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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:
1997-9-22 to 1997-10-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A guideline for LLNA was not available when the test was conducted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Creatine monohydrate
- Substance type: organic
- Physical state: slightly yellow solid
- Analytical purity: 101.1%
- Purity test date: 1997-11-26
- Lot/batch No.:725 201
- Expiration date of the lot/batch: 1998-9-15
- Stability under test conditions: at least 96 h
- Storage condition of test material: at room temperature in the dark

In vivo test system

Test animals

Species:
guinea pig
Strain:
Himalayan
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd. Basel, Switzerland
- Age at study initiation: approx. 7 weeks old
- Weight at study initiation: group mean did not exceed 500 g
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 50 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
(1 % aqueous carboxymethyl cellulose)
Concentration / amount:
Test substance concentrations selected for the main study were based on the results of a preliminary study.
In the main study, ten experimental animals were intradermally injected with a 2% concentration and epidermally exposed to a 50% concentration. Five control animals were similarly treated, but with the vehicle (1% Aqueous Carboxymethyl cellulose) only. Approximately 24 hours before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all animals were challenged with a 50% test substance concentration and the vehicle.

Induction: intradermal injection 2 % (w/w); epidermal treatment with 50% (w/w)
Challenge: epidermal application of 50% test substance (0.5 ml)
Challengeopen allclose all
Route:
other: epidermal
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
(1 % aqueous carboxymethyl cellulose)
Concentration / amount:
Test substance concentrations selected for the main study were based on the results of a preliminary study.
In the main study, ten experimental animals were intradermally injected with a 2% concentration and epidermally exposed to a 50% concentration. Five control animals were similarly treated, but with the vehicle (1% Aqueous Carboxymethyl cellulose) only. Approximately 24 hours before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all animals were challenged with a 50% test substance concentration and the vehicle.

Induction: intradermal injection 2 % (w/w); epidermal treatment with 50% (w/w)
Challenge: epidermal application of 50% test substance (0.5 ml)
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: selection of test substance concentrations suitable for induction and challenge;
Test concentrations: undiluted, 50%, 20%, 10%, 5%, 2%, 1%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: day 1 to 8
- Test groups: 1 group consisting of 10 animals
- Control group: consisting of 5 animals; was treated as described for experimental animal, except that, instead of the test substance, the vehicle was administered
- Site: scapular region
- Duration: 8 days
- Concentrations: 2% and 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1 (on day day 21)
- Exposure period: 24 h
- Test groups: all animals
- Control group: consisting of 5 animals; was treated as described for experimental animals, except that, instead of the test substance, the vehicle was administered
- Site: scapular region
- Concentrations: 50%
- Evaluation (hr after challenge): 24 and 48 h
Challenge controls:
negative/vehicle control: instead of the test substance , the vehicle was administered
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamic aldehyde, tech. 85%

Results and discussion

Positive control results:
The sensitivity of female albino Himalayan guinea pigs to alpha-hexylcinnamicaldehyde, tech. 85% was checked. The experiments led to determination of a sensitisation rate of 100% to both the 10% and 5% concentrations of the substance.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
96
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
50%
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:
96
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
score 2 and 3
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
score 2 and 3
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
score 2 and 3
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5%
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
score 1, 2 and 3
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this study creatine monohydrate is not skin sensitizing
Executive summary:

In a dermal sensitization study based on OECD guideline No. 406 "Skin Sensitization (maximization test) creatine monohydrate in 1 % aqueous carboxymethyl cellulose was tested in female albino guinea pigs (Himalayan strain; approx. 7 weeks old; body weight mean < 500 g). A reliability check was carried out with alpha-hexylcinnamicaldehyde. No skin reactions were evident after the challenge exposure in the experimental and control animals. There was no evidence for skin hypersensitivity. A sensitization rate of 0% was determined. In this study creatine monohydrate is not a dermal sensitizer.