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EC number: 276-127-2 | CAS number: 71873-51-3
- 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:
- From February 19 to 25, 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 020
- Report date:
- 2020
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 22 July 2010
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Acid Yellow 218
- IUPAC Name:
- Acid Yellow 218
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA/Ca
- Remarks:
- CBA/Ca Ola Hsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: TOXI-COOP ZRT. H-1103, Budapest, Cserkesz u. 90.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 19.9 – 23.9 g ( The weight variation in animals involved in the study did not exceed ± 20 % of the mean weight).
- Housing: Grouped caging (4 animals/cage)
- Diet (e.g. ad libitum): ssniff® Rat/Souris-Elevage E complete ad libitum
- Water (e.g. ad libitum): tap water from watering bottles ad libitum
- Acclimation period: 14 days
- Indication of any skin lesions: Only healthy animals (and not showing any sign of skin lesion) were used
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 – 70 %
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.
- IN-LIFE DATES: From: To:
Study design: in vivo (LLNA)
- Vehicle:
- dimethyl sulphoxide
- Concentration:
- 50 %, 25 %, 10 % and 5 % (w/v) as formulation (apparently solutions)
- No. of animals per dose:
- 4 animals for treatment group
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: soluble in DMSO and formulated at 50 %, 25 % and 10 % (w/v)
- Irritation: the effect on the ear thicknesses observed in the 50 % (w/v) dose group was not considered as obvious sign of a significant irritation.
- Systemic toxicity: No mortality, significant, treatment related effect on body weights or any other sign of systemic toxicity were observed.
- Ear thickness measurements: an increase of > 25 % of ear thickness (compared to the initial values) was observed in the 50 % (w/v) dose group for one of the two animals on Day 6 (30 % or 25 % increase was observed on the left or right ear, respectively). No significantly (> 25 %) increased ear thicknesses were observed for the other animals in this dose group or in the other dose groups on the days of measurement (Day 3 or Day 6).
- Erythema scores: No erythema or any other local effect was observed in any dose group during the test.
MAIN STUDY
The test item was examined in the main test at concentrations of 50 %, 25 %, 10 % and 5 % (w/v).
An appropriate positive control (α-Hexylcinnamaldehyde, HCA), and furthermore two negative control groups dosed with the vehicles of the test and positive control groups, respectively, were employed.
The positive control item [25 % (w/v) HCA in Acetone: Olive oil 4:1 (v/v) mixture (AOO)] induced significant stimulation over the relevant control (SI = 5.6) thus confirming the validity of the assay.
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: the test item is considered as a skin sensitizer, if:
Exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than recorded in control mice, as indicated by the stimulation index (SI ≥ 3). However, the strength of the dose-response, the statistical significance and the consistency of the solvent/vehicle and positive control responses may also be used when determining whether a borderline result is declared positive.
TREATMENT PREPARATION AND ADMINISTRATION: Each mouse was topically treated with 25 μL of the appropriate formulations of the test item, the positive control substance or the vehicles using a pipette, on the dorsal surface of each ear. After the treatment animals were returned to their cages. Each animal was dosed once a day for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
Results and discussion
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 6.1
- Test group / Remarks:
- Group treated at 50 % (w/v) test item concentration
- Parameter:
- SI
- Value:
- 2.7
- Test group / Remarks:
- Group treated at 25 % (w/v) test item concentration
- Parameter:
- SI
- Value:
- 1.9
- Test group / Remarks:
- Group treated at 10 % (w/v) test item concentration
- Parameter:
- SI
- Value:
- 1.5
- Test group / Remarks:
- Group treated at 5 % (w/v) test item concentration
- Parameter:
- EC3
- Value:
- > 25
- Test group / Remarks:
- Due to the unreliable SI value at the 50 % (w)v) test concentration no EC3 value for the test item was calculated in this LLNA. On the other hand, it is evident from the test results that the theoretical EC3 value is > 25 %
Any other information on results incl. tables
Body Weight Measurement
Body weight decrease by > 5 % was observed in the following test groups: positive control group (1 of the 4 animals with 7 % decrease) and in the 25 % (w/v) dose group (1 of the 4 animals with 9 % decrease). No body weight decrease by > 5 % was observed in the other groups. In spite of these observations no significant, dose related effect on the body weights was believed during the test.
Clinical Observations, Signs of Irritation
No mortality was observed in any treatment group. The following symptoms of a possible systemic toxicity were observed in the 50 % (w/v) dose group (4 of the 4 animals): hunched back posture, increased respiratory rate on Day 2 (after the treatment); hunched back posture, narrow eyes and restlessness on Day 3 (after the treatment). All animals were symptom-free before the treatments on these days as well as on the other days. Loss of hair on the head was also observed in this dose group as a sign of a local or systemic effect. No local or systemic effects were observed in the other dose groups.
Irritation was monitored by erythema scoring in all test groups and by ear thickness measurements in the DMSO control group and in the test item treated groups. No erythema was observed in any test group during the test. Significantly increased ear thickness values (i. e. an increase of ≥ 25 % compared to the initial value) were observed in the 50 % (w/v) dose group both on Day 3 and on Day 6: the minimum or maximum increase was 15 % or 40 %, respectively. No significantly increased ear thicknesses were observed in the other groups.
Other Observations
Test item residuals were observed on the ears of animals. Amount of the residual was dose related and was not completely removed by normal animal grooming hence the residuals were observed from the first treatment to the end of the test (from Day 1 to Day 6).
Proliferation Assay
Visually larger lymph nodes compared to the relevant vehicle controls (AOO or DMSO) were observed in the positive control group and in the 50 % (w/v) dose group. The appearance of the lymph nodes was normal in both vehicle control groups (AOO or DMSO) and in the other test item treated groups.
Significant lymphoproliferative response (indicated by an SI ≥ 3) compared to the concurrent control (DMSO) was noted for Acid Yellow 218 at 50 % (w/v) concentration. No SI ≥ 3 was observed at the other test concentrations. The observed stimulation index (SI) values were 6.1, 2.7, 1.9 and 1.5 at test item concentrations of 50 %, 25 %, 10 % and 5 % (w/v), respectively. Dose-related response was observed.
Significance of the dose-response was evaluated by linear regression by using SI values of all four test concentrations and also by using three SI values (not including the 50 % (w/v) test concentration).
Significant dose-related response was observed (p = 0.019, r2 = 0.96) when all SI values were used. No statistical significance was observed when three concentrations were evaluated (p = 0.058, r2 = 0.99) although the response was dose-related.
Reliability of the Test
The positive control group animals were treated with 25 % (w/v) HCA solution (formulated in AOO) concurrent to the test item groups. No mortality, cutaneous reactions or signs of toxicity were observed in the positive control group.
A significant lymphoproliferative response (SI ≥ 3) was noted for HCA (SI = 5.6). The results of the positive control item demonstrated an appropriate performance of the test in accordance with the relevant guidelines and confirmed the validity of the assay.
Interpretation of Observations
The maximum dose selection was based on results of the formulation evaluation and the dose range finding test (DRF).
The test item was soluble in most of the standard LLNA vehicles. The maximum soluble concentration was 50 % (w/v) in Dimethyl sulfoxide (DMSO). Since no significant adverse effects (systemic toxicity or irritation) were observed in the dose range finding test up to this maximum concentration, the test item was examined in the main test as 50 %, 25 %, 10 % and 5 % (w/v) formulations in the selected vehicle.
Based on the positive control result the test was valid.
In this LLNA the observed stimulation index values were 6.1, 2.7, 1.9 and 1.5 at test item concentrations of 50 %, 25 %, 10 % and 5 % (w/v), respectively.
No confounding effects of irritation or systemic toxicity were observed in the 25 %, 10 % or 5 % (w/v) dose groups hence the proliferation values related to these test concentrations are considered reliable.
Symptoms of a possible systemic toxic effect were observed at the 50 % (w/v) test concentration however it was not expected (based on the preliminary test results). The symptoms were not excessive, the animals recovered in all cases and no effect on the body weights were observed in this dose group. The significantly increased ear thicknesses may indicate irritation effect of the test item at 50 % (w/v) concentration although it is believed that the observed test item residuals could have effect on the outcome of the ear thickness measurements, especially on Day 3.
Based on all these it is concluded that the proliferation value obtained at the 50 % (w/v) concentration was influenced by effects other than sensitisation hence is not reliable. On the other hand, only its magnitude is questionable hence it should not be excluded from the evaluation of the dose-response correlation.
The SI value of 2.7 observed at 25 % (w/v) concentration was close to the threshold value of 3. The response was clearly dose-related and biologically relevant. The lack of the statistical significance is probably a consequence of an inadequate number of data points in case of evaluation of three test concentration.
Based on the overall results the significantly increased lymphoproliferation at the 50 % (w/v) concentration as well as the dose-related response are considered as evidence that Acid Yellow 218 is a skin sensitizer.
Chemicals can be classified according to their relative skin-sensitization potency using EC3 value (dose calculated to induce a stimulation index of 3) calculated by linear interpolation using data points lying immediately above and below the SI value of 3 on the LLNA dose-response curve according to published method.
Due to the unreliable SI value at the 50 % (w)v) test concentration no EC3 value for the test item was calculated in this LLNA. On the other hand, it is evident from the test results that the theoretical EC3 value is > 25 % hence the test item can be ranked among weak skin sensitizers according to the published data for classification of contact allergens
Applicant's summary and conclusion
- Interpretation of results:
- other: Category 1B (indication of skin sensitising potential) based on CLP criteria
- Conclusions:
- Skin sensitizer
- Executive summary:
The aim of this study was to evaluate the skin sensitization potential of Acid Yellow 218 following dermal exposure in the Local Lymph Node Assay, according to the OECD guideline 429.
Preliminary tests were performed according to the relevant guidelines to find an appropriate vehicle and the maximum applicable concentration.
The test item was soluble in most of the standard LLNA vehicles. The maximum soluble concentration was 50 % (w/v) in Dimethyl sulfoxide (DMSO).
No significant adverse effects (systemic toxicity or irritation) were observed in the dose range finding test up to this maximum concentration. According to this the test item was examined in the main test at concentrations of 50 %, 25 %, 10 % and 5 % (w/v).
An appropriate positive control (α-Hexylcinnamaldehyde, HCA), and furthermore two negative control groups dosed with the vehicles of the test and positive control groups, respectively, were employed.
The positive control item [25 % (w/v) HCA in Acetone: Olive oil 4:1 (v/v) mixture (AOO)] induced significant stimulation over the relevant control (SI = 5.6) thus confirming the validity of the assay.
No mortality was observed during the test. No significant treatment related effect on body weights was observed in any test group. Body weight decrease by > 5 % were observed in some cases but without dose relevance and the mean body weights did not decrease significantly in any test groups. Although it was not expected, signs of systemic toxic effect of the test item (hunched back posture, increased respiratory rate, narrow eyes and restlessness) as well as loss of hair (on the head) were observed in the 50 % (w/v) dose group. The symptoms were not excessive, the animals recovered in all cases and no effect on the body weights were observed in this dose group.
Sign of irritation (significantly increased ear thickness values) was also observed in the 50 % (w/v) dose group. On the other hand, it is considered that the ear thickness measurement could have influenced by the test item residuals observed during the whole test on the ears of animals in the test item treated groups.
Significantly increased lymphoproliferation [indicated by a Stimulation Index (SI) ≥ 3] compared to the relevant control (DMSO) was noted for Acid Yellow 218 at 50 % (w/v) test concentration. No SI ≥ 3 was observed in the other dose groups. The observed stimulation index values were 6.1, 2.7, 1.9 and 1.5 at test item concentrations of 50 %, 25 %, 10 % and 5 % (w/v), respectively.
It is concluded that the proliferation value obtained at the 50 % (w/v) concentration was influenced by effects other than sensitisation hence is not reliable. On the other hand, only its magnitude is questionable hence it should not be excluded from the evaluation of the dose-response correlation. The SI value of 2.7 observed at 25 % (w/v) was close to the threshold value of 3. Significance of the dose-response was evaluated by linear regression by using SI values of all four test concentrations and also by using three SI values (not including the 50 % (w/v) test concentration).
Significant dose-related response was observed (p = 0.019, r2 = 0.96) when all SI values were used. No statistical significance was observed when three concentrations were evaluated (p = 0.058, r2 = 0.99).
The response was clearly dose-related and biologically relevant. The lack of the statistical significance is considered as consequence of an inadequate number of data points in case of evaluation of three test concentrations.
Based on the overall results the significantly increased lymphoproliferation at the 50 % (w/v) concentration as well as the dose-related response are considered as evidence that Acid Yellow 218 is a skin sensitizer.
Chemicals can be classified according to their relative skin-sensitization potency using EC3 value (dose calculated to induce a stimulation index of 3) calculated by linear interpolation using data points lying immediately above and below the SI value of 3 on the LLNA dose-response curve according to published method.
Due to the questionable magnitude of the SI value at the 50 % (w)v) test concentration no EC3 value for the test item was calculated in this LLNA. On the other hand, it is evident from the test results that the theoretical EC3 value is > 25 % hence the test item can be ranked among weak skin sensitizers (10 ≤ EC3 ≤ 100) according to the published data for classification of contact allergens.
Conclusion
In conclusion, under the conditions of the present assay, Acid Yellow 218 tested at the maximum feasible concentration of 50 % (w/v, based on the solubility) and also at concentrations of 25 %, 10 % or 5 % (w/v) as adequate homogeneous formulations (solution, prepared with Dimethyl sulfoxide as vehicle) was shown to have skin sensitization potential (skin-sensitizer) in the Local Lymph Node Assay.
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