Registration Dossier

Administrative data

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 guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test item was formulated immediately prior to application in polyethylene glycol 400. During application the test item was stirred.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: SPF-breeded, strain Hsd/Win:DH
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen/Paderborn, Germany
- Age at study initiation: approx. 5-7 weeeks
- Weight at study initiation: 314-395 g
- Diet and water: ad libitum
- Acclimation period: at least 7 days

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Concentration / amount:
concentrations were based on results of range finding tests:
intradermal induction: 5% test substance
epidermal induction: undiluted test substance
first challenge: 12 and 25% test substance
second challenge: 1 and 3% test substance
application volume: 0.5 ml each
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Concentration / amount:
concentrations were based on results of range finding tests:
intradermal induction: 5% test substance
epidermal induction: undiluted test substance
first challenge: 12 and 25% test substance
second challenge: 1 and 3% test substance
application volume: 0.5 ml each
No. of animals per dose:
experimental group: 20
control group: 10
Details on study design:
RANGE FINDING TESTS:
- for intradermal induction: 1 guinea pig was intradermally treated with 0.1 ml of 0%, 1%, 2.5% and 5% test substance in PEG 400. 24 and 48 hours later the skin was scored. All treatments led to a whitish area with red border.
- for epidermal induction: 4 guinea pigs were topically treated for 24 hours (occlusive) with 0.5 ml of 12, 25, and 50% test substance in PEG 400 and with the undiluted test substance. The 50% formulation led to slight skin reddening in one animal, the neat test material to slight to moderate skin reddening in all 4 animals.
- for challenge: 5 guinea gigs, primary treated as control animals in the induction phase, were topically treated for 24 hours (occlusive) with 0.5 ml of 6, 12, 25, and 50% test substance in PEG 400. Slight reddening of the skin became obvious only in the 50% group.

OTHER:
In addition to the skin reactions the following data were recorded: Mortality and clinical signs at least once daily; Body weights prior to start and at termination of the study.
Challenge controls:
Day 1: Animals were intradermally injected similar to the above described protocol with the omission of the test substance; 1 week after intradermal induction: PEG 400 treatment according to the standard procedure; 3 and 4 weeks after intradermal induction: animals were treated epidermally with 0.5 ml with the same test substance concentrations as the treatment groups
Positive control substance(s):
yes
Remarks:
The sensitivity and reliability of the Maximization Test was routinely proved with the positive substance 2-mercaptobenzothiazole.

Study design: in vivo (LLNA)

Positive control substance(s):
mercaptobenzothiazole (CAS No 149-30-4)
Statistics:
not applicable

Results and discussion

Positive control results:
The routine positive control experiments showed the expected results and confirmed the sensitivity and reliability of the test system.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: no clinical signs.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
12%
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 12%. No with. + reactions: 13.0. Total no. in groups: 20.0. Clinical observations: no clinical signs.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
25%
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 25%. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: no clinical signs.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
12%
No. with + reactions:
16
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 12%. No with. + reactions: 16.0. Total no. in groups: 20.0. Clinical observations: no clinical signs.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
3%
No. with + reactions:
11
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 3%. No with. + reactions: 11.0. Total no. in groups: 20.0. Clinical observations: no clinical signs.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical signs.
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
Dose level:
3%
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 3%. No with. + reactions: 12.0. Total no. in groups: 20.0. Clinical observations: no clinical signs.
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
Dose level:
1%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 1%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: no clinical signs.
Reading:
other: 1st and 2nd reading
Group:
negative control
Dose level:
25 and 12%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs
Remarks on result:
other: Reading:
Reading:
other: rechallenge, 48 and 72 hour reading
Group:
negative control
Dose level:
3 and 1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs
Remarks on result:
other: Reading:

Any other information on results incl. tables

Induction - test substance group: After the second (topical) induction with the neat test material the treatment area showed bleedings (day 9 after first induction) and subsequent encrustations in 17 of 20 animals. These areas recovered between days 14 to 24. One animal showed skin encrustations up to the end of the experiment.

Induction - control group: The control animals showed no skin reaction after induction treatment.

First challenge - test substance group: After the challenge treatment with 25% or 12% test substance in PEG 400 17 (85%) or 16 (80%) of the in total 20 animals of the group exhibited slight to well defined skin reddening and partly squamation.

Second challenge (rechallenge) - test substance group: After the second challenge treatment with 3 % test substance in PEG 400 12 (60%) animals exhibited slight skin reddening and/or partly squamation. After second challenge treatment with 1% test substance in PEG 400 only 1 animal (5%) reacted with a partly squamation.

First and second challenge - control group: No skin reactions became evident after challenge exposure.

No mortalites, no symptoms of systemic toxicity and no influences on body weight were observed during the study period.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Executive summary:

A skin sensitization test according to OECD guideline 406 (Guinea Pig Maximization Test, GPMT) was conducted on male guinea pigs with test substance concentrations of 5% for intradermal induction (formulated in PEG 400) and 100% for topical induction. Treatment with the neat test material led to bleedings and encrustations in 17 of 20 animals. In one animal this effect appeared to be not reversible during the entire experimental period.

Two challenge experiments were performed. For the first challenge test concentrations of 25 or 12% (in PEG 400) were applied leading to slight to well defined skin reddening and partly squamation in 85% (17 animals) and 80% (16 animals) of the in total 20 animals of the group. After the second challenge treatment with 3 or 1% test substance 60% (12 animals) or 5% (1 animal) exhibited slight skin reddening and/or partly squamation. No skin reactions became evident in the control group after first or second challenge exposure. Thus, under the conditions of this assay the test item has to be regarded as skin sensitizer.