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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:
01 Dec 1998 - 15 Feb 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Ibm: GOHI; SPF- quality guinea pigs
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Fullinsdorf, Switzerland
- Age at study initiation: 5-7 weeks
- Weight at beginning of acclimation period: 304-380 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: One week for the control and test group under test conditions after health examination. No acclimation of animals of the pre-test. Only animals without any visible signs of illness were used.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
olive oil
Concentration / amount:
Induction 100%, challenge 50%, positive control: intradermal induction 5% , epidermal induction 50% , challenge 50% (vehicle mineral oil)
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
Induction 100%, challenge 50%, positive control: intradermal induction 5% , epidermal induction 50% , challenge 50% (vehicle mineral oil)
No. of animals per dose:
Control group: 5
Test group: 10
Intradermal pre-test: 1
Epidermal pre-test: 2
Positive control: 10 test, 5 control
Details on study design:
PRE TEST: This was carried out to identify a suitable concentration of the test article for the induction phase of the main study and a non-irritant concentration for the challenge phase. The concentrations tested were for the epidermal application the most qualified to assure an optimum technical application procedure and for the intradermal injection the selected concentrations were tested at 1, 3 and 5%.

MAIN STUDY:

INTRADERMAL INJECTIONS (DAY 1)

Three pairs of intradermal injections (0.1 ml/sire) were made at the border of a 4x6 cm area in the clipped region as follows:

TEST GROUP:
1. 1:1 (v/v) mixture of FCA and physiological saline.
2. The test article, at 5% in olive oil.
3. The test article at 5% in a 1:1 (v/v) mixture of FCA and physiological saline
CONTROL GROUP:
1. 1:1 (v/v) mixture of FCA and physiological saline.
2. Olive oil.
3. 1:1 (w/w) mixture of olive oil in a 1:1 (v/v) mixture of FCA and physiological saline.


EPIDERMAL APPLICATIONS (DAY 8)

TEST GROUP:
One week after the injections the scapular area was shaved free of hair again prior to the epidermal application. Filter paper was saturated with the undiluted test material and placed over the injection sites of the test animals. The volume of the test article was ca. 0.3 ml. The patch was covered withaluminium foil and firmly secured by an elastic plaster wrapped around the trunk of the animal and secured with impervious adhesive tape. The dressings were left in place for 48 hours. The epidermal application procedure described ensured intensive contact of the test article. The reaction sites were assessed for erythema and oedema 24 and 48 hours after removal of the dressing, using the numerical grading system according to Draize.

CONTROL GROUP:
The guinea pigs of the control group were treated as described above with olive oil only, also applied at a volume of ca. 0.3 ml.


CHALLENGE TEST (DAY 22)

The test and control animals were challenged two weeks after the epidermal induction application. The test and control guinea pigs were treated in the same way.
Hair was clipped and shaved from a 5x5 cm area on the left and right flank of each guinea pig just prior to application. Two patches of filter paper were saturated with the test article at the highest non-irritating concentration of 50% (left flank) and the vehicle only (olive oil applied to the right flank) using the same method as for the epidermal application. The volume of test article or vehicle applied was approximately 0.2 ml. The dressings were left in place for 24 hours.
After ca. 21 hours after removal of the dressing the test sites treated with the test article were depilated as described in the epidermal pre-test. Approximately 24 and 48 hours after the removal of the dressing the application sites were assessed for erythema and oedema using the numerical scoring system according to Draize.
Challenge controls:
Challenge controls were treated in the same way as the test group.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% in olive oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was found not sensitising in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.