Registration Dossier
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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

Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 6 mg/m³
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- The study is GLP compliant and is of sufficient quality (Klimisch score=2)
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 0.2 mg/m³
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- The study is GLP compliant and is of sufficient quality (Klimisch score=2)
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity - read-across with other MDI substances
Since no data on repeated dose toxicity are available for MDI-TPG, such data have been 'read across' from polymeric MDI. Inhalation exposure is the most appropriate route for assessing occupational risk in humans. Effects from repeated exposure of animals to 4,4-MDI are limited to effects on the respiratory tract caused by local irritation.
In a combined chronic toxicity and carcinogenicity key study (Reuzel et al., 1990, 1994; GLP reliability 2 study conducted according to OECD Duideline 453 - combined chronic toxicity/carcinogenicity studies) rats were exposed for 6 hours/day, 5 days/week for 1 year (satellite groups) or 2 years (main groups) to polymeric MDI aerosol concentrations of 0, 0.2, 1.0 or 6.0 mg/m3 (analytical conc.: 0, 0.19, 0.98, 6.03 mg/m3) . The effect of chronic exposure of rats to respirable polymeric MDI aerosol was confined to the respiratory tract. The compound-related changes were found in the nasal cavity, the lungs and the mediastinal lymph nodes, and to some degree they were already present after 1 year of exposure. Histopathology of the organs/tissues investigated showed that exposure to 6.0 mg/m³ over 2 years was related to the occurence of pulmonary tumors in males (6 adenomas and 1 adenocarcinoma) and females (2 adenomas). In this 2-year rat study the NOAEC was 0.2 mg/m3 for the repeated dose toxicity of polymeric MDI. The LOAEC was set on 1.0 mg/m3.
A chronic inhalation study (Hoymann et al., 1995) has been conducted with monomeric 4,4-MDI. Female Wistar rats were exposed to 0.23, 0.70 or 2.05 mg/m3 4,4-MDI aerosols for 17 hours/day, 5 days /week for up to 24 months. Essentially, a dose-dependent impairment of the lung function in the sense of an obstructive-restrictive malfunction with diffusion disorder, increased lung weights, an inflammatory reaction with increased appearance of lymphocytes in the lung in the high dose group as a sign of specific stimulation of the immune system by MDI, an intermediately retarded lung clearance in the high dose group as well as dose-dependent interstitial and peribronchiolar fibrosis, alveolar bronchiolisations and a proliferation of the alveolar epithelium, which was classified as preneoplastic, as well as a bronchiolo-alveolar adenoma were ascertained. Therefore, the LOAEC for the female rat was 0.23 mg/m3 after long-term inhalation of 4,4-MDI aerosols. The proof of MDA-DNA adducts in marginal amount after 12 months MDI exposure is possibly feigned by the strong protein binding. The toxicological relevance of this finding is doubtful since MDI leads only in high concentrations to degeneration of the olfactory epithelium (Greim H (ed.) 2008, in: Occupational Toxicants - Critical data evaluation for MAK values and classification of carcinogens, Wiley-VCH, Weinheim, Vol. 14).
In a chronic rat study with polymeric MDI the NOAEC was 0.2 mg/m3 after aerosol exposure over 2 years (6 hours/day, 5 days/week) (Reuzel et al. (1990,1994). A comparison of the both chronic rat studies with 4,4'-MDI and polymeric MDI has shown very good consistency across the studies with respect to gradation of inhaled dose and the observed histopathological changes. In this review it was concluded that a daily 17 hr-exposure of 0.23 mg/m3 4,4-MDI corresponds approximately to a daily 6 hr-exposure of 1 mg/m3 polymeric MDI (Feron et al. (2001), Arch. Toxicol. 75: 159-175).
In this 2-year rat study the NOAEC was 0.2 mg/m3 for the repeated dose toxicity of polymeric MDI. The LOAEC was set on 1.0 mg/m3.
Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Only one key study available
Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Only one key study available
Justification for classification or non-classification
Based on the classification of monomeric MDI according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008 (CLP) the following classification is recommended for MDI-TPG (read-across based on grouping of substances - category approach):
Repeated inhalation toxicity
With regard to repeated dose inhalation toxicity MDI was classified according to Directive 67/548/EEC with R48/20 (danger of serious damage to health by prolonged exposure) and according to Regulation (EC) No. 1272/2008 (CLP) with STOT Repeated Exp. Cat 2 (H373: may cause damage to the respiratory system through prolonged or repeated exposures).
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