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EC number: 271-282-2 | CAS number: 68527-77-5
- 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
Skin sensitisation (OECD TG 406): sensitising
Skin sensitisation (OECD TG 429): not sensitising
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1981, June 1 - 1981, July 8
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Justification for type of information:
- The in vivo information is retrieved from a Buehler test which was conducted before the REACH regulation on requesting in vitro information, came into force (October, 2016)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- 1981
- Deviations:
- yes
- Remarks:
- The test item is from IFF and therefore according to internal standards. Ten animals are used in the treatment group and 5 in the negative control group in view of the positive result this does not affect the outcome of the study.
- GLP compliance:
- yes
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- LLNA method was not available yet by the time the study was conducted. An appropriate Buehler test is available which would not justify conducting an additional LLNA due to animal welfare.
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Perfection Breeders, Inc., Douglasville, Pennsylvania
- Age at Acclimatization Start: No data
- Weight at Acclimatization Start: 290 - 500g
- Housing: Fill: two per cage in stainless steel wire mesh cages
- Diet: free access to Wayne Guinea Pig diet
- Water: free access to tap water
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: June 1, 1981 To: July 8, 1981 - Route:
- epicutaneous, occlusive
- Vehicle:
- other: Ethanol
- Concentration / amount:
- test substance: 0.4 mL 60%
- Day(s)/duration:
- 3 times/week for 3 weeks (total 9 exposures), 6 hours
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Ethanol
- Concentration / amount:
- Test substance: 0.4 mL 60%
- Day(s)/duration:
- 17 days after last induction, 6 hours
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- Test animals: 10
Positive Control animals: 10
Negative Control animals: 5 - Details on study design:
- RANGE FINDING TESTS
Four unexposed animals were exposed to 0.4 mL 20%, 40%, 60% and 100% concentration of the test substance by patching technique as described for main study. Treated sites were scored at 24 hours. The highest non-irritating concentration was 60%.
MAIN STUDY
A. INDUCTION EXPOSURE
The dorsal area of each animal was clipped free of hair 24 hours pior to the 1st, 4th, 6th and challenge applications of the test material. The shaved area was approx. 5 x 10 cm, i.e. 10% of the body surface. The test area was divided into three application sites, which were dosed on a rotating basis. The test material was applied beneath a 20 x 20 mm Webril pad on a 37 x 40 mm Readi-Bandage, and covered with dental dam held in place with a suitable bandage. Animals were exposed for 6 hours after which the dams and patches were removed. The treated sites were examined after each dosing day and scored at 24 and 48 hours. This procedure was performed three times weekly for three weeks (total 96-hour insults)
- Concentration: 60% in ethanol (control animals: ethanol 95% (negative) or 0.3% DNCB in 80% ethanol (positive))
- Amount: 0.4 mL
- Area: 4 cm2
- Exposure period: 6 hours (occlusive)
- Readings: 24 and 48 hours after patch removal
B. CHALLENGE EXPOSURE (control and test group)
Twenty-four hours after the challenge all animals were depilated with Neet Cream Hair Remover (Whitehalll Laboratories) for no more than 30 minutes after which the depilatory was thoroughly washed off.
- Day of challenge: approximately 17 days after last epidermal induction application
- Concentrations: 60%
- Exposure period: 6 hours (occlusive)
- Sites: site of sensitizing exposure and second naive site
- Amount: 0.4 mL
- Readings: 24 (a minimum of two hours after depilation) and 48 hours after patch removal - Challenge controls:
- Control group was treated with 0.4 mLvehicle (Ethanol 95%) during induction phase and challenged with 0.4 mL 60% test substance.
- Positive control substance(s):
- yes
- Remarks:
- DNCB
- Positive control results:
- The results of the positive control animals show that the system is responsive (9/10 and 5/10 animals reacted positive at the induction site and naive site, respectively)
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: negative control - induction and naive site
- Dose level:
- 60%
- No. with + reactions:
- 0
- Total no. in group:
- 4
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: negative control - induction and naive site
- Dose level:
- 60%
- No. with + reactions:
- 0
- Total no. in group:
- 4
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: test group - induction site
- Dose level:
- 60%
- No. with + reactions:
- 8
- Total no. in group:
- 10
- Clinical observations:
- Animals showed slight or confluent or moderate patchy erythema (mean score 0.9)
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: test group - naive site
- Dose level:
- 60%
- No. with + reactions:
- 8
- Total no. in group:
- 10
- Clinical observations:
- Animals showed slight or confluent or moderate patchy erythema (mean score 0.8)
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: test group - induction site
- Dose level:
- 60%
- No. with + reactions:
- 10
- Total no. in group:
- 10
- Clinical observations:
- Animals showed slight or confluent or moderate patchy erythema (mean score 1.2)
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: test group - naive site
- Dose level:
- 60%
- No. with + reactions:
- 7
- Total no. in group:
- 10
- Clinical observations:
- Animals showed slight or confluent or moderate patchy erythema (mean score 0.7)
- Interpretation of results:
- other: Sensitising
- Remarks:
- According to Regulation (EC) No. 1272/2008 and its amendments.
- Conclusions:
- In a Buehler test performed similar to OECD 406 (1981) and according to GLP principles, the substance is considered a skin sensitiser.
- Executive summary:
The skin sentisation potential of the substance was investigated by performing a Buehler test similar to OECD 406 (1981) and according to GLP principles. Ten animals were used in the treatment group and 5 in the negative control group (instead of 20 resp. 10 animals according the guideline). A concentration of 60% was used for the inductions (total of 9) and the challenge. After the inductions, patchy erythema was observed among the animals. After the challenge with the substance 8 of the 10 and 7 of 10 animals showed slight or confluent or moderate patchy erythema (score 1) at the naive site at 24 and 48 hours, respectively. At the induction site slightly more effects were observed. Reliable negative (no response during challenge) and positive controls were included. Based on the positive results, the substance is considered to be a sensitiser under the conditions of the test.
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2004, August 18 - 2004, August 24
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2002
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Version / remarks:
- 2003
- Deviations:
- no
- GLP compliance:
- yes
- 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: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 6 - 8 weeks (beginning of acclimatization period)
- Weight at study initiation: 15.1 to 18.3 g (beginning of acclimatization period)
- Housing: In groups of four in appropriate cages with environmental enrichment (tents, bases and nestlets).
- Diet: Free access to pelleted RM1 diet (Special Diet Services Limited, Witham, Essex, UK)
- Water: Free access to community tap water
- Acclimation period: Under test conditions, at least 5 days.
ENVIRONMENTAL CONDITIONS (target ranges)
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- other: 1:3 EtOH:DEP
- Concentration:
- the test item at concentrations of 1, 2.5, 5, 10 or 25 % w/v in vehicle
- No. of animals per dose:
- Groups of four mice were treated
- Details on study design:
- TREATMENT PROCEDURES:
TOPICAL APPLICATION:
Each test group of mice was treated with different test item concentrations of 1, 2.5, 5, 10 or 25% in EtOH:DEP, 1:3 (w/v). 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 a variable volume micropipette.
A further group of four mice received the vehicle alone in the same manner.
The positive control animals were similarly treated to the test animals except that 25 µl of the positive control item, α-Hexylcinnamaldehyde, at a concentration of 5, 10 or 25 % w/v in acetone/olive oil 4:1 was applied to the dorsal surface of each ear.
3H-Methyl Thymidine Administration
Three days following the third topical application of the test item, vehicle control or positive control item (Day 6) all mice were injected via the tail vein with 250 µl of phosphate buffered saline (PBS) containing 3H methyl thymidine (3HTdR:80µCi/ml, specific activity 2.0 Ci/mmol) giving a total of 20 µCi to each mouse.
Observations
Clinical Observations: All animals were checked at least once daily for systemic toxicity.
Bodyweights: The bodyweight of each mouse was recorded on Day 1 (prior to dosing) and Day 6 (prior to injection fo 3HTdR).
Terminal Procedures
Termination: Five hours following the administration of 3HTdR all mice were killed by inhalation of halothane followed by cervical dislocation. For each individual animal of each group the draining auricular lymph nodes were excised and processed together with the nodes from the other animals in te group.
Preparation of Single Cell Suspension: A single cell suspension of the lymph node cells was prepared by mechanical disaggregation through a 200 mesh stainless steel gauze. The cell suspensions were then washed three times by centrifugation with approximately 10 mL of PBS. To precipitate out the radioactive material, the pellet was resuspended in 3 ml of 5% Trichloroacetic acid (TCA).
Determination of 3HTdR Incorporation: After overnight precipitation at 4°C, the samples were pelleted by centrifugation and the supernatant was discarded. The cells were resuspended in 1 ml of TCA and transferred to 10 ml of scintillation fluid (Optiphase). 3HTdR incorporation was measured by beta scintillation counting using a Packard Tri-Carb Liquid Scintillation Counter. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- No statistics were performed.
- Positive control results:
- The positive control item, Hexylcinnamaldehyde, gave a Stimulation Index of 3.3 and 10.9 when tested at a concentration of 10% and 25 % v/v, respectively, in acetone/olive oil 4:1.
- Parameter:
- SI
- Remarks on result:
- other: The SI values calculated for the substance concentration 1, 2.5, 5, 10 and 25% were 1.0, 1.5, 2.0, 1.5 and 2.3, respectively.
- Key result
- Parameter:
- EC3
- Remarks:
- %
- Value:
- > 25
- Interpretation of results:
- other: Not sensitising.
- Remarks:
- According to Regulation (EC) No. 1272/2008.
- Conclusions:
- The test item was considered not to be a sensitiser under the conditions of the test.
- Executive summary:
The skin sensitisation potential of the test substance has been tested according to OECD TG 429: "Local Lymph Node Assay" method. At 1, 2.5, 5, 10, and 25% the substance showed SI values of 1.0, 1.4, 2.0, 1.5 and 2.3, respectively. EC3 was estimated to be >25% indicating a NOAEL of 25%. Reliable negative and positive controls were included. The test substance was considered not te be a sensitiser under the conditions of the test.
- Endpoint:
- skin sensitisation: in vitro
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Reason / purpose for cross-reference:
- data waiving: supporting information
- Reason / purpose for cross-reference:
- data waiving: supporting information
Referenceopen allclose all
Observations:
Slight edema was present and erythema was observed during induction at 48 hours post dose 3 with test material. In positive control animals erythema was observed during induction at 24 hours post dose 9 and 48 hours post dose 3, 4, and 8. No irritation was observed in the negative control animals during induction or challenge periods.
One control animal was found dead on day 29.
The following results were obtained:
Concentration of test substance (% w/v) |
Desintegrations per minute (DPM) | Dpm per lymph node a) | Test:control ratio |
0 (vehicle only) | 3686 | 461 | N/A |
1 | 3832 | 479 | 1.0 |
2.5 | 5171 | 646 | 1.4 |
5 | 7383 | 923 | 2.0 |
10 | 5332 | 667 | 1.5 |
25 | 8641 | 1080 | 2.3 |
a) Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured DPM by 8.
EC3: estimated to be greater than 25% w/v (>6250 µg/cm3 )
Body weights
Treatment group (%(w/v)) |
Animal number |
Body weight (g) |
|
Day 1 |
Day 6 |
||
0 |
1 |
17.5 |
19.0 |
2 |
18.3 |
20.9 |
|
3 |
16.1 |
17.6 |
|
4 |
16.7 |
18.1 |
|
1 |
5 |
15.1 |
16.9 |
6 |
16.3 |
17.3 |
|
7 |
16.9 |
17.9 |
|
8 |
16.9 |
17.6 |
|
2.5 |
9 |
16.0 |
16.7 |
10 |
18.3 |
18.9 |
|
11 |
17.8 |
18.1 |
|
12 |
17.2 |
18.0 |
|
5 |
13 |
16.1 |
17.9 |
14 |
17.6 |
18.3 |
|
15 |
16.8 |
17.8 |
|
16 |
17.3 |
18.1 |
|
10 |
17 |
15.9 |
17.2 |
18 |
16.2 |
17.8 |
|
19 |
16.7 |
17.9 |
|
20 |
18.1 |
19.4 |
|
25 |
21 |
17.8 |
19.3 |
22 |
16.4 |
18.7 |
|
23 |
16.9 |
19.0 |
|
24 |
17.0 |
18.6 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
Two skin sensitisation studies are performed one according to the Buehler protocol and one LLNA. The Buehler is considered the key study because the reliability is 1, the study is positive and tested at higher concentrations than the LLNA (60 and 25%, respectively). Both tests are summarised below.
Key information: Skin sensitisation in a Buehler test:
The skin sentisation potential of the substance was investigated by performing a Buehler test similar to OECD 406 (1981) and according to GLP principles. Ten animals were used in the treatment group and 5 in the negative control group (instead of 20 resp. 10 animals according the guideline). A concentration of 60% was used for the inductions (total of 9) and the challenge. After the inductions, patchy erythema was observed among the animals. After the challenge with the substance 8 of the 10 and 7 of 10 animals showed slight or confluent or moderate patchy erythema (score 1) at the naive site at 24 and 48 hours, respectively. At the induction site slightly more effects were observed. Reliable negative (no response during challenge) and positive controls were included. Based on the positive results, the substance is considered to be a sensitiser under the conditions of the test.
Supporting information: Skin sensitisation in an LLNA (OECD TG 429)
The skin sensitisation potential of the test substance has been tested according to OECD TG 429: "Local Lymph Node Assay" method. At 1, 2.5, 5, 10, and 25% the substance showed SI values of 1.0, 1.4, 2.0, 1.5 and 2.3, respectively. EC3 was estimated to be >25%. The test substance was considered not to be a sensitiser under the conditions of the test.
Based on the Buehler study the substance is considered a sensitizer and classified catergory 1B (>15% responding at >20% topical induction dose). Classification in this sub-category is supported by the LLNA test which showed an EC of >25%.
Justification for classification or non-classification
The substance was considered to be a sensitiser and should be classified as skin sensitizer (Category 1B) and labeled as H317: May cause an allergic skin reaction according to Regulation (EC) No. 1272/2008 and GHS.
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