Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015-9-2 to 2015-9-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl (1R,3S,4R,5R)-3-amino-5-({2,4,6-tri-O-benzoyl-3-O-[(2S)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl]-β-D-galactopyranosyl}oxy)-4-[(2,3,4-tri-O-benzyl-6-deoxy-α -L-galactopyranosyl)oxy]cyclohexanecarboxylate hydrochloride
EC Number:
945-311-0
Molecular formula:
C78H85NO18 HCl
IUPAC Name:
Methyl (1R,3S,4R,5R)-3-amino-5-({2,4,6-tri-O-benzoyl-3-O-[(2S)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl]-β-D-galactopyranosyl}oxy)-4-[(2,3,4-tri-O-benzyl-6-deoxy-α -L-galactopyranosyl)oxy]cyclohexanecarboxylate hydrochloride
Details on test material:
- State of aggregation: white solid powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: E010016142
- Expiration date of the lot/batch: 31 March 2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dissolved in the appropiate amount of DMSO vehicle

FORM AS APPLIED IN THE TEST (if different from that of starting material)
10% in DMSO (w/w)
25% in DMSO (w/w)
50% in DMSO (w/w)

In vivo test system

Test animals

Species:
mouse
Strain:
CBA:J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Females nulliparous and non-pregnant: yes
- Age at study initiation: ~10 weeks old
- Weight at study initiation: Within 20% of the sex mean
- Housing: Labeled 18 cm tall Makrolon cages containing sterilised sawdust as bedding material. Paper and shelters were supplied as cage enrichement.
- Diet (e.g. ad libitum): Ad libitum access to peleted rodent diet (SM R/M-Z)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >=5 days
- Indication of any skin lesions: None

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
dimethyl sulphoxide
Concentration:
0% in DMSO (w/w) (contorl)
10% in DMSO (w/w)
25% in DMSO (w/w)
50% in DMSO (w/w)
No. of animals per dose:
5
Details on study design:
PRE-SCREEN TESTS:
- Compound solubility: 50% (w/w) in DMSO was the maximum practical solubility
- Irritation: None
- Systemic toxicity: None
- Ear thickness measurements: <25% increase

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA Test
- Criteria used to consider a positive response: SI test

TREATMENT PREPARATION AND ADMINISTRATION:
Induction - Days 1, 2 and 3
The dorsal surface of both ears was topically treated (25 NL/ear) with the test substance, at
approximately the same time on each day. The concentrations were stirred with a magnetic stirrer
immediately prior to dosing.
The control animals were treated in the same way as the experimental animals, except that the vehicle
was administered instead of the test substance.

Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
None

Results and discussion

Positive control results:
The Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing for contact hypersensitivity.

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
ca. 0
Variability:
None
Test group / Remarks:
Control (0% in DMSO (w/w))
Key result
Parameter:
SI
Value:
ca. 0
Variability:
None
Test group / Remarks:
Test Group 1 (10% in DMSO (w/w))
Key result
Parameter:
SI
Value:
ca. 0
Variability:
None
Test group / Remarks:
Test Group 2 (25% in DMSO (w/w))
Key result
Parameter:
SI
Value:
ca. 0
Variability:
None
Test group / Remarks:
Test Group 3 (50% in DMSO (w/w))
Cellular proliferation data / Observations:
BODY WEIGHTS
Most animal body weights increased over the course of the study. No variation in body weight was determined to have an effect on the results.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance does not have to be classified as a skin sensitizer according to GHS.