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Description of key information

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:
from February to March 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported GLP Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
other: Hsd Poc:DH
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Sex: 17 females
- Source: Harlan Winkelmann GmbH Laboratory Animal Breeders; 33176 Borchen
- Age at study initiation: 3 - 5 weeks
- Weight at study initiation: 290 -325 g
- Housing: 5 per cage (adaptation period); 2 - 3 per cage (study period)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40 - 60
- Air changes (per hr): >= 10 times
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
intradermal and epicutaneous
Vehicle:
other: polyethylene glycol 400
Concentration / amount:
Intradermal induction: 5 % (= 20 mg test substance/animal)
Topical induction: 25% (= 125 mg test substance/animal)
Challenge: 25% (= 125 mg test substance/animal)
Route:
epicutaneous, occlusive
Vehicle:
other: polyethylene glycol 400
Concentration / amount:
Intradermal induction: 5 % (= 20 mg test substance/animal)
Topical induction: 25% (= 125 mg test substance/animal)
Challenge: 25% (= 125 mg test substance/animal)
No. of animals per dose:
control group: 10
test substance group: 20
dose range-finding groups: 1 (for intracuteneous induction), 4 (for topical indiction), 5 (for challenge)
Details on study design:
RANGE FINDING TESTS:

Dose-range finding study for intradermal induction:
One guinea pig (animal No.1) was given intradermal injections twice, in each case, with 0.1 ml of the following test item concentrations: 0%, 1 %, 2.5 and 5%.
The injection sites were evaluated after 24 and 48 hours: Animal no. 1: 0%, 1 %, 2.5% and 5%: grey wheal with red surrounding after 24 and 48 hours.

Dose range-finding study for topical induction:
Three different concentrations (6%; 12%; 25%) and the vehicle (0%) were tested in each case on four guinea pigs. The patches moistened with 0.5 ml of the test item formulations or the vehicle were applied to each animal under occlusive conditions for 24 hours. At the end of the exposure period, the remaining test item or the vehicle were removed with physiological saline solution and twenty-one hours later the treated areas were shorn. The skin reactions were evaluated 48 hours and 72 hours after the start of the application. No animal of the test item groups and the control group exhibited a skin reaction.

Dose range-finding study for challenge:
One week prior to the challenge, the challenge concentration was determined on 2 guinea pigs in the main study that were treated in the same manner as the control animals during the inductions. Four patches each loaded with 0.5 ml test item formulation (6%; 12%; 25%) or the vehicle (0%) were applied to each animal under occlusive conditions for 24 hours. At the end of the exposure period, the remaining test item was removed with physiological saline solution and twenty-one hours later the treated areas were shorn. The skin reactions were evaluated 48 hours and 72 hours after the start of the application. No animal of the test item groups and the control group exhibited a skin reaction.

MAIN STUDY
A. INDUCTION EXPOSURE (intradermal followed by topical induction one week after the intradermal induction)
- No. of exposures: three injections on each site
- Test groups: three
- Control group: three
- Site: on the left an the right side of the spinal column
- Frequency of applications: once
- Duration: injection sites were visually assessed 2 and 7 days after the injection.
- Concentrations: 5% (intradermal); 25% (topical)

B. CHALLENGE EXPOSURE
- No. of exposures: once
- Day(s) of challenge: three weeks after intradermal induction
- Exposure period: 24 hours
- Test groups: 1 (10 animals)
- Control group: 1 (5 animals)
- Site: dorsal region of the left flank
- Concentrations: 25%
- Evaluation (hr after challenge): 21 hours after removal of the test item

Positive control substance(s):
not required
Remarks:
Using 2-mercaptobenzothiazole the methodological reliability and the sensitivity of the strain are verified separately at regular intervals.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Appearance and behaviour of the test substance group were not different from the control groups with the following exceptions: At the end of the study, the mean body weight of the treatment group animals was slightly higher as in the control group animals. No mortalities occurred.

The animals in the test item group and in the control group showed reddening and wheals and grey wheals with red surrounding at the injection sites after 48 hours. Red wheals and encrustations at the injection sites of the first induction were recorded after 7 days in the control group and in the test item group. 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 4 of 10 animals in the testitem group and in 1 of 5 animals in the control group as a signs of local irritation.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:

To determine the skin-sensitizing properties of the test substance the guinea pig maximization test was performed on female guinea pigs according to OECD guideline 406. The study was conducted with the following test substance concentrations:

intradermal induction: 5%

topical induction: 25%

challenge: 25%

The test substance was formulated in polyethylene glycol 400 to yield a suspension. The challenge using a 25% test item formulation led to no skin effects in the animals in the treatment group and to none of the animals in the control group.

Under the condition of the maximization test and with respect to the evaluation criteria the test substance exhibits no skin-sensitization potential.

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

To determine the skin-sensitizing properties of the test substance the guinea pig maximization test was performed on female guinea pigs according to OECD guideline 406. The study was conducted with the following test substance concentrations:

intradermal induction: 5%

topical induction: 25%

challenge: 25%

The test substance was formulated in polyethylene glycol 400 to yield a suspension. The challenge using a 25% test item formulation led to no skin effects in the animals in the treatment group and to none of the animals in the control group.

Under the condition of the maximization test and with respect to the evaluation criteria the test substance exhibits no skin-sensitization potential.


Migrated from Short description of key information:
The test substance has no skin sensitizing potential.

Justification for selection of skin sensitisation endpoint:
Only one study available

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the study result a classification according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is not warranted.