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EC number: 939-657-1 | CAS number: -
- 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
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Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- yes
- Remarks:
- - modified LLNA (IMDS): Measurement of cell counts instead of radioactive labeling. In addition, measurements of ear swelling and ear weights were done to discriminate the irritating potential from the sensitizing potential of the test substance.
- Principles of method if other than guideline:
- Modified LLNA (IMDS; Integrated Model for the Differentiation of Skin Reactions). Modifications are authorized in the OECD TG 429 and in the Note for Guidance SWP/2145/00 of the CPMP (2001). Information on validation of IMDS and scientific justification is given in: Vohr HW et al., Arch. Toxicol., 73, 501-509 (2000); Ehling G et al., Toxicology 212, 60-68 and 69-79 (2005).
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- HDI oligomers, allophanate
- EC Number:
- 939-657-1
- Molecular formula:
- not applicable (UVCB substance)
- IUPAC Name:
- HDI oligomers, allophanate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- - Stability under test conditions: The stability of the test item in the vehicle was analytically verified for up to 4 days.
The test item formulations in the vehicle were visually described as solutions.
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Strain: HsdWin:NMRI (SPF)
- Source: Harlan Nederland, 5960 AD Horst, The Netherlands
- Age at study initiation: 7 weeks
- Weight at study initiation: 26 - 32 g
- Housing: single housing in conventional Makrolon Type III cages
- Diet: Provimi Kliba SA 3883 maintenance diet for rats and mice, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 40 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 0 (vehicle control), 10, 30, 100 %
- No. of animals per dose:
- 6
- Details on study design:
- TREATMENT PREPARATION AND ADMINISTRATION:
The test item was formulated once before application in A/OO. The formulation was applied epicutaneously onto the dorsal part of both ears of the animals. This treatment was repeated on three consecutive days (d1, d2 and d3). The volume administered was 25 µl/ear. The used concentrations were based on the experiences with the test system and the toxic properties of the test substance. For negative and positive control a dose group treated only with the vehicle A/OO and one treated with hexyl cinnamic aldehyde in A/OO, respectively, in the above described manner was used.
The animals were anaesthetized by inhalation of carbon dioxide and sacrificed one day after the last application (d4). The appropriate organs were then removed. Lymphatic organs (the auricular lymph nodes) were transferred into physiological saline (PBS).
Investigations:
- weight of lymph nodes
- cell counts in lymph nodes
- stimulation index is calculated by dividing the absolute number of weight or cell counts of the substance treated lymph nodes by the vehicle treated ones.
- ear swelling
- ear weight
- body weights
The test is positive if the stimulation index exceeds 1.4 for cell count indices; for ear swelling if the "positive level" of 0.02 mm increase is reached. These levels are exclusively defined for the NMRI outbreed mice used in this study. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- When it was statistically reasonable, the values from treated groups were compared with those from the control group by a one-way analysis of variance (ANOVA) when the variances are considered homogeneous according to a homogeneity testing like Cochran's test. Alternatively, if the variances are considered to be heterogenous (p<=0.05), a non-parametric Kruskal-Wallis test has been used (Kruskal-Wallis ANOVA) at significance levels of 5 %. Two sided multiple test procedures were done according to Dunnett or Bonferroni-Holm, respectively. Outlying values in the LN weights were eliminated at a probability level of 99 % by Nalimov's method. In addition, for the LLNA/IMDS the smallest significant differentes in the means were calculated by Scheffels method, which according to Sachs can be used for both equal and unequal sample sizes.
Results and discussion
- Positive control results:
- After treatment with Alpha Hexyl Cinnamic Aldehyde mice showed clear increases in the weights of the draining lymph nodes and in the stimulation indices for cell counts compared to control animals, which are of statistical significance.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Remarks on result:
- other: see Remark
- Remarks:
- The “positive level”, which is 1.4 for cell counts has been exceeded in all dose groups. This increase was of statistical significance. Cell count index (test item concentration): 1.00 (0 %) / 2.31 (10 %) / 2.45 (30 %) / 2.90 (100 %). Although it is not possible to calculate an exact EC value from the data obtained, it can be assumed that the EC value is in any case below 10 %.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: modified LLNA; measurement of cell counts instead of radioactive labeling
Any other information on results incl. tables
This study pointed to a non-specific (irritant) and to a specific immunostimulating (sensitizing) potential of the test item. This applies to NMRI mice, for weight and cell counts of the draining lymph nodes as well as ear swelling and ear weight indices evaluated after application of the test substance.
Compared
to vehicle treated animals there were clear increases regarding the
weights of the draining lymph nodes and the cell counts, which were of
statistical significance in all dose groups. The "positive level" of
index 1.4 for the cell counts has been exceeded in all dose groups.
(Weight index: 1.0 (0%), 2.07 (10%), 2.41 (30%), 2.18 (100%); Cell count
index: 1.00 (0 %) / 2.31 (10 %) / 2.45 (30 %) / 2.90 (100 %).)
The
"positive level" of ear swelling which is 2x 10exp-2 mm increase, i.e.
about 10 % of the control values, has been exceeded in all dose groups.
These changes were of statistical significance.
(Ear swelling: day 1 = 17.17 (0 %) / 17.25 (10 %) / 17.25 (30 %) / 17.75
(100 %); day 4 = 17.50 (0 %) / 24.50 (10 %) / 26.42 (30 %) / 27.17 (100
%); Index day 4 = 1.00 (0 %) / 1.4 (10 %) / 1.51 (30 %) / 1.55 (100 %).)
A
significant increase compared to vehicle treated animals regarding ear
weights was detected in all dose groups.
(Ear weight = 11.78 (0 %) / 16.92 (10 %) / 18.28 (30 %) / 18.18 (100 %);
Index day 4 = 1.00 (0 %), 1.44 (10 %), 1.55 (30 %), 1.54 (100 %)).
Differentiation indices (DI), which is the quotient of the relative lymph node reaction divided by the relative acute skin reaction was < 1 for all concentrations tested, i.e. 0.82, 0.71 and 0.86 (for calculation of DI see: Homey et.al., Toxicol. and Appl. Pharmacol. 153, 1998, 83 -94; Vohr et.al. Arch. Toxicol. 73, 2000, 501 -509). These DI values point to an irritating potential of the test item. However, such an irritant property could also be combined with a skin sensitizing potential of a test compound. Thus, a skin sensitizing property cannot be excluded.
The body weights of the animals were not affected by any treatment.
Applicant's summary and conclusion
- Executive summary:
A modified LLNA (IMDS; OECD TG 429) was performed on 6 female NMRI mice per dose group using test substance of 0 % (vehicle control), 10 %, 30 % and 100 %.
Compared to vehicle treated animals clear increases regarding the weights of the draining lymph nodes and the cell counts were seen. The "positive level" of index 1.4 for the cell counts has been exceeded in all dose groups.
The "positive level" of ear swelling has also been significantly exceeded and a significant increase regarding ear weights was detected. These changes were of statistical significance in all dose groups. An increase in these parameters would point to an acute irritating (inflammatory) response. However, such an irritant property could also be combined with a skin sensitizing potential of a test compound. Thus, a skin sensitizing property cannot be excluded.
Also it is not possible to calculate an exact EC value from the data obtained, it can be assumed that the EC value is in any case below 10%.
Summarizing, the study does point to a non-specific (irritant) and to a specific immunostimulating (sensitizing) potential of the test item.
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