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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
11 May - 10 Sep 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
adopted in 1996
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Type of study:
Buehler test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Dunkin-Hartley, Pirbright White Hsd/Poc:DH
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany.
- Age at study initiation: young adults
- Weight at study initiation: < 500 g
- Housing: maximum 5 animals per cage in Type IV Makrolon cages.
- Diet: Ssniff G 4 diet in pellet form (laboratory standard guinea pig dietdiet, Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70 (temporary deviations were caused by cleaning the animal room)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Induction: 50%
Challenge: 50%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Induction: 50%
Challenge: 50%
No. of animals per dose:
10 (controls), 20 (in test groups)
Details on study design:
RANGE FINDING TESTS:
In a preliminary miscibility test, a test substance concentration of 50% (w/w) was determined as the highest concentration which was easily miscible and well applicable.
In a preliminary skin irritation test with 3 female animals, test substance formulations of 10, 20, 30 and 50% were topically applied to the flank under occlusive conditions for 6 h. The maximum non-irritant concentration of 50% was used for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in vehicle
- Control group: vehicle
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-14
- Concentrations: 50% test substance in vaseline

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: test substance in vehicle and vehicle only
- Control group: test substance in vehicle and vehicle only
- Site: posterior right flank (test substance) and anterior right flank (vehicle)
- Concentrations: 50% test substance in vaseline
- Evaluation (hr after challenge): 24 and 48 h after test substance removal with corn oil.
Challenge controls:
In the 4th week of the test, 3 additional animals (accompanying group), kept under the same conditions, but without treatment, were used to re-determine the maximum non-irritant concentration for the challenge treatment.
This additional determination of the challenge concentration was carried out because it was suspected that the sensitivity of the skin changed as the weight of the animals increased. This ensured that the challenge concentration was determined on animals which had approximately the same weight as the 30 animals in the challenge phase. In this test, the concentrations administered and the experimental conditions corresponded to those of the preliminary test.
The determination of the challenge concentration in the 4th week of the test on 3 untreated animals of the same age led to no signs of dermal irritation in any animal 24 and 48 h post-application of formulations containing 10, 20, 30 and 50% test substance in vehicle.
On the basis of these results and the results of the induction period, the 50% test substance in vehicle was administered for the challenge treatment in the main test.
Since this test was conducted with untreated animals approximately at the same time as the challenge application, it can be considered as a challenge control test.
Positive control substance(s):
yes
Remarks:
α-hexylcinnamaldehyde

Results and discussion

Positive control results:
The positive control substance α-hexylcinnamaldehyde (100% induction, 50% challenge concentration) induced positive reactions in 10/20 and 9/20 animals at 24 and 48 h after challenge, respectively. Thus, the reliability criteria for the Buehler test (≥ 15% positive response) were met.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
100% induction, 50% challenge
No. with + reactions:
10
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
100% induction, 50% challenge
No. with + reactions:
9
Total no. in group:
20

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified