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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
Study period:
29 October 2000 to 01 December 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
BAYERISCHES LANDESAMT FÜR ARBEITSSCHUTZ, ARBEITSMEDIZIN UND SICHERHEITSTECHNIK, München, Germany
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The guinea pig maximisation test was selected since the test substance is a functional silane and the Local Lymph Node Assay as the preferred alternative has shown to provide false positive results for silicone substances.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Hsd Poc: DH Guinea pigs
- Source: Harlan Winkelmann GmbH (Borchen, Germany)
- Weight at study initiation: 300- 500 g
- Housing: in groups of max. 10 in Terluran cages on Altromin saw fiber bedding
- Diet: Altromin 3122 maintenace diet for guinea pigs, rich in crude fiber, totally-pathogen-free-TPF, ad libitum
- Water: tap water, ad libitum
- Acclimation period: Adequate

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±3 °C
- Humidity (%): 55±10%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12 (artificial light from 6.30-18.30)

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
cotton seed oil
Concentration / amount:
For the intradermal injection (induction stage), 0.5 ml of the test item (purity 98.53%) was diluted with 9.5 ml of cotton seed oil (= 5%).
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
For topical applications the item was applied at a 100% concentration.
Challenge
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Concentration / amount:
100%
No. of animals per dose:
10/test group, 5/control group.
Details on study design:
RANGE FINDING TESTS:
For the justification of dose levels a prelimnary test was performed. Four animals were topically treated with 25%, 50%, and 100% concentration of the test item. No signs of irritation and systemic toxicity were recorded after a contact priod of 48 h after application of 100% concentration. Therefore, the 100% concentration was chosen for the topical induction and for the challenge as well.
For the justification of the first stage of the induction three animals were intradermally treated with 1%, 2.5%, and 5%. Slight erythema was found in the animal treated with the 5% concentration. These symptoms lasted until 48 h after application. No other signs of irritation and systemic toxicity were recorded until 72 h after application. Therefore, the highest concentration (5%) was chosen for the intradermal induction.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections) on day 0:
Injection 1: a 1+1 mixture (v/v) FCA/isotonic saline
Injection 2: prepared test item
Injection 3: prepared test item at a concentration of 50% (v/v) in FCA, 1+1 (v/v) diluted with isotonic saline
Epicutaneous on day 6: 0.5 ml of the test item (100%)
- Control group:
Intradermal (3 pairs of injections) on day 0:
Injection 1: a 1+1 mixture (v/v) FCA/isotonic saline
Injection 2: vehicle
Injection 3: vehicle at a concentration of 50% (v/v) in FCA, 1+1 (v/v) diluted with isotonic saline
Epicutaneous on day 6: 0.5 ml of the vehicle
- Site: shoulder region
- Frequency of applications: every 6 days
- Duration: days 0-6
- Concentrations: intradermal 5%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: 0.5 ml of 100% test substance
- Control group: 0.5 ml of 100% test substance
- Site: flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48, and 72 h

OTHER: During challenge the patches were held in contact by occlusive dressing. At the end of the challenge skin was cleaned with the aid of moistened gauze patches.
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole, purity > 98% (historical positive control data; the latest check was performed in August/September 2000)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
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
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
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
tested on regular basis in the laboratory

Any other information on results incl. tables

After intradermal injection of the test item slight erythema (grade 1) were observed in all animals.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for skin sensitisation according to the OECD TG 406 (Guinea Pig Maximization Test) and in compliance with GLP. There were no signs of sensitisation recorded for any of the tested animals. Based on these findings classification for skin sensitisation according to 67/584/EEC and EC/1272/2008 is not warranted.