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: 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

Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards; sufficiently documented and acceptable for assessment.
- Justification for type of information:
- Hypothesis: By dermal contact, the majority of the available NCO groups react with proteins and moisture on the skin, leading to the formation of an insoluble polymerized mass limiting absorption such that only a small fraction is available to penetrate into the viable skin layers. Residual toxicity, as demonstrated by mild irritation potential, is consistent with the hypothesized MoA that effects are driven by the rapid MDI-adduct formation with extracellular biological nucleophiles, which results in tissue damage and acute inflammation with the release of inflammatory mediators and cytokines.
Justification: All tested substances caused signs of skin irritation including inflammation (erythema and oedema) and additionally in some cases hyperplasia (thickening (coriaceousness), scaling, flaking or fissuring). Although not all studies demonstrated full reversibility of these signs, their severity decreased towards the end of the studies, such that only mild symptoms remained by the end of the observation periods. Furthermore, no signs of irreversible skin damage (i.e. ulcers, bleeding, bloody scabs, skin blanching, alopecia, scars or other signs indicative of necrosis into the dermis) were reported in any of the available studies, justifying all substances of the MDI category being regarded as skin irritants of category 2 as opposed to category 1
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 977
- Report date:
- 1977
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- 0.5 ml of undiluted compound was applied to the clipped, intact abd abraded skin of six albino male and female rabbits under a one inch by one inch square patch, two single layers thick. The patches were held in place with adhesive tape. The trunk of each animal was wrapped with plastic strips, to retard evaporation and avoid contamination, for the 24-hr exposure period. Observations were made over a period of seven days. The data were scored according to the method of Draize, Woodard and Calvery (Journal of Pharm. and Exp. Therapeutics, Vol. 82, Dec. 1944).
- GLP compliance:
- no
Test material
- Reference substance name:
- 75880-28-3
- Cas Number:
- 75880-28-3
- IUPAC Name:
- 75880-28-3
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- other: albino
- Details on test animals or test system and environmental conditions:
- no data
Test system
- Type of coverage:
- occlusive
- Preparation of test site:
- other: shaved (intact) and abraded
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not specified
- Amount / concentration applied:
- Amount(s) applied: 0.5 ml/animal
- Duration of treatment / exposure:
- 24 hours
- Observation period:
- 1, 24, 48, 72 hours and 5, 7 days after removal of patches
- Number of animals:
- intact skin: 3 males and 3 femals,
abraded skin: 3 males and 3 femals - Details on study design:
- see "Principles of method"
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- other: erythema score (intact skin)
- Basis:
- animal: #1, 2, 3, 4, 5, 6
- Time point:
- other: 24, 48, 72 hours
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: mean score after 24, 48 and 72 hours: 2.0
- Irritation parameter:
- other: edema score (intact skin)
- Basis:
- animal: #1, 2, 3, 4, 5, 6
- Time point:
- other: 24, 48, 72 hours
- Score:
- 1 - 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: mean score after 24, 48 and 72 hours: 1.1
- Irritation parameter:
- other: erythema score (abraded skin)
- Basis:
- animal: #1, 2, 3, 4, 5, 6
- Time point:
- other: 24, 48, 72 hours
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: mean score after 24, 48 and 72 hours: 2.0
- Irritation parameter:
- other: edema score (abraded skin)
- Basis:
- animal: #1, 2, 3, 4, 5, 6
- Time point:
- other: 24, 48, 72 hours
- Score:
- 1 - 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: mean score after 24, 48 and 72 hours: 1.4
- Irritant / corrosive response data:
- Observations following application (intact and abraded skin):
1 hour: no erythema or edema (zero readings)
24 hours: slight erythema, very slight to slight edema
48-120 hours: gradual improvement
168 hours: all scored zero - Other effects:
- none
Any other information on results incl. tables
Applicant's summary and conclusion
- Interpretation of results:
- other: slightly irritating
- Conclusions:
- The test substance 4,4'-MDI/TPG was slightly irritating when tested on male and female rabbits. However, 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. 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 (for more details see Category Justification Document IUCLID section 13).
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. Therefore, the harmonized CLP classification as skin irritant category 2 (H315) for 4,4’-MDI is adopted for all category substances, including the substance 4,4’-MDI-TPG. - Executive summary:
The test substance 4,4'-MDI/TPG was slightly irritating when tested on male and female rabbits under occlusive conditions. 24 hours after application slight erythema and very slight to slight edema were observed. All effects were fully reversible within 7 days.
Even the test results indicate only a slightly irritating effect, reversible within 7 days, the MDI group approach is followed and a worst-case approach is adopted in which the most bioaccessible substances are read across to all substances of the MDI category. Therefore, the harmonized CLP classification as skin irritant category 2 (H315) for 4,4’-MDI is adopted for all category substances, including the substance 4,4’-MDI-TPG.
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.
