Trimethylentrinitramin

Other Uses -> Explosives

Carcinogens

log Kow = 0.87

0.87

0.87

1.82 (NIOSH, 2024) - Denser than water; will sink

1.82 g/cu cm at 20 °C

1.8 g/cm³

1.82

1.82 @25 °C

1.82

White, crystalline powder

White crystalline solid

Orthorhombic crystals from acetone

Insoluble (NIOSH, 2024)

Insoluble in ethanol; slightly soluble in ether

Slightly soluble in ethyl acetate, methanol, glacial acetic acid; practically insoluble in carbon tetrachloride, carbon disulfide

Readily sol in hot aniline, phenol, warm nitric acid.

1 g dissolves in 25 mL acetone

In water, 59.7 mg/L at 25 °C

Explodes (NIOSH, 2024)

Explodes

explodes

Explodes

401 °F (NIOSH, 2024)

205.5 °C

Impure military grades containing about 10% HMX /hexamethylenetetramine, has a melting point of/ about 190 °C.

205.5 °C

401 °F

202 °C

0.0004 mmHg at 230 °F (NIOSH, 2024)

4.10X10-9 mm Hg at 20 °C

negligible

0.0004 mmHg at 230 °F

0.0004 [mm Hg] @110 °C

(230 °F): 0.0004 mmHg

Danger

H201 (97.4%): (Deleted) Explosive; mass explosion hazard [Danger Explosives]

P210, P230, P240, P250, P260, P261, P262, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P308+P316, P316, P319, P321, P330, P332+P317, P361+P364, P362+P364, P370+P380, P372, P373, P401, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 116 reports by companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H201: (Deleted) Explosive; mass explosion hazard [Danger Explosives]

Chemical: 1,3,5-Triazine, hexahydro-1,3,5-trinitro-

Hazard Traits - Carcinogenicity; Neurotoxicity

1,3,5-Triazine, hexahydro-1,3,5-trinitro- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1,3,5-Triazine, hexahydro-1,3,5-trinitro- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 23-09-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/13732

1,3,5-Triazine, hexahydro-1,3,5-trinitro-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Explosive 1.1D

Explosive 1.1D

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

Gives off irritating or toxic fumes (or gases) in a fire. Risk of explosion. Explosive.

Excerpt from NIOSH Pocket Guide for Cyclonite:

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

RDX stands for Royal Demolition eXplosive. It is also known as cyclonite or hexogen. The chemical name for RDX is 1,3,5-trinitro-1,3,5-triazine. It is a white powder and is very explosive. RDX is used as an explosive and is also used in combination with other ingredients in explosives. Its odor and taste are unknown. It is a synthetic product that does not occur naturally in the environment. It creates fumes when it is burned with other substances.

In subchronic feeding studies of dogs (50 mg/kg/day for 6 weeks), one of seven dogs died, and the others had weight loss and seizures. Methemoglobinemia was not reported. Animals in chronic studies show liver injury. Workers have experienced central nervous system effects including seizures after occupational exposure. [ACGIH]

Azo, Diazo, Azido, Hydrazine, and Azide Compounds

Nitro, Nitroso, Nitrate, and Nitrite Compounds, Organic

MILLER KC; TOXICITY AND ADVERSE EFFECTS OF RDX: AN ANNOTATED BIBLIOGRAPHY; (ORNL-TIRC-73-14): 7 PP (1973). AN ANNOTATED BIBLIOGRAPHY & REVIEW OF THE TOXICITY & ADVERSE EFFECTS OF RDX.

Spanggord RJ et al; Environmental fate studies on certain munition wastewater constituents, Phase III, Part 1 - model validation: Project LSU-7934, Menlo Park, CA; SRI Int. (1981).

U.S. Dept Health & Human Services/Agency for Toxic Substances Disease Registry; Toxicological Profile for RDX (1995) NTIS# PB/95/264263

National Technical Information Service (NTIS); Plastic Explosive RDX: Cyclotrimethylenetrinitramine. (Latest Citations from the NTIS Bibliographic database). NTIS/PB95-868170 (1995). This bibliography contains citations concerning the properties and handling of plastic explosive RDX.

Daniels JI, Knezovich JP; Human Health Risks from TNT, RDX and HMX in Environmental Media and Consideration of the US Regulatory Environment. NTIS/DE95009480 (1995). /Information concerning disposal of unwanted energetic high explosives ... including RDX/.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date 9/29/06; Reporting date: 11/28/06.

[40 CFR 716.120] Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,3,5-Triazine, hexahydro-1,3,5-trinitro- is included on this list. Effective date: 9/29/06; Sunset date: 11/28/09.

Explosive

Explosive

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

Use water in large amounts, powder, carbon dioxide. Combat fire from a sheltered position. In case of fire: keep drums, etc., cool by spraying with water.

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Do NOT induce vomiting. Give a slurry of activated charcoal in water to drink. Refer immediately for medical attention.

Excerpt from NIOSH Pocket Guide for Cyclonite:

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

(General first aid procedures)

If material on fire or involved in fire: Dangerously explosive. Do not fight fires in a cargo of explosives. Evacuate area and let burn.

Evacuation: If the material is on fire or involved in fire consider evacuation of one (1) mile radius.

After covering the spills with soda ash, mix, & spray with water. Scoop into a bucket of water and let it stand for 2 hr. Neutralize with 6 molar hydrochloric acid ... .

Wastewater containing RDX (Cyclonite) was treated by adsorption on activated carbon; the carbon was regenerated by ozonization, which oxidizes the absorbed substance.

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The use of ultraviolet-ozone and ultraviolet-oxidant to treat pink water from ammunition plants was evaluated. Dissolved RDX was removed to <1 mg/L with no by products requiring disposal.

The feasibility of treating explosive contaminated wastewater using an oxidant (hydrogen peroxide) in conjunction with short wavelength UV light was evaluated. The process achieves high degree of decontamination without troublesome byproducts.

The feasibility of treating the wastewaters from site X RDX/HMX manufacturing facilities in aerobic rotating biological contactor was evaluated. The results from the pilot-scale evaluation indicate that 95-100% soluble /biological oxygen oxygen (BOD)/ removal can be achieved and maintained at soluble BOD loading rates of <2.5 lb/1000 cu ft/day.

For more Disposal Methods (Complete) data for CYCLONITE (8 total), please visit the HSDB record page.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.

...Floors of sheds and workrooms should be kept scrupulously clean. Special rules about acceptable types of footwear and clothing, and provision of shoe-cleaning mats prevent the bringing of exposed metal fasteners, loose metal and gritty dirt into explosives buildings. ...Smoking and bringing of incendiary equipment into explosive buildings is forbidden. /Explosive substances/

For more Preventive Measures (Complete) data for CYCLONITE (16 total), please visit the HSDB record page.

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

Excerpt from ERG Guide 112 [Explosives - Division 1.1, 1.2, 1.3 or 1.5]:

Following oral exposure, symptomatic patients should be given adequate respiratory support during seizures. Monitor liver and renal function tests and urinalysis in patients with significant exposure. Following inhalation exposure, move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. Following eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. Following dermal exposure, remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. (T36)

In one study TNT and RDX were coadministered in the feed of rats for 13 weeks. This co-administration potentiated the decrease in body weight gain as compared to RDX alone. TNT antagonized the lethal effects and the hypotriglyceridemia induced by RDX. RDX antagonized the hypercholesterolemia, splenomegaly, testicular atrophy, hepatocytomegaly, degeneration of the seminiferous tubules, and pigmentation of renal cortices induced by TNT. Investigated the effects of a mixture of 10% RDX and 0.32% TNT in dogs, rats, and mice. All three species showed depression of body weight gain, depressed food intake, and alterations in the spleen, liver, and testes at the highest dose levels. However, RDX was not tested alone.

Explosive compounds such as TNT and RDX are recalcitrant contaminants often found co-existing in the environment. In order to understand the joint effects of TNT and RDX on earthworms, an important ecological and bioindicator species at the molecular level, we sampled worms (Eisenia fetida) exposed singly or jointly to TNT (50 mg/kg soil) and RDX (30 mg/kg soil) for 28 days and profiled gene expression in an interwoven loop designed microarray experiment using a 4k-cDNA array. Lethality, growth and reproductive endpoints were measured. Sublethal doses of TNT and RDX had no significant effects on the survival and growth of earthworms, but significantly reduced cocoon and juvenile counts. The mixture exhibited more pronounced reproductive toxicity than each single compound, suggesting an additive interaction between the two compounds. In comparison with the controls, we identified 321 differentially expressed transcripts in TNT treated worms, 32 in RDX treated worms, and only 6 in mixture treated worms. Of the 329 unique differentially expressed transcripts, 294 were affected only by TNT, 24 were common to both TNT and RDX treatments, and 3 were common to all treatments. The reduced effects on gene expression in the mixture exposure suggest that RDX might interact in an antagonistic manner with TNT at the gene expression level. The disagreement between gene expression and reproduction results may be attributed to sampling time, absence of known reproduction-related genes, and lack of functional information for many differentially expressed transcripts. A gene potentially related to reproduction (echinonectin) was significantly depressed in TNT or RDX exposed worms and may be linked to reduced fecundity. Sublethal doses of TNT and RDX affected many biological pathways from innate immune response to oogenesis, leading to reduced reproduction without affecting survival and growth. A complex interaction between mixtures of RDX and TNT was observed at the gene expression level that requires further study of the dynamics of gene expression and reproductive activities in E. fetida. These efforts will be essential to gain an understanding of the additive reproductive toxicity between RDX and TNT.

Hematological (Blood Forming), Hepatic (Liver), Neurological (Nervous System)

Nervous

Eyes, skin, central nervous system

LC50; Species: Daphnia magna (Water flea); Conditions: flow through; Concentration: >15 mg/L for 96 hr

LC50; Species: Lepomis macrochirus (Bluegill); Conditions: static, pH 6.0; Concentration: 3.6 mg/L for 96 hr (95% confidence interval: 1.9-6.6 mg/L)

LC50; Species: Lepomis macrochirus (Bluegill); Conditions: static; Concentration: 14 mg/L for 24 hr (95% confidence interval: 12-17 mg/L)

LC50; Species: Lepomis macrochirus (Bluegill); Conditions: static; Concentration: 8.5 mg/L for 48 hr (95% confidence interval: 7.5-9.5 mg/L)

For more Ecotoxicity Values (Complete) data for CYCLONITE (9 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 42-167 measured in sediment(2), indicate that cyclonite is expected to have high to moderate mobility in soil(SRC). Volatilization of cyclonite from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.1X10-11 atm-cu m/mole(SRC), based upon its vapor pressure, 4.1X10-9 mm Hg(2), and water solubility, 59.7 mg/L(3). Cyclonite is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). Cyclonite, at concentrations of 50 or 100 ug/L, was completely removed after 4 days under anaerobic conditions using a sewage sludge inoculum(4). Cyclonite was mineralized by mixed populations of microorganisms under anaerobic conditions when supplemental carbon was provided(2,5); under aerobic conditions, however, when added to 3 different soil samples and incubated for 56 days it was not biodegraded(6).

AQUATIC FATE: Based on a classification scheme(1), Koc values of 42-167 measured in sediment(2), indicate that cyclonite is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.1X10-11 atm-cu m/mole(SRC), derived from its vapor pressure, 4.1X10-9 mm Hg(2), and water solubility, 59.7 mg/L(4). According to a classification scheme(5), BCFs of 0.6 in sheepshead minnows(6) to 11 in fathead minnows(7), suggest the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis should not be an important fate process in fresh waters, although cyclonite was hydrolyzed in sea water with 11.6% loss after 112 days(8). In water, the dominant fate of cyclonite is expected to be direct photochemical degradation by sunlight; experimental half-lives of a few weeks are reported in translucent waters(2). Cyclonite was mineralized by mixed populations of microorganisms under anaerobic conditions in systems such as groundwater, lakes and other shallow waters when supplemental carbon was provided(2,9-10); under aerobic conditions, however, biodegradation proceeds very slowly(11).

AQUATIC FATE: In an ecosystem study using sediment, characteristic aquatic vegetation, and cyclonite contaminated groundwater from the Milan Ammunition Plant in Milan, TN, the initial cyclonite concentration in groundwater was 1,529 ug/L. Following a 13-day incubation of sediment, autoclaved-sediment, gravel, and autoclaved gravel concentrations of cyclonite were 1,443, 2,606, 3,120, and 2,583 ug/L, respectively(1). Half-lives of 1853 and 771 hours were reported for freshwater/sediment studies using sediments from Brown's lake and University Lake(2).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cyclonite, which has an extrapolated vapor pressure of 4.1X10-9 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase cyclonite may be removed from the air by wet or dry deposition(SRC). Direct photochemical degradation of cyclonite on aerosols may also be an important fate process(2).

The substance can be absorbed into the body in hazardous amounts by inhalation and by ingestion.

inhalation, skin absorption, ingestion, skin and/or eye contact

Oral (L259); inhalation (L259) ; dermal (L259)

RDX can get into the lungs after breathing in the fumes of burning RDX or breathing in the dust from powdered RDX. It can also enter the body after ingestion of contaminated water. It may also pass through the skin into the bloodstream or enter through cuts or breaks in the skin. It also blocks electron transport. (T10, L259)

/BIRDS and MAMMALS/ ...An acute lethal dose (ALD) and 14- and 90-day 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-day dietary trial suggested that RDX exposure inhibited food consumption, weight gain, and egg production. Dietary RDX exposure for 90-days produced a dose-dependant decreasing trend in total feed consumption, total egg production, and hen-housed production parameters.

/BIRDS and MAMMALS/ 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.

/BIRDS and MAMMALS/ Northern bobwhite (Colinus virginianus) were orally exposed via gavage to 0, 0.5, 3, 8, 12, or 17 mg/kg of RDX (1,3,5-trinitro-1,3,5-triazine) in corn oil daily for 14 days to evaluate sublethal effects of this explosive in birds. Mortality occurred at a rates of 100, 67, and 25% for the 17, 12, and 8 mg/kg/day dose groups, respectively. Death was preceded by clonic and tonic convulsions and weight loss caused by gastrointestinal effects. Increases in serum globulin and total leukocytes were observed in the two highest-dose groups. Degeneration of testicular and splenic tissue also was observed. The no-observed-adverse-effects and lowest-observed-adverse-effects levels were determined as 3.0 and 8.0 mg/kg/day, respectively.

/BIRDS and MAMMALS/ Military activities associated with training have resulted in soil residues of munition compounds and their breakdown products. Often, these areas are valuable habitats used by birds. To evaluate the possibility of adverse effects in birds, the effects from oral exposures of 2,6-dinitrotoluene (2,6-DNT) and 1,3,5-trinitro-1,3,5-triazine (RDX) were tested using a controlled dosing regime in northern bobwhite (Colinus virginianus). Nine groups of birds of mixed sex received either corn oil or 50, 100, 190, or 350 mg 2,6-DNT/kg body weight/day or 20, 80, 125, or 180 mg RDX/kg body weight/day mixed in corn oil via gavage for 14 day. Etiology of disease was markedly different between compounds. Increased RDX exposure caused an inverse relationship to time of death, symptoms including clonic followed by tonic convulsions, and death shortly thereafter. Brain concentrations of RDX postmortem, however, were relatively consistent (mean +/- standard error, 20.5 +/- 2.9 mg/kg tissue). Observations of 2,6-DNT effects included gastrointestinal distress, dehydration, and a reduction in body mass and feed consumption. Together, these data suggest that RDX is more toxic from short, repeated exposures than 2,6-DNT, resulting in central nervous system-related effects, whereas 2,6-DNT causes gastrointestinal disturbances at higher exposures.

For more Ecotoxicity Excerpts (Complete) data for CYCLONITE (24 total), please visit the HSDB record page.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date 9/29/06; Reporting date: 11/28/06.

[40 CFR 716.120] Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,3,5-Triazine, hexahydro-1,3,5-trinitro- is included on this list. Effective date: 9/29/06; Sunset date: 11/28/09.

Hexolite

A Commercial Grade

5000

A Commercial Grade

400

Explosive chemical that can be released at a facility.

(FL) FLORIDA 10 ug/L

(ME) MAINE 3 ug/L

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, RDX /may/ elicits seizures by inhibition of neuronal cell repolarization postaction potential leading to heightened neuronal excitability and seizures facilitated by multiple molecular mechanisms.

Arabidopsis thaliana root transcriptome responses to the munition, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), were assessed using serial analysis of gene expression (SAGE). Sequencing of SAGE libraries from control and RDX-exposed root tissues revealed induction of genes known to respond to a variety of general stresses. Among the highly induced genes were several encoding molecular chaperones and transcription factors as well as vacuolar proteins and peroxidases. Strongly repressed transcripts included ones encoding ribosomal proteins, a cyclophilin, a katanin, and a peroxidase. Comparison of the transcriptional profile for the RDX response to a profile previously described for Arabidopsis roots exposed to trinitrotoluene (TNT) revealed significant differences in the inferred gene expression patterns. This suggests that Arabidopsis employs drastically different mechanisms for coping with these two compounds. With respect to the goal of engineering plants to better tolerate and degrade explosives at contaminated sites, these results suggest that enhancement of different genes and metabolic pathways may be required to deal effectively with each type of explosive. This has ramifications for phytoremediation efforts since many contaminated sites harbor both compounds.

Hexahydro-1,3,5-trinitro-1,3,5-triazine is a synthetic, high-impact, relatively stable compound commonly known as Rapid Detonation Explosive (RDX) ...Though several studies have correlated measurements of RDX in the brains and plasma of dosed animals with frank seizures, little work has been carried out on the effects of RDX at the molecular level. In this study, we examined the impact of a single orally administered RDX dose on the brain, using a combination of analytical chemistry and gene chip microarrays. At nominal doses of 3 and 18 mg/kg in male adult rats, a time course of RDX tissue levels showed peak brain concentrations at 3.5 hours, returning to baseline at 24 and 48 hours, respectively. RNA from dosed and control animals was hybridized to Affymetrix Rat 230 2.0 arrays. Analysis was performed in JMP Genomics with the differentially expressed gene cut-off at p>0.001. /The study/ found sets of genes that were early and late responders to RDX treatment. In addition, pathway analysis indicated effects on the nervous system, cell-to-cell signalling, and cell development, among other...

The extensively used military explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been widely released to the environment during production, usage, and disposal operations. Toxic effects of RDX have been reported in terrestrial and aquatic receptors, but investigations regarding the bioaccumulation potential of RDX in aquatic systems are scarce. The objective of the present study was to describe the toxicokinetics of RDX during aqueous exposure for the channel catfish (Ictalurus punctatus) and aquatic oligochaetes (Lumbriculus variegatus) and to compare the amount of RDX accumulation in juvenile catfish following aqueous exposure only, dietary exposure only, and a combination of dietary and aqueous exposure. The toxicokinetics measurements included bioconcentration factors (BCFs), uptake rates, elimination rates, and biological half-lives. First-order, single-compartment models described the toxicokinetics for both species. Uptake of RDX into oligochaetes was relatively rapid (uptake clearance constant [k(u)] of 5.17 mL/g/hr) compared to that in catfish (k(u) = 1.28 mL/g/hr). However, elimination also was more rapid in oligochaetes, with biological half-lives of 0.28 and 1.09 hr for oligochaetes and catfish, respectively. Thus, both species had very similar estimated BCFs of 2.1 mL/g for oligochaetes and 2.0 mL/g for catfish. Accumulation of RDX in fish that were fed oligochaetes exposed to an exceedingly high water concentration of RDX was minimal. The present investigation indicates that RDX uptake via the aqueous route is the expected dominant uptake pathway, with dietary uptake contributing minimally to the overall body burden in fish inhabiting RDX-contaminated sites. Because of the exceedingly low bioaccumulative potential and low reported toxicity of RDX, the presence of this explosive in aquatic systems is unlikely to pose unacceptable risks to invertebrates and fish.

Poplar plants (Populus deltoides x nigra, DN34) growing under hydroponic conditions were exposed to 50 mg /per/ L of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) for 24 hr. The expression of genes potentially involved in the metabolism of toxic explosives was analyzed by reverse-transcriptase (RT) real-time PCR. Genes under study were selected by reference to corresponding genes that were previously shown to be upregulated in the model plant Arabidopsis thaliana by exposure to 2,4,6-trinitrotoluene (TNT)... The target genes investigated include several genes encoding for enzymes known to be involved in the detoxification of xenobiotic pollutants, such as glutathione S-transferases (GSTs), cytochrome P-450s (CYPs), NADPH-dependent reductases, and peroxidases. Starting from A. thaliana TNT-inducible genes, corresponding Populus sequences were retrieved from the JGI Poplar Genome Project database and were used to design gene-specific primers. 18S ribosomal DNA (rDNA) was used as an internal standard and recorded gene expression levels were normalized by reference to nonexposed plants. In three separate experiments, five genes were found to be significantly amplified in leaf tissues by exposure to RDX, including GST (9.7 fold), CYP (1.6 fold), reductases (1.6-1.7 fold), and peroxidase (1.7 fold). In root tissues, only a single GST gene was found to be significantly amplified by exposure to RDX (2.0 fold). These results show, for the first time, that the exposure of poplar plants to RDX results in the induction of several genes that are potentially involved in explosive detoxification.

The study ... examined the metabolism of (14)C-labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) resulting from a single oral gavage of 5 mL/kg to male and female Yucatan miniature pigs (43 mg/kg, 56 microCi/kg in 0.5% carboxymethylcellulose in water). Blood, urine, and feces were collected at selected times of 1, 6, 12, and 24 hr post dose. At 24 hr post dose, liver samples were collected. Blood, plasma, liver, and excreta were analyzed for total RDX-derived radioactivity and metabolites were identified. ... Analysis of urine by liquid chromatography-mass spectrometry (LC/MS) identified quantifiable levels of two ring-cleavage metabolites, 4-nitro-2,4-diazabutanal and 4-nitro-2,4-diaza-butanamide, as well as parent RDX. ... Analysis by a more sensitive method (LC/MS/MS) also showed trace amounts of the RDX metabolites 1-nitroso-3,5-dinitro-1,3,5-triazacyclohexane (MNX) (in both male and female urine) and 1-nitro-3,5-dinitroso-1,3,5-triazacyclohexane (DNX) (in male urine). Analysis of plasma by LC/MS/MS also revealed quantifiable levels of RDX and trace levels of MNX, DNX, and 1,3,5-trinitroso-1,3,5-triazacyclohexane (TNX). None of the liver extracts showed quantifiable levels of RDX or any identifiable metabolites. Most of the radioactivity was in the form of water-soluble high-molecular-weight compounds. RDX when given orally to pigs was rapidly metabolized by loss of two nitro groups followed by ring cleavage.

Sprague-Dawley rats of both sexes (200-250 g) were either dosed with unlabeled or (14)C-RDX by gavage at 20 mg/kg/day for up to 90 days or allowed free access to unlabeled RDX or (14)C-RDX-saturated drinking water (50-70 ug/mL) for up to 90 days. The majority of the label was excreted as exhaled (14)C-carbon dioxide and as unidentified metabolites in the urine.

...A cytochrome P450 2B4 from rabbit liver catalyzed a biotransformation of RDX to 4-nitro-2,4-diazabutanal. Both the cytochrome P450 2B4 and intact cells of Rhodococcus sp. strain DN22 catalyzed the release of two nitrite ions from each reacted RDX molecule. A comparative study of cytochrome P450 2B4 and Rhodococcus sp. strain DN22 revealed substantial similarities in the product distribution and inhibition by cytochrome P450 inhibitors.

For more Metabolism/Metabolites (Complete) data for CYCLONITE (9 total), please visit the HSDB record page.

There are no studies available regarding RDX metabolites in humans following inhalation, oral, or dermal exposure. Some studies reported that 4-nitro-2,4-diazabutanal, and nitrite ions are produced through biotransformation of RDX by cytochrome P450. The limited toxicological data show that RDX is absorbed through the gastrointestinal system, lungs, and skin, and is distributed to the cerebrospinal fluid, plasma, urine, and feces. RDX will leaves the body in the breath and urine within a few days. (L259,A162)

Substances used to destroy or inhibit the action of rats, mice, or other rodents.

Substances that are energetically unstable and can produce a sudden expansion of the material, called an explosion, which is accompanied by heat, pressure and noise. Other things which have been described as explosive that are not included here are explosive action of laser heating, human performance, sudden epidemiological outbreaks, or fast cell growth.

The study ... examined the metabolism of (14)C-labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) resulting from a single oral gavage of 5 mL/kg to male and female Yucatan miniature pigs (43 mg/kg, 56 uCi/kg in 0.5% carboxymethylcellulose in water). Blood, urine, and feces were collected at selected times of 1, 6, 12, and 24 hr post dose. At 24 hr post dose, liver samples were collected. Blood, plasma, liver, and excreta were analyzed for total RDX-derived radioactivity and metabolites were identified. Urine was the major route of elimination of (14)C-RDX-derived radioactivity in both males and females. Relatively low levels of radioactivity were found in gastrointestinal contents and in feces, suggesting nearly complete absorption of (14)C-RDX following an oral dose. ...

... The toxicokinetics of (14)C-RDX-derived radioactivity was examined following administration of a single oral dose formulated as an aqueous suspension in 0.1% carboxymethylcellulose at a target dose level of 43 mg/kg ... to male and female Yucatan mini pigs. Blood was collected at 1, 6, 12 and 24 hr post dose from each animal. Urine and feces were collected through 24 hr post dose. ... Urine was the major route for elimination of (14)C-RDX-derived radioactivity, with 17.3 and 17.6% of the radioactive dose, respectively, in males and females. RDX was well absorbed. Feces accounted for less than 1% of administered dose and gastrointestinal contents for about 5.6% of the dose. The distribution of (14)C-RDX derived radioactivity was extensive, with radioactivity observed in all collected tissues. The highest concentrations of radioactivity were observed in liver and kidney. The calculated percent of radioactive dose was high in liver (3.5 to 5.8%) and muscle (2.5 to 4.7%).

It is slowly absorbed from the stomach and apparently from the lungs, but there is no evidence of skin absorption.

Sprague-Dawley rats of both sexes (200-250 g) were either dosed with unlabeled or (14)C-RDX by gavage at 20 mg/kg/day for up to 90 days or allowed free access to unlabeled RDX or (14)C-RDX-saturated drinking water (50-70 ug/mL) for up to 90 days. RDX did not accumulate in any tissue examined nor were there any tendencies for plasma RDX to increase continuously with repeated dosing in rats. In the 90-day drinking water study the daily recovery of the (14)C label, estimated at the end of 1, 4, 8, and 13 wk, varied between 54 and 89%. The majority of the label was excreted as exhaled (14)-carbon dioxide and as unidentified metabolites in the urine.

For more Absorption, Distribution and Excretion (Complete) data for CYCLONITE (12 total), please visit the HSDB record page.

Used as an explosive and rodenticide; [ACGIH]

Transportation forbidden for Cyclonite; Transportation forbidden by passenger aircraft/rail and cargo aircraft for Cyclonite (desensitized or wetted with >15% water; [HMT]

High explosive

It has been widely used as a base charge for detonators and as an ingredient of bursting-charge and plastic explosives by the military.

RDX is used as an explosive and is also used in combination with other ingredients in explosives. Exposure may occur by breathing dust containing RDX, contact with the skin, or drinking contaminated water. (L259)

Impure military grades ... /contain/ about 10% HMX /hexamethylenetetramine/ ...

Many other by-products are formed during the Bachmann process but may not always be present: 1,5-endo-methylene-3,7-dinitro-1,3,5,7-tetrazacyclooctane; 1,7-diacetoxy-2,4,6-trinitro-2,4,6-triazaheptane; 1,5-endo-ethylene-3,7-dinitro-1,3,5,7-tetrazacyclooctane; 1,5-endo-ethylidine-3,7-dinitro-1,3,5,7-tetrazacyclooctane; 1-nitro-3,5--dicyclohexyl-1,3,5-triazacyclohexane; N,N'-dimethylol-N,N'-dicyclohexyldiaminoethane; 3,7-dinitro-3,7-diaza-1,5-dioxacyclooctane; dinitroxydimethylnitramide; diacetoxydimethylnitramide; 1,3,5-trinitroso-1,3,5-triazacyclohexane.

2023: 7,000,000 - <8,500,000 lb

The production of cyclonite (RDX) was listed as 102X10+6 lb in l972.

Production of RDX peaked in the 1960s when it was ranked third in explosive production by volume in the United States. The average volume of RDX produced from 1969 to 1971 was 15 million pounds per month. However, production of RDX decreased to a yearly total of 16 million pounds for 1984.

1,3,5-Triazine, hexahydro-1,3,5-trinitro- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#3839]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: 1,3,5-Triazine, hexahydro-1,3,5-trinitro-. Aggregated National Production Volume: 1 to < 10 million pounds.

... Manufactured by nitrolysis of hexamine with nitric acid alone or with acetic anhydride.

Prepared by treating methenamine with fuming nitric acid

Manufactured by nitrolysis of hexamethylenetetramine.

Hexamethylenetetramine + ammonium nitrate + paraformaldehyde + nitric acid, concentrated (Bachmann process)

A second process that has been used to manufacture RDX, the direct nitration of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), has not yielded a percentage of RDX as high as the percentage produced in the Bachmann process.

RDX is more powerful as explosive than TNT with which it is mixed to form a castable mixture containing 60% RDX and 40% TNT.

Mixture with pentaerythritol tetranitrate - Semtex. Plastic explosive manufactured in two forms, Semtex H and Semtex A, which differ in the proportion of the two components RDX and pentaerythritol tetranitrate (PETN).

The cyclonite formed during the Bachmann Process is known as Type B in contrast to Type A, which does not contain HMX as an impurity.

The plasticized form of RDX, composition C-4, contains 91% RDX, 2.1% polyisobutylene, 1.6% motor oil, and 5.3% 2-ethylhexyl sebacate.

Transportation Equipment Manufacturing

1,3,5-Triazine, hexahydro-1,3,5-trinitro-: ACTIVE

RDX is not produced commercially in the United States. Production in the United States is limited to Army ammunition plants such as Holston Army ammunition plant in Kingsport, Tennessee, which has been operating at 10-20% capacity. Several Army ammunition plants, such as Louisiana (Shreveport, Louisiana), Lone Star (Texarkana, Texas), Iowa (Middletown, Iowa), and Milan (Milan, Tennessee), also handle and package RDX.