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EC number: 297-668-0 | CAS number: 93686-18-1
- 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
In this study Stimulation Indices (S.I.) of 1.74, 1.57, and 4.18 were determined with the test item at concentrations of 25 and 50% in ethanol/water (3+7, v/v), as well as undiluted (100%), respectively.
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
- Study period:
- initiated: 2016-08-22, experimental: 2017-03-08 to 2017-04-04
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- OECD 429 testing has been considered to be best for this type of substance. In addition the study has been commissioned before Regulation (EU) 2016/1688 entered into force. The delay of the experimental study was due to a change of testing facility.
Sensibilisation studies according to OECD 442C (KeratinoSens) and OECD442D (h-CLAT) have been considered but finally rejected, since they appear not suitabel for week sensitizers and may lead to false negative results. - Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2010
- Deviations:
- yes
- Remarks:
- The age of the animals was 12 to 13 weeks (beginning of acclimatisation). This deviation to the study plan, however, does not affect the validity of the study.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2008
- Deviations:
- yes
- Remarks:
- The age of the animals was 12 to 13 weeks (beginning of acclimatisation). This deviation to the study plan, however, does not affect the validity of the study.
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, date of inspection: 13.-16. Juli 2015
- Type of study:
- mouse local lymph node assay (LLNA)
- Specific details on test material used for the study:
- technical grade: aqueous solution (31% dry matter in water)
- Species:
- mouse
- Strain:
- other: CBA/CaOlaHsd
- Remarks:
- Recognised as the recommended test system.
- Sex:
- female
- Details on test animals and environmental conditions:
- Source: Envigo RMS B.V., Inc, Postbus 6174, 5960 AD Horst / The Netherlands
Number of animals for the pre-test: 2 females
Number of animals for the main study: 16 females
Number of animals per group: 4 females (nulliparous and non-pregnant)
Number of test groups: 3
Number of control (vehicle) groups: 1
Age (beginning of treatment): Pre-test: 12 - 13 weeks
Main study: 9 - 10 weeks
Body weight: 19.3 ± 0.3 g (start),
19.7 ± 1.1 g (prior administration);
see Appendix 1 and 2 of the study report
Identification:
The animals were distributed into the test groups at random. All animals belonging to the same experimental group were kept in one cage. In the main experiment, the animals were identified by fur clipping. In the pre-experiment, animals were identified by cage number.
Acclimation: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study.
HUSBANDRY
The animals were kept conventionally. The experiment was conducted under standard laboratory conditions.
Housing: group
Cage Type: Makrolon Type II (pre-test) / III (main study), with wire mesh top
Bedding: granulated soft wood bedding
Feed: 2018C Teklad Global 18% protein rodent diet (certified), ad libitum
Water: tap water, ad libitum
Environment: temperature 22 ± 2°C
relative humidity: approx. 45-65%
artificial light: 6.00 a.m. - 6.00 p.m. - Vehicle:
- other: Ethanol/water (3+7, v/v)
- Remarks:
- Ethanol: Purity: ≥99.9%; Water: Sterile
- Concentration:
- 0, 25, 50, and 100%
- No. of animals per dose:
- 4
- Details on study design:
- TEST ITEM ADMINISTRATION
Each test group of mice was treated by (epidermal) topical application to the dorsal surface of each ear with test item concentrations of 25 and 50% in ethanol/water (3+7, v/v), and 100%. The application volume, 25 μL/ear/day, was spread over the entire dorsal surface (ø ~ 8 mm) of each ear once daily for three consecutive days. A further group of mice (control animals) was treated with an equivalent volume of the relevant vehicle alone (control animals).
ADMINISTRATION OF ³H-METHYL-THYMIDINE
Five days after the first topical application (day 6) 250 μL of phosphate-buffered saline containing 20.1 μCi of 3H-methyl thymidine (equivalent to 80.4 μCi/mL 3HTdR) were
injected into each test and control mouse via the tail vein.
TERMINAL PROCEDURE
Approximately five hours after treatment with 3HTdR all mice were euthanized by using CO2, which was, after harvesting of the lymph nodes, followed by cervical dislocation to ensure death. The draining lymph nodes were rapidly excised and pooled for each experimental group (8 nodes per group).
PREPARATION OF SINGLE CELL SUSPENSIONS
Single cell suspensions (in phosphate buffered saline) of pooled lymph node cells were prepared by gentle mechanical disaggregation through stainless steel gauze (200 μm mesh size). After washing two times with phosphate buffered saline (approx. 10 mL) the lymph node cells were resuspended in 5 % trichloroacetic acid (approx. 3 mL) and incubated at approximately +4 °C for at least 18 hours for precipitation of macromolecules.
DETERMINATION OF CELLULAR PROLIFERATION (incorporation of ³HTdR)
The precipitates were then resuspended in 5 % trichloroacetic acid (1 mL) and transferred to scintillation vials with 10 mL of scintillation liquid and thoroughly mixed. The level of ³HTdR incorporation was then measured in a β-scintillation counter. Similarly, background ³HTdR levels were also measured in two 1 mL-aliquots of 5 % trichloroacetic acid. The β-scintillation counter expresses ³HTdR incorporation as the number of radioactive disintegrations per minute (DPM).
OBSERVATIONS
Clinical Observations: All animals were observed on a daily basis, including pre- and post-dose observations on days 1, 2 and 3. Any clinical signs of systemic toxicity, local skin irritation or signs of ill health during the study were recorded.
Determination of Ear Thickness: In the pre-test, the ear thickness was determined prior to the first application of the test item (day 1), on day 3, and on day 6 prior to sacrifice using a micrometer.
Determination of ear weights: In the pre-test, after the lymph nodes had been excised, both ears of mice were punched at the apical area using a biopsy punch (Ø 8 mm corresponding to 0.5 cm2). For each animal both punches were immediately weighed per animal using an analytical balance. The values obtained were taken down manually. The results are described in the report.
Determination of Body Weights: The body weights were recorded on day 1 (prior to dosing) and prior to sacrifice (pre-test) or prior to treatment with 3HTdR (main experiment) - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The mean values and standard deviations were calculated in the body weight tables. Where appropriate, the EC3 value were calculated according to the equation
EC3 = (a-c) [(3-d)/(b-d)] + c
where EC3 is the estimated concentration of the test item required to produce a 3-fold increase in draining lymph node cell proliferative activity; (a, b) and (c, d) are respectively the coordinates of the two pair of data lying immediately above and below the S.I. value of 3 on the local lymph node assay dose response plot. All calculations conducted on the DPM values were performed with a validated test script of “R”, a language and environment for statistical computing and graphics. - Positive control results:
- RESULTS OF THE GLP POSITIVE CONTROL
Experiment performed in October 2016 (Envigo study number 1792800). Positive control substance: α-Hexylcinnamaldehyde Vehicle: acetone:olive oil (4+1, v/v)
Test Item [%] Stimulation Index [S.I.]
0 1.00
5 1.78
10 3.43
25 10.06 - Key result
- Parameter:
- SI
- Value:
- 0
- Test group / Remarks:
- 1
- Key result
- Parameter:
- SI
- Value:
- 1.74
- Test group / Remarks:
- 2
- Remarks on result:
- other: 25% in ethanol/water (3+7, v/v)
- Key result
- Parameter:
- SI
- Value:
- 1.57
- Test group / Remarks:
- 3
- Remarks on result:
- other: 50% in ethanol/water (3+7, v/v)
- Key result
- Parameter:
- SI
- Value:
- 4.18
- Test group / Remarks:
- 4
- Remarks on result:
- other: 100% in ethanol/water (3+7, v/v)
- Parameter:
- other: DPM per lymph node
- Value:
- 551.2
- Test group / Remarks:
- 1
- Parameter:
- other: DPM per lymph node
- Value:
- 960.8
- Test group / Remarks:
- 2
- Remarks on result:
- other: 25% in ethanol/water (3+7, v/v)
- Parameter:
- other: DPM per lymph node
- Value:
- 866.6
- Test group / Remarks:
- 3
- Remarks on result:
- other: 50% in ethanol/water (3+7, v/v)
- Parameter:
- other: DPM per lymph node
- Value:
- 2 303.7
- Test group / Remarks:
- 4
- Remarks on result:
- other: 100% in ethanol/water (3+7, v/v)
- Cellular proliferation data / Observations:
- It cannot be ruled out that the physical damage on the ear skin observed in high dose animals had a possible effect on S.I. value in this dose group. The lesions could have caused mild unspecific proliferation of lymphocytes, leading to a weakly positive S.I. value in the high dose only. Furthermore, no conventional dose response was obtained.
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- The results obtained with sulfonic acids, shale oil, sodium salts, were found to be inconclusive under the test conditions of this study since a possible effect of skin irritation on lymphocyte proliferation in high dose animals cannot be ruled out.
- Executive summary:
In the study the test item sulfonic acids, shale oil, sodium salts, formulated in ethanol/water (3 +7, v/v) was assessed for its possible skin sensitising potential. For this purpose a local lymph node assay was performed using test item concentrations of 25, 50% (w/w), and 100%.
The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. The animals treated with a test item concentration of 50 and 100% showed a very slight erythema of the ear skin (Score 1) on few days. Additionally hair loss was observed (see Appendix 2 for details). Animals treated with 25% test item concentration did not show any signs of local skin irritation. On test day 6, upon preparation, focal eschar (crust) formation was observed on the ears of the animals treated with the undiluted test item. This minor physical damage of the skin was possibly caused by attempted removal of adhered test item.
In this study Stimulation Indices (S.I.) of 1.74, 1.57, and 4.18 were determined with the test item at concentrations of 25 and 50% in ethanol/water (3+7, v/v), as well as undiluted (100%), respectively. It cannot be ruled out that the physical damage on the ear skin observed in high dose animals
had a possible effect on S.I. value in this dose group. The lesions could have caused mild unspecific proliferation of lymphocytes, leading to a weakly positive S.I. value in the high dose only. Furthermore, no conventional dose response was obtained. The results obtained with sulfonic acids, shale oil, sodium salts, were thus found to be inconclusive.
Reference
EC3 Value
An EC3 value could not be derived since no conventional dose response was obtained and the
results were found to be inconclusive due to substantial skin irritation in high dose animals.
Deaths
No deaths occurred during the study period.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
It cannot be ruled out that the physical damage on the ear skin observed in high dose animals had a possible effect on S.I. value in this dose group. The lesions could have caused mild unspecific proliferation of lymphocytes, leading to a weakly positive S.I. value in the high dose only. Furthermore, no conventional dose response was obtained. The results obtained with sulfonic acids, shale oil, sodium salts, were thus found to be inconclusive.
Justification for classification or non-classification
The results obtained with sulfonic acids, shale oil, sodium salts, were found to be inconclusive.
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