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EC number: 940-393-4 | CAS number: 1702355-94-9
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- N,N'-dibutyl-N,N'-bis(1,2,2,6,6-pentamethylpiperidin-4-yl)-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamine
- EC Number:
- 940-393-4
- Cas Number:
- 1702355-94-9
- Molecular formula:
- C35 H66 N8
- IUPAC Name:
- N,N'-dibutyl-N,N'-bis(1,2,2,6,6-pentamethylpiperidin-4-yl)-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamine
- Test material form:
- solid: bulk
- Details on test material:
- - State of aggregation: solid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Germany GmbH
- Age at study initiation: 5 - 8 weeks
- Weight at study initiation: 27.63 g
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Based on preliminary solubility testing dimethyl sulfoxide (DMSO) was the most suitable
vehicle, whereas only a homogeneous suspension was obtained. Using the vehicles DMSO
and corn oil subsequently a homogeneous suspension of the test substance was obtained.
Therefore, a mixture of DMSO and corn oil (ratio 2:3) was selected as vehicle, which has
been demonstrated to be suitable in the mouse micronucleus test and for which historical
control data are available. - Details on exposure:
- The substance to be administered per kg body weight was suspended in DMSO/corn oil.
To achieve homogeneity of the test substance in the vehicle, the test substance preparation
was stirred with an ultraturrax.
All test substance formulations were prepared immediately before administration. - Duration of treatment / exposure:
- 24h and 48h
- Frequency of treatment:
- single
Doses / concentrations
- Remarks:
- Doses / Concentrations:
500, 1000, 2000 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Positive control
20 mg cyclophosphamide (CPP)
10 mL positive control preparation
sacrifice after 24h
Examinations
- Tissues and cell types examined:
- preparation of the bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: pre-test
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): single treatment, exposure for 24h and 48h
DETAILS OF SLIDE PREPARATION: stained with eosin and methylene blue for about 5 minutes, were stained with Giemsa solution for 15 min, rinsing twice in deionized water and clarifying in xylene, the preparations were mounted in Corbit-Balsam
METHOD OF ANALYSIS: 2 000 polychromatic erythrocytes (PCE) were evaluated for the occurrence of micronuclei from each animal of every test group, so in total 10 000 PCEs were scored per test group. The normochromatic erythrocytes (= normocytes / NCE) were also scored
OTHER: - Evaluation criteria:
- A finding is considered positive if the following criteria are met:
• A statistically significant and dose-related increase in the number of PCEs containing
micronuclei.
• The number of PCEs containing micronuclei has to exceed both the concurrent vehicle
control value and the range of the historical vehicle control data (see Appendix 4).
A test substance is considered negative if the following criteria are met:
• The number of cells containing micronuclei in the dose groups is not statistically significant
increased above the concurrent vehicle control value and is within the range of the
historical vehicle control data - Statistics:
- The statistical evaluation of the data was carried out using the program system MUKERN
(BASF SE). The asymptotic U test according to MANN-WHITNEY (modified rank test
according to WILCOXON) was carried out to clarify the question whether there are
statistically significant differences between the untreated control group and the treated dose
groups with regard to the micronucleus rate in polychromatic erythrocytes. The relative
frequencies of cells containing micronuclei of each animal were used as a criterion for the
rank determination for the U test. Statistical significances were identified as follows:
* p ≤ 0.05
** p ≤ 0.01
However, both biological relevance and statistical significance were considered together.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- An inhibition of erythropoiesis induced by the treatment of mice with was detected at a dose of 2 000 mg/kg body weight at 48-hour sacrifice interval
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- The administration of the test substance led to severe clinical signs of toxicity at the top dose
of 2 000 mg/kg body weight 48 hours after administration. Following clinical symptoms were
observed shortly before sacrifice: piloerection, hunched posture, reduced general condition,
eyelid closure, lacrimation and diarrhea.
The single statistical significant increase in the number of micronucleated polychromatic
erythrocytes after treatment with 2 000 mg/kg body weight at 48-hour sacrifice interval is
based on the low value of the respective vehicle control group, and therefore, it has to be
regarded as biologically irrelevant.
The ratio of PCE/NCE was clearly influenced at the highest administered dose of
2 000 mg/kg body weight at delayed 48-hour preparation interval as indication for target
organ toxicity. These data confirm the severe clinical observations in the treated animals
48 hours after test substance administration.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
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