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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 -27 November 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD Guideline 429 without any deviation.
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:
2008
Report date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.42 (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

Constituent 1
Chemical structure
Reference substance name:
reaction mass of 1-chloro-3-(dodecyloxy)propan-2-ol and alpha-dodecyl-omega-hydroxy-di[oxy[(chloromethyl)-1,2-ethanediyl]] and alpha-dodecyl-omega-hydroxy-tri[oxy[(chloromethyl)-1,2-ethanediyl]]
Cas Number:
63727-39-9
Molecular formula:
C15H31ClO2 C18H36Cl2O3 C21H41Cl3O4
IUPAC Name:
reaction mass of 1-chloro-3-(dodecyloxy)propan-2-ol and alpha-dodecyl-omega-hydroxy-di[oxy[(chloromethyl)-1,2-ethanediyl]] and alpha-dodecyl-omega-hydroxy-tri[oxy[(chloromethyl)-1,2-ethanediyl]]
Test material form:
other: liquid
Details on test material:
- Physical state: Thick colorless to pale yellow liquid
- Date of receipt: 12 October 2006
- Expiration date of the lot/batch: 04 October 2007
- Storage condition of test material: Room temperature


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: Main test - Approximately 9 weeks
- Weight at study initiation: Main test - 20.4 ± 1.2 g
- Housing: Animals were housed individually in disposable crystal polystyrene cages (22.00 cm x 8.50 cm x 8.00 cm).
- Diet: sniffR/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:
Acetone, batch No. I301612625 (Merck, Chelles, France) and olive oil, batch No. 045K6094 (Sigma, Saint-Quentin-Fallavier, France)
Concentration:
Preliminary test: 10, 25, 50 and 100 %
Main test: 0.5, 1, 2.5, 5 and 10 %
No. of animals per dose:
Preliminary test: 1 female/dose
Main test: 4 females/dose
Details on study design:
PRELIMINARY TEST:
- Compound solubility: Test item was soluble at the concentration of 50 % in Acetone/Olive Oil (4/1; v/v) (AOO)
- Irritation: Erythema and/or a dryness of the skin were noted at the concentrations of 25, 50 and 100 %. Moreover, an increase in ear thickness was recorded at these concentrations, showing the irritant potential of the test item at these concentrations. The highest concentration retained for the main test was therefore 10 %.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT: Animals were assigned to the treatment groups by hand procedure.
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: The test item was considered as a skin sensitizer when the SI for a dose group is ≥ 3. Other relevant criteria such as cellularity, radioactivity levels and ear thickness were also taken into account for the interpretation of results.

TREATMENT PREPARATION AND ADMINISTRATION: 25 µL of control and test item were applied to the dorsal surface of both ears on Days 1, 2 and 3. On Day 6, 250 µL of 0.9 % NaCl containing 20 μCi of 3H-TdR (specific activity of 25 Ci/mmol) was injected into the tail vein of each experimental mouse. Five hours later, all mice were killed by cervical dislocation and the auricular lymph nodes were 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. Cell suspensions 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. The results were expressed as disintegrations per minute (dpm) per group and as dpm/node.

Stimulation Index (SI) were calculated according to the following formula:
SI = dpm of the treated group / dpm of the control group
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
No data

Results and discussion

Positive control results:
Stimulation index for α-hexylcinnamaldehyde at 25 % v/v was 10.03 and classified as a sensitiser.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Stimulation index for 0.5, 1, 2.5, 5 and 10 % were 0.84, 1.10, 0.74, 1.75 and 6.21, respectively.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
- DPM per group for vehicle, 0.5, 1, 2.5, 5 and 10 % were 1389.50, 1160.79, 1526.07, 1021.58, 2435.60 and 8633.94, respectively. - DPM per node for vehicle, 0.5, 1, 2.5, 5 and 10 % were 173.69, 145.10, 190.76, 127.70, 304.45 and 1079.24, respectively.

Any other information on results incl. tables

See attached Document for Tables of Results

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under these test conditions, the test item is classified as "R43: May cause sensitization by skin contact" according to the Annex VI to the Directive 67/548/EEC and as a "skin sensitizer: category 1" according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In a GLP-compliant local lymph node assay performed according to OECD Guideline 429, groups of CBA/J mice (4 females/dose) were exposed to 25 µL of the test item in Acetone/Olive oil (4/1; v/v) at the concentrations of 0 (vehicle), 0.5, 1, 2.5, 5 and 10 % to the dorsal surface of both ears for three consecutive days. On Day 6, the proliferation of lymphocytes in the lymph node draining the application site was measured by incorporation of tritiated methyl thymidine. The results were expressed as disintegrations per minute (dpm) per group; dpm/node and the obtained values were used to calculate Stimulation Indices (SI). Animals were observed for mortality, clinical signs and body weight during the study. The test concentrations for the main study were determined from a preliminary study (10, 25, 50 and 100 %) using one animal per exposure.

No mortality and no clinical signs were observed during the observation period. Body weight of the animals was unaffected by the test item treatment. Erythema and dryness of the skin were noted on Day 6 in all the animals treated at the concentration of 10 %. No noteworthy increase in ear thickness was observed in the animals of the treated groups. DPM per group for vehicle, 0.5, 1, 2.5, 5 and 10 % were 1389.50, 1160.79, 1526.07, 1021.58, 2435.60 and 8633.94, respectively. DPM per node for vehicle, 0.5, 1, 2.5, 5 and 10 % were 173.69, 145.10, 190.76, 127.70, 304.45 and 1079.24, respectively. Stimulation index for 0.5, 1, 2.5, 5 and 10 % were 0.84, 1.10, 0.74, 1.75 and 6.21, respectively. In the absence of local irritation, the significant lymphoproliferative response observed at the concentration of 10 % (SI>3) was attributed to contact sensitization.

The calculated EC3 value for the test item was 6.4 %. In the positive control group given HCA at the concentration of 25%, a moderate increase in cellularity and a stimulation index exceeding the threshold value of 3 (SI = 10.03) were noted, therefore the study was considered valid.

Under these test conditions, the test item is classified as "R43: May cause sensitization by skin contact" according to the Annex VI to the Directive 67/548/EEC and as a "skin sensitizer: category 1" according to the CLP Regulation (EC) N° (1272-2008).