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EC number: 202-966-0 | CAS number: 101-68-8
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- toxicity to reproduction
- Remarks:
- other: Chronic repeated dose toxicity test
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: This is only a short summary of the repeated dose toxicity study related to the reproductive organs, the full study can be found in section 7.5.2
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
- Principles of method if other than guideline:
- Chronic repeated dose toxicity test including macroscopically and gross pathologically assessment of the reproductive organs and tissues.
- GLP compliance:
- yes
Test material
- Reference substance name:
- 4,4'-methylenediphenyl diisocyanate
- EC Number:
- 202-966-0
- EC Name:
- 4,4'-methylenediphenyl diisocyanate
- Cas Number:
- 101-68-8
- Molecular formula:
- C15H10N2O2
- IUPAC Name:
- 1-isocyanato-4-[(4-isocyanatophenyl)methyl]benzene
- Details on test material:
- Monomeric 4,4'-methylenediphenyl diisocyanate (Desmodur 44 M Schuppen from Bayer AG, Leverkusen); 13 batches were tested (purity: >99.5 %)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- See section 7.5.2a Hoymann et al 1995 (rat, 2y)
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- See section 7.5.2a Hoymann et al 1995 (rat, 2y)
- Details on mating procedure:
- Not included in the test as this is a repeated dose test.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- See section 7.5.2a Hoymann et al 1995 (rat, 2y)
- Duration of treatment / exposure:
- up to 2 years
- Frequency of treatment:
- 17 hours per day; 5 days per week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 0.2, 0.7, 2.1 mg/m3
Basis:
nominal conc.
- No. of animals per sex per dose:
- 80 females per dose; at each dose level there were additional 80 rats per group in satellite groups for : chronic toxicity over 12 months (20 animals); lung function over 20 months (12 animals); lung clearance over 20 months (8 animals); bronchoalveolar lavage, biochemistry over 3 months +1 week recovery (20 animals); bronchoalveolar lavage, biochemistry over 12 months + 1 week recovery (20 animals).
- Control animals:
- yes, sham-exposed
- Details on study design:
- See section 7.5.2a Hoymann et al 1995 (rat, 2y)
Results and discussion
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Full pathological examination was done on 20 rats/dose of a 12 months exposure group and 20 rats/dose of a 24 months exposure group. Reproductive organs assessed included e.g. adrenals, ovaries, uterus, vagina and mammary gland. Compound-related changes were found in the respiratory tract(LOAEC 0.23 mg/m³), but no treatment related findings on reproductive or any other systemic organ effects were reported.
Applicant's summary and conclusion
- Executive summary:
In a further chronic inhalation study with respirable aerosols of 4,4’-MDI, 80 female rats per dose group were whole-body exposed to atmospheres of 0.23, 0.70 or 2.05 mg/m³ for 17 hours/day, 5 days /week for up to 24 months. Full pathological examination was done on 20 rats/dose of a 12 months exposure group and 20 rats/dose of a 24 months exposure group. Reproductive organs assessed included e.g. adrenals, ovaries, uterus, vagina and mammary gland. Again compound-related changes were found in the respiratory tract(LOAEC 0.23 mg/m³), but no treatment related findings on reproductive or any other systemic organ effects were reported (Hoymann et al. 1995; see repeated dose toxicity).
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