Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 268-028-8 | CAS number: 67990-05-0
- 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
Skin sensitisation (OECD 429, in vivo): not sensitising
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 11 APR 2012 to 25 APR 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study (OECD 429 and GLP without deviations)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
- Specific details on test material used for the study:
- In October 2011 the EU commission published a recommendation (2011/696/EU) on the definition of nanomaterials. From the results of analyses it is concluded that the registered substance C.I.Pigment Red 269 falls within the boundaries of the nanomaterial definition. Hence, studies were performed using the nanomaterial.
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS: mice, CBA/CaOlaHsd
- Source: Harlan Laboratories B.V., Postbus 6174, 5960 AD Horst / The Netherlands
- Age at study initiation: 8 - 11 weeks
- Weight at study initiation: 18.6 - 21.5 g
- Housing: group caging
- Diet: pelleted standard diet (Harlan Laboratories B.V., 5960 AD Horst, The Netherlands), ad libidum
- Water: tap water, (Gemeindewerke, 64380 Rossdorf, Germany), ad libitum
- Acclimation period: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 45-65 %
- Photoperiod (hrs dark / hrs light): artificial light 6:00 a.m. - 6:00 p.m.
- Bedding: granulated soft wood bedding (Rettenmaier & Söhne GmbH + Co. KG, 73494 Rosenberg, Germany)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 0%, 10%
- No. of animals per dose:
- 5
- Details on study design:
- RANGE FINDING TESTS:
A solubility experiment was performed according to the recommendations given by OECD 429. The highest test item concentration, which could be technically used was a 10 % (w/w) solution in acetone:olive oil (4+1 v/v). Vortexing and sonicating for about 5 minutes were necessary to formulate the test item.
To determine the highest non-irritant test concentration that did at the same time not induce signs of systemic toxicity, a pre-test was performed in two animals and stated in raw data and report. Two mice were treated by (epidermal) topical application to the dorsal surface of each ear with test item concentrations of 5 and 10 % once daily each on three consecutive days. Prior to the first application of the test item and before sacrifice the body weight was determined. Clinical signs were recorded at least once daily. Eventual signs of local skin irritation were documented and a score was used to grade a possible erythema of the ear skin. Furthermore, prior to the first application of the test item (day 1), on day 3 and before sacrifice (day 6) the ear thickness was determined using a micrometer (S0247 Kroeplin, 36381 Schlüchtern, Germany). Additionally, for both animals, the ears were punched after sacrifice (day 6) at the apical area using a biopsy punch (Stiefel, Ø 8 mm corresponding to 0.5 cm2) and were immediately pooled per animal and weighed using an analytical balance. Eventual ear irritation was considered to be excessive if an erythema of the ear skin of a score value ≥3 was observed at any observation time and/or if an increase in ear thickness of >= 25% was recorded on day 3 or day 6 (for individual results see Annex 1).
At the tested concentrations the animals did not show any signs of irritation or systemic toxicity. Eventual formation of erythema of the ear skin could not be examined due to the intense coloration of the ear skin by the test item.
The test item in the main study was thus assayed at 10% test item concentration. Since a negative prediction is made based on test results of substances with similar chemical structure (such as C.I. Pigment Red 147, 170, or 187) the rLLNA protocol was considered to be appropriate.
MAIN STUDY:
TOPICAL APPLICATION:
The test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear (left and right) with different test item concentrations of 10 % (w/w) in A:OO. The application volume, 25 µL was spread over the entire dorsal surface (~ 8 mm) of each ear once daily for three consecutive days. A futher group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
ADMINISTRATION OF 3H-METHYL THYMIDINE AND DETERMINATION OF INCORPORATED 3H-METHYL THYMIDINE
Five days after the first topical application, all mice were intraveneously injected into a tail vein with radio-labelled thymidine (3HTdR). Approximately five hours after treatment with 3HTdR all mice were sacrificed and the draining lymph nodes were excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed with phosphate buffered saline and incubated with trichloroacetíc acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a beta-scintillation counter.
INTERPRETATION OF RAW DATA
The proliferation response of lymph node cells is expressed as the number of radioactive disintegrations per minute per lymph node (DPM/node) and as the ratio of 3HTdR incorporated into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes (stimulation index). Before DPM/node values were determined, mean scintillation-background DPM was subtracted from test and control raw data. A test item is regarded as a sensitiliser in the LLNA if the following criteria are fulfilled:
-First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
-Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.
OBSERVATIONS
In addition to the sensitising reactions the following observations and data were recorded during the test and observation period:
Mortality / Viability: At least once daily from experimental start to necropsy.
Body weights: In the pre-test: prior to the first application and prior to sacrifice. In the main experiment: prior to the first application and prior to treatment with 3HTdR.
Ear thickness: In the pre-test prior to the first application of the test item (day 1), on day 3 and before sacrifice (day 6).
Ear weights: In the pre-test and main test after sacrifice; biopsy punches were taken from each ear.
Clinical signs (local / systemic): Clinical signs (systemic toxicity or local skin irritation) were recorded at least once daily. Especially the treatment sites were observed carefully. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The mean values and standard deviations were calculated in the body weight tables.
- Positive control results:
- Experiment performed in December 2011 (Harlan study number 1486301) using concentrations of 5, 10, and 25 % alpha-hexyl cinnamic aldehyde in acetone:olive oil (4:1). These concentrations yielded S.I.´s of 1.70, 1.81, and 5.90, respectively.
The EC3 value calculated was 14.4 % (w/v).
The positive control substance alpha-hexyl cinnamic aldehyde was found to be a skin sensitizer under the described conditions, demonstrating the validity of the study. - Parameter:
- SI
- Value:
- 0.86
- Test group / Remarks:
- 10%
- Remarks on result:
- other: Group Calculation, S.I. Vehicle Control Group: 1.00 10 % Test item: 0.86
- Parameter:
- SI
- Value:
- 1
- Test group / Remarks:
- Vehicle control
- Parameter:
- SI
- Remarks on result:
- other: no other concentration could be tested
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: Group Calculation, Mean DPM per animal (2 lymph nodes) Vehicle Control Group: 103.9 10 % Test item: 83.7
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The test item was not a skin sensitiser under the test conditions of this study.
- Executive summary:
In order to study a possible skin sensitising potential of the test item, one group of five female mice was treated once daily with the test item at a concentration of 10 % (w/w) in acetone:olive oil (4+1 v/v) by topical application to the dorsum of each ear for three consecutive days (according to OECD 429 reduced LLNA). A test item solution was achieved in the chosen vehicle. The highest concentration tested was the highest concentration which could be technically used and could be applied whilst avoiding systemic toxicity and excessive local skin irritation as confirmed by a pre-experiment. A control group of five mice was treated with the vehicle (acetone:olive oil (4+1 v/v)) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per animal. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a beta-scintillation counter.
The animals did not show any signs of systemic toxicity or local skin irritation during the course of the study and no cases of mortality were observed. Eventual formation of erythema of the ear skin could not be examined due to intense coloration of the ear skin by the test item. A statistically significant increase in ear weights was not observed in the group treated with the test item in comparison to the vehicle control group.
A test item is regarded as a sensitiser in the LLNA if the exposure to one or more test concentration resulted in a 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated concentration of test item required to produce a S.I. of 3 is referred to as the EC3 value.
In this study a Stimulation Index (S.I.) of 0.86 was determined with the test item at a concentration of 10 % (w/w) in acetone:olive oil (4+1 v/v). A statistically significant increase in comparison to the vehicle control group was not observed.
An EC3 value was not calculated, because only one test item concentration was tested. Furthermore, the determined Stimulation Index was below the threshold value of 3 for a positive response.
Reference
Calculation and results of individual data
Vehicle: acetone:olive oil (4+1 v/v)
Test item concentration |
DPM values measured |
DPM-BG per animal |
S.I.b) |
||
% (w/v) |
Group no. |
Animal no. |
|||
--- |
--- |
BG I |
20 |
--- |
--- |
--- |
--- |
BG II |
37 |
--- |
--- |
0 |
1 |
1 |
420 |
392 |
--- |
0 |
1 |
2 |
525 |
497 |
--- |
0 |
1 |
3 |
601 |
573 |
--- |
0 |
1 |
4 |
423 |
395 |
--- |
0 |
1 |
5 |
333 |
305 |
--- |
10 |
2 |
6 |
376 |
348 |
0,8 |
10 |
2 |
7 |
502 |
474 |
1,1 |
10 |
2 |
8 |
282 |
254 |
0,6 |
10 |
2 |
9 |
455 |
427 |
1,0 |
10 |
2 |
10 |
389 |
361 |
0,8 |
BG = Background (1 mL 5% trichloroacetic acid) in duplicate
1 = Control Group
2 = Test Group
S.I. = Stimulation Index
a) = values corrected for mean background value (BGI and BGII).
b) = Stimulation Indices relative to the mean of the control group (Group 1)
Table 2: Calculation of Stimulation Indices per Dose Group
Test item concentration |
Group Calculation |
||
Mean DPM per |
SD |
S.I. |
|
Vehicle Control Group (acetone:olive oil (4+1 v/v)) |
431.9 |
103.9 |
1.00 |
10 % |
372.3 |
83.7 |
0.86 |
a) Mean DPM/animal was determined by dividing the sum of the measured values from lymph nodes of all animals within a group by the number of animals in that group (5 animals)
An EC3 value could not be calculated, because only one test item concentration was tested. Furthermore, the determined Stimulation Index was below the threshold value of 3 for a positive response.
VIABILITY / MORTALITY
No deaths occurred during the study period.
CLINICAL SIGNS
No signs of systemic toxicity were observed during the study period. Eventual formation of erythema of the ear skin could not be examined due to intense coloration of the ear skin by the test item.
BODY WEIGHTS
The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.
EAR WEIGHT
The measured ear weight of all animals treated was recorded on day 6 after necropsy. A statistically significant relevant increase in ear weights was not observed in the test item treated group in comparison to the vehicle control group.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Additional information:
The skin sensitising potential of the registered (target) substance was assessed in a GLP-compliant reduced Local Lymph Node Assay (LLNA) according to OECD guideline 429 (Harlan_1474302). A group of five female mice was treated once daily with the test item at a concentration of 10% (w/w) in acetone:olive oil (4:1 v/v) by topical application to the dorsum of each ear for three consecutive days. The concentration tested was the highest concentration which could technically be used. Five days after the first topical application the mice were injected with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per animal. Single cell suspensions of lymph node cells were prepared. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a beta-scintillation counter. The animals did not show any signs of systemic toxicity or local skin irritation during the course of the study and no cases of mortality were observed. Eventual formation of erythema of the ear skin could not be examined due to intense coloration of the ear skin by the test item. In this study a Stimulation Index (S.I.) of 0.86 was determined with the test item at a concentration of 10% (w/w) in acetone:olive oil (4:1 v/v). An EC3 value was not calculated, because only one test item concentration was tested.
Justification for classification or non-classification
The available data on skin sensitisation obtained with C.I.Pigment Red 269 do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.