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EC number: 248-383-5 | CAS number: 27277-00-5
- 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
Endpoint summary
Administrative data
Description of key information
The test substance showed no indication of skin sensitizing potential in a GLP compliant OECD 429 study.
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
- 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)
- Version / remarks:
- 22 July 2010
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2008
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA/Ca
- Remarks:
- CBA/CaOlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 15 to 23 g
- Housing: Suspended solid floor polypropylene cages furnished with softwood wood flakes. The animals were provided with environmental enrichment items (cardboard fun tunnels or suitable alternatives) which were considered not to contain any contaminant of a level that might have affected the integrity of the study.
- Diet: 2014C Teklad Global Rodent diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- propylene glycol
- Concentration:
- PRE-SCREEN TEST
25% w/w
MAIN STUDY
5, 10 and 25% w/w - No. of animals per dose:
- 4
- Details on study design:
- PRE-SCREEN TEST
One mouse was treated by daily application of 25 µL of test item solution to the dorsal surface of each ear for 3 consecutive days. The mouse was observed twice daily on Days 1, 2 and 3 and once daily on Days 4, 5 and 6. Local skin irritation was scored daily. Any clinical signs of toxicity, if present, were also recorded. The body weight of the mouse was recorded on Day 1 (prior to dosing) and on Day 6. The thickness of each ear was measured using a Mitutoyo 547-300S gauge, pre-dose on Day 1, post dose on Day 3 and on Day 6. Any changes in the ear thickness were noted. Mean ear thickness changes were calculated between time periods Days 1 and 3 and Days 1 and 6. A mean ear thickness increase of equal to or greater than 25% was considered to indicate excessive irritation and limited biological relevance to the endpoint of sensitization.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: The test item would be regarded as a sensitizer if at least one concentration of the test item results in a threefold or greater increase in 3HTdR incorporation compared to vehicle control values. Any test item failing to produce a threefold or greater increase in 3HTdR incorporation would be classified as a ‘non-sensitizer’.
TREATMENT PREPARATION AND ADMINISTRATION
- The mice were treated by daily application of 25 μL of the appropriate concentration of the test item to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3).
- The test item formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the disposable pipette tip.
- A further group (vehicle control group) of four mice received the vehicle alone in the same manner.
³H-METHYL THYMIDINE ADMINISTRATION
- Five days following the first topical application of the test item or vehicle (Day 6) all mice were injected via the tail vein with 250 μL of phosphate buffered saline (PBS) containing ³H-methyl thymidine (³HTdR: 80 μCi/mL, specific activity 2.0 Ci/mmoL) giving a total of 20 μCi to each mouse.
OBSERVATIONS
- Clinical Observations: All animals were observed twice daily on Days 1, 2 and 3 and on a daily basis on Days 4, 5 and 6. Any signs of toxicity or signs of ill health during the test were recorded.
- Body Weights: The body weight of each mouse was recorded on Day 1 (prior to dosing) and Day 6 (prior to termination).
TERMINAL PROCEDURES
- Termination: Five hours following the administration of ³HTdR, all mice were killed by carbon dioxide asphyxiation followed by cervical separation. For each individual animal of each group, the draining auricular lymph nodes were excised and processed. For each individual animal, 1 mL of PBS was added to the lymph nodes.
- Preparation of Single Cell Suspension: A single cell suspension of the lymph node cells for each individual animal was prepared by gentle mechanical disaggregation through a 200-mesh stainless steel gauze. The lymph node cells were rinsed through the gauze with 4 mL of PBS into a petri dish labelled with the study number and dose concentration. The lymph node cells suspension was transferred to a centrifuge tube. The petri dish was washed with an additional 5 mL of PBS to remove all remaining lymph node cells, and these were added to the centrifuge tube. The lymph node cells were pelleted at 1400 rpm (approximately 190 g) for ten minutes. The pellet was re-suspended in 10 mL of PBS and re-pelleted. To precipitate out the radioactive material, the pellet was re-suspended in 3 mL of 5% trichloroacetic acid (TCA).
- Determination of ³HTdR Incorporation: After approximately 18 hours incubation at approximately 4 °C, the precipitates were recovered by centrifugation at 2100 rpm (approximately 450 g) for 10 minutes, re-suspended in 1 mL of TCA and transferred to 10 mL of scintillation fluid. 3HTdR incorporation was measured by β-scintillation counting. The Poly Q™ vials containing the samples and scintillation fluid were placed in the sample changer of the scintillator and left to stand in darkness for approximately 20 minutes. The purpose of this period of time in darkness was to reduce the risk of luminescence, which has been shown to affect the reliability of the results. After approximately 20 minutes, the vials were shaken vigorously. The number of radioactive disintegrations per minute was then measured using the Beckman LS6500 scintillation system.
DATA EVALUATION
The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per animal and as the ratio of ³HTdR incorporation into lymph node cells of test nodes relative to that recorded for the vehicle control nodes (Stimulation Index). - Positive control substance(s):
- other: Phenylacetaldehyde
- Statistics:
- - Data was processed to give group mean values for disintegrations per minute and standard deviations where appropriate.
- Individual and group mean disintegrations per minute values were assessed for dose response relationships. Data were first assessed for suitability by analysis of normality and homogeneity of variance. If the assumptions that the data were both normally distributed and had homogeneity of variances were met, a parametric one way analysis of variance (ANOVA) and Dunnett’s multiple comparison procedure were used to determine statistical significance. If the assumptions were not met, non-parametric Kruskal-Wallis Rank Sum and Mann-Whitney U test procedures were used. - Parameter:
- SI
- Value:
- 1.35
- Test group / Remarks:
- 5% test item
- Parameter:
- SI
- Value:
- 1.55
- Test group / Remarks:
- 10% test item
- Parameter:
- SI
- Value:
- 1.62
- Test group / Remarks:
- 25% test item
- Cellular proliferation data / Observations:
- PRE-SCREEN TEST
- Clinical observations: Off white coloured residual test item on the ears was noted on Days 2 and 3. No signs of systemic toxicity or visual local skin irritation were noted.
- Ear thickness: A greater than 25% (53.659%) increase in mean ear thickness was noted. As no other signs of irritation were noted the greater than 25% increase was considered to be due to residual test item on the ears rather than excessive irritation. Based on this the test item concencentrations of the main study were selected.
CELLULAR PROLIFERATION DATA
The results of the statistical analysis of the data indicated there was no significant difference between the control group and the test groups. (See Table in ‘any other information on results incl. tables)
DETAILS ON STIMULATION INDEX CALCULATION
The mean Stimulation Index is expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group
CLINICAL OBSERVATIONS
There were no deaths. No signs of systemic toxicity were noted in the test or vehicle control animals during the test.
BODY WEIGHTS
Body weight change of the test animals between Day 1 and Day 6 were comparable to that observed in the corresponding vehicle control group animals over the same period. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- In this LLNA test according to OECD 429, the test item was not found to be sensitizing to the skin.
- Executive summary:
A GLP compliant study according to OECD 429 was performed to assess the skin sensitization potential of the test item in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of 25% w/w (the highest concentration that produced a suitable formulation), this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay (LLNA). Three groups, each of four animals, were treated with 50 μL (25 μL per ear) of the test item as a suspension in propylene glycol at concentrations of 25%, 10% or 5% w/w. A further group of four animals was treated with propylene glycol alone.
No mortality or signs of systemic toxicity was observed in the test item treated animals during the study. No treatment related effects were observed on body weight. The Stimulation Index (SI) expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows: 5% w/w, SI 1.35 (negative); 10% w/w, SI 1.55 (negative); 25% w/w, SI 1.62 (negative). The results of the statistical analysis of the data indicated there was no significant difference between the control group and the test groups. In conclusion, under the conditions of the present assay, the substance tested in a suitable vehicle was shown not to have skin sensitisation potential in the Local Lymph Node Assay.
Reference
Table: Disintegrations per Minute and Stimulation Indices
Concentration (% w/w) in propylene glycol |
Mean dpm/Animal (Standard Deviation) |
Stimulation Index |
Result |
Vehicle |
2198.54 (±1030.98) |
na |
na |
5 |
2976.82 (±584.65) |
1.35 |
Negative |
10 |
3416.71 (±2003.39) |
1.55 |
Negative |
25 |
3564.86 (±764.13) |
1.62 |
Negative |
The results of the statistical analysis of the data indicated there was no significant difference between the control group and the test groups
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Skin sensitisation: in vivo
A GLP compliant OECD 429 study was performed to assess the skin sensitization potential of the test item in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. Following a preliminary screening test, three groups, each of four animals, were treated with 50 μL (25 μL per ear) of the test item as a suspension in propylene glycol at concentrations of 25%, 10% or 5% w/w. A further group of four animals was treated with propylene glycol alone. No mortality or signs of systemic toxicity was observed in the test item treated animals during the study. No treatment related effects were observed on body weight. The Stimulation Index (SI) expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows: 5% w/w, SI 1.35 (negative); 10% w/w, SI 1.55 (negative); 25% w/w, SI 1.62 (negative). The results of the statistical analysis of the data indicated there was no significant difference between the control group and the test groups. In conclusion, under the conditions of the present assay, the substance tested in a suitable vehicle was shown not to have skin sensitisation potential in the Local Lymph Node Assay (Pooles, 2016).
A sensitisation test in guinea pigs according to the Stevens Ear / Flank Method, 1967 was performed. The animals were exposed to 10% w/v solution in dimethylformamide during the induction. The challenge was performed with 10.0, 1.0, 0.1% w/v solutions in dimethylformamide. None of the test or control animals developed erythema following challenge applications. It may be concluded that the test substance did not cause strong sensitisation to guinea pig skin (Moses, 1979).
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the available data on skin sensitisation, the substance is not classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
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