Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 274-159-1 | CAS number: 69852-45-5
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- September 2016 - October 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- Updated and adopted 26 September 2014
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: Erythrocyte micronucleus assay
Test material
- Reference substance name:
- 3-[[3-(dimethylamino)propyl]amino]propiononitrile
- EC Number:
- 274-159-1
- EC Name:
- 3-[[3-(dimethylamino)propyl]amino]propiononitrile
- Cas Number:
- 69852-45-5
- Molecular formula:
- C8H17N3
- IUPAC Name:
- 3-{[3-(dimethylamino)propyl]amino}propanenitrile
- Reference substance name:
- 3,3'-[[3-(dimethylamino)propyl]imino]bispropiononitrile
- EC Number:
- 275-331-9
- EC Name:
- 3,3'-[[3-(dimethylamino)propyl]imino]bispropiononitrile
- Cas Number:
- 71326-27-7
- Molecular formula:
- C11H20N4
- IUPAC Name:
- 3,3'-{[3-(dimethylamino)propyl]imino}dipropanenitrile
- Test material form:
- liquid
- Remarks:
- colorless
Constituent 1
impurity 1
- Specific details on test material used for the study:
- ID: 3-[[3-(dimethylamino)propyl]amino]propiononitrile
Purity : >96%
Molecular Weight: 155.24068 g/mol
Chemical Name: 3-[[3-(dimethylamino)propyl]amino]propiononitrile
Batch/Lot No.: AAE1131000
Expiration Date: 27-July-2018 (provided by Sponsor)
Description: Clear colorless liquid
Storage Conditions: Room temperature, protected from light
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Envigo RMS, Inc., Frederick, MD
- Age at study initiation: 6 weeks
- Weight at study initiation: 165.3 - 191.1g
- Assigned to test groups randomly: [no/yes, under following basis: ] Yes (Excel method)
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72 +/- 3 °F
- Humidity (%): 50 +/- 2%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12hr dark/ 12 hr light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Deoionised water
- Details on exposure:
- Dose formulations were administered at a volume of 10 mL/kg by oral gavage using appropriately sized disposable polypropylene syringes with gastric intubation tubes (needles).
- Duration of treatment / exposure:
- Single dose
- Frequency of treatment:
- Single dose
- Post exposure period:
- 24 and 48 hours
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- Since no significant differences in toxicity or mortality were observed in the dose range-finding test, only male rats were used for the micronucleus assay.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide
Examinations
- Tissues and cell types examined:
- Bone marrow
- Details of tissue and slide preparation:
- Femoral bone marrow was collected at approximately 24 or 48 hours after the final dose, as indicated above. Animals were euthanized by carbon dioxide inhalation. Immediately following euthanasia, the femurs were exposed, cut just above the knee, and the bone marrow was aspirated into a syringe containing fetal bovine serum. The bone marrow was transferred to a centrifuge tube containing 2 mL fetal bovine serum, the cells were pelleted by centrifugation, and the supernatant was drawn off leaving a small amount of fetal bovine serum with the pellet. Cells were re-suspended and a small drop of the bone marrow suspension was spread onto a clean glass slide. At least four slides were prepared from each animal, air dried and fixed by dipping in methanol. One set of two slides (including at least five positive control slides) was stained with acridine orange for microscopic evaluation. The other set of slides was kept as backup and will be archived at report finalization. Stained slides will be discarded prior to report finalization. Each slide was identified by the harvest date, study number, and animal number. Slides were coded using a random number table by an individual not involved with the scoring process.
- Evaluation criteria:
- A test substance was considered to have induced a positive response if:
a) at least one of the test substance doses exhibited a statistically significant increase when compared with the concurrent negative control (p ≤ 0.05), and
b) when multiple doses were examined at a particular sampling time, the increase was dose-related (p ≤ 0.01), and
c) results of the group mean or of the individual animals in at least one group were outside the 95% control limit of the historical negative control data.
A test substance was considered to have induced a clear negative response if none of the criteria for a positive response were met and there was evidence that the bone marrow was exposed to the test substance (unless intravenous administration was used).
If the response was neither clearly positive nor clearly negative, or in order to assist in establishing the biological relevance of a result, the data were evaluated by expert judgment and/or further investigations. Possible additional work may include scoring additional cells (where appropriate) or performing an additional experiment that could employ the use of modified experimental conditions. Such additional work was only carried out following consultation with, and at the request of, the Sponsor.
In some cases, even after further investigations, the data set precluded making a conclusion of positive or negative, at which time the response was concluded to be equivocal. In such cases, the Study Director used sound scientific judgment and reported and described all considerations. - Statistics:
- Statistical analysis was performed on the micronucleus frequency (MnPCE%) and PCE% using the animal as the unit. The mean and standard deviation of MnPCE% and PCE% were presented for each treatment group.
The use of parametric or non-parametric statistical methods in the evaluation of data was based on the variation between groups. The group variances for micronucleus frequency for the vehicle and test substance groups at the respective sampling time were compared using Levene’s test (significant level of p 0.05). Since the variation between groups was found not to be significant, a parametric one-way ANOVA was performed followed by a Dunnett’s post hoc analysis to compare each dose group to the concurrent vehicle control.
A linear regression analysis was conducted to assess dose responsiveness in the test substance treated groups (p 0.01).
A pair-wise comparison (Student’s T-test) was used to compare the positive control group to the concurrent vehicle control group.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
Definitive Assay - Clinical Signs
Treatment |
Observation |
Number of Animals With Observed Signs/Number of Surviving Animals |
Number of Animals Found Dead/Total Number of Animals Dosed |
||||
Males |
|||||||
Day 1 |
Day 2 |
Day 3 |
Males |
||||
Pre-Dose |
Post-Dose |
||||||
1 Hr |
2 Hr |
||||||
Deionized water |
Normal |
10/10 |
10/10 |
10/10 |
10/10 |
5/5 |
0/10 |
3-[[3(dimethylamino)propyl] amino]propiononitrile 250 mg/kg |
Normal |
5/5 |
5/5 |
5/5 |
5/5 |
N/A |
0/5 |
500 mg/kg |
Normal |
5/5 |
5/5 |
5/5 |
5/5 |
N/A |
0/5 |
1000 mg/kg |
Normal |
10/10 |
10/10 |
10/10 |
10/10 |
5/5 |
0/10 |
Definitive Assay - Group Mean Body Weights
|
|
Group Mean Body Weights (g ± SD) |
|
% Change¹ |
|
|||
Treatment |
Sex |
Day 1 |
Day of Euthanasia |
|
Day of Euthanasia |
|
Mortality² |
|
Deionized water |
||||||||
24 Hour |
M |
200.2 |
210.7 |
5.2% |
0/5 |
|||
±2.8 |
±2.4 |
|||||||
48 Hour |
M |
203.1 |
213.3 |
5.0% |
0/5 |
|||
±6.4 |
±7.1 |
|||||||
3-[[3(dimethylamino)propyl] |
||||||||
250 mg/kg/day |
M |
201.5 |
206.8 |
2.6% |
0/5 |
|||
±3.4 |
±2.5 |
|||||||
500 mg/kg/day |
M |
203.2 |
202.0 |
-0.6% |
0/5 |
|||
±6.0 |
±3.2 |
|||||||
1000 mg/kg/day |
|
|
|
|
|
|
|
|
24 Hour |
M |
204.8 |
202.9 |
-0.9% |
0/5 |
|||
±4.8 |
±5.5 |
|||||||
48 Hour |
M |
203.8 |
196.1 |
-3.8% |
0/5 |
|||
±7.6 |
±20.9 |
|||||||
|
|
|
|
|
|
|
|
|
SD = Standard deviation ¹% Change =[(Post-treatment weight - Pretreatment weight) x 100]/Pretreatment weight ²Reported as number of animals found dead after dose administration/total number tested. |
Summary of Bone Marrow Micronucleus Assay
|
Time |
%PCE |
Change from Control |
% MnPCE |
Number of |
|||||||||||
Treatment |
Gender |
(Hrs) |
Animals |
(Mean +/- SD) |
(%) |
(Mean +/- SD) |
MnPCE/PCE Scored |
|||||||||
Deionized water |
|
|
|
|
|
|
||||||||||
M |
24 |
5 |
54.1 |
± |
1.7 |
--- |
0.06 |
± |
0.03 |
12 |
/20000 |
|||||
|
|
|
|
|
|
|||||||||||
3-[[3-(dimethylamino)propyl] |
|
|
|
|
|
|
||||||||||
250 mg/kg/day |
M |
24 |
5 |
53.2 |
± |
1.0 |
-2 |
0.06 |
± |
0.02 |
11 |
/20000 |
||||
|
|
|
|
|
|
|||||||||||
500 mg/kg/day |
M |
24 |
5 |
52.5 |
± |
0.7 |
-3 |
0.07 |
± |
0.02 |
13 |
/20000 |
||||
|
|
|
|
|
|
|||||||||||
1000 mg/kg/day |
M |
24 |
5 |
52.3 |
± |
0.7 |
-3 |
0.11 |
± |
0.03* |
21 |
/20000 |
||||
|
|
|
|
|
|
|||||||||||
Deionized water |
|
|
|
|
|
|
||||||||||
M |
48 |
5 |
54.8 |
± |
1.9 |
--- |
0.05 |
± |
0.02 |
9 |
/20000 |
|||||
|
|
|
|
|
|
|||||||||||
3-[[3-(dimethylamino)propyl] |
|
|
|
|
|
|
||||||||||
1000 mg/kg/day |
M |
48 |
5 |
50.8 |
± |
1.3 |
-7 |
0.07 |
± |
0.03 |
14 |
/20000 |
||||
|
|
|
|
|
|
|||||||||||
CP |
|
|
|
|
|
|
||||||||||
40 mg/kg/day |
M |
24 |
5 |
42.4 |
± |
1.8** |
-22 |
2.30 |
± |
0.18** |
459 |
/20000 |
||||
|
|
|
|
|
|
|||||||||||
PCE – Polychromatic Erythrocytes; MnPCE – Micronucleated Polychromatic Erythrocytes *p < 0.05 or **p < 0.01, One-Way ANOVA with Post-Hoc Dunnett's Test or T-Test 24 Hrs MnPCE Male GLM P-value = 0.015, R-sqr = 47.27% |
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the assay described in this report, 3-[[3-(dimethylamino)propyl]amino]propiononitrile was concluded to be negative for the induction of micronucleated polychromatic erythrocytes.
- Executive summary:
The test substance,3-[[3-(dimethylamino)propyl]amino]propiononitrile, was evaluated for its clastogenic activity and/or disruption of the mitotic apparatus by detecting micronuclei in polychromatic erythrocyte (PCE) cells in rat bone marrow. Deionized water was selected as the vehicle. Test and/or control substance formulations were administered at a dose volume of 10 mL/kg by single oral gavage.
In the dose range-finding assay (DRF), the maximum dose tested was 2000 mg/kg. The dose levels tested were 500, 1000, and 2000 mg/kg in 3 animals/sex. Based upon the results, the high dose for the definitive assay was 1000 mg/kg, which is the maximum tolerated dose (MTD).
The definitive assay dose levels tested were 250, 500, and 1000 mg/kg.
A statistically significant increase in the incidence of MnPCEs was observed in animals 24 hours after treatment with 1000 mg/kg relative to the vehicle control. However, the increase was within the 95% historical vehicle control range. The positive control induced a statistically significant increase in the incidence of MnPCEs. The number of MnPCEs in the vehicle control groups did not exceed the historical control range.
Under the conditions of this study, the administration of3-[[3-(dimethylamino)propyl] amino]propiononitrileat doses up to and including a dose of 1000 mg/kg was concluded to be negative in the Micronucleus assay.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.