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: 202-974-4 | CAS number: 101-77-9
- 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

Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Remarks:
- Incomplete histopathology. Only one dose tested. Atmosphere analyzed gravimetrically only.
Data source
Reference
- Reference Type:
- publication
- Title:
- Retinopathy from inhaling 4,4'-methylenedianiline aerosols
- Author:
- Leong BKJ, Lund JE, Groehn JA, Coombs JK, Sabaitis CP, Weaver RJ & Griffin RL
- Year:
- 1 987
- Bibliographic source:
- Fund.Appl.Toxicol. 9: 645-58
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test: Guinea pigs were exposed for 2 weeks to aerosols of the test item.
- Short description of test conditions: Animals were exposed nose-only. After the 2 weeks of exposure the exposed animals were kept for a 2-week "incubation" period.
- Parameters analysed / observed: Following a 2-week incubation period, each animal was tested for dermal irritation, dermal sensitization (0.05, 2, 20, 200 mg test item/mL PEG) followed by tests for pulmonary sensitization in tracheostomized animals (200 mg test item/mL PEG). The animals were then killed, and histopathologically examined (only few organs were investigated, no histopathology on the upper respiratory tract).
- GLP compliance:
- no
Test material
- Reference substance name:
- 4,4'-methylenedianiline
- EC Number:
- 202-974-4
- EC Name:
- 4,4'-methylenedianiline
- Cas Number:
- 101-77-9
- Molecular formula:
- C13H14N2
- IUPAC Name:
- 4,4'-methylenedianiline
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Purity: 94.6 % Test substance, 2.1 % of test substance isomere, plus small percentages of trimers and monoformamide
Test animals
- Species:
- guinea pig
- Strain:
- other: albino Hartley and pigmented guinea pigs of mixed variety
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 350 - 539 g
- Housing: individually in regular caging facilities
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: polyethylene glycol 200 (PEG)
- Remarks on MMAD:
- MMAD / GSD: The average aerosol particle size was 2.4 micrometers as determined by light scattering.
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: The test atmosphere was generated by atomizing a solution of 200 mg test item/mL PEG into an air elutriator.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Air samples were taken through preweighed glass filters (1 L/min for 5 min). The quantity of test item-PEG was determined gravimetrically. The actual quantity was calculated with the density of the solution.
The aerosol particle size distribution was monitored using a light scattering particle size analyser. - Duration of treatment / exposure:
- 10 exposures in 14 days
- Frequency of treatment:
- 4 hours/day; 5 days/week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/L air
- Remarks:
- time-weighted average aerosol concentration
- Dose / conc.:
- 0.44 mg/L air
- Remarks:
- time-weighted average aerosol concentration
- No. of animals per sex per dose:
- 8
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: 14 days
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: not specified
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:
Irritation assay:
Observations for erythema and edema were performed 1, 2, 3, 4, and 24 h postapplication and graded according to the Draize procedure.
Pulmonary sensitization assay:
Measurement of the lung insufflation pressures (LIP) following aerosol application of 10 and 50 µl (200mg MDA/ml PEG) to tracheostomized and cannulated animals. - Sacrifice and pathology:
- GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes, eyes, lungs, liver, kidney, spleen
Results and discussion
Effect levels
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 0.44 mg/L air
- Sex:
- male
Any other information on results incl. tables
During exposures no overt respiratory
distress was observed. Ten 4 h-exposures to 0.44 mg/mL test item aerosol
produced no visible symptoms in guinea pigs (albino and pigmented). Even
after challenge by dermal application of a solution of the test item in
polyethylene glycol (2, 20 or 200 mg/mL) 2 weeks after the last
inhalation application no symptoms were detected. Likewise challenge
with an test item-PEG aerosol (200 mg/mL) did not result in changes in
lung insufflation pressure of tracheostomized guinea pigs. There
was slight body weight loss during the exposure days,
and recovery during the 2 resting weekend days. It was said
that this might have been due to stress rather than exposure to the test
item, since the trends in body weight gain for the entire
experimental period were comparable between the exposed and
control animals.
The most prominent histopathological findings were degeneration
of the inner and outer segments of the photoreceptor cells
and the pigmented epithelial cell layer of the retina in both kinds
of guinea pig.
7/16 exposed animals had pulmonary granulomas against 1/8 control
animals. The granulomas were small and
consisted of an aggregate of macrophages surrounded by a
think mantle of lymphocytes. MDA particles were not evident.
3/16 exposed animals had a slight to mild granulomatous pneumonitis, as
had 1/8 control animals which had received a challenge dose of test
item-PEG aerosol during the pulmonary sensitization test.
There were no histological changes in liver or kidneys related to test
item-PEG treatments.
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.
