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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 619-966-5 | CAS number: 825633-86-1
- 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 sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2022-02-14 to 2022-06-08
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The information for this endpoint study record was obtained from an experimental study. The OECD GLP criteria were met and the methods applied are fully compliant with OECD TG 429
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
- Report date:
- 2022
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 06 July 2012
- Deviations:
- yes
- Remarks:
- Please refer to "Principles of method".
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 22 July 2010
- Deviations:
- yes
- Remarks:
- Please refer to "Principles of method".
- Principles of method if other than guideline:
- The relative humidity in the animal room was between approximately 20-65% instead of 45-65% for severaours on several days during the first few days of the acclimation period of the animals used in the main experiment.
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 4-[4-(but-3-en-1-yl)phenyl]-4'-ethyl-3-fluoro-1,1'-biphenyl
- EC Number:
- 619-966-5
- Cas Number:
- 825633-86-1
- Molecular formula:
- C24H23F
- IUPAC Name:
- 4-[4-(but-3-en-1-yl)phenyl]-4'-ethyl-3-fluoro-1,1'-biphenyl
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA/Ca
- Remarks:
- CBA/CaOlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Envigo RMS B.V., Inc, Postbus 6174, 5960 AD Horst, The Netherlands
- Females nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: No details provided but only animals without any visible signs of illness were used for the study.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 16.0 - 20.3 g
- Housing: group, Makrolon Type II (pre-test) / III (main study) with wire mesh top, on granulated soft wood bedding
- Diet: ad libitum, 2018C Teklad Global 18 % protein rodent diet
- Water: ad libitum, tap water
- Acclimation period: at least 5 days
- Indication of any skin lesions: Not specified.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2
- Humidity (%): approx. 45-65 (20-65 for several hours due to a defective humidity sensor)
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 25, 50, and 100 %
- No. of animals per dose:
- 5
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: 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 50% solution in MEK. Vortexing was used to formulate the test item.
- Irritation: At the tested concentrations the animals did not show any signs of local skin irritation
- Systemic toxicity: Both animals showed transient, mild and unspecific signs of discomfort: The animal treated with 50% of the test item showed partially closed eyes (transiently at the post-dose observation time after the 2nd and 3rd application). Additionally, the animal treated with 50% test item concentration showed piloerection and decreased activity at the post-dose observation time on day 3. Both animals showed a normal gain in body weight over the course of the study.
- Ear thickness measurements: No findings
- Erythema scores: No irritation observed
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: A test item was regarded as a sensitiser in the LLNA if the following criteria were 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 were compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.
TREATMENT PREPARATION AND ADMINISTRATION:
The test item was placed into an appropriate container on a tared balance and MEK was added (weight per weight). The different test item concentrations were prepared individually.
The preparations were made freshly before each dosing occasion.
Each test group of mice was treated by (epidermal) topical application to the dorsal surface of each ear with test item concentrations of 10, 25, and 50% in MEK. The application volume, 25 µL/ear/day, was spread over the entire dorsal surface ( 8 mm) of each ear once daily for three consecutive days. A further group of mice (control animals) was treated with an equivalent volume of the relevant vehicle alone (control animals). Five days after the first topical application (day 6) 250 µL of phosphate-buffered saline containing 19.8 µCi of 3H-methyl thymidine (equivalent to 79.3 µCi/mL 3HTdR) were injected into each test and control mouse via the tail vein. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The mean values and standard deviations were calculated in body weight tables.
All calculations conducted on the DPM values were performed with a validated test script of “R”, a language and environment for statistical computing and graphics.
Within the program, the Dean-Dixon-Test and Grubb’s Test were used for identification of possible outliers. One outlier (DPM value determined for animal 19) was detected in the Grubb’s Test but not in the Dean-Dixon-Test, and was therefore not excluded from any calculations. Furthermore, exclusion of the outlier value would not change the overall test result.
Results and discussion
- Positive control results:
- In the positive control experiment the group S.I. values were determined to be 2.4, 3.4 and 9.8 after treatment with 5, 10 and 25 % alpha-Hexylcinnamaldehyde, respectively.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Value:
- 1.11
- Test group / Remarks:
- 50 %
- Parameter:
- SI
- Value:
- 1.64
- Test group / Remarks:
- 25 %
- Parameter:
- SI
- Value:
- 1.19
- Test group / Remarks:
- 10 %
- Parameter:
- EC3
- Value:
- 57.1
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
Please refer to “Any other information on results” for tables.
DETAILS ON STIMULATION INDEX CALCULATION
The proliferative response of the lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph nodes of each animal (DPM/animal) and as the ratio of 3HTdR incorporated into lymph node cells of test animals relative to that recorded for lymph nodes of control animals (Stimulation Index; S.I.). Before DPM/animal values were determined, mean scintillation-background DPM was subtracted from test and control raw data.
Please refer to “Any other information on results” for tables.
EC3 CALCULATION
EC3 value were calculated according to the equation EC3 = (a-c) [(3-d)/(b-d)] + c; where EC3 is the estimated concentration of the test item required to produce a 3-fold increase in draining lymph node cell proliferative activity; (a, b) and (c, d) are respectively the co-ordinates of the two pair of data lying immediately above and below the S.I. value of 3 on the local lymph node assay dose response plot.
Please refer to “Any other information on results” for tables.
CLINICAL OBSERVATIONS AND SIGNS OF TOXICITY
No deaths occurred during the study period. No symptoms of local skin irritation at the ears of the animals were observed during the study period. The animals treated with a test item concentration of 50% showed mild and unspecific signs of discomfort, namely, partially closed eyes and piloerection at the post-dose observation time points on days 2 and 3, possibly due to substance residuals on the ears. Animals treated with 10 and 25%% test item concentration did not show any clinical signs.
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.
Any other information on results incl. tables
Calculation and Results of Individual Data
Vehicle: MEK
Test item concentration % |
Group |
Measurement DPM |
Calculation |
Result |
||
DPM-BGa) |
number of lymph nodes |
DPM per lymph nodeb) |
S.I. |
|||
--- |
BG I |
12 |
--- |
--- |
--- |
--- |
--- |
BG II |
26 |
--- |
--- |
--- |
--- |
0 |
1 |
5480 |
5461 |
8 |
682.6 |
1.00 |
10 |
2 |
6540 |
6521 |
8 |
815.1 |
1.19 |
25 |
3 |
8957 |
8938 |
8 |
1117.2 |
1.64 |
50 |
4 |
6100 |
6081 |
8 |
760.1 |
1.11 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item was not a skin sensitiser under the test conditions of this study.
- Executive summary:
In the study the test item formulated in MEK (methyl ethyl ketone) was assessed for its possible skin sensitising potential.
For this purpose a local lymph node assay was performed using test item concentrations of 10, 25, and 50% (w/w). The highest concentration tested was the highest concentration that could technically be achieved.
The animals did not show any signs of local skin irritation during the course of the study and no cases of mortality were observed. The animals treated with a test item concentration of 50% showed mild and unspecific signs of discomfort, such as partially closed eyes and piloerection, directly after the 2nd and 3rd application only. Animals treated with 10 and 25%% test item concentration did not show any clinical signs.
In this study Stimulation Indices (S.I.) of 1.19, 1.64, and 1.11 were determined with the test item at concentrations of 10, 25, and 50% (w/w) in MEK, respectively.
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.