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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 232-477-8 | CAS number: 8050-18-8
- 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
OECD 429 (LLNA): Skin Sensitiser 1 (H317: May cause an allergic skin reaction)
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:
- 2020-09-24 to 2021-02-11
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA/Ca
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Envigo, Blackthorn
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: Only healthy animals were used for the study.
- Age at study initiation: 9-10 weeks old on Day 1
- Weight at study initiation: 19 to 23g on Day 1
- Housing: Group caging (up to five during acclimatisation) in cages that conformed to the ‘Code of Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific Purposes’ (Home Office, London, 2014). From Day 1, the preliminary study animal was individually housed and the main study animals were housed in groups of up to three.
- Diet (e.g. ad libitum): 5LF2 EU Rodent Diet 14% (provided by LabDiet, PMI Nutrition), ad libitumm.
- Water (e.g. ad libitum): tap water from the municipal supply from 500 mL bottles, ad libitum.
- Acclimation period:8 to 16 days
- Indication of any skin lesions: Not specified
but only healthy animals were used for the study. Health status was certified by the veterinarian.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 40 - 70 %
- Air changes (per hr): 15 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark
- IN-LIFE DATES: 2020-10-07 To: 2020-10-21
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- Test material formulations at 100%, 50% and 25% in AOO (acetone/olive oil (4:1 v/v))
- No. of animals per dose:
- 5/dose
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility:
The solubility of the test material was determined in acetone/olive oil 4:1 v/v. This vehicle was chosen as this is one of the standard OECD vehicles and the formulation produced an overtly stable solution, emulsion or dispersion incorporating
50% v/v of the test article.
The test material formulations were prepared daily
- Irritation:
In the Preliminary Irritation / Toxicity Test, a single mouse was treated by daily application of 25 μL of the undiluted test article to the dorsal surface of each ear for three consecutive days (Days 1, 2 and 3). The mouse was observed daily for any signs of toxicity or irritation at the application site. The body weight was recorded on Day 1 and prior to termination on Day 6. Both ears were observed for erythema and scored.
- Ear thickness measurements: Ear thickness measurements were taken using a thickness gauge on Day 1 (pre-dose), Day 3 (approximately 48 hours after the first dose) and Day 6. Excessive local irritation is indicated by an erythema score ≥3 and/or an increase in ear thickness of ≥25% on any day of measurement.
- Erythema scores: Both ears of the mouse were observed for erythema and scored using the criteria detailed below:
Erythema Scoring
Observation Score
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema 4
Excessive local irritation is indicated by an erythema score ≥3 and/or an increase in ear thickness of ≥25% on any day of measurement.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
Three consecutive concentrations were selected on the basis of the preliminary screening test so that the highest concentration maximised exposure whilst avoiding systemic toxicity and excessive local irritation. Mice were allocated into groups of five female mice. 100, 50 and 25% of the test formulations were selected as the most appropriate concentrations for the main study. The outer aspect of both pinnae of each mouse was treated by direct application of the appropriate test or control formulation (25 μL/pinna) dispensed from an automatic micro pipette.
TREATMENT PREPARATION AND ADMINISTRATION:
The five groups of five female mice were subjected to application of the vehicle control, positive control or one of the test formulations to the outer aspect of the auditory pinnae, once daily on Days 1, 2 and 3. On Day 6 the mice were placed in a thermacage in order to dilate the peripheral blood vasculature and thus facilitate intravenous dosing. Each mouse was transferred to a cylindrical restrainer. A plastic syringe and fine gauge hypodermic needle were used to administer 0.25 mL phosphate buffered saline incorporating 20 μCi of 3HTdR into a tail vein of each mouse by slow bolus injection.
Approximately five hours after intravenous injection of the 3HTdR, all mice were killed by exsanguination under a deep plane of inhalation anaesthesia. Killing was organised to minimise the interval between death and the recovery of the auricular lymph nodes to no more than fifteen minutes.
CLINICAL SIGNS: Treated mice were observed twice daily on Days 1 to 5 and once on Day 6 for clinical signs of reaction to treatment or for irritation or other changes at the sites of application of the test article.
BODY WEIGHTS: Mice were weighed on Day 1 (the first day of dosing) and on Day 6 prior to intravenous administration of 3HTdR.
On the following day the suspension was re-centrifuged at 200 g for 10 minutes and the supernatant was drawn off and discarded. The pellet was resuspended in 1 mL 5% w/v aqueous trichloroacetic acid then subjected to ultrasonic dispersion for 25 minutes to ensure a homogenous suspension. The suspension (1 mL) was transferred to a scintillation vial containing ca 10mL scintillation fluid and counted by Liquid scintillation (LSC). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Number of radioactive disintegrations per minute (DPM) were measured for each individual animal. The measured DPM values were corrected with the background DPM value (“DPM”). The average of the two measured DPM values of 5 % (w/v) TCA solutions was used as background DPM value.
Stimulation index (SI = DPM value of each treated group divided by the mean DPM value of the negative control group) for each treatment group was also calculated.
As a Stimulation Index value of 3 or more was obtained in all groups, DPM values were analysed using the methods detailed below.
Tests were performed using a one-sided risk for increased response with increasing dose.
The positive control group was excluded from statistical analyses. The vehicle control group was taken as the baseline group with which the treated groups were compared.
Significant results are reported as P<0.05, P<0.01 or P<0.001. - Positive control results:
- The threshold level for the Stimulation Index to be considered a positive indicator of the potential to cause skin sensitisation is 3.0. The positive control article produced a Stimulation Index of 8.81, demonstrating adequate performance of the assay.
- Key result
- Parameter:
- SI
- Value:
- 1
- Test group / Remarks:
- Negative control (AOO)
- Key result
- Parameter:
- SI
- Value:
- 6.54
- Test group / Remarks:
- 25% v/v
- Key result
- Parameter:
- SI
- Value:
- 13.69
- Test group / Remarks:
- 50% v/v
- Key result
- Parameter:
- SI
- Value:
- 14.84
- Test group / Remarks:
- 100% v/v
- Key result
- Parameter:
- SI
- Value:
- 8.81
- Test group / Remarks:
- Positive control
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Conclusions:
- Under the conditions of the Local Lymph Node Assay, it was demonstrated that AA-948-61 (Decarboxylated Rosin, CAS No. 8050-18-8) has the potential to cause skin sensitisation.
- Executive summary:
A key OECD 429 study was conducted to assess the potential of the test article, AA-948-61 (Decarboxylated Rosin, CAS No. 8050-18-8), to cause skin sensitisation in the mouse.
Following a preliminary screening test using the undiluted test article, the main study was conducted using the undiluted test article and 50 and 25% v/v formulations in acetone/olive oil 4:1 (v/v).
Groups of five female CBA/CaOlahsd mice were subjected to topical applications of positive control, vehicle control or of one the test formulations (100, 50 or 25%) to the outer aspect of the auditory pinnae once daily on Days 1, 2 and 3.
On Day 6, a 20 μCi dose of tritiated 3H-methyl thymidine was injected intravenously into each mouse. Approximately five hours later the auricular lymph nodes were recovered from each animal. The pairs of nodes from each animal were pooled and suspensions of the cellular components of the lymph nodes were prepared in 5% w/v trichloroacetic acid and processed through a scintillation counter for each animal.
Test results are expressed in terms of Stimulation Indices, the ratios of the mean scintillation counts obtained from the test groups relative to the corresponding mean scintillation count obtained from controls. The threshold level for the Stimulation Index to be considered a positive indicator of the potential to cause skin sensitisation is 3.0.
The stimulation index values were 14.84, 13.69 and 6.54 at concentrations of 100%, 50% (w/v) and 25% (w/v), respectively.
Under the conditions of the Local Lymph Node Assay, it was demonstrated that AA-948-61 (Decarboxylated Rosin, CAS No. 8050-18-8) has the potential to cause skin sensitisation.
The positive control substance produced a Stimulation Index of 8.81, demonstrating adequate performance of the assay.
Reference
Table 1 – Preliminary Screening Test – Observations, Body Weights and Mortality Data
Concentration % |
Animal Number |
Body Weight (g) on Day: |
Observations (Days) |
||||||
1 |
6 |
1 |
2 |
3 |
4 |
5 |
6 |
||
100 |
583 |
22 |
21 |
GF |
GF |
GF |
GF |
GF, DS |
GF, DS |
Key
DS – Dry skin behind ears
GF – Greasy fur behind ears, top of head and back of neck
Table 2 – Preliminary Screening Test – Erythema
Concentration % |
Animal Number |
Grade of Erythema on Day: |
|||||
1 |
2 |
3 |
4 |
5 |
6 |
||
100 |
583 |
0 |
0 |
2 |
1 |
1 |
0 |
Key
0 – No erythema
1 – Very slight erythema (barely perceptible)
2 – Well- defined erythema
Table 3 – Preliminary Screening Test – Erythema
Concentration % |
Animal Number |
Ear |
Thickness (mm) on Day: |
||
1 |
3 |
6 |
|||
100 |
583 |
Left |
0.24 |
0.24 |
0.23 |
Right |
0.21 |
0.21 |
0.23 |
Table 4 – individual DPMs and Stimulation Index (SI)
Concentration (% v/v in AOO 4:1 (v/v)) |
Group Number |
Animal Number |
DPM / Animal |
Mean DPM / Animal (Standard Deviation) |
Stimulation Index (SI) a |
Vehicle |
1 |
584 585 586 587 588 |
317 407 384 332 267 |
341 (±55.5) |
NA |
25 |
2 |
589 590 591 592 593 |
2064 3003 3376 2124 602 |
2234 (±1072.4) * |
6.54 |
50 |
3 |
594 595 596 597 598 |
2876 4714 5703 4649 5422 |
4673 (±1101.5) *** |
13.69 |
100 |
4 |
599 600 601 602 603 |
4993 5402 2932 4739 7260 |
5065 (±1548.6) *** |
14.84 |
Positive control |
5 |
604 605 606 607 608 |
2792 1627 2416 3902 4306 |
3009 (±1094.1) |
8.81 |
a = Stimulation Index of 3.0 or greater indicates a positive result
AOO = Acetone in olive oil 4:1 (v/v)
NA = Not applicable
* = Significantly different from control group p<0.05
*** = Significantly different from control group p<0.001
Table 5 – Body weights
Concentration (% v/v in AOO 4:1 (v/v)) |
Group Number |
Animal Number |
Body Weights (g) |
|
Day 1 |
Day 6 |
|||
Vehicle
|
1 |
584 585 586 587 588 |
21 21 21 20 22 |
21 23 21 22 24 |
25
|
2 |
589 590 591 592 593 |
22 19 22 20 23 |
23 21 24 21 23 |
50
|
3 |
594 595 596 597 598 |
23 23 20 21 22 |
22 24 21 20 23 |
100
|
4 |
599 600 601 602 603 |
22 21 21 20 21 |
22 22 22 21 22 |
Positive control
|
5 |
604 605 606 607 608 |
22 23 20 22 20 |
22 22 22 22 22 |
AOO – Acetone in olive oil 4:1 (v/v)
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
A key OECD 429 study was conducted to assess the potential of the test article, AA-948-61 (Decarboxylated Rosin, CAS No. 8050-18-8), to cause skin sensitisation in the mouse.
Following a preliminary screening test using the undiluted test article, the main study was conducted using the undiluted test article and 50 and 25% v/v formulations in acetone/olive oil 4:1 (v/v).
Groups of five female CBA/CaOlahsd mice were subjected to topical applications of positive control, vehicle control or of one the test formulations (100, 50 or 25%) to the outer aspect of the auditory pinnae once daily on Days 1, 2 and 3.
On Day 6, a 20 μCi dose of tritiated 3H-methyl thymidine was injected intravenously into each mouse. Approximately five hours later the auricular lymph nodes were recovered from each animal. The pairs of nodes from each animal were pooled and suspensions of the cellular components of the lymph nodes were prepared in 5% w/v trichloroacetic acid and processed through a scintillation counter for each animal.
Test results are expressed in terms of Stimulation Indices, the ratios of the mean scintillation counts obtained from the test groups relative to the corresponding mean scintillation count obtained from controls. The threshold level for the Stimulation Index to be considered a positive indicator of the potential to cause skin sensitisation is 3.0.
The stimulation index values were 14.84, 13.69 and 6.54 at concentrations of 100%, 50% (w/v) and 25% (w/v), respectively.
Under the conditions of the Local Lymph Node Assay, it was demonstrated that AA-948-61 (Decarboxylated Rosin, CAS No. 8050-18-8) has the potential to cause skin sensitisation. Based on the results observed, AA-948 -61 meets the criteria to be classified as a skin sensitiser Category 1 (H317: May cause an allergic skin reaction) under EU REgulation (EC) No 1272/2008 (CLP) and GHS (rev.7) 2017.
The positive control substance produced a Stimulation Index of 8.81, demonstrating adequate performance of the assay.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
AA-948 -61 meets the criteria to be classified as a skin sensitiser Category 1 (H317: May cause an allergic skin reaction) under EU REgulation (EC) No 1272/2008 (CLP) and GHS (rev.7) 2017.
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.