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Diss Factsheets

Administrative data

Description of key information

OECD 406 (GPMT): not sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 Nov 2003 - 15 Jan 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Arbeitsschutz, Arbeitsmedizin und Sicherheitstechnik, München, Germany
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was performed in 2004 when the OECD Guideline 406 adopted in 1992 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) [...] and the non-adjuvant Buehler Test are given preference over other methods.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: 300 - 500 g
- Fasting period before study: no
- Housing: animals were barrier maintained (semi-barrier) in an air-conditioned room, animals were kept in groups in Terluran-cages on Altromin saw fiber bedding
- Diet: Altromin 3122 maintenance diet for guinea pigs (totally pathogen-free, rich in crude fiber), ad libitum
- Water: tap water, ad libitum
- Acclimation period: adequate acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
5%
Day(s)/duration:
Day 0
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
Day 7 / 48 h
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
Day 20 / 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Range-finding assay: 4
Main test: 5 controls and 10 test animals
Details on study design:
RANGE FINDING TESTS:
2 animals were intradermally treated with 1%, 2.5%, 5% and 10% of the test item (diluted in corn oil). For the 1% and 2.5% concentration erythema grade 1 were observed 48 h and 72 h after application. For the 5% and 10% concentrations erythema grade 1 and necrosis (5%: 0.2 cm diameter; 10%: 0.3 cm diameter) were observed 48 h and 72 h post-dose, respectively. The concentration of 5% was chosen for intradermal induction.
2 further animals were topically treated with 50% and 100% concentration for 24 and 48 h, respectively. No signs of irritation and systemic toxicity were recorded during the observation time for the animals. Therefore the 100% concentration was chosen for the topical induction as well as for the challenge.

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):
Injection 1: a 1:1 mixture (v/v) FCA/isotonic saline
Injection 2: test substance in corn oil
Injection 3: test substance in a 1:1 mixture (v/v) FCA/isotonic saline

Epicutaneous: test substance (undiluted)

- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/isotonic saline
Injection 2: Corn oil
Injection 3: Corn oil at 50% (w/v) in a 1:1 mixture (v/v) FCA/isotonic saline

Epicutaneous: Corn oil

- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-9
- Concentrations:
Test item: intradermal 5%, epicutaneous 100%
Control: intradermal 0%, epicutaneous 0%


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: day 20
- Exposure period: 24 h
- Test groups: 0.5 mL of the undiluted test item
- Control group: 0.5 mL of the undiluted test item
- Site: left flank (test item), right flank (vehicle)
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48, and 72 h
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole
Positive control results:
The positive control substance (15% mercaptobenzothiazole in vaseline) induced positive reactions in 8/10 animals (80%), thus meeting the reliability criteria for the GPMT test (≥ 15% positive response). Positive control substances are used periodically as a reliability check (last check before study May 2013) and not during the study itself.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
15%
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Induction readings: 3 animals showed erythema (grade 1) after 24 h at injection position 1. 48 h post-dose erythema (grade 1) were observed in 4 animals and necrosis (0.1-0.2 cm diameter; injection position 2) was observed in 6 animals. Erythema (grade 1) were observed in 8/10 animals after injection in position 3. No other signs of irritation were observed after the intradermal application (Induction first stage). No signs of irritation were observed after the topical application (Induction second stage). No signs of irritation and no signs of general toxicity were observed after challenge. Body weights were comparable within the test and control groups and the historical controls.

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In a GPMT according to OECD 406 and in compliance with GLP, the test item was not sensitizing. Induction (intradermal: 5%; topical: 100%) and challenge (100%) with the test item revealed no skin reactions in any of the 10 animals. Furthermore no skin reactions were observed in the negative controls (induction with corn oil, topical challenge with 100% test item).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitization

The skin sensitizing properties of methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7) were tested in a study according to OECD TG 406 under GLP conditions using the Guinea pig maximization test (GPMT, BSL, 2004). The GPMT test was performed on 15 female Dunkin Hartley guinea pigs. For the intradermal inductions the initial test item concentration was 5% (v/v) which was the highest concentration to cause mild to moderate skin irritation. A 100% (v/v) formulation of the test item was selected for the epicutaneous induction and the challenge exposure was based on the results of a preliminary irritation study. At the beginning of the induction exposure 10 test animals and 5 control animals were either intradermally treated with 5% of the test substance or vehicle (Day 0), followed by a topical induction (100% or vehicle) under occlusive conditions one week later. On Day 20 all animals were challenged with the test substance at a concentration of 100%. Skin reactions of all animals were evaluated 24 and 48 hours after challenge administration. Challenge exposure with the neat test item revealed no skin reactions in any of the 10 animals. Furthermore no skin reactions were observed in the negative controls. Periodic reliability checks with the positive control (mercaptobenzothiazole) gave the expected results. Therefore, the test substance had no sensitizing potential under the conditions of this test.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on the skin sensitization of the registered substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but nor sufficient for classification.