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EC number: 202-966-0 | CAS number: 101-68-8
- 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
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with acceptable restrictions (analytical purity of the test substance not reported, only 8 days observation)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 981
- Report date:
- 1981
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- analytical purity of the test substance not reported, only 8 days observation
- GLP compliance:
- no
Test material
- Reference substance name:
- 4,4'-methylenediphenyl diisocyanate
- EC Number:
- 202-966-0
- EC Name:
- 4,4'-methylenediphenyl diisocyanate
- Cas Number:
- 101-68-8
- Molecular formula:
- C15H10N2O2
- IUPAC Name:
- 1-isocyanato-4-[(4-isocyanatophenyl)methyl]benzene
- Reference substance name:
- benzene, 1,1'- methylenebis[4-isocyanato-
- IUPAC Name:
- benzene, 1,1'- methylenebis[4-isocyanato-
- Details on test material:
- - Name of test material (as cited in study report): Diphenylmethan-4,4'-diisocyanate
- Analytical purity: not reported
Constituent 1
Constituent 2
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Mean weight at study initiation: 2.3 Kg
- Housing: single
- Diet (e.g. ad libitum): ssniff (Seoest)
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12/12
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml in both eyes. - Duration of treatment / exposure:
- The right eye was wahed 30 s after application. The left eyes was kept unwashed
- Observation period (in vivo):
- 8 days
- Number of animals or in vitro replicates:
- 6
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): The right eye was wahed 30 s after application. The left eyes was kept unwashed
- Time after start of exposure:
SCORING SYSTEM: Draize score
Fluorescein-testing was performed a tthe right eye 24h after instillation.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- 6 animals
- Time point:
- other: 24-48-72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: no effects
- Remarks on result:
- other: Right eye (30 s exposure)
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- 6 animals
- Time point:
- other: 24-48-72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: no effects
- Remarks on result:
- other: Right eye (30 s exposure)
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- 6 animals
- Time point:
- other: 24-48-72 h
- Score:
- 0.78
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: Right eye (30 s exposure)
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- 6 animals
- Time point:
- other: 24-48-72 h
- Score:
- 0.61
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: Right eye (30 s exposure)
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- 6 animals
- Time point:
- other: 24-48-72 h
- Score:
- 0.05
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Remarks on result:
- other: left eye
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- 6 animals
- Time point:
- other: 24-48-72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: no effects
- Remarks on result:
- other: left eye
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- other: 24-48-72 h
- Score:
- 0.61
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: left eye
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- 6 animals
- Time point:
- other: 24-48-72 h
- Score:
- 0.56
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: left eye
Any other information on results incl. tables
Table 1: Individual draize scores in the left eye of rabbits (not rinsed)
Animal No. |
DRAIZE grade after |
Mean (24-48-72 h) |
|||||||||||
1h |
24h |
48h |
72h |
8days |
|||||||||
Conj. |
Che. |
Conj. |
Che. |
Conj. |
Che. |
Conj. |
Che. |
Conj. |
Che. |
Conj. |
Che. |
||
1 |
2 |
2 |
1 |
1 |
1 |
1 |
1 |
1 |
0 |
0 |
1.0 |
1.0 |
|
2 |
2 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
0 |
0 |
1.0 |
1.0 |
|
3 |
2 |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0.0 |
0.33 |
|
4 |
2 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0.0 |
0.0 |
|
5 |
2 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1.0 |
1.0 |
|
6 |
2 |
1 |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0.67 |
0.0 |
|
Mean |
2 |
1.16 |
0.67 |
0.67 |
0.67 |
0.5 |
0.5 |
0.5 |
0.16 |
0.16 |
|||
Mean of 6 animals (24-48-72 h) |
Conj. = 0.61 |
Che. = 0.56 |
Conj.: conjuctivae; Che.:Chemosis
Applicant's summary and conclusion
- Interpretation of results:
- other: harmonized CLP classification as eye irritant category 2 (H319)
- Conclusions:
- The current study is used as key source study used (Schneider 1981) for read-across to MDI category and indicates only slightly eye irritating effect after instillation of 4,4’-MDI. Only minimal cornea opacity was observed. Conjunctivae redness and chemosis up to grade 2 were observed in all animals 1 hour after substance instillation, but the severity decreased within 72 hours. Both effects were not fully reversible within 8 days of observation continued to subside so that on day 8, only one animal showed grade 1 redness and chemosis. No lesions of the iris were observed. The results of this study cannot be exactly compared to the CLP classification criteria as a reading on day 21 was not included. Given the low initial severity and the observed decrease of the effects over 8 days, it is likely that the results would not trigger a CLP classification as irritating to the eyes. However, five of the six tested MDI category substances did show signs of eye irritation. There is limited human information on mMDI (not further specified) which has been reported to cause eye irritation in exposed workers (Jennison et al., 1994). Members of the MDI category are officially classified as eye irritant (Cat.2) EU GHS 1272/2008 CLP.
- Executive summary:
In the eyes, the NCO functional group on MDI substances reacts with biological nucleophiles including glutathione and proteins (e.g. in the tear film, the conjunctival epithelium, or the corneal epithelium) leading to inflammatory irritation. Reliable eye irritation data from animal studies are available for only representative substances of the MDI category. With five of the six tested substances, signs of eye irritation, but not of corrosion, were observed. The onset of irritating properties observed in the available studies is consistent with the hypothesized MoA and that local toxicity of the category substances is driven by the rapid reaction of the bioaccessible NCO group on mMDI with extracellular biological nucleophiles such as glutathione and protein, resulting in ocular irritation and an acute inflammatory response.
All substances of the MDI category share similar chemical features namely that they a) all contain a significant amount of mMDI, and b) contain at least two NCO functional groups per molecule which is bound to an aromatic ring and this ring is connected to a second aromatic ring by a methylene group. It is the NCO value (driven by the bioaccessible groups on monomeric MDI and low molecular weight constituents (e.g. three-ring oligomer) which is responsible for chemical and physiological reactivity and subsequent toxicological profile. As reactive NCO groups are a common feature of all substances of the MDI category, it is predicted that these have a similar reactivity profile and a read across within the category is warranted (detailed information on the Mode of Action is available in Category Justification Document).
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