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Administrative data

Description of key information

Two valid studies for skin sensitization are available. Both studies are suitable for the evaluation of the skin sensitization potential. Due to the higher purity of the substance used in the GPMT, this study is nominated as key study

Non-human information
The skin-sensitization potential of the test substance Vulcuren (purity: 99.7%) was evaluated in a Guinea pig maximization test. The intradermal induction was performed using 2.5% test substance, and the topical induction was performed with 25% test substance concentration. The challenge using 25 % test substance formulation led to no skin effects in the treatment group and control group after 48 and 72 hours.
In summary, by comparing the results in the treatment group and in the control group the test substance did not show a skin-sensitization potential (Bayer 1999).

Human information
There are no human data available.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and OECD Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
other: 96/54/EG, B.6 (Meerschweinchen-Maximierungstest (GPMT))
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time of the test the guine pig maximisation test (OECD 406) was the standard test; the LLNA as OECD guideline was introduced in 2002.
Species:
guinea pig
Strain:
other: Hsd Poc: DH
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH Laboratory Animal Breeders in 33176 Borchen
- Age at study initiation: 3 to 5 weeks
- Weight at study initiation: mean weight: 332 g
- Housing: in type IV Makrolon cages
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 40-60%
- Air changes (per hr): 10 times per h
- Photoperiod: 12hrs dark / 12hrs light


Route:
intradermal
Vehicle:
polyethylene glycol
Concentration / amount:
Concentration of test material and vehicle used at induction:
a) Intradermale Induction: 2,5 % in Polyethylenglykol 400
b) Topic Induction: 25,0 % in Polyethylenglykol 400

Concentration of test material and vehicle used for each challenge:
25,0 % in Polyethylenglykol 400
Concentration / amount:
Concentration of test material and vehicle used at induction:
a) Intradermale Induction: 2,5 % in Polyethylenglykol 400
b) Topic Induction: 25,0 % in Polyethylenglykol 400

Concentration of test material and vehicle used for each challenge:
25,0 % in Polyethylenglykol 400
No. of animals per dose:
Number of animals in test group: 10
Number of animals in negative control group: 5
Details on study design:
RANGE FINDING TESTS: yes
MAIN STUDY
A. INDUCTION EXPOSURE intradermal
- No. of exposures: intradermal
- Exposure period: once
- Test groups: test group consisting of 10 animals
- Control group: control group consisting of 5 animals
- Site: intradermal induction/injection site cranial/bilateral (Freud's adjuvant diluted 1: 1 with steril physiological saline solution), medial/bilateral (2.5 % test substance formulated in polyethylene glycol 400),caudal/bilateral (2.5% ) test substance formulated at equal parts in steril physiological saline and complete Freud's adjuvant)
- Frequency of applications: once
- Duration: 7 days observation period

B.
INDUCTION EXPOSURE topical
- No. of exposures: one intradermal, topical induction
- Exposure period: once
- Test groups: test group consisting of 10 animals
- Control group: control group consisting of 5 animals
- Site: topical induction: test group: 0.5 ml 25% test substance formulated in polyethylen glycol 400, control: 0.5 ml polyethylene glycol 400
- Frequency of applications: once
- Duration: 48 h
C. CHALLENGE EXPOSURE
challenge was performed 3 weeks after intradermal induction
- No. of exposures: once
- Exposure period: 24 h
- Test groups: 25 % test item formulation
- Control group: vehicle
- Site: left flank (caudal)
- Evaluation (hr after challenge): 48 h, 72 h

Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
alpha-hexylzimtaldehyd
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Group:
positive control
Remarks on result:
other: see 'Remarks'
Remarks:
The Guinea Pig Maximization Test methodology was checked for reliability in a test on female guinea pigs using alpha-Hexylzimtaldehyd formulated in polyethylene glycol 400 at the concentrations indicated below: For the intradermal induction a 2.5% test item formulation was used, and for the topical induction a 25% formulation. After the challenge with a 12% test item formulation 50% of the test animals exhibited dermal reactions in the challenge treatment. There was no reddening of the skin to be observed on control group animals. The sensitivity as well as the reliability of the experimental technique is thus confirmed by this study.

Maximum concentration not causing irritating effects in preliminary test: 25 %
Signs of irritation during induction:
After the intradermal induction the animals in the control group showed after 48 h: white wheals with red surrounding or red wheals.

The animals in the test item group showed after 48 h:
Red surrounding at the injection sites or white wheals with red surrounding or red wheals.
The animals in the control group and the test item group showed after 7 days: wheals or encrustations.
At day 9, directly after removal of the patch of the second induction, the treatment area of the second induction showed skin effects (grade 1) in 3 of 10 animals in the test item group and no skin effects in the control group.

Evidence of sensitisation of each challenge concentration: None

Other observations: None

Interpretation of results:
GHS criteria not met
Executive summary:

The skin-sensitization potential of the test substance Vulcuren Trial Product KA 9188 was evaluated in a Guinea pig maximization test. The intradermal induction was performed using 2.5% test substance, and the topical induction was performed with 25% test substance concentration. The challenge using 25 % test substance formulation led to no skin effects in the treatment group and control group after 48 and 72 hours. In summary, by comparing the results in the treatment group and in the control group the test substance did not show a skin-sensitization potential (Bayer 1999).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Non-human information

The skin-sensitization potential of the test substance Vulcuren (purity: 99.7%) was evaluated in a Guinea pig maximization test. The intradermal induction was performed using 2.5% test substance, and the topical induction was performed with 25% test substance concentration. The challenge using 25 % test substance formulation led to no skin effects in the treatment group and control group after 48 and 72 hours.

In summary, by comparing the results in the treatment group and in the control group the test substance did not show a skin-sensitization potential (Bayer 1999).

Human information

There are no human data available.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Non-human information
There are no data available.

Human information
There are no human data available.

Justification for classification or non-classification

The skin-sensitization potential of the test substance Vulcuren (purity: 99.7%) was evaluated in a Guinea pig maximization test. No skin-sensitising potential of the test substance was detected.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Respiratory sensitization: There are no data available.