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EC number: 203-584-7 | CAS number: 108-45-2
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Study does not state a specific OECD guideline and is not GLP compliant, but it does seem to follow OECD guideline 414 closely with a well documented methodology and results.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 981
- Report date:
- 1981
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 1 981
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- m-phenylenediamine
- EC Number:
- 203-584-7
- EC Name:
- m-phenylenediamine
- Cas Number:
- 108-45-2
- Molecular formula:
- C6H8N2
- IUPAC Name:
- m-phenylenediamine
- Details on test material:
- - Name of test material (as cited in study report): M-phenylenediamine (PD.)
- Physical state: A pale gray, finely-crystalline, odorless and water-soluble substance.
- Analytical purity: 99%.
- Stability under test conditions: Stability was checked.
- Storage condition of test material: Protected from light and kept under nitrogen in a refrigerator.
- Other: Received from Fluka AG, Buchs, Switzerland.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Him: OFA (SD) SPF
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Forschungs-insitut fur Verscuchstierzucht (Research Institute for Test Animal Breeding), Himberg
- Age at study initiation: 6-10 months old
- Weight at study initiation: 200-250 g
- Housing: Kept individually in Type III Makrolon cages
- Diet (e.g. ad libitum): Ad litbitum with Altromin Breeding Diet 1314 ff, 10-mm pellets sterilized by gamma radiation, 2 Mrad
- Water- Autoclaved tap water ad libitum from drinking bottles
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21± 2°C
- Humidity (%): 55± 5%
- Air changes (per hr): 15 times per hour with pure fresh air
- Photoperiod (hrs dark / hrs light): Exclusively artificial light (200 lux at a height of 2m) for 10 hours ( from 7 AM - 5 PM) without dawn.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- The test substance was dissolved or suspended fresh daily and administered perorally once daily in the morning from the 6th to the 15th test days inclusive, using a metal esophageal probe.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data.
- Details on mating procedure:
- - Impregnation procedure: Co-housed
- If cohoused:
- M/F ratio per cage: No data
- Verification of same strain and source of both sexes: Yes
- Proof of pregnancy: Vaginal plug, referred to as gestational day (GD) 0 of pregnancy - Duration of treatment / exposure:
- Daily from GD 6 to GD 15
- Frequency of treatment:
- Daily
- No. of animals per sex per dose:
- 25 mated rats
- Control animals:
- yes, concurrent vehicle
- other: Acetylsalicylic acid was given as a positive control
- Details on study design:
- - Dose selection rationale: Range-finding study
- Rationale for animal assignment (if not random): Based on a random number table
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes.
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: 0, 6, 15, and 20th day
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: ovaries and uterus - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes.
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - Approximately one third of the judgable fetuses were collectively fixed for later evaluation of internal organs. The other two thirds were eviscerated and the organs were evaluated for completeness and possible malformations.
- Spinal column: The number of cervical, thoracic, lumbar and caudal vertebrae and the number of ossification centers.
- Sacrum was evaluated.
- Pelvic bones and ribs were evaluated and counted.
- Bones of extremities.
- Sternal ossification centers were determined.
- All cranial bones were investigated for the presence and degree of ossification.
- Number of ribs and sternal ossification centers were recorded. - Statistics:
- Either the mean x together with the standard deviation s and sample size n or the absolute or percentage frequency is given. Data, with means and standard deviations, were compared by simple variance analysis and then a Scheffe test. With events for which there are absolute numbers and percentages or these can be calculated, first of all a kth 2-field chi2 test was applied using the related numbers that were also used for the calculation of the percentages. If significant differences were indicated, further checking was done with the four-field chi2 test. With small population numbers, Fischer's Exact Test was used. A significant limit of p = 0.05 was established for all tests.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Six of the dams in the highest-dose group died before the 20th day.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 90 mg/kg bw/day
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Statistically significant differences as compared to the negative control were found only in the highest-dose group. These differences manifested themselves as a reduction in the number of litters with live pups, lower average placenta weights, fewer total number of live pups, fewer live pups per litter, lower average body weight of a live pup, as well as an increase in the total resporptions, greater total number of late-dying embryos, greater total number of early dying embryos, higher percentage of dams with fetuses having minor alterations and greater frequency of fetuses having minor malformations. Major malformations were not found.
The postive control group showed the expected malformations in proportionate frequency and confirmed the sensitivity of the testing system.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day
- Basis for effect level:
- other: fetotoxicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- The test substance is strongly fetotoxic and might be weakly teratogenic, although only with doses high enough to be injurious to the dam.
- Executive summary:
Rats were evaluated in a developmental toxicity study via oral doses of 10, 30, and 90 mg/kg bw/day. Maternal toxicity in the form of lethality occurred in the 90 mg/kg bw/day exposure group only. Reduction in the number of litters with live pups, lower average placenta weights, fewer total number of live pups, fewer live pups per litter, lower average body weight of a live pup, as well as an increase in the total resporptions, greater total number of late-dying embryos, greater total number of early dying embryos, higher percentage of dams with fetuses having minor alterations and greater frequency of fetuses having minor malformations occurred in the 90 mg/kg bw/dayexposure group. Thus, these effects occurred at maternally toxic concentrations. The test substance was not uniquely toxic to the developing fetus. The NOAEL for maternal systemic effects was 30 mg/kg bw/day. The NOAEL for fetal developmental effects was 30 mg/kg bw/day.
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