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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-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:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
study conducted when the guinea pig test methods (acc. to OECD TG 406) were still standard

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Bacth 1190567/006 provided by EnviroService International GmbH
- Expiration date of the lot/batch: not available
- Purity test date: not available

RADIOLABELLING INFORMATION (if applicable): not applicable

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: stable
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: none

TREATMENT OF TEST MATERIAL PRIOR TO TESTING: not applicable

FORM AS APPLIED IN THE TEST (if different from that of starting material): not applicable

OTHER SPECIFICS: none

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre de Production animale (45160 Olivet, France)
- Females (if applicable) nulliparous and non-pregnant: not specified
- Microbiological status of animals, when known: unknown
- Age at study initiation: not available
- Weight at study initiation: 238 - 366 g
- Housing: no information available
- Diet (e.g. ad libitum): no information available
- Water (e.g. ad libitum): no information available
- Acclimation period: 5 days
- Indication of any skin lesions: no information available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22 °C
- Humidity (%): 39 -79%
- Air changes (per hr): no information available
- Photoperiod (hrs dark / hrs light): no information available

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
25%
Day(s)/duration:
7
Adequacy of induction:
other: no necrosis induced
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
2
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
50% and 100%
Day(s)/duration:
2
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
1. The maximum non-necrotising concentration was determined by injecting intradermally 1.562%, 3.125%, 6.25%, 12.5%, 25% and 50% of test substance (diluted in physiological saline) into two female guinea pigs. No necrosis was observed up to 25%.
2. The pre-maximum non-irritant concentration was determined by appliying topically (occlusive) 12.5%, 25% and 50% and 100% of test substance (diluted in physiological saline) to two female guinea pigs for 24 hours. No cutaneous reaction were observed up to 100%.
3. The maximum non-irritant concentration was determined by appliying topically (occlusive) 12.5%, 25% and 50% and 100% of test substance (diluted in distilled water) to three female guinea pigs for 24 hours, after an intradermal injection with hysiological saline, a topical application with distilled water and a 17-day rest phase. No cutaneous reaction were observed up to 100%.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 9 days
- Test groups: 1
- Control group: 1
- Site: intradermal (twice) and topical (same skin area)
- Frequency of applications: 2 intradermal (7 days) and 1 topical (2 days)
- Duration: 9 days
- Concentrations: 25%, Freud's Complte Adjuvant at 50% (diluted in physiological saline) and Freud's Complte Adjuvant at 50% and 50% test item (both diluted in physiological saline) intradermally, and 100% topically (24 h after brushing with 0.5 mL of a 10% SLS solution)

Between induction and challgenge phase, the guinea pigs rested for 18 days.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2
- Exposure period: 48 h
- Test groups: 1
- Control group: 1
- Site: topical
- Concentrations: 50% and 100%
- Evaluation (hr after challenge): 24 and 48
Positive control substance(s):
no

Results and discussion

Positive control results:
No concurrent control was used, but data of earlier test with benzocaine and neomycin sulfate are provided, showing clear cutaneous reactions in at least 38% (at 48h) of the guinea pigs

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

In a GLP-study according to OECD TG 406 (Guinea Pig Maximisation Test), the substance did not induce any adverse effects and is therefore considered to be not skin sensitising.

Guinea pig weight evolved comparably in the control and the treated groups.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

The skin sensitisation effects of the substance were investigated in a guinea pig maximisation tests according to OECD TG 406 under GLP-conditions. In three preliminary studies the concentrations to be applied during the various experimental phases were determined using two or three female guinea pigs. After a 9-day induction phase, consisting of 7 days intradermal exposure (twice) with the test substance (diluted to 25% in physiological saline) and a 2-day two topical application with 100% (after brushing with 10% SLS), the guinea pigs (all females) rested for 18 days.

Then the guinea pigs were challenged for two days by applying the substance topically (occlusive) in concentrations of 50% and 100%. At both reading times (24h and 48h) no cutaneous reactions were observed. Therefore, the substance is considered to be not skin sensitising.