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EC number: 218-485-4 | CAS number: 2162-73-4
- 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:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Please refer to Read-across statement in section 13
Data source
Materials and methods
Test material
- Reference substance name:
- 2,4,6-triisopropyl-m-phenylene diisocyanate
- EC Number:
- 218-485-4
- EC Name:
- 2,4,6-triisopropyl-m-phenylene diisocyanate
- Cas Number:
- 2162-73-4
- Molecular formula:
- C17H22N2O2
- IUPAC Name:
- 2,4-diisocyanato-1,3,5-tris(propan-2-yl)benzene
- Test material form:
- liquid
Constituent 1
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 1 of 10 males died in the 60 mg/kg bw group. 2 males died in the 120 mg/kg bw group. 1 of 10 males died in the 240 mg/kg bw group. 1 of 10 males (60 and 120 mg/kg bw) and 3 males (240 mg/kg bw) showed respiratory noises.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 1 of 10 males died in the 60 mg/kg bw group. 2 males died in the 120 mg/kg bw group. 1 of 10 males died in the 240 mg/kg bw group. 1 of 10 males (60 and 120 mg/kg bw) and 3 males (240 mg/kg bw) showed respiratory noises.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight decrease in body weights of all groups of males was evident (down to 89.7 % of the controls in the 240 mg/kg bw dose group).
- 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
- Description (incidence and severity):
- Mukoid bronchopneumonia was evident in 1 of 10 males (60 mg/kg bw), 3 of 10 males and 1 of 10 females (120 mg/kg bw) and in 8 of 10 males and 2 of 10 females (240 mg/kg bw).
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- no further details available
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 60 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: not specified
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
- Conclusions:
- The study is considered to be not reliable (reliability Klimisch 3). However, the validity criteria of the test system were fulfilled. The test material did induce slight signs of toxicity (depression in body weight gain, mucoid bronchopneumonia, mortality). The test material was considered to be toxic via the oral exposure route under the conditions of the test, which is based on the NOEAL values derived from this study (NOAEL: 30 mg/kg bw (male rats) and 60 mg/kg bw (females).
- Executive summary:
The study was conducted to provide information on the possible health hazards likely to arise from repeated treatment with the test article m-tolylidene diisocyanate (Gordon, 1978). The test material was administered once daily via oral gavage, 5 days a week, for 13 weeks. The test material was solved in corn oil and administered to six groups, each of ten male and ten female Fischer344 rats, at dietary concentrations of 15, 30, 60, 120 and 240 mg/kg/day. A further group of ten males and ten females was exposed to vehicle only to serve as a control. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy examination and a comprehensive histopathological evaluation of organs and tissues was performed.
There were mortalities and clinically observable signs of toxicity in the test animals the study period. Of the Males treated with 60 mg/kg bw 1 animal died. Additionally 2 males died in the 120 mg/kg bw group and 1 died in the 240 mg/kg bw group. One intercurrent death was noted in females treated at 240 mg/kg bw, which was judged to be related to treatment. 1 of 10 males (60 and 120 mg/kg bw) and 3 males (240 mg/kg bw) showed respiratory noises. A slight decrease in body weights of males treated with 60 mg/kg bw and above was evident (down to 89.7 % of the controls in the 240 mg/kg bw dose group) and in females treated with 120 mg/kg bw and above . Toxicological significant effects (respiratory noises) noted were detected in male animals treated with 60, 120 and 240 mg/kg bw. Histopathological findings were detected in males treated at 60 mg/kg bw and above and in females treated at 120 mg/kg bw and above a dose-related appearance of accumulated mucoid material in the pulmonary bronchioles. Thus, in this rat subchronic repeat dose toxicity study, the No-Observable-Adverse-Effect Level (NOAEL) of the test article m-tolylidene diisocyanate for males is 30 mg/kg/day and for females 60 mg/kg/day.
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