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EC number: 220-260-0 | CAS number: 2691-41-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vivo
Description of key information
A mouse micronucleus test was negative with RDX, a chemically similar substance to HMX suitable for reading across to the test substance. Several supporting studies also gave negative results. These included six Ames tests, a mouse lymphoma forward mutation assay and a mammalian cell mutagenicity assay. The in vivo a dominant lethal test in rats was also negative.
HMX therefore shows no signs of genetic toxicity.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- It is a GLP study following international guidelines and has been published in a peer reviewed journal. The restriction is also due to the use of the read across approach: the test was performed not with HMX but with RDX, a substance which has been demonstrated to be very similar in structure, physical/chemical properties and toxicological profile .
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: well known breeder
- Age at study initiation:
- Weight at study initiation:
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C):18-26°C
- Humidity (%):30% to 70%
- Photoperiod (hrs dark / hrs light):12hrs dark /12 hrs light - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil
- Concentration of test material in vehicle:
- Amount of vehicle (if gavage or dermal): 10ml/kg
- Lot/batch no. (if required):lot no. 12-394 - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Test article wasdissolved in corn oil - Duration of treatment / exposure:
- 24h and 48h
- Frequency of treatment:
- single dose
- Remarks:
- Doses / Concentrations:
62.5 mg/kg
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
125 mg/kg
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
250 mg/kg
Basis:
actual ingested - No. of animals per sex per dose:
- 5 males/dose for the negative and positive control and the 62.5 and 125 mg/kg and 10/sex/dose for the 250 mg/kg
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide in sterile deionized water
- Route of administration: gavage
- Doses / concentrations: 80mg/kg - Tissues and cell types examined:
- Bone marrow. micronuclei in polychromatic erythrocytes (PCEs) and norchromatic erythrocytes (NCEs)
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:Based upon the result of the dose range-finding study, the estimated maximum tolerated doses was 250 mglkg after one oral gavage administration
SAMPLING TIMES ( in addition to information in specific fields): 24h and 48h
DETAILS OF SLIDE PREPARATION:Bone marrow smears were prepared and allowed to air dry. The slides were then fixed in methanol, stained in May-Grunwald-Giemsa stain and protected by permanently mounted cover slips.
METHOD OF ANALYSIS:The slides were blind scored for micronuclei in polychromatic erythrocytes (PCEs) and norchromatic erythrocytes (NCEs) and determination of PCE/NCE ratios to access possible bone marrow cytotoxicity.
The micronucleus frequency (expressed as percent micronucleated cell) wasdetennlned by analyzing number of micronucleated PCEs from at least 2000 PCEs per animal. The PCE:NCE ratio was determined by scoring the number of PCEs and NCEs observed while scoring at least the first 500 erythrocytes per animal. - Evaluation criteria:
- The criteria for the identification of micronuclei were those of Schmid (1976).
- Statistics:
- Yes but no details
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- no significant decreases in the PCE:NCE ratios observed at any RDX dose or bone marrow sampling time point
- Toxicity:
- no effects
- Remarks:
- RDX at doses 62.5, 125, and 250 mg/kg were not cytotoxic to bone marrow (i.e.no statistically significant decrease in PCE:NCE ratios)
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: up to 500 mg/kg
- Clinical signs of toxicity in test animals: Mice dosed at all dose levels showed neurotoxic signs (hyperactive) and deaths at high dose of 500 mg/kg. - Conclusions:
- Interpretation of results (migrated information): negative
RDX was found to be negative in the in vivo mouse bone marrow micronucleus assay. - Executive summary:
HMX and RDX, which is tested for its genotoxicity in a mouse micronucleus assay, are both explosive compounds used in military munitions formulations.
These substances have been demonstrated to be very similar in structure, physical/chemical properties and toxicological profile in the Analogue Approach - Read Across High Melting Explosive (HMX) (2013) document (see Section 13). Due to the fact that HMX and RDX have nearly the same chemical structure, the same mode of interaction with bio-macromolecules, living cells and tissue and metabolic pathway is expected. Therefore, a read-across from HMX to data obtained with RDX is scientifically justified.
Reference
Summary data from micronuleus assay for RDX in bone marrow of CD-l mouse
Treatment | Dose | Harvest time | % Micronucleated PCE (mean of 2000 per animal ±SE) | Ratio PCE:NCE (mean ± S.E.) |
Positive control | CP 80 mg/kg | 24h | 2.39 ± 0.31* | 0.57 ± 0.05 |
Test article | 62.5 mg/kg | 24h | 0.04 ± 0.02 | 0.47 ± 0.07 |
125 mg/kg | 24h | 0.03 ± 0.01 | 0.36 ± 0.04 | |
250 mg/kg | 24 | 0.02 ± 0.01 | 0.60 ± 0.05 | |
48h | 0.10 ± 0.02 | 0.69 ± 0.11 | ||
Vehicle control | Corn oil | 24h | 0.05 ± 0.02 | 0.50 ± 0.07 |
48h | 0.08 ± 0.03 | 0.71 ± 0.06 |
*Significantly greater than the corresponding vehicle control, P =0.01
CP = cyclophosphamide.
PCE = polychromatic erythrocyte.
NCE = normochromatic erythrocyte.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Additional information from genetic toxicity in vivo:
In vitro studies
Gene mutations
A key study, a mouse lymphoma forward mutation assay, was performed using RDX, a chemically similar substance to HMX for which read-across can be scientifically justified. The study was performed according to GLP guidelines and OECD guideline 476 (Reddy et al, 2005). Pure RDX (99.99%) af concentrations ranging from 3.93 to 500 μg/mL showed no cytotoxicity and no mutagenicity in forward mutations at the thymidine kinase (TK) locus in L5178Y mouse lymphoma cells, with and without metabolic activation. The finding was confirmed by repeat assays under identical conditions. A supporting mammalian cell mutagenicity assay was done (Lachance et al, 1999). V79 chinese hamster lung cells were used. There was no evidence of mutagenic activity in the mammalian cells tested, either in the presence or absence of metabolic activation at concentrations up to 33 μM.
Six bacterial reverse cell mutation (Ames) test results were available, including a robust GLP-compliant test according to OECD TG 471 using 5 bacterial strains (among which E. coli WP2 uvrA).
Results were negative in every case, therefore there is enough weight of evidence in these supporting studies to suggest that the negative result arising from the read-across from RDX is justified and scientifically valid.
In vivo studies
Two in vivo studies were available, both using RDX, from which a read-across approach is justified. One study was a mouse micronucleus assay (Reddy et al. 2005). The study was conducted according to OECD guideline 474. Groups of CD-1 male mice were dosed orally with 62.5, 125 and 250 mg/kg RDX. Bone marrow samples were taken and slides were scored for micronulei in polychromatic erythrocytes (PCE's) and norchromatic erythrocytes (NCE's). PCE/NCE ratios were determined. There were no significant decreases in the PCE:NCE ratios observed at any RDX dose or bone marrow sampling time point. RDX gave a negative result in the in vivo mouse bone marrow micronucleus assay, therefore HMX can be said to also be negative using the read-across approach.
The other in vivo study was a dominant lethal assay in rats using RDX. Four groups of 22 male and 22 female rats were fed diets containing RDX at daily doses of 0, 5, 16 or 50 mg/kg. The F0 generation was treated for 13 weeks. After 13 weeks F0 males were mated with nontreated females. There were no statistically significant effects on any parameters examined, therefore RDX was not mutagenic and by using read-across, HMX can be said to be non-mutagenic also.
Justification for selection of genetic toxicity endpoint
Study conducted to international guidelines and to GLP. Read-across from chemically similar substance RDX.
Justification for classification or non-classification
HMX is not classified for mutagenic effects as all the tests undertaken (including Ames test, mammalian cell mutagenicity, mouse lymphoma forward mutation, mouse micronucleus and dominant lethal assay in rats) were negative.
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