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Diss Factsheets
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EC number: 227-534-9 | CAS number: 5873-54-1
- 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
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Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Hypothesis: The molecular initiating event (MIE) for skin sensitization has been identified as reaction of bioaccessible NCO with glutathione. Since all MDI substances contain significant amounts of bioaccessible NCO, all substances of the MDI category are considered sensitizers.
Justification: The AOP for the acquisition of skin sensitization is well recognized. In the case of substances of the MDI category, the MIE of the sensitization process is the reaction of bioaccessible NCO on MDI with biological nucleophiles and particularly glutathione. All data including research and animal test data are consistent with this hypothesized MoA. All substances of the MDI category contain sufficient bioaccessible NCO to elicit the MIE of dermal sensitization. For an overview of skin sensitization data across the category members, see attached table under "overall remarks, attachments".
For more details see category justification document attached in IUCLID section 13 and field “Executive Summary” below.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test material
- Reference substance name:
- 2,4'-methylenediphenyldiisocyanate
- IUPAC Name:
- 2,4'-methylenediphenyldiisocyanate
Constituent 1
Results and discussion
In vivo (non-LLNA)
Results
- Reading:
- other: summary assessment of sensitization parameters from guinea pig studies that are part of the WoE
- Remarks on result:
- other: The four substances of the MDI category for which data are available consistently show skin sensitization.
Applicant's summary and conclusion
- Interpretation of results:
- other: harmonized CLP classification as skin sensitizer category 1 (H317)
- Conclusions:
- Based on the available read-across data, the target substance 2,4’-MDI is considered a skin sensitizer. This is based on the hypothesis that the skin sensitization potential of all MDI category members results from highly reactive NCO groups that react with extracellular biological nucleophiles and cellular proteins. These reactive NCO groups are present in all category substances to significant percentages. Therefore, for all category members for which no substance-specific data is available (including the target substance 2,4’-MDI), the harmonized EU classification of 4,4’-MDI as Skin Sens. Cat. 1 (H317) is adopted. This is in line with the current harmonized classification, with 2,4’-MDI classified as skin sensitizers category 1 (H317) CLP Annex VI Regulation (EC) No 1272/2008 (CLP regulation).
- Executive summary:
No skin sensitization data exist for the target substance 2,4’-MDI. This endpoint is satisfied by weight of evidence and read across from six valid skin sensitization studies performed with 4,4’-MDI, 2,2’-MDI, 4,4’-MDI homopolymer, and 4,4’-MDI/DPG, all belonging to the MDI category. All of the available studies are assigned Klimisch ratings of either 1 or 2.
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 are 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 low molecular weight bioaccessible groups on monomeric MDI and three-ring oligomer) which is responsible for chemical and physiological reactivity and subsequent toxicological profile. As mentioned above, all substances of the MDI category contain a high content of monomeric MDI. This is key to the hypothesised MoA for all substances of the MDI category.
Since it has been demonstrated that NCO value (as attenuated by solubility) is responsible for toxicity and the higher molecular weight, low solubility components do not contribute to the observed toxicity, it is reasonable to assume that their presence in these mixtures diminishes the overall toxicity causing variation in effect. However, as all substances contain sufficient bioaccessible MDI constituents to elicit effects, a worst-case approach is adopted in which the most bioaccessible substances are read across to all substances of the MDI category. Accordingly, the harmonized CLP classification (Category 1, H317) for 4,4’-MDI is adopted for all substances of the MDI category, including the target substance 2,4’-MDI. This is in line with the current harmonized classification, with 2,4’-MDI classified as skin sensitizers category 1 (H317) CLP Annex VI Regulation (EC) No 1272/2008 (CLP regulation).
For more details see category justification document attached in IUCLID section 13.
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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