,5‐triazine in the northern bobwhite (Colinus virginianus)

Accumulation of hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine by the earthworm Eisenia andrei in a sandy loam soil

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