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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:
2010
Report Date:
2010

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)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Zinc dibenzyldithiocarbamate (Perkacit ZBEC pdr)
- Physical state: white to light cream powder
- Analytical purity: 99.0 %
- Expiration date of the lot/batch: 19 April 2011 (allocated by NOTOX, 1 year after receipt of the test substance)
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark

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: approx. 11 weeks old)
- Weight at study initiation: within +/- 20% of the sex mean
- Housing: Individually in labeled Macrolon cages (MI type; height 12.5 cm) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France). Paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom) was supplied as cage-enrichment. The paper was removed on Day 1 prior to dosing and was supplied again after scoring of the ears on Day 3.
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7– 22.9
- Humidity (%): 43 - 62
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
dimethyl sulphoxide
Concentration:
0, 10, 25 and 50% in DMSO
No. of animals per dose:
5 females/dose
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: the vehicle (DMSO) was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor. Homogeneity was obtained to visually acceptable levels.
- Irritation: a preliminary irritation study was conducted in order to select the highest test substance concentration to be used in the main study. In principle, this concentration should be well tolerated systemically by the animals and may give moderate irritation (maximally grade 2) at the highest concentration.
Two test substance concentrations were tested; a 25% and 50% concentration. The highest concentration was the maximum concentration as required in the test guidelines (50% for solids).
- Lymph node proliferation response: no necropsy performed

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: Stimulation Index (SI) calculated for each group. If the results indicate a SI ≥ 3, the test substance may be regarded as a skin sensitizer, based on the test guideline and recommendations done by ICCVAM

TREATMENT PREPARATION AND ADMINISTRATION: the dorsal surface of both ears was epidermally treated (25 μL/ear) with the test substance
concentration, at approximately the same time per day. The concentrations were mixed thoroughly using a vortex mixer immediately prior to dosing. The control animals were treated the same 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)

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
0.7
Test group / Remarks:
substance concentration 10%
Key result
Parameter:
SI
Value:
0.8
Test group / Remarks:
substance concentration 25%
Key result
Parameter:
SI
Value:
0.9
Test group / Remarks:
substance concentration 50%
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: 1058, 706, 880 and 975 DPM (mean/animal) for concentrations 0 (vehicle), 10, 25 and 50% test substance, respectively.

Applicant's summary and conclusion