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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 203-702-7 | CAS number: 109-76-2
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- pre-GLP Trimethylenediamine is structurally very similar to ethylenediamine (difference: chain length / one CH2-group) or ethylenediammonium dichloride (doses of ammonium and chloride not toxicological relevant), respectively. Thus, the test result is justified for read across to assess the teratogenic potential / developmental toxicity of trimethylenediamine.
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 987
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Rats were dosed via diet during gestation day 6-15. Standard endpoints for teratogenicity were evaluated.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Ethylenediamine dihydrochloride
- IUPAC Name:
- Ethylenediamine dihydrochloride
- Reference substance name:
- Ethylenediammonium dichloride
- EC Number:
- 206-369-6
- EC Name:
- Ethylenediammonium dichloride
- Cas Number:
- 333-18-6
- IUPAC Name:
- ethane-1,2-diaminium dichloride
- Details on test material:
- Ethylenediamine dihydrochloride was prepared from high purity ethylenediamine, 99,9%. The salt was analysed by chromatography and spectrophotometric methods, and found to be free of impurities.
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY).
- Age at study initiation: 100 days
- Housing: stainless-steel cages
- Diet : Purina Certified Rodent Chow 5002
- Water (e.g. ad libitum): Yes
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: no data (most likely feed only)
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis indicated that the test diet preparations were accurate and homogeneous. The stability of the test diets was also confirmed. Substance was added to diet based on established diet consumption data and an established growth curve to produce the dosage goals.
- Details on mating procedure:
- At approximately 100 days of age, female rats were introduced into the male rats' cages. The rats were mated one male to one female to achieve a goal of approximately 20 pregnant females per treatment group, and 40 in the negative control group. Expelled vaginal plugs were used as evidence that mating had occurred
- Duration of treatment / exposure:
- Gestation day 6 - 15
- Frequency of treatment:
- daily
- Duration of test:
- cesarean section on gestation day 21
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
50 mg/kg bw/day
Basis:
- Remarks:
- Doses / Concentrations:
250 mg/kg bw/day
Basis:
- Remarks:
- Doses / Concentrations:
1000 mg/kg bw/day
Basis:
- No. of animals per sex per dose:
- 20 and 40 in control group.
- Control animals:
- yes, concurrent no treatment
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 250 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 23 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- recalculated to EDA
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 113 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- recalculated to EDA
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 27.9 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- calculated from EDA to trimethylenediamine
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 139.6 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- calculated from EDA to trimethylenediamine
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 250 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 250 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- LOAEL
- Effect level:
- 113 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 113 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- recalculated to EDA
- Basis for effect level:
- other: fetotoxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 452 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- recalculated to EDA
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- LOAEL
- Effect level:
- 139.6 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- calculated from EDA to trimethylenediamine
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 139.3 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- calculated from EDA to trimethylenediamine
- Basis for effect level:
- other: fetotoxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 557.2 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- calculated from EDA to trimethylenediamine
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Significant
reduction in maternal body weight gain in the intermediate dose group
during gestation day 6 - 15 and in the high dose group during gestation
day 6 - 21; significant decreased diet consumption in the intermediate
and high dose group during gestation day 6 - 15; significant increased
number of resorptions/litter and significant decreased mean fetal body
weight and reduced fetal crown-rump length in the high dose group;
significant higher incidence of a shortened mandible, edematous eye
bulge, shortened or missing innominate artery, unossified sternebrae in
fetuses of the high dose group.
Number of pups affected | |||||
Dosage level (mg/kg/day) | |||||
Control | 50 | 250 | 1000 | ||
No. of litters | 40 | 23 | 21 | 24 | |
No. of pups | 379 | 232 | 201 | 242 | |
Pup body weight, males (g) | 4.5+0.3 | 4.5+0.2 | 4.5+0.2 | 4.1+0.3 | |
Pup body weight, females (g) | 4.2+0.2 | 4.2+0.2 | 4.2+0.3 | 3.8+0.3 | |
Fetal crown rump length, males (mm) | 40+2 | 40+2 | 40+2 | 39+2 | |
Fetal crown rump length, females (mm) | 38+1 | 39+2 | 39+2 | 37+2 | |
Slightly edematous eye bulge | |||||
F | 0 | 0 | 0 | 4 | |
L | 0 | 0 | 0 | 4 | |
Shortened mandible | |||||
F | 0 | 0 | 0 | 18 | |
L | 0 | 0 | 0 | 4 | |
Missing innominate artery | |||||
F | 0 | 0 | 1 | 9 | |
L | 0 | 0 | 1 | 6 | |
Shortened innominate artery | |||||
F | 4 | 2 | 0 | 27 | |
L | 4 | 1 | 0 | 14 |
F = fetuses L = litters
The first artery to branch off of the aorta is the brachiocephalic which becomes the innominate after the left carotid branches off. The innominate then branches into the right subclavian and right carotid artery. When the authors stated it was missing, they really mean that the right and left carotid branch off of the brachiocephalic artery at the same time. Thus there is no innominate. However, this would not affect blood supply to areas served by these arteries.
Applicant's summary and conclusion
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.