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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
Study period:
24/06/2015 - 07/07/2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

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:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymphnode assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
- Batch: E15-01025
- Purity: 100%
- Physical state / Appearance: black powder
- Storage Conditions: oom temperature in the dark

In vivo test system

Test animals

Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Horst, The Netherlands
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-23g
- Housing: On receipt the animals were randomly allocated to cages.
- Diet (e.g. ad libitum): Free access to and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd.,Oxon, UK)
- Water (e.g. ad libitum): Free access to mains tap water
- Acclimation period: min 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15x
- Photoperiod (hrs dark / hrs light): 12/12 (6,00-18,00h)

Study design: in vivo (LLNA)

Vehicle:
propylene glycol
Remarks:
This vehicle was chosen as it produced the highest concentration that was suitable for dosing.
Concentration:
- Preliminary screening test: no clinical signs of toxicity were noted at a concentration of 50% w/w, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay.
- 50 µL (25 µL per ear) of the test item as a suspension in propylene glycol at concentrations of 50%, 25% or 10% w/w.
No. of animals per dose:
3 groups of 4 animals
Details on study design:
- application to the dorsal surface of the ear for 3 consecutive days
- Five days following the first topical application of the test item or vehicle (Day 6) all mice were injected via the tail vein with 250 \iL of phosphate buffered saline (PBS) containing 3H-methyl thymidine (3HTdR: 80 jj-Ci/mL, specific activity 2.0 Ci/mmoL, ARC UK Ltd) giving a total of 20 jiCi to each mouse.
- control: treatment with propylene glycol alone

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
0.83
Test group / Remarks:
concentration in propylene glycol: 10 %w/w
Parameter:
SI
Value:
1.24
Test group / Remarks:
concentration in propylene glycol: 25 %w/w
Parameter:
SI
Value:
1.18
Test group / Remarks:
concentration in propylene glycol: 50 %w/w
Cellular proliferation data / Observations:
Black staining on the ears and fur was noted post dose on Days 1 to 3 in all test animals.
There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test.
Body weight change of the test animals between Day 1 and Day 6 was comparable to that observed in the corresponding control group animals over the same period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item was considered to be a non-sensitizer under the conditions of the test.
The test item does not meet the criteria for classification according to the Globally Harmonized Classification System and to the Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.
Executive summary:

Introduction

A study was performed to assess the skin sensitization potentialofthe test item in the CBA/Ca strain mouse following topical application to the dorsal surfaceofthe ear.

Methods

Following a preliminary screening test in which no clinical signsoftoxicity were noted at a concentrationof50%w/w, this concentration was selected as the highest dose investigated in the main testofthe Local Lymph Node Assay. Three groups,eachoffour animals, were treated with 50\xL(25\xLper ear)ofthe test item as a suspension in propylene glycol at concentrationsof50%, 25%or 10%w/w. A further groupoffour animals was treated with propylene glycol alone.

Results

The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporationofthe vehicle control group are as follows:

0.83 / 1.24 / 1.18

The test item was considered to be a non-sensitizer under the conditionsofthe test.

The test item does not meet the criteria for classification according to the Globally Harmonized Classification System and to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and PackagingofSubstances and Mixtures.