Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Acute Toxicity: dermal
Administrative data
- Endpoint:
- acute toxicity: dermal
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Hypothesis: In the case of dermal exposure, before the reactive NCO groups present on MDI substances have opportunity to be absorbed to any significant extent through the stratum corneum they react with proteins and moisture at the skin surface leading to the formation of an insoluble polymerized mass thereby limiting dermal absorption and systemic availability. Modified MDI substances, having a higher molecular weight than mMDI isomers and due to their higher molecular volume, increased octanol-water partition coefficient and decreased water solubility will in any event not be able to penetrate the stratum corneum.
Justification: Considering that there is only data available for two substances of the MDI category this is insufficient to serve as the sole basis for concluding consistency of effects within the data matrix. However, since the formation of inert polyureas is dependent on the presence of reactive NCO groups and all substances acting via this common mechanism contain high levels of such groups, this justifies the claim of consistency within the matrix with high confidence.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 964
Materials and methods
Test material
- Reference substance name:
- 2,4'-methylenediphenyldiisocyanate
- IUPAC Name:
- 2,4'-methylenediphenyldiisocyanate
Constituent 1
Results and discussion
Effect levels
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- > 9 400 mg/kg bw
- Remarks on result:
- other: Weight of evidence, Based on the available study data all members of the MDI category are regarded as relatively non-toxic for the endpoint acute dermal toxicity and
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- No acute dermal data exist for the target substance 2,4'-MDI . Accordingly, this endpoint is satisfied by a weight of evidence and read-across from valid acute oral toxicity studies on category substances . The study used (Wazeter et al. 1964) ) for read-across did not find lethality up to the maximum dose tested, and the LD50 was greater than 9,400 mg/kg bw (Wazeter et al., 1964a). A lack of acute dermal toxicity is confirmed by the available acute dermal toxicity studies of the MDI category (see table attached background material). Based on the available study data all members of the MDI category are regarded as relatively non-toxic for the endpoint acute dermal toxicity and are not classified according EU GHS 1272/2008 CLP.
- Executive summary:
The available acute dermal toxicity studies indicate that all substances of the MDI category have low acute dermal toxicity. The study describing the acute dermal toxicity of pMDI in rabbits did not find lethality up to the maximum dose tested, and the LD50 was greater than 9,400 mg/kg bw (Wazeter et al., 1964a). Other less reliable studies on pMDI or 4,4’-MDI are consistent with this. Observed differences in LD50 values between pMDI and 4,4'-MDI/TPG are not considered to be significant or represent a trend since they are significantly higher than the limit for classification and are indicative of a lack of systemic exposure. The available data for the substances of the MDI category is consistent with the hypothesis that NCO groups present on MDI substances react with proteins and moisture at the skin surface leading to the formation of an insoluble polymerized mass resulting in limited dermal absorption and systemic availability. The available data and hypothesis is supported by the key dermal absorption study that shows that MDI substances have very low systemic bioavailability (<1 %) (Leibold et al., 1999). By comparison, modified MDI substances, with molecular weight greater than mMDI, will
demonstrate even further reduced dermal absorption based upon physico-chemical properties (i.e. increased octanol-water partition coefficient, decreased water solubility, and increased molecular weight), and this has been confirmed with GastroPlus™ modeling (Bartels, 2021). Although a reliable, acute dermal in vivo toxicity data is only available on two category substances, it is considered sufficient for assessment of this endpoint for the category.
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).
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)