Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
25 March - 21 July 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Full read-across justification report is attached in section 13.

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:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Anhydrous Sodium Perchlorate
- Physical state: white powder
- Analytical purity: 98.21%
- Impurities (identity and concentrations): Water: 1.67% Chlorate: (ClO3) 0.081% Chromium: (Cr) 2.08%
- Purity test date: 10 January 2008
- Lot/batch No.: lot moyen du 10/01/08 (Sponsor's filing number: GRL 0005/08)
- Expiration date of the lot/batch: February 2008
- Storage condition of test material: Room temperature, keep hermatically closed. Store away from heat and ignition sources

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 21.4 ± 1.1g
- Housing: Disposable crystal polystyrene cages (22.00x8.5x8.0cms) containing autoclaved sawdust
- Diet: SSNIFF R/M-H pelleted maintenance diet batch no. 3016578 (SSNIFF Spezialdiaten GmbH, Soest, Germany)
- Water: Tap water (filtered using a 0.22 µm filter) ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 -70
- Air changes (per hr): 12 cycles/hr of non-recycled air
- Photoperiod (hrs dark / hrs light): 12 hr/12 hr (7:00 - 19:00)


IN-LIFE DATES: From: 25 March 2008 To: 07 April 2008

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
Vehicle (0% test item); 1%. 2.5%, 5%, 10%, 25%, HCA 25%
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: Due to the unsatisfactory solubility of the test item in the first recommended vehicle
(acetone/olive oil (4/1, v/v)), dimethylformamide was chosen from the other proposed vehicles.
A solution was obtained at the maximum concentration of 25%.
- Irritation: The test item was non-irritant in the preliminary test, whatever the concentration.
The highest concentration retained for the main test was therefore the maximal practicable
concentration (25%), according to the criteria specified in the International Guidelines.
- Lymph node proliferation response:


MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: murine Local Lymph Node Assay (LLNA)

- Criteria used to consider a positive response:
% increase in ear thickness
between day 1 and day 3 or 6 Irritation level Interpretation
< 10% I Non-irritant
10 - 30% II Slightly irritant
> 30% III Irritant

TREATMENT PREPARATION AND ADMINISTRATION: On days 1, 2 and 3, a dose-volume of
25 μL of the control or dosage form preparations was applied to the dorsal surface of both ears,
using an adjustable pipette fitted with a plastic tip. In order to avoid licking and to ensure an
optimized application of the test materials, the animals were placed under light isoflurane
anesthezia during the administration. No massage was performed but the tip was used to
spread the preparation over the application sites. No rinsing was performed between each application.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
no data

Results and discussion

Positive control results:
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 = 8.83) were noted.
The study was therefore considered valid.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Test item 1% 1.59 Test item 2.5% 1.49 Test item 5% 1.71 Test item 10% 1.21 Test item 25% 0.54 HCA 25% 8.83
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: dpm per group: Vehicle 589.6 Test item 1% 935.26 Test item 2.5% 878.25 Test item 5% 1007.9 Test item 10% 715.00 Test item 25% 319.85 HCA 5205.31

Any other information on results incl. tables

Due to the unsatisfactory solubility of the test item in the first recommended vehicle (acetone/olive oil (4/1, v/v)), dimethylformamide was chosen from the other proposed vehicles. A solution was obtained at the maximum concentration of 25%. Consequently, the concentrations selected for the preliminary test were 2.5, 5, 10 and 25%. Since the test item was non-irritant in the preliminary test, the highest concentration retained for the main test was the maximal practicable concentration (25%). No mortality and no clinical signs were observed during the study. No cutaneous reactions and no noteworthy increase in ear thickness were observed in the animals of the treated groups.

Treatment

Concentration

(%)

Irritation level

Stimulation index

(SI)

Test item

1

non-irritant

1.59

Test item

2.5

non-irritant

1.49

Test item

5

non-irritant

1.71

Test item

10

non-irritant

1.21

Test item

25

non-irritant

0.54

HCA

25

-

8.83

Under the experimental conditions of this study, the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) did not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the experimental conditions of this study, the test item ANHYDROUS SODIUM PERCHLORATE did not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay.
Executive summary:

A GLP study was conducted to evaluate the potential of the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) to induce delayed contact hypersensitivity using the murine Local Lymph Node Assay (LLNA). Evaluation of local irritation was also carried out in parallel. Under the experimental conditions of this study, the test item ANHYDROUS SODIUM PERCHLORATE did not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay and is therefore considered as non sensitising.