Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1994-02-14 and 1994-04-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The test was conducted by means of Read Across approach. The reliability of the source study report is 1. Further information was attached at section 13

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate guinea pig maximisation test was already avaiable, which would not justify conducting an additional LLNA due to animal welfare.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Weight at study initiation: 312 to 417 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets -NAFAG No. 845, ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
intradermal injection: 5% in physiol. saline (w/v)
epidermal applicaion: 50% in physiol. saline
epidermal, challenge: 30% in physiol. saline
Challenge
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
intradermal injection: 5% in physiol. saline (w/v)
epidermal applicaion: 50% in physiol. saline
epidermal, challenge: 30% in physiol. saline
No. of animals per dose:
control group: 10
test group: 20
Details on study design:
MAIN STUDY
A.1. INDUCTION EXPOSURE (intradermal); on day: 0
- Exposure period: three pairs of indermal injections (0.1 mL per injection) were made simultaneously
- Test groups: adjuvant/ saline mixture 1:1 (v/v), 5% test substance in physiol. saline (w/v), 5% test substance in the adjuvant/saline mixture (w/v)
- Control group: injection: adjuvant/ saline mixture 1:1 (v/v), adjuvant/saline mixture 1:1 (v/v), physiol. saline
- Site: injection: left and right side of the shaved neck
- Duration: single injection

A.2. INDUCTION EXPOSURE (epidermal); on day: 8
- Test group: 50% test substance in physiol. saline
- Control group: physiol. saline only
- Site: neck of the animal
- Duration: 48 hours

B. CHALLENGE EXPOSURE; on day 21
- No. of exposures: 1
- Exposure period: 24 hours
- Test groups and Control group: one flank: 30% test substance in physiol. saline; other flank: physiol. saline alone
- Site: flank
- Evaluation (hr after challenge): 24 and 48

Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole

Results and discussion

Positive control results:
All of the animals showed skin reactions after 24 h and 48 h after removing the dressings.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group (vehicle control)
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group (test article control)
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group (vehicle control)
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group (test article control)
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
other: test group (vehicle group)
Dose level:
30%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
other: test group (test article)
Dose level:
30%
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
1 animal showed erythema and edema, 4 animals showed only erythema
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test group (test article). Dose level: 30%. No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: 1 animal showed erythema and edema, 4 animals showed only erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test group (vehicle control)
Dose level:
30%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test group (test article)
Dose level:
30%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:

Applicant's summary and conclusion

Interpretation of results:
other: CLP criteria not met
Conclusions:
Not skin sensitising
Executive summary:

The test substance (80 % act. ingr.) was tested in male and female Pirbright guinea pigs by using the Guinea Pig Maximisation Test of Magnusson and Kligman (induction treatment: 5 % given intradermal on day 0, 50 % given epidermal on day 8; epidermal challenge treatment: 30 % on day 21). Body weights were not affected by treatment. Under the experimental conditions employed, 25 % of the animals of the test group showed skin reactions (erythema and/or edema) 24 hours after removing dressing.

On the basis of the results the test material (80 % act. intgr.) is considered to be not skin-sensitising.