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EC number: 209-544-5 | CAS number: 584-84-9
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- other information
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Significant methodological deficiencies: The test substance orally is degraded very rapidly to a variety of breakdown and polymerization products including 2,4-TDA and 2,6-TDA salts under the acidic conditions in the stomach; this study used a route of exposure inappropriate for assessing occupational risk in humans.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 978
- Report date:
- 1978
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Ten male and 10 female rats per group were dosed by gavage at 2.5 ml TDI solution in corn oil per kg body weight. Rats were 11 weeks old at start of dosing and were housed 5 males or 5 females per cage. The animals were observed twice daily, body weights measured weekly and gross necropsy
were performed on all rats. Histopathological examination was carried out on all control and high dose animals on 28 tissues as well as on
intercurrent deaths. Low and mid dose animals were subjected to similar histopathologic examination if high dose animals displayed effects. - GLP compliance:
- no
Test material
- Reference substance name:
- m-tolylidene diisocyanate
- EC Number:
- 247-722-4
- EC Name:
- m-tolylidene diisocyanate
- Cas Number:
- 26471-62-5
- Molecular formula:
- C9 H6 N2 O2
- IUPAC Name:
- m-tolylidene diisocyanate
- Details on test material:
- - Name of test material (as cited in study report): TDI unspecified.
Data on physical and chemical properties, eco-toxicity and toxicity can be used for read-across from 2,4-TDI to 2,6-TDI and mixed TDI isomers (i.e. 80/20, 65/35, 2,4/2,6 ratios). 2,4 TDI is the major component of the TDI mixed isomers and so has the major influence on their properties and effects. The reactivity of the 2,6-TDI isomer is somewhat less than that of 2,4-TDI but is of the same order of magnitude. It may therefore be concluded that the effects of 2,6-TDI will be similar to those of 2,4-TDI. This is in fact observed where there are overlapping data.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- 5 days per week, 13 weeks
Doses / concentrations
- Remarks:
- Doses / Concentrations:
15, 30, 60, 120, 240 mg/kg bw day
Basis:
actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day (actual dose received)
- Sex:
- male
- Dose descriptor:
- NOAEL
- Effect level:
- 60 mg/kg bw/day (actual dose received)
- Sex:
- female
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1: Clinical signs and mortality
Dose (mg/kg bw) |
60 |
120 |
240 |
Mortality (intercurrent deaths) |
1/10 males |
2/10 males |
1/10 females |
Respiratory noises |
1/10 males |
1/10 males |
3/10 males |
Table 2: Body weight
Dose (mg/kg bw) |
Body weight (percent controls at week 12 |
|
Males |
Females |
|
60 |
97.7 |
100 |
120 |
90.7 |
96.4 |
240 |
89.7 |
94.8 |
Table 3: Histopathology
Dose (mg/kg bw) |
60 |
120 |
240 |
Mucoid bronchopneumonia (accumulation of mucoid material in the bronchioles) - mild to moderate - moderate to severe - less severe |
1/10 males |
3/10 males 1/10 females |
8/10 males 2/10 females |
Applicant's summary and conclusion
- Executive summary:
Administration of m-tolylidene diisocyanate in corn oil to rats by oral gavage for five times per week for 13 weeks at dose levels of 0, 15, 30, 60, 120, and 240 mg/kg bw produced evidence of toxicity as seen by a depression in body weight gain in males treated at 60 mg/kg and above and in females treated at 120 mg/kg and above. Histopathologically, a dose-related appearance of accumulated mucoid material in the pulmonary bronchioles was observed in males treated at 60 mg/kg and above and in females treated at 120 mg/kg and above. One intercurrent death in females at 240 mg/kg was judged to be related to treatment.
In this subchronic rat study the NOAEL for males is 30 mg/kg/day and for females 60 mg/kg/day.
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