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EC number: 202-039-0 | CAS number: 91-08-7
- 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
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer reviewed journal
Data source
Reference
- Reference Type:
- publication
- Title:
- Dermal uptake and excretion of 14C-toluene diisocyante (TDI) and 14C-methylene diphenyl diisocyanate (MDI) in male rats. Clinical signs and histopathology following dermal exposure of male rats to TDI
- Author:
- H.D. Hoffmanna, E. Leiboldb, C. Ehnesb, E. Fabiana, R. Landsiedela, A.Gamera, A. Poolec
- Year:
- 1 999
- Bibliographic source:
- Toxicology Letters 199 (2010) 364–371
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: as per mentioned below
- Principles of method if other than guideline:
- To evaluate the skin irritation effect of Toluene Diisocyanate in male Crl:WI (HAN) rats.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 2, 4Toluene diisocyanate
- IUPAC Name:
- 2, 4Toluene diisocyanate
- Reference substance name:
- 2-methyl-m-phenylene diisocyanate
- EC Number:
- 202-039-0
- EC Name:
- 2-methyl-m-phenylene diisocyanate
- Cas Number:
- 91-08-7
- Molecular formula:
- C9H6N2O2
- IUPAC Name:
- 1,3-diisocyanato-2-methylbenzene
- Test material form:
- other: liquid
- Details on test material:
- - Name of test material (as cited in study report): 2,6-Toluene diisocyanate
- Molecular formula: C9H6N2O2
- Molecular weight: 174.1584 g/mol
- Smiles notation: c1(cccc(c1C)N=C=O)N=C=O
- InChl: 1S/C9H6N2O2/c1-7-8(10-5-12)3-2-4-9(7)11-6-13/h2-4H,1H3
- Substance type: Organic
- Physical state: Liquid
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Crl:WI (HAN)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Germany.
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 300 to 350 g
- Fasting period before study: No data available
- Housing: They were housed individually,
in Macrolon cages or all glass metabolism cages
- Diet (e.g. ad libitum): Feed was Kliba lab diet was available for consumption ad libitum Water (e.g. ad libitum): Tap water was available for ad libitum
- Acclimation period: No data available.
Test system
- Type of coverage:
- semiocclusive
- Preparation of test site:
- other: 24hours before dermal administration of the test material an area on the back of the animals was clipped free of hair (about 10 cm2) and washed with acetone.
- Vehicle:
- not specified
- Controls:
- other: Untreated skin areas of each animal served as control
- Amount / concentration applied:
- Preparation of test site (only for skin irritation):
24hours before dermal administration of the test material an area on the back of the animals was clipped free of hair (about 10 cm2) and washed with acetone. Prior to application a silicone ring spacer (2mm×34mm;
thickness×diameter) was glued on the skin (Histoacryl®; B. Braun, Germany). Test
material preparations were applied on the surface of the application site using a pipette
. Nylon mesh gauze was then glued on the surface of the silicone ring and a porous bandage was used to encircle the trunk of the animal.
Amount/concentration applied: 350 mg/kg - Duration of treatment / exposure:
- 8hour
- Observation period:
- 48Hour
- Number of animals:
- 6 male rats
- Details on study design:
- Details on study design
TEST SITE
- Area of exposure: The back of the animals.
- % coverage: 10 cm2
- Type of wrap if used: Nylon mesh gauze
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 8 hour
SCORING SYSTEM: Draize Method
Results and discussion
In vivo
Results
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: 48
- Max. score:
- 5
- Reversibility:
- no data
- Remarks on result:
- other: The local skin changes observed during visual assessment of skin reaction were irritation with prominent skin oedema and an increase in severity of signs during the post exposure period of two days
- Irritant / corrosive response data:
- The clinical observation of progressive irritation was verified by the histopathological changes which showed minimal to slight effects at 8 h which became more severe 48 h after treatment.
- Other effects:
- Due to the fact that dead animals in general do not show dermal erythema or dermal oedema no skin macroscopic changes were observed during necropsy. Histopathological examination of samples of skin from 6 non treated animals as control for the dermal exposure with 2,6 TDI revealed minimal focal serocellular crusts in 2 samples and in one sample a focally extensive sub- and intraepidermal and perifollicular micro abscesses with necroses.
Any other information on results incl. tables
TABLE 1:The assessment of skin reactions according to Draize and definition of gradings used for histopathology |
|||
Grading |
Erythema |
Oedema |
Histopathology |
0 |
No erythema |
No oedema |
- |
1 |
Very slight; barely perceptible |
Very slight; barely perceptible |
Minimal |
2 |
Well defined |
Slight; edges well defined by raising |
slight |
3 |
Moderate to severe |
Moderate raised approximately 1mm |
Moderate |
4 |
Severe (beet redness) eschar formation preventing grading of E |
Severe raised more than 1 mm; extending beyond area of exposure |
Marked, severe
|
5 |
- |
- |
Massive. extreme |
Table 2 Clinical skin findings and histopathological findings following treatment with 2, 6 TDI at a dose level of about 350 mg/kg body weight; 12mg/cm2. |
|||
|
Exposure time (dermal) 8 h (2,6 TDI) |
||
Clinical observation (hours after start of exposure |
8 |
24 |
48 |
Number of animals clinical observation |
6 |
3 |
3 |
Number of animals sacrificed + histopathology |
3 |
- |
3 |
Clinical findings |
|
|
|
Erythrema (number of animals/grading) |
6/none |
2/none 1/1 |
1/1 2/2 |
Oedema (number of animals/grading) |
1/12/23/3 |
2/1 1/2 |
1/1 2/2 |
Dryness of skin (number of animals) |
6 |
3 |
3 |
Intensified sensitivity to touch at application site (number of animals) |
None |
None |
3 |
Histopathological findings Minimal to slight multifocal to coalescing subepidermal edema//minimal to slight multifocal hydropic degeneration of basal cell layer with cleft formation//slight diffuse spongiosis//multifocal full thickness necrosis of epidermis//minimal diffuse and perivascular lymphoplasmacytic infiltration//foreign material (yellow-brownish) with keratin scales (number of animals/grading) |
|
|
|
1/1-2 2/2 |
- |
-
|
|
Multifocal serocellular crusts//moderate to severe multifocal to coalescing epidermal full thickness necrosis with sub- and intraepidermal as well as follicular and perifollicular micro-abscesses, exocytosis and numerous degenerated neutrophilic granulocytes with erosion and ulceration//slight to moderate perivascular lymphoplasma-histiocytic and neutrophilic infiltration//Slight to moderate diffuse spongiosis, acanthosis and hydropic degeneration of basal cell layer (number of animals/grading) |
- |
- |
1/2-3 1/3 1/3-4 |
Note: No macropathologic abnormalities of the treated skin were observed in the dead animals prior to skin sampling for histopathology. |
Applicant's summary and conclusion
- Interpretation of results:
- irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The test chemical 2, 6-Toluene diisocyanate (CAS No: 91-08-7) was considered to be an irritant in male Crl: WI (HAN) rats.
- Executive summary:
The skin irritation study for 2,6Toluenediisocyanate was conducted inmale Crl: WI (HAN) rats for observation period of 48 hour period.
For this experiment 4 groups of 3 animals were treated with test chemical on clipped area on the back of the animals which was carefully checked for pre-existing signs of skin irritation or dense patches of hair. Only animals with intact healthy skin were used. From the selected animals 6 were dosed with pure liquid 2,6-TDI (nominal 350 mg/kg body weight; 12mg/cm2) and placed in Macrolon cages (single caging). After the exposure period of 8 h the protective cover was removed from all animals and the treated skin was examined clinically. Afterwards 3 animals dosed with 2, 6-TDI were sacrificed. Without prior washing treated and untreated skin (control) was excised and processed for histopathological examination. Two groups of 3 animals dosed with 2,6-TDI were kept for further clinical observation. After washing of the exposed skin with Lutrol E 400. These animals were kept in Macrolon cages (single housing) until sacrifice about 48 h post exposure. Subsequently treated and untreated skin (control) was excised and processed for histopathological examination.Grading of skin reactions used according to Draize and grading used for histopathology show that the chemical is slightly irritant to skin.
At 8 h the findings were characterized by minimal to slight multifocal to coalescing subepidermal oedema, minimal to slight multifocal hydropic degeneration of basal cell layer, slight diffuse spongiosis and multifocal full thickness necrosis of epidermis. At 48 h the effects were more severe with findings of multifocal serocellular crusts, moderate to severe multifocal to coalescing epidermal full thickness necrosis with sub- and intra-epidermal as well as follicular and perifollicular micro-abscesses, exocytosis and numerous degenerated neutrophilic granulocytes with erosion, slight to moderate perivascular lymphoplasma-histiocytic and neutrophilic infiltration, slight to moderate diffuse spongiosis, acanthosis and hydropic degeneration of basal cell layer. No mortality and no signs of systemic toxicity occurred in any animal during the observation periods up to 48 h
On the basis of observed skin effects, the test material 2, 6-Toluene diisocyanate (CAS No: 91-08-7) was considered as irritant to the skin of rats
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