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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 481-880-7 | CAS number: 949495-68-5
- 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:
- key study
- Study period:
- May 06 to 28, 2008
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- GLP study conducted in compliance with OECD Guideline No. 429 without some restrictions: pooled method was used instead of individual method; and ear thickness measurements were not included. However, these deviations did not affect the outcome of this study since the observed positive evidence of skin sensitisation is coherent with the composition of the UVCB tested.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted 24 April 2002
- Deviations:
- yes
- Remarks:
- pooled method instead of individual method; no ear thickness measurements
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- national GLP Compliance Programme (inspected on September 02, 2006/ signed on January 19, 2007)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- -
- EC Number:
- 481-880-7
- EC Name:
- -
- Cas Number:
- 949495-68-5
- Molecular formula:
- not available (UVCB)
- IUPAC Name:
- Essential oil of Schinus Terebinthifolius (Anacardiaceae) obtained from red berries by supercritical carbon dioxide extraction
- Test material form:
- liquid
- Details on test material:
- - Storage conditions: In the refrigerator at 2 – 8 °C, protected from light in N2 atmosphere
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: Harlan Netherlands, B.V. Postbus 6174, NL - 5960 AD Horst / The Netherlands
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 17.5-22 g
- Housing: single housing. Makrolon Type I, with wire mesh top (EHRET GmbH, D-79302 Emmendingen). Granulated soft wood bedding (Harlan Winkelmann GmbH, D-33178 Borchen)
- Diet: pelleted standard diet, ad libitum (Harlan Winkelmann GmbH, D-33178 Borchen)
- Water: tap water, ad libitum, (Gemeindewerke, D-64380 Rossdorf)
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature:122 +/- 3°C
- Humidity: 30-70 %
- Air changes: not reported
- Photoperiod: 12 hours continuous light and 12 hours darkness
- IN-LIFE DATES: not reported
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 10%, 25% or 50% w/w
- No. of animals per dose:
- 4
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: up to 50% in acetone/olive oil (4:1 v/v)
- Irritation & systemic toxicity: To determine the highest non-irritant test concentration, a pre-test was performed in two animals. Two mice were treated with concentrations of 10, 25, 50, and 100 % on one ear each on three consecutive days. Clinical signs were recorded 24 ± 4 hours after each application. The animal treated with 50 and 100% of the test item died after the second application of the test item. Therefore, a second experiment was performed using test item concentrations of 25% on both ears of one animal and 50 % on both ears of the second animal. At the tested concentrations the animals did not show any signs of irritation or systemic toxicity.
- Ear thickness measurements: not included
- Erythema scores: not reported
The test item in the main study was assayed at 10, 25, and 50%. The top dose is the highest technically achievable concentration whilst avoiding systemic toxicity and excessive local irritation. No severe irritant effects were tolerated choosing the test concentrations.
MAIN STUDY:
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay - pooled method
- Criteria used to consider a positive response: A test item is regarded as a sensitiser 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.
TREATMENT PREPARATION AND ADMINISTRATION:
The test item was placed into a volumetric flask on a tared balance and acetone:olive oil (4+1) was quantitatively added.
The preparations were made freshly before each dosing occasion.
Concentrations were in terms of material as supplied.
- Topical Application:
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 10, 25,and 50% (w/v) in acetone:olive oil (4+1). The application volume, 25 Ql, was spread over the entire dorsal surface (diameter ca. 8 mm) of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
- Administration of 3H-Methyl Thymidine:
3H-methyl thymidine (3HTdR) was purchased from GE Healthcare (GE Healthcare product code no. TRA 310; specific activity, 2 Ci/mmol; concentration, 1 mCi/ml). Five days after the first topical application, all mice were administered with 250 Ql of 81.0 QCi/ml 3HTdR (corresponds to 20.25 QCi 3HTdR per mouse) by intravenous injection via a tail vein.
- Determination of Incorporated 3HTdR
Approximately five hours after treatment with 3HTdR all mice were euthanised by intraperitoneal injection of Pentobarbital-Natrium (Release, WDT, D-30827 Garbsen). The draining lymph nodes were rapidly excised and pooled per group (8 nodes per group). Single cell suspensions (in phosphate buffered saline) of pooled lymph node cells were prepared by gentle mechanical disaggregation through stainless steel gauze (200 Qm mesh size). After washing two times with phosphate buffered saline (approx. 10 ml) the lymph node cells were resuspended in 5 % trichloroacetic acid (approx. 1 ml) and incubated at approximately +4 °C for at least 18 hours for precipitation of macromolecules. The precipitates were then resuspended in 5 % trichloroacetic acid (1 ml) and transferred
to plastic scintillation vials with 10 ml of ‘Ultima Gold’ scintillation liquid (Perkin Elmer (LAS) GmbH, D-63110 Rodgau) and thoroughly mixed. The level of 3HTdR incorporation was then measured on a beta-scintillation counter (Tricarb 2900 TR, Perkin Elmer (LAS) GmbH, D-63110 Rodgau). Similarly, background 3HTdR levels were also measured in two 1ml-aliquots of 5 % trichloroacetic acid. The beta-scintillation counter expresses 3HTdR incorporation as the number of radioactive
disintegrations per minute (DPM). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The mean values and standard deviations were calculated.
A statistical analysis was conducted for assessment of the dose-response relationship, and the EC3 value was 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.
Results and discussion
- Positive control results:
- The positive control α Hexylcinnamaldehyde gave a Stimulation Index of greater than 3 (4.87) when tested at a concentration of 25% w/v in acetone/olive oil 4:1 and an EC-3 of 15.7 % (w/v) , thus, demonstrating the sensitivity and reliability of the test system.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Value:
- 1.62
- Test group / Remarks:
- 10% w/v in acetone/olive oil 4:1
- Key result
- Parameter:
- SI
- Value:
- 3.3
- Test group / Remarks:
- 25% w/v in acetone/olive oil 4:1
- Key result
- Parameter:
- SI
- Value:
- 4.77
- Test group / Remarks:
- 50% w/v in acetone/olive oil 4:1
- Key result
- Parameter:
- EC3
- Value:
- 22.3
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION
Stimulation index for 10, 25 and 50% w/v in acetone/olive oil 4:1 were 1.62, 3.30 and 4.77, respectively.
EC3 CALCULATION
EC3 = (a-c) [(3-d)/(b-d)] + c = 22.3% (w/v)
a = 10
b = 1.62
c = 25
d = 3.30
VIABILITY/MORTALITY/ No deaths occurred during the study period
CLINICAL SIGNS: No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the main experiment.
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
Table 7.4.1/1: Grouped Disintegrations per Minute and Stimulation Index
Test item concentration % (w/v) |
Group |
Measurement DPM |
Calculation |
Result |
||
DPM-BGa) |
number of lymph nodes |
DPM per lymph nodeb) |
S.I. |
|||
--- |
BG I |
27 |
--- |
--- |
--- |
--- |
--- |
BG II |
27 |
--- |
--- |
--- |
--- |
--- |
1 |
6405 |
6378 |
8 |
797.3 |
|
10 |
2 |
10364 |
10337 |
8 |
1292.1 |
1.62 |
25 |
3 |
21102 |
21075 |
8 |
2634.4 |
3.30 |
50 |
4 |
30476 |
30449 |
8 |
3806.1 |
4.77 |
BG = Background (1 ml 5% trichloroacetic acid) in duplicate
1 = Control Group
2-4 = Test Group
S.I. = Stimulation Index
a) = The mean value was taken from the figures BG I and BG II
b) = Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled
Applicant's summary and conclusion
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- Under the test conditions, test material is classified as a contact sensitizer (Category 1B) according to the Regulation (EC) No. 1272/2008 and to the GHS.
- Executive summary:
A study was performed to assess the skin sensitisation potential of test material in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. The method was conducted according to the OECD test guideline No 429 and in compliance with GLP.
In the preliminary screening test, two mice were treated with concentrations of 10, 25, 50, and 100 % w/v on one ear each on three consecutive days. Clinical signs were recorded 24 ± 4 hours after each application. The animal treated with 50 and 100% w/vof the test item died after the second application of the test item. Therefore, a second experiment was performed using test item concentrations of 25% w/v on both ears of one animal and 50 % w/v on both ears of the second animal. At the tested concentrations the animals did not show any signs of irritation or systemic toxicity, therefore, the concentration of 50% w/v was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of four animals, were treated with 50 µL (25 µL per ear) of the test item as a solution in acetone/olive oil 4:1 at concentrations of 10%, 25% or 50% w/v. A further group of five animals was treated with acetone/olive oil 4:1 alone. The results of a positive control test, using a group of four animals, performed with the known sensitizer, α‑Hexylcinnamaldehyde, at concentrations of 5%, 10% and 25% w/v in acetone/olive oil 4:1 is reported. The proliferative response of the lymph node cells (LNC) from the draining auricular lymph nodes was assessed five days following the initial application, by measurement of the incorporation of 3H-methyl Thymidine (3HTdR) by β-scintillation counting of LNC suspensions. The response was expressed as radioactive disintegrations per minute per pooled lymph node and as the ratio of 3HTdR incorporation into LNC of test nodes relative to that recorded for control nodes (test/control ratio), termed as Stimulation Index (SI).
Stimulation index for 10%, 25% and 50% w/v in acetone/olive oil 4:1 were 1.62, 3.30 and 4.77, respectively. The concentration of test item expected to cause a 3 fold increase in 3HTdR incorporation (extrapolated EC3 value) was calculated to be 22.3 % (w/v). No sign of systemic toxicity or excessive local skin irritation were noted at the concentrations tested.
The positive control α Hexylcinnamaldehyde gave a Stimulation Index of greater than 3 (4.87) when tested at a concentration of 25% w/v in acetone/olive oil 4:1 and an EC-3 of 15.7 % (w/v) , thus, demonstrating the sensitivity and reliability of the test system.
Under the test conditions, test material is classified as a contact sensitizer (Category 1B) according to the Regulation (EC) No. 1272/2008 and to the GHS.
This study is considered as acceptable and satisfies the requirement for sensitisation endpoint.
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.