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EC number: 249-934-2 | CAS number: 29895-73-6
- 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)
- Remarks:
- LLNA was performed before October 2016
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- The study was conducted between 8 August 2016 and 7 September 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- LLNA was performed before October 2016 when the REACH regulation came into force requesting in vitro testing first.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- adopted 22 July 2010
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Benzeneacetaldehyde, cyclic acetal with glycerol
- EC Number:
- 249-934-2
- EC Name:
- Benzeneacetaldehyde, cyclic acetal with glycerol
- Cas Number:
- 29895-73-6
- Molecular formula:
- C11H14O3
- IUPAC Name:
- Reaction mass of cis-2-benzyl-1,3-dioxan-5-ol and rel-[(2R,4R)-2-benzyl-1,3-dioxolan-4-yl]methanol and rel-[(2R,4S)-2-benzyl-1,3-dioxolan-4-yl]methanol and trans-2-benzyl-1,3-dioxan-5-ol
- Test material form:
- liquid
1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA/Ca
- Sex:
- female
- Details on test animals and environmental conditions:
- Animal Information:
Female CBA/Ca (CBA/CaOlaHsd) strain mice were supplied by Envigo RMS B.V., Inc., Horst, The Netherlands. On receipt the animals were randomly allocated to cages. The animals were nulliparous and non-pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were in the weight range of 15 to 23 g, and were 8 to 12 weeks old.
Animal Care and Husbandry:
The animals were housed in suspended solid floor polypropylene cages furnished with softwood woodflakes. Free access to mains tap water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 oC and 30 to 70%, respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- Undiluted test item or the test item at concentrations of 30% or 10% v/v in dimethyl formamide.
- No. of animals per dose:
- Groups of five mice were treated
- Details on study design:
- Preliminary Screening Test
As no toxicological information was available regarding the systemic toxicity/irritancy potential of the test item, a preliminary screening test was performed using one mouse. The mouse was treated by daily application of 25 µL of the undiluted test item to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). 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 according to the scale for erythema. Any clinical signs of toxicity, if present, were also recorded. The body weight 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 (Mitutoyo Corporation), 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 Test
Test Item Administration
Groups of five mice were treated with the undiluted test item or the test item at concentrations of 30% or 10% v/v in dimethyl formamide. The preliminary screening test suggested that the test item would not produce systemic toxicity or excessive local skin irritation at the highest suitable concentration. 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 tip of the pipette.
A further group of five mice received the vehicle alone in the same manner.
Routine positive control study (reduced LLNA) was performed to assess the sensitivity of the strain of mouse used at these laboratories to a known sensitizer. A group of five animals was treated with 50 µL (25 µL per ear) of α-Hexylcinnamaldehyde, tech., 85% as a solution in dimethyl formamide at a concentration of 25% v/v. A further control group of five animals was treated with dimethyl formamide alone.
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, ARC UK Ltd) 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 labeled 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 10 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 oC, 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 beta-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 (Beckman Instruments Inc, Fullerton, CA, USA). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- 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 was first assessed for suitability by analysis of normality and homogeneity of variance. If the assumptions that the data are both normally distributed and has homogeneity of variances, then 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.
Probability values (p) are presented as follows:
P<0.001 ***
P<0.01 **
P<0.05 *
P>=0.05 (not significant)
Results and discussion
- Positive control results:
- The positive control item, α-Hexylcinnamaldehyde, tech., 85%, gave a Stimulation Index of >3 (6.08) when tested at a concentration of 25 % v/v in dimethyl formamide and was considered to be a sensitizer under the conditions of the test.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- EC3
- Remarks on result:
- other: The test item, tested up to 100%, did not produce a threefold or greater increase in 3HTdR incorporation compared to control values.
- Parameter:
- SI
- Remarks on result:
- other: The following SI values were derived at 10, 30 and 100%: 0.82, 0.62 and 0.79, respectively.
- Cellular proliferation data / Observations:
- Clinical Observations and Mortality Data
There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test.
Body Weight
Body weight change of the test animals between Day 1 and Day 6 was comparable to that observed in the corresponding control group animals over the same period.
Any other information on results incl. tables
Preliminary Screening Test:
No signs of systemic toxicity, visual local skin irritation or irritation indicated by an equal to or greater than 25% increase in mean ear thickness were noted.
Based on this information the undiluted test item (100%) and the test item at concentrations of 30% and 10% v/v in dimethyl formamide were selected for the main test.
Estimation of the Proliferative Response of Lymph Node Cells:
The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:
Concentration (% v/v) in |
Stimulation Index |
Result |
10 |
0.82 |
Negative |
30 |
0.62 |
Negative |
100 |
0.79 |
Negative |
The test item, tested up to 100%, did not produce a threefold or greater increase in3HTdR incorporation compared to control values.
Clinical Observations, Body Weight and Mortality Data – Preliminary Screening Test:
Concentration |
Animal Number |
Body Weight (g) |
Day |
|||||||||
1 |
2 |
3 |
4 |
5 |
6 |
|||||||
Day 1 |
Day 6 |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
|||||
100% |
S-1 |
20.3 |
20.6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0= No signs of systemic toxicity
Local Skin Irritation – Preliminary Screening Test:
Concentration |
Animal Number |
Local Skin Irritation |
|||||||||||
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
||||||||
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
||
100% |
S-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Measurement of Ear Thickness and Mean Ear Thickness Changes – Preliminary Screening Test:
Concentration |
Animal Number |
Ear Thickness Measurement (mm) |
|||||
Day 1 |
Day 3 |
Day 6 |
|||||
pre‑dose |
post dose |
||||||
left |
right |
left |
right |
left |
right |
||
100% |
S-1 |
0.22 |
0.21 |
0.22 |
0.22 |
0.22 |
0.22 |
overall mean (mm) |
0.215 |
0.220 |
0.220 |
||||
overall mean ear thickness change (%) |
na |
2.326 |
2.326 |
na= Not applicable
Individual Disintegrations per Minute and Stimulation Index:
Concentration |
Animal Number |
dpm/ |
Mean dpm/Animal |
Stimulation Index (b) |
Result |
Vehicle |
1-1 |
2533.24 |
2578.18 |
na |
na |
1-2 |
3182.37 |
||||
1-3 |
1798.34 |
||||
1-4 |
2738.61 |
||||
1-5 |
2638.35 |
||||
10 |
2-1 |
2816.29 |
2107.34 |
0.82 |
Negative |
2-2 |
2166.11 |
||||
2-3 |
2370.71 |
||||
2-4 |
1749.61 |
||||
2-5 |
1433.98 |
||||
30 |
3-1 |
1742.74 |
1588.82* |
0.62 |
Negative |
3-2 |
1583.59 |
||||
3-3 |
1164.23 |
||||
3-4 |
2053.62 |
||||
3-5 |
1399.92 |
||||
100 |
4-1 |
1837.89 |
2031.54 |
0.79 |
Negative |
4-2 |
2056.53 |
||||
4-3 |
2211.82 |
||||
4-4 |
2611.47 |
||||
4-5 |
1440.01 |
dpm= Disintegrations per minute
a= Total number of lymph nodes per animal is 2
b= Stimulation Index of 3.0 or greater indicates a positive result
na= Not applicable
*= Significantly different from control group p<0.05
Individual Clinical Observations and Mortality Data:
Concentration |
Animal Number |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
|||
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
|||||
Vehicle |
1-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
10 |
2-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
30 |
3-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
100 |
4-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
4-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0= No signs of systemic toxicity
Individual Body Weights and Body Weight Change:
Concentration |
Animal Number |
Body Weight (g) |
Body Weight Change (g) |
|
Day 1 |
Day 6 |
|||
Vehicle |
1-1 |
22.9 |
23.4 |
0.5 |
1-2 |
20.3 |
22.0 |
1.7 |
|
1-3 |
20.8 |
21.0 |
0.2 |
|
1-4 |
21.2 |
22.1 |
0.9 |
|
1-5 |
19.8 |
20.3 |
0.5 |
|
10 |
2-1 |
19.0 |
20.1 |
1.1 |
2-2 |
19.2 |
19.9 |
0.7 |
|
2-3 |
19.0 |
20.1 |
1.1 |
|
2-4 |
19.2 |
20.4 |
1.2 |
|
2-5 |
17.8 |
17.8 |
0.0 |
|
30 |
3-1 |
20.2 |
20.0 |
-0.2 |
3-2 |
19.4 |
19.1 |
-0.3 |
|
3-3 |
21.1 |
21.3 |
0.2 |
|
3-4 |
19.8 |
20.1 |
0.3 |
|
3-5 |
20.3 |
20.7 |
0.4 |
|
100 |
4-1 |
20.2 |
20.2 |
0.0 |
4-2 |
22.2 |
22.1 |
-0.1 |
|
4-3 |
20.4 |
20.4 |
0.0 |
|
4-4 |
19.0 |
18.8 |
-0.2 |
|
4-5 |
18.1 |
18.3 |
0.2 |
Applicant's summary and conclusion
- Interpretation of results:
- other: not a skin sensitizer
- Remarks:
- in accordance with EU CLP 1272/2008 and its amendments
- Conclusions:
- The test item, tested up to 100%, did not produce a threefold or greater increase in 3HTdR incorporation compared to control values, therefore the test item was considered not to be a skin sensitiser under the conditions of the test.
- Executive summary:
The skin sensitization potential of the test substance has been tested according to OECD TG 429: Local Lymph Node Assay and GLP. Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of 100%, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of five animals, were treated with 50 µL (25 µL per ear) of the undiluted test item (100%) or the test item as a solution in dimethyl formamide at concentrations of 30% or 10% v/v. A further group of five animals was treated with dimethyl formamide alone. At 10, 30 and 100% the substance showed SI values of 0.82, 0.62 and 0.79, respectively. The test item, tested up to 100%, did not produce a threefold or greater increase in 3HTdR incorporation compared to control values. The test item was considered not to be a skin sensitizer under the conditions of the test.
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