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EC number: 701-124-4 | CAS number: -
- 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
Respiratory sensitisation
Administrative data
- Endpoint:
- respiratory sensitisation: in vivo
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Hypothesis: Available NCO groups present on the substances react readily with nucleophilic groups such as amines, thiols and alcohols, the primary reaction partner in the epithelial lung fluid being glutathione. Subsequent transcarbamoylation from GSH to a protein, or direct reaction of NCO with a protein, marks antigen formation and the MIE of the sensitization process. Upon re-exposure via the respiratory route, protein-hapten complexes are recognized by the immune system, triggering an immunological response resulting in the induction of sensitization. Therefore, as the MIE is driven by the NCO groups on MDI substances, NCO reactivity with biological nucleophiles is the critical chemical reaction that drives the sensitization response and has been demonstrated for worst-case boundary substances (4,4’-MDI and pMDI). All category substances containing bioaccessible NCO will be classified as respiratory sensitizers.
Justification: Although there are no guidelines available for respiratory sensitization studies in animals, several researchers have shown respiratory changes in animals after induction exposure and subsequent challenge with both 4,4’-MDI and pMDI. The studies showed some type of respiratory response (alterations in respiratory rate, non-specific hyperreactivity, influx of inflammatory cells), however differences in immunogenicity observed clearly reflect variation in induction exposure route and/or challenge concentration. Attempts to sensitize guinea pigs by single inhalation exposure only to 4,4’-MDI showed borderline responses at best as compared with potent respiratory sensitizers such as ovaalbumin and trimellitic anhydride. Respiratory responses were only provoked in animals challenged with overtly irritant concentrations of 4,4’-MDI or pMDI. For an overview of respiratory 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:
- 1 994
- Report date:
- 1994
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 994
Materials and methods
Test material
- Reference substance name:
- 75880-28-3
- Cas Number:
- 75880-28-3
- IUPAC Name:
- 75880-28-3
Constituent 1
Results and discussion
- Results:
- Attempts to sensitize guinea pigs by inhalation exposure to MDI were unsuccessful. No animals exhibited pulmonary responses following challenge with atmospheric MDI. In contrast, a proportion of animals exhibited pulmonary responses following inhalation challenge after induction by intradermal injection or topical application
Any other information on results incl. tables
GROUP |
% MDI |
PULMONARY RESPONSES |
PCA |
Topical 1 |
0 |
0/8 |
0/8 |
Topical 2 |
10 |
2/8 |
0/8 |
Topical 3 |
30 |
2/8 |
2/8 |
Topical 4 |
100 |
3/7 |
2/8 |
Intradermal 1 |
0 |
0/8 |
0/8 |
Intradermal 2 |
0.0003 |
0/6 |
0/8 |
Intradermal 3 |
0.003 |
1/8 |
0/8 |
Intradermal 4 |
0.03 |
5/8 |
1/8 |
Intradermal 5 |
0.3 |
5/8 |
3/8 |
Inhalation 1 |
0 mg/m3 |
1/7 |
0/8 |
Inhalation 2 |
19.4-23.7 mg/m3 |
0/16 |
0/16 |
Applicant's summary and conclusion
- Interpretation of results:
- sensitising
- Conclusions:
- Based on the available read-across data, the target substance 4,4'-MDI/TPG is considered a respiratory sensitizer. This is based on the hypothesis that the respiratory 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, all category members for which no substance-specific data is available (including the target substance 4,4'-MDI/TPG) are assigned the CLP classification as respiratory sensitizer (Cat. 1, H334) for 4,4’-MDI.
- Executive summary:
No respiratory sensitization data exist for the target substance 4,4'-MDI/TPG. This endpoint is satisfied by weight of evidence and read across from two respiratory sensitization studies performed with 4,4’-MDI and pMDI, both 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 CLP classification (Cat. 1, H334) for 4,4’-MDI is adopted for all other substances in the MDI category, including the target substance 4,4'-MDI/TPG.
For more details see category justification document attached in IUCLID section 13.
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