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EC number: 800-940-9 | CAS number: 35836-72-7
- 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
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- Nanomaterial pour density
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- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
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- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 March - 04 April 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- The study was performed according to the OECD guideline No 429 and in compliance with GLP without any deviations.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- (1R,5S)-2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl) ethyl acetate
- EC Number:
- 800-940-9
- Cas Number:
- 35836-72-7
- Molecular formula:
- C13H20O2
- IUPAC Name:
- (1R,5S)-2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl) ethyl acetate
- Reference substance name:
- Non identified impurities
- Molecular formula:
- Not applicable
- IUPAC Name:
- Non identified impurities
- Test material form:
- liquid
- Details on test material:
- Batch No.: 117042
Purity: 99.3%
Name of test material (as cited in study report): NOPYL ACETATE
Physical state: colourless - slightly amber liquid
Storage conditions: +2°C to +8°C, under nitrogen and protected from light
Expiry date: 10 April 2013
Constituent 1
impurity 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: CBA/J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
Source: Janvier, Le Genest-Saint-Isle, France.
Age at study initiation: 8-12 weeks
Weight at study initiation: 18.9-23.3 g
Housing: animals were housed by group of two (preliminary test) or four (main test) in polycarbonate cages (Techniplast 1145T, 435 cm2, 36.9 x 15.6 x 13.2 cm) containing autoclaved sawdust (SICSA, Alfortville, France). In the main test, on day 6 before the [3H] methyl-thymidine (3H-TdR) injections, the animals were individually housed in disposable crystal polystyrene cages (22.0 cm x 8.5 cm x 8.0 cm).
Diet: SSNIFF R/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
Water: Tap water (filtered using a 0.22 µm filter), ad libitum
Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
Temperature: 22 ± 2 °C
Humidity: 30-70 %
Air changes: approximately 12 cycles/hour of filtered, non-recycled air
Photoperiod: 12 h dark / 12 h light
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Remarks:
- The vehicle used for the test item and positive control was a mixture Acetone/Olive Oil (4/1, v/v) (AOO): - acetone: batch No. K41254613, supplied by Merck, - olive oil: batch No. 0001428703, supplied by Sigma.
- Concentration:
- Preliminary test: 10, 25, 50 and 100 %
Main test: 5, 10, 25, 50 and 100 % - No. of animals per dose:
- Preliminary test: 2 females/dose (right and left ear were treated with different concentrations)
Main test: 4 females/dose and controls - Details on study design:
- RANGE FINDING TEST:
Compound solubility: the test item was soluble in the first recommended vehicle, acetone/olive oil (4/1, v/v). A solution was obtained at all tested dilutions (10-50%).
Irritation: for 3 consecutive days, the animals received applications of 25 µL of the dosage form preparations to the external surface of both ears (one concentration per ear). Measurement of the ear thickness (using a micrometer) was performed each day before treatment and 72 hours after the last application. No cutaneous reaction and no increase in ear thickness were observed at any concentration up to 100%. The highest concentration retained for the main test was therefore the maximal practicable concentration (100%).
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
Name of test method: Local Lymph Node Assay
Criteria used to consider a positive response: the results were expressed as disintegration per minute (dpm) per group. Stimulation indices (SI) were calculated according to the following formula: SI = dpm of treated group / dpm of control group. The test item was considered as a skin sensitizer when the SI for a dose group is higher than or equal to 3. Other relevant criteria such as radioactivity levels and ear thickness were also taken into account to evaluate the data.
TREATMENT PREPARATION AND ADMINISTRATION:
The test item was administered as a solution in the vehicle and was mixed with the required quantity of vehicle. Dose formulations were prepared by the CIT Pharmacy extemporaneously on the day of each administration. They were stored at between 2 and 8°C and delivered to the study room in brown flasks.
On days 1, 2 and 3, a dose-volume of 25 μL of the appropriate dose formulations was applied to the dorsal surface of both ears (one concentration per ear), using an adjustable pipette fitted with a plastic tip. In order to avoid licking, to ensure an optimized application of the test material and to facilitate ear thickness measurement, the animals were placed under light isoflurane anesthesia during the administration.
No massage was performed but the tip was used to spread the preparation over the application site. No rinsing was performed.
25 µL of test material at concentrations of 0 (vehicle control), 5, 10, 25, 50 and 100 % were applied to the dorsal surface of each ear on Days 1, 2 and 3. On Day 6, 250 µL NaCl 0.9 % containing 20 μCi of 3H-TdR (specific activity of 20 Ci/mmol) was injected into the tail vein of each experimental mouse. Five hours later, all mice were killed by a lethal intraperitoneal injection of pentobarbital sodium followed by a cervical dislocation and the auricular lymph node of each ear was excised. The lymph nodes were pooled for each experimental group. A single cell suspension of auricular lymph node cell (ALNC) was prepared by mechanical disaggregation in Petri dishes using the plunger of a syringe. LNC were washed with 0.9 % NaCl and precipitated with 5 % (w/v) trichloroacetic acid (TCA) at 4 °C. Pellets were re-suspended in 1 mL TCA and 3 mL of Ultima GoldxR scintillation fluid (Packard) was added in order to measure incorporation of 3H-TdR using β-scintillation counting. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- no data
Results and discussion
- Positive control results:
- The threshold positive value of 3 for the SI was reached in the positive control group (SI = 10.08). The experiment was therefore considered valid.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Value:
- ca. 0.73
- Test group / Remarks:
- concentration 5%
- Remarks on result:
- other: see table 7.4.1/1
- Key result
- Parameter:
- SI
- Value:
- 1.44
- Test group / Remarks:
- concentration 10%
- Remarks on result:
- other: see table 7.4.1/1
- Key result
- Parameter:
- SI
- Value:
- 7.14
- Test group / Remarks:
- concentration 25%
- Remarks on result:
- other: see table 7.4.1/1
- Key result
- Parameter:
- SI
- Value:
- 3.61
- Test group / Remarks:
- concentration 50%
- Remarks on result:
- other: see table 7.4.1/1
- Key result
- Parameter:
- SI
- Value:
- 3.63
- Test group / Remarks:
- concentration 100%
- Remarks on result:
- other: see table 7.4.1/1
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: see table 7.4.1/1
Any other information on results incl. tables
Table 7.4.1/1: Results of skin sensitization
Treatment and concentrations |
No. of nodes per group |
dpm per group |
dpm per node |
Stimulation index (SI) |
Increase in ear thickness (% between Day 1 and Day 6) |
Irritation level |
EC3 value |
Vehicle |
8 |
3942 |
492.75 |
- |
-1.02 |
- |
- |
5 % |
8 |
2883 |
360.38 |
0.73 |
3.09 |
I |
14.11 % |
10 % |
8 |
5658 |
707.25 |
1.44 |
3.09 |
I |
|
25 % |
8 |
28159 |
3519.88 |
7.14 |
3.00 |
I |
|
50 % |
8 |
14238 |
1779.75 |
3.61 |
-3.06 |
I |
|
100 % |
8 |
14325 |
1790.63 |
3.63 |
2.06 |
I |
|
α-hexylcinnamaldehyde 25 % |
8 |
39751 |
4968.88 |
10.08 |
- |
- |
- |
dpm = disintegrations per minute
I = non-irritant (increase in ear thickness < 10 %)
EC3 value = theoretical concentration resulting in a SI value of
stimulation index = dpm of treated group / dpm of control group
Applicant's summary and conclusion
- Interpretation of results:
- sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- A significant lymphoproliferation (SI > 3) was noted at concentrations ≥ 25%. In the absence of local irritation, the significant lymphoproliferative responses observed were attributed to delayed contact hypersensitivity.
Therefore, nopyl acetate is classified as sensitising "R43: may cause sensitisation by skin contact" according to Directive 67/548/EEC and skin sensitiser Category 1B according to Regulation (EC) No 1272/2008 (CLP). - Executive summary:
In a local lymph node assay performed according to OECD Guideline No 429 and in compliance with GLP, groups of CBA/J mice (4 females/dose)
were exposed to 25 µL of nopyl acetate in Acetone/Olive oil (4/1, v/v) at concentrations of 0 (vehicle control), 5, 10, 25, 50 and 100 % (v/v) to the dorsal surface of both ears for three consecutive days. On Day 6, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and measured for radioactivity, expressed as number of disintegrations per minute (DPM) and stimulation index. The test concentrations for the main study were determined from a preliminary study where no cutaneous reaction and no increase in ear thickness were observed at any concentration up to 100%.
No clinical signs and no mortality were observed during the main test. No local reactions and no notable increase in ear thickness were observed at any of the tested concentrations. Stimulation Index for 5, 10, 25, 50 and 100 % was 0.73, 1.44, 7.14, 3.61 and 3.63, respectively. The calculated effective concentration inducing a SI of 3 (EC3) was 14.11 %. Positive control (α-hexylcinnamaldehyde) exhibited evidence of sensitisation (SI = 10.08).
A significant lymphoproliferation (SI > 3) was noted at concentrations ≥ 25%. In the absence of local irritation, the significant lymphoproliferative responses observed were attributed to delayed contact hypersensitivity.
Therefore, nopyl acetate is classified as sensitising "R43: may cause sensitisation by skin contact" according to Directive 67/548/EEC and skin sensitiser Category 1B according to Regulation (EC) No 1272/2008 (CLP).
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