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Diss Factsheets
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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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 993
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Principles of method if other than guideline:
- Investigation of percutaneous absorption of 4.4'-methylenedianiline (MDA) after topical application to full-thickness skin from male Fischer 344 rats in flow-through diffusion cells, on four separate occasions.
- 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:
- RADIOLABELLING INFORMATION
- Radiochemical purity: >95%
- Specific activity: 56 mCi/mmol
- Locations of the label: [ring14C]4,4 '-methylenedianiline (Amersham) - Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan-OLAC (Oxford, Oxon, UK)
- Diet: CRM pellets, Biosure (Manea, Cambs., UK); ad libitum
- Water: ad libitum
Administration / exposure
- Type of coverage:
- other: occlusive and open
- Vehicle:
- ethanol
- Duration of exposure:
- 72 h
- Doses:
- - Actual doses: 39.4, 20.1, 21.6, 23.6 µg/cm²
- Dose volume: 5-10 µL - No. of animals per group:
- 4
- Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: dorsal region of male Fischer 344 rats
- Type of skin: full thickness
- Preparative technique: following sacrificion, the dorsal region was shaved with animal clippers and the shaved area was cut out with dissecting scissors. The rat skin sections were placed, epidermal side uppermost, on a plastic dissecting board and circles, 1.7 cm in diameter, were cut out using a circular sharpened steel cutter. Excess subcutaneous tissue was removed with a scalpel.
PRINCIPLES OF ASSAY
- Flow-through diffusion cell system: consisted of seven teflon diffusion cells and a fraction collector (Crown Glass Co Inc., Somerville, NJ, USA), a thermostatically controlled Churchill water circulator and a model 202V/AA16 cassette peristaltic pump (Watson-Marlow, Falmouth, Cornwall, UK). The receptor volume of each diffusion cell was 130 ul.
- Receptor fluid: HEPES buffered Hanks' balanced salt solution supplemented with 0.5% (v/v) gentamicin, continuously flowing
- Test temperature: 32°C
- the skin was placed in the diffusion cells in the flow-through apparatus, and allowed to equilibrate for about 30min.
- aliquots of 5-10 µL [14C]-MDA (17.7-40.6 µg/cm²) in ethanol were applied to the exposed skin surface.
- occlusion with teflon caps or left open.
- receptor fluid (1.5 mL) was collected hourly for up to 72h.
- at the end of the experiment (72h) the epidermal surface of the skin was washed, and the washings and skin were counted to determine radioactivity remaining on the skin surface.
ANALYSIS
- Liquid scintillation counting
STATISTICAL EVALUATION:
- Student`s t-Test for unpaired data, level of significance p<0.05.
Results and discussion
- Absorption in different matrices:
- See table 1
- Total recovery:
- - Total recovery: 94.5 +/-6 %
Percutaneous absorptionopen allclose all
- Dose:
- 20.1-39.4 µg/cm³
- Parameter:
- percentage
- Absorption:
- ca. 6.1 %
- Remarks on result:
- other: 72 h
- Remarks:
- open
- Dose:
- 20.1-39.4 µg/cm²
- Parameter:
- percentage
- Absorption:
- ca. 13.3 %
- Remarks on result:
- other: 72h
- Remarks:
- occlusive
Any other information on results incl. tables
Table 1: Recovery of radioactivity at 72h after topical application of [14C] MDA to rat skin in vitro (% of applied dose).
Rat (unoccluded) (n=12) | Rat (occluded) (n=16) | |
Receptor fluid | 6.1 ± 2 | 13.3 ± 4.0* |
Skin surface | 25.5 ± 6.8 | 21.5 ± 7.2 |
Diffusion cell | 5.4 ± 4.4 | 3.9 ± 2.6 |
Teflon cap | - | 0.3 ± 0.2 |
Skin surface | 57 ± 5.6 | 53.1 ± 8.6 |
Total | 94.5 ± 6.0 | 92.1 ± 6.5 |
* significantly different from unoccluded value (p<0.05)
A typical absorption profile showed a lag phase of about 2 hr before a rapid increase in absorption, reaching an equilibrium at 72 hr (data not shown).
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.
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