Registration Dossier
Registration Dossier
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: 203-468-6 | CAS number: 107-15-3
- 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

Toxicity to reproduction
Administrative data
- Endpoint:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- before 1984
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 984
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Ethylenediamine
- EC Number:
- 203-468-6
- EC Name:
- Ethylenediamine
- Cas Number:
- 107-15-3
- Molecular formula:
- C2H8N2
- IUPAC Name:
- ethane-1,2-diamine
- Details on test material:
- - Name of test material (as cited in study report): Ethylendiamine
- Analytical purity: 99 %
Constituent 1
- Specific details on test material used for the study:
- Due to corrosivity of EDA, ethylene diammonium dichloride (ECDA.2HCl) was used (CAS no. 333-18-6; EC no. 206-369-6).
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Charles River Breeding Laboratories, Inc., Portage, Michigan.
- Age at study initiation: (P) 43 wks;
- Weight at study initiation: (P) Males: 112-141 g; Females: 85-111 g;
- Housing: Two or three males or three or five females were housed per cage prior to mating;
- Diet: ad libitum, Purina Certified Rodent Chow 5002.
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Photoperiod (hrs dark / hrs light): 12 hr light cycle
Administration / exposure
- Route of administration:
- oral: feed
- Details on exposure:
- Fresh diet was prepared biweekly with the percentage of EDA*2HCl in the diet adjusted to maintain a constant dosage level in grams per kilogram for each sex according to the average animal body weight gain and diet consumption. At monthly intervals two diet samples were analysed.
- Details on mating procedure:
- The F0 parents were mated afier having received dietary EDA * 2HCl for 100 days. Twenty-six females and 13 males (randomly selected from 25 males) were mated per treated group while 52 females and 26 males (randomly selected from 50 males) were mated for the control group. During mating, two females were placed in a cage with one male; at this time all rats received EDA * 2HCl at the concentration in the diet for the respective female groups. Fifteen days after cohabitation, mating was discontinued and the females were placed in individual shoebox cages fitted with wire rod metal tops.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- At monthly intervals two diet samples were analysed.
- Duration of treatment / exposure:
- for two generations
- Frequency of treatment:
- daily
- Details on study schedule:
- At each dose level 13 male and 26 female rats were mated in both F0 and F1 generation (control group: 26 male and 52 female rats each); continuous treatment starting 100 days prior to cohabitation of F0 rats until weaning of F2 rats.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 50 mg/kg bw/day
- Dose / conc.:
- 150 mg/kg bw/day
- Dose / conc.:
- 500 mg/kg bw/day
- No. of animals per sex per dose:
- 13 male and 26 female. Control group: 26 male and 52 female rats
- Control animals:
- yes, concurrent no treatment
Examinations
- Parental animals: Observations and examinations:
- BODY WEIGHT: Yes, measured weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Food consumption determined on each cage of animals every 2 week. Dosage adjusted to keep a constant dosage level.
Parameters examined included indices of fertility, days from first mating to parturition, gestation index. - Litter observations:
- Parameters examined included survival rate on lactation day 4, 14 and 21, pups born alive/litter, pup body weight (by litter) at lactation day 14 and individual pup body weight at weaning day 21.
- Postmortem examinations (parental animals):
- Complete necropsies were performed on 10 adults/sex/ dose group of F1 generation and on 20 rats/sex of control group. parameters examined included indices of fertility, days from first mating to parturition, gestation index, survival rate on lactation day 4, 14 and 21, pups born alive/litter, pup body weight (by litter) at lactation day 14 and individual pup body weight at weaning day 21.
- Postmortem examinations (offspring):
- Complete necropsies were performed on 5 weanlings from both F1 and F2 generation at each dose group.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Description (incidence):
- No substance-related parental deaths in the F0 or F1 generation.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant reduction in parental body weight gain of female rats in the intermediate and high dose group of the F0 generation, in the high dose group of the F1 generation and of male rats in the high dose group of both F0 and F1 generations.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- No histopathologic findings except for a significant higher incidence of hepatocellular pleomorphism in both sexes of the high dose group of the F1 generation (6/10 male, 10/10 female; control: 0/20 each) and a significant decreased prevalence of kidney tubular mineralization in female rats of the high dose group of the F1 generation (0/10 female; control: 10/20).
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 23 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Changes in body weight, food consumption, organ weights, and histopathology at the next higher dose (recalculated to EDA base)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 227 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects on reproductive performance (recalculated to EDA base)
Results: P1 (second parental generation)
Effect levels (P1)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 23 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Changes in body weight, food consumption, organ weights and histopathology at the next higher dose (recalculated to EDA base)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 227 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects on reproductive performance (recalculated to EDA base)
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 227 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: absence of embryotoxicity (recalculated to EDA base)
Results: F2 generation
Effect levels (F2)
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- >= 227 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: absence of embryotoxicity (recalculated to EDA base)
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Significant reduction in parental body weight gain of female rats in the intermediate and high dose group of the F0 generation, in the high dose group of the F1 generation and of male rats in the high dose group of both F0 and F1 generations.
No substance-related parental deaths in the F0 or F1 generation.
Significant decrease of absolute liver weight in male rats of the high dose F1 generation.
No macroscopic or histopathologic findings except a significant higher incidence of hepatocellular pleomorphism in both sexes of the high dose group of the F1 generation (6/10 male, 10/10 female; control: 0/20 each) and a significant decreased prevalence of kidney tubular mineralization in female rats of the high dose group of the F1 generation (0/10 female; control: 10/20).
In conclusion there was no evidence of fertility impairment or embryotoxic effect at dose levels that show maternal or paternal toxicity.
REPRODUCTIVE INDICES | ||||
Dosage (g/kg,lday) | ||||
0.50 | 0.15 | 0.05 | 0 | |
F0 → F1 | ||||
Fertility index (%) | ||||
Male | 92 | 100 | 92 | 92 |
Female | 81 | 77 | 73 | 77 |
Gestation index (%) | 100 | 100 | 100 | 100 |
Gestation survival index (%) | 99.0 ± 3.4 | 100.0 ± 0.0 | 97.2 ± 11.8 | 99.2 ± 5.2 |
0- to 4-Day survival index (%) | 90.0 ± 30.0 | 100.0 ± 0.0 | 94.4 ± 23.6 | 93.2 ± 22.4 |
4- to 14-day survival indexb (%) | 99.4 ± 2.5 | 100.0 ± 0.0 | 94.1 ± 24.3 | 100.0 ± 0.0 |
4- to 2I-day survival indexb (%) | 99.4 ± 2.5 | 100.0 ± 0.0 | 94.1 ± 24.3 | 99.7 ± 2.0 |
Pups born alive/litter | 6.8 ± 3.5 | 8.6 ± 2.8 | 6.2 ± 3.9 | 8.4 ± 3.0 |
Days from first mating to parturition | 28.3 ± 3.8 | 29.6 ± 2.0 | 29.8 ± 3.0 | 28.1 ± 3.0 |
F1 → F2 | ||||
Fertility index (%) | ||||
Male | 100 | 92 | 92 | 100 |
Female | 92 | 88 | 73 | 88 |
Gestation index (%) | 100 | 100 | 100 | 100 |
Gestation survival index (%) | 98.6 ± 6.7 | 99.1 ± 3.1 | 99.4 ± 2.5 | 99.5 ± 2.0 |
0- to 4-Day survival index (%) | 98.0 ± 4.1 | 99.3 ± 3.5 | 98.6 ± 3.3 | 98.5 ± 4.1 |
4- to 14-day survival index (%) | 100.0 ± 0.0 | 98.7 ± 6.3 | 100.0 ± 0.0 | 99.6 ± 3.0 |
4- to 21-day survival index (%) | 100.0 ± 0.0 | 98.3 ± 8.3 | 100.0 ± 0.0 | 99.6 ± 3.0 |
Pups born alive/litter | 8.5 ± 3.0 | 8.8 ± 2.2 | 9.4 ± 2.8 | 10.0 ± 2.5 |
Days from first mating to parturition | 28.5 ± 3.2 | 28.8 ± 3.3 | 27.3 ± 3.6 | 28.4 ± 3.8 |
Applicant's summary and conclusion
- Conclusions:
- There was no indication of reproductive and embryotoxicity in Fischer 344 rats, following exposure to dietary EDA for two generations.
- Executive summary:
In a two-generation study, male and female Fischer 344 rats were fed diets containing 0, 50, 150 or 500 mg/kg bw/day of EDA*2HCl. At each dose level 13 male and 26 female rats were mated in both F0 and F1 generation. In the high dose group effects noted were decreased body weight gain in both F0 and F1 generations, a higher incidence of hepatocellular pleomorphism in F1 generation, and decreased liver weights in male rats in F1 generation. In the intermediate dose group female rats of F0 generation showed a decreased body weight gain. No evidence of impaired fertility or embryotoxicity was seen at any dose level. NOAEL parental toxicity was 50 mg/kg bw/day (23 mg/kg bw/day calculated as Ethylenediamine base), NOAEL reproductive performance at least 500 mg/kg bw/day (227 mg/kg bw/day calculated as Ethylenediamine base) and NOAEL F1 offspring was at least 500 mg/kg (227 mg/kg bw/day calculated as Ethylenediamine base; highest dose tested).
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.
