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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
Deviation in sample preparation without any presumed effect on the study
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
Deviation in sample preparation without any presumed effect on the study
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Product no. B4429, Lot no. SLBK5235V
- Expiration date of the lot/batch: 30 April 2018
- Purity test date: na

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: no

In vivo test system

Test animals

Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: TOXI COOP ZRT. Cserkesz u. 90., 1103 Budapest, Hungary
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: SPF
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 18.2 - 21.0 g
- Fasting period before study: unknown
- Housing: group caging (4 mice/cage)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): not available
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
other: Pluronic
Remarks:
aequous 1% (w/v) Pluronic(R)PE9200
Concentration:
5, 10 and 25% (max. concentration determined by solubility)
No. of animals per dose:
4
Details on study design:
PRE-SCREEN TESTS:
- Compound solubility: The substance's solubility in seven recommended solvents was tested.
- Irritation: no irritation was observed for the three concentration 5, 10 and 25% in a preliminary test
- Systemic toxicity: no toxicity was observed for the three concentration 5, 10 and 25% in a preliminary test
- Ear thickness measurements: no changes in ear thickness were observed for the three concentration 5, 10 and 25% in a preliminary test
- Erythema scores: all 0 for all concentrations, mice and time points (days 1, 2, 3, 4, 5, 6)

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: animals were assigned randomly achieving body weight homogeneity between groups
- Criteria used to consider a positive response: stimulation index of one concentration > 3

TREATMENT PREPARATION AND ADMINISTRATION: 25µL of the three respective formulations (substance dissolved in Pluronic) were applied to the dorsal surface of each ear using a pipette
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
none

Results and discussion

Positive control results:
Stimulation index (SI) of 25% (w/v) hexyl cinnamic aldehyde: 6.7

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
0.6
Test group / Remarks:
5%
Key result
Parameter:
SI
Value:
1
Test group / Remarks:
10%
Key result
Parameter:
SI
Value:
1.7
Test group / Remarks:
25%
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA
Disintegration per minute (per mouse (average)):
vehicle control: 772.8
5.0%: 478.3
10%: 764.0
25%: 1290.3


DETAILS ON STIMULATION INDEX CALCULATION: ratio of DPM/mouse of test concentrations and vehicle control

EC3 CALCULATION: not applicable

CLINICAL OBSERVATIONS: no irritation or other effects observed

BODY WEIGHTS: no treatment related effects

Any other information on results incl. tables

In a GLP-Study according to OECD TG 429 (LLNA), the substance, which was tested up to 25% in aqueous 1% Pluronic

(limited due to solubility), did not induce any skin sensitisation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

The substance potential to induce skin sensitisation was investigated in a GLP-study according to OECD TG 429 (Local Lymph Node Assay).

Based on solubility experiments with seven potential vehicles, the substance was solved in aqueous 1% Pluronic. In a preliminary test, concentrations of 5, 10 and 25% did not induce irritation, increase ear thickness or show any other toxicity effects.

In the main test with four female CBA/CA mice per concentration and control (randomly assigned), the concentrations of 2 5, 10 and 25%

resulted in stimulation indices of 0.6, 1.0 and 1.7, respectively. As all indices were below 3 and no dose-response was apparent, the substance is considered as non skin sensitising.