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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
Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- The supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: Prediction is done using QSAR Toolbox version 3.4
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.4
- GLP compliance:
- no
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- not specified
- Specific details on test material used for the study:
- - 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 - Species:
- guinea pig
- Strain:
- not specified
- Sex:
- female
- Details on test animals and environmental conditions:
- no data
- Route:
- intradermal
- Vehicle:
- other: olive oil or Freund's adjuvant
- Concentration / amount:
- not specified
- Day(s)/duration:
- not specified
- Adequacy of induction:
- not specified
- Route:
- epicutaneous, semiocclusive
- Vehicle:
- no data
- Concentration / amount:
- not specified
- Day(s)/duration:
- not specified
- Adequacy of challenge:
- not specified
- No. of animals per dose:
- no data
- Details on study design:
- no data
- Challenge controls:
- no data
- Positive control substance(s):
- not specified
- Vehicle:
- not specified
- Concentration:
- not specified
- No. of animals per dose:
- not specified
- Details on study design:
- not specified
- Positive control results:
- not specified
- Reading:
- 1st reading
- Group:
- test chemical
- Clinical observations:
- sensitizing
- Remarks on result:
- positive indication of skin sensitisation
- Interpretation of results:
- sensitising
- Conclusions:
- The substance 2, 6-Toluene diisocyanate (CAS No: 91-08-7) is estimated to be sensitising to skin of female guinea pigs.
- Executive summary:
The skin sensitization potential for 2, 6-Toluene diisocyanate (CAS No: 91-08-7) is estimated using OECD QSAR toolbox version 3.4
The test substance 2, 6-Toluene diisocyanate (CAS No: 91-08-7) is estimated to be sensitising to skin of female guinea pigs.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
(((((("a"
or "b" or "c") and("d"
and(not
"e")) ) and("f"
and(not
"g")) ) and
"h") and("i"
and(not
"j")) ) and("k"
and "l") )
Domain
logical expression index: "a"
Referential
boundary:The
target chemical should be classified as Acylation AND Acylation >>
Isocyanates and Isothiocyanates AND Acylation >> Isocyanates and
Isothiocyanates >> Isocyanates by DNA binding by OECD
Domain
logical expression index: "b"
Referential
boundary:The
target chemical should be classified as Acylation AND Acylation >>
(Tio)carbamoylation of protein nucleophiles AND Acylation >>
(Tio)carbamoylation of protein nucleophiles >> Isothiocyanates,
Isocyanates AND AN2 AND AN2 >> Direct carbamoylation of protein amines
AND AN2 >> Direct carbamoylation of protein amines >> Isocyanates and
Diisocyanates by Protein binding by OASIS v1.4
Domain
logical expression index: "c"
Referential
boundary:The
target chemical should be classified as Acylation AND Acylation >>
Isocyanates and Related Chemicals AND Acylation >> Isocyanates and
Related Chemicals >> Isocyanates by Protein binding by OECD
Domain
logical expression index: "d"
Referential
boundary:The
target chemical should be classified as Acylation AND Acylation >>
Isocyanates and Isothiocyanates AND Acylation >> Isocyanates and
Isothiocyanates >> Isocyanates by DNA binding by OECD
Domain
logical expression index: "e"
Referential
boundary:The
target chemical should be classified as Michael addition OR Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals OR Michael addition >> P450 Mediated Activation to Quinones
and Quinone-type Chemicals >> Arenes OR SN1 OR SN1 >> Iminium Ion
Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
by DNA binding by OECD
Domain
logical expression index: "f"
Referential
boundary:The
target chemical should be classified as Acylation AND Acylation >>
(Tio)carbamoylation of protein nucleophiles AND Acylation >>
(Tio)carbamoylation of protein nucleophiles >> Isothiocyanates,
Isocyanates AND AN2 AND AN2 >> Direct carbamoylation of protein amines
AND AN2 >> Direct carbamoylation of protein amines >> Isocyanates and
Diisocyanates by Protein binding by OASIS v1.4
Domain
logical expression index: "g"
Referential
boundary:The
target chemical should be classified as SN2 OR SN2 >> SN2 Reaction at a
sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated
alkyl esters and thioesters by Protein binding by OASIS v1.4
Domain
logical expression index: "h"
Referential
boundary:The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "i"
Referential
boundary:The
target chemical should be classified as Isocyanate and isothiocyanate
groups AND Primary aromatic amine, hydroxyl amine and its derived esters
by in vivo mutagenicity (Micronucleus) alerts by ISS
Domain
logical expression index: "j"
Referential
boundary:The
target chemical should be classified as H-acceptor-path3-H-acceptor by
in vivo mutagenicity (Micronucleus) alerts by ISS
Domain
logical expression index: "k"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 3.2
Domain
logical expression index: "l"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 4.48
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
Skin sensitization
Skin sensitization behaviour of test compound 2, 6-Toluene diisocyanate (CAS No: 91-08-7)have been summarized below by using data from prediction model based estimation and its read across substances.
The OECD QSAR toolbox version 3.4 estimated the skin sensitization potential of test chemical e 2, 6-Toluene diisocyanate (CAS No: 91-08-7) on guinea pigs by guinea pig maximization test. According to this prediction model, the test chemical was able to induce skin sensitization in guinea pigs. Thus the test compound 2, 6-Toluene diisocyanate (CAS No: 91-08-7)is estimated to be sensitizing to skin of guinea pigs.
According to Danish (Q) SAR Database 2017, the sensitization effects were observed for target e 2, 6-Toluene diisocyanate (CAS No: 91-08-7) in guinea pig and human. Based on the QSAR prediction done using the Danish (Q)SAR Database, the skin sensitization was estimated to be skin sensitizer on guinea pig and human for 2, 6-Toluene diisocyanate (CAS No: 91-08-7). Thus it can be concluded that the substance 2, 6-Toluene diisocyanate (CAS No: 91-08-7) has positive skin sensitization effects.
The skin sensitization study was conducted by FRANCIS J. KOSCHIER, EDWARD J. BURDEN, CINDY S. BRUNKHORST, AND MARVIN A. FRIEDMAN (1983)for similar read across substance 2, 4-Toluene diisocyanate (CAS No: -584-84-9) on guinea pigs via open epicutaneous test for test chemical. This study was designed to determine the concentration-dependent elicitation of dermal sensitization in guinea pigs treated with TDI. In this study, young adult guinea pigs received two open, epicutaneous induction applications (25 µL) of 8, 20, or 40% TDI in n-butyl ether on two separate areas. During induction at 20 and 40%concentrations, both the 24- and 48-hr readings (2.0) were much greater than those for the solvent group. Five days later, animals were challenged with 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4% TDI (25 µL per concentration site). The vehicle application did not produce any significant reactions at challenge. On the other hand, 0.025 to 0.4% TDI produced mean scores of 2.0 to 4.2 in all three TDI groups. All challenge applications except the 0.0% solution elicited a positive response in 75 to 100% of the animals. Fourteen days after induction, the 8, 20, and 40% groups were rechallenged and the 0% group was challenged. Control animals did not respond with dermal hypersensitivity reactions when challenged with applications of n-butyl ether or TDI. For the TDI-induction groups, 100% of the animals had dermal reactions when challenged with 0.1 to 0.4% TDI, and the severity of the skin reactions was dependent on the concentrations of the challenge and induction application. Based upon the observations the test material2, 4-Toluene diisocyanate(CAS No: -584-84-9)was considered to be sensitizing on guinea pigs.
Another skin sensitization study was carried out for same read across substance 2, 4-Toluene diisocyanate (CAS No: -584-84-9) by Kazumasa YAsuDA, Goro NozAwA, Tomoko Goto, Norihiro SASAKI and Sumiko ISHIZU (1890)on BALB/c (hairy) mice via the ear swelling test. In this test, the mice were divided into 2 groups: group A-28 hairy mice sensitized with TDI; Group B- 28 unsensitized hairy mice, the control for group A. During induction, a solution of1%, 5% and 30%TDI in olive oil was applied on depilated skin of group A for 5 consecutive days and then left without any treatment for next 3 days. On the 4thday after the fifth sensitizing application, a solution of1% TDI in olive oil was applied on ears for challenge. The results were obtained my measurement of the ear thickness after 24 and 48 hours post-challenge. It was observed that the ears of group A began to redden and swell drastically following the challenge. The ear thickness increased from 25.1X10 -2mm to 56.7 X 10-2. The increase rate was 126%. The ear of group B showed a slight reddening and swelling 24hr after challenge. The ear thickness increased from 24.3x10-2mm before challenge to 27.5X 10-2mm in group B receiving challenge. The increased percentage of ear thickness was 13%. At microscopic examination, tenement related pathological changes were notably observed in the thymus. As animals showed atrophy of the thymus. The weight decreased from 41.2 ±5.5 mg in group B to 22.9 ± 4.0 mg in group a being reduced by nearly half.in addition, it was observed that the weight of the spleen (140.5 ± 9.3mg) increased in group A as compared with group B (110 ± 9.7mg). As for the liver there was no special changes in gross observation, while the differences in weight between group A and group B being 1.20 ± 0.13G and 1.22 ± 0.12 g respectively, were not significant On the basis of observed effects, the test material2, 4-Toluene diisocyanate(CAS No: -584-84-9)was considered to be sensitizing on BALB/c (hairy) mice.
Thus the available data estimated by prediction model for target substance 2, 6-Toluene diisocyanate (CAS No: 91-08-7) as well as available data for read across substance 2, 4-Toluene diisocyanate (CAS No: -584-84-9) and applying weight of evidence approach suggests that the test chemical substance 2, 6-Toluene diisocyanate (CAS No: 91-08-7) is likely to cause skin sensitization and thus can be classified as skin sensitizer.
Migrated from Short description of key information:
The OECD QSAR toolbox version 3.4 estimated the skin sensitization potential of test chemical e 2, 6-Toluene diisocyanate (CAS No: 91-08-7) on guinea pigs by guinea pig maximization test. According to this prediction model, the test chemical was able to induce skin sensitization in guinea pigs. Thus the test compound 2, 6-Toluene diisocyanate (CAS No: 91-08-7) is estimated to be sensitizing to skin of guinea pigs.
Justification for selection of skin sensitisation endpoint:
The substance 2, 6-Toluene diisocyanate (CAS No: 91-08-7) is estimated to be sensitising to skin of female guinea pigs.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The skin sensitization potential of test chemical substance 2, 6-Toluene diisocyanate (CAS No: 91-08-7)and its read acrosssubstance 2, 4-Toluene diisocyanate (CAS No: -584-84-9) were observed in various studies. From the results obtained from these studies it is concluded that the chemical substance 2, 6-Toluene diisocyanate (CAS No: 91-08-7) was able to cause skin sensitization and hence can be classified as skin sensitizing.
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