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Diss Factsheets

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Although this test was performed after 2009, the study was conducted using the Buehler method to fulfill testing requirements for registration in another region.

Test material

Constituent 1
Details on test material:
- Purity: 100%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Preliminary Irritation Group: Young Adult (5-8 weeks); Test and Naive Control Groups: Young adult (6 weeks)
- Weight at study initiation: 460-607 g
- Housing: animals were gang housed in stainless steel solid bottom cages
- Diet: Harlan Teklad Global Guinea Pig Diet® #2040. A designated amount of the diet was available to each guinea pig (approximately 20 grams/day).
- Water: Filtered tap water was supplied ad libitum.
- Acclimation period: 19-43 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23ºC
- Humidity (%): 44-82%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% test substance
Challenge
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% test substance
No. of animals per dose:
Test Group: 20
Naive Control Group: 10
Details on study design:
RANGE FINDING TESTS:
A group of animals was used to determine the highest non-irritating concentration (HNIC) of the test substance prior to the challenge dose. The fur was removed from four guinea pigs by clipping the flanks of each guinea pig. This area was divided into four test sites (two sites on each side of the midline) on each animal. The test substance was applied neat (100%) and also diluted with acetone to yield w/w concentrations of 75%, 50% and 25%. Each concentration was applied (0.4 millilitre) onto an occlusive 25 mm Hill Top Chamber and applied to the appropriate test site. The sites were wrapped with non-allergenic Durapore™ adhesive tape. After six hours of exposure, the chambers were removed and the test sites were gently cleansed of any residual test substance. Approximately 24 and 48 hours after application, each site was evaluated for local reactions (erythema) according to the scoring system.
From these results, the HNIC (the highest concentration that produced responses in 4 guinea pigs no more severe than two scores of 0.5 and two scores of zero) was established and used for challenge. The HNIC selected for the challenge phase was 100%.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Once each week for three weeks
- Exposure period: After the six hour exposure period, the chambers were removed and the test sites were gently cleansed of any residual test substance
- Test groups: 1 at 100% test substance
- Control group: 1
- Site: the left flank of each test animal
- Frequency of applications: Once each week for three weeks
- Duration: After the six hour exposure period, the chambers were removed and the test sites were gently cleansed of any residual test substance
- Concentrations: 100% test substance

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: After the six hour exposure period, the chambers were removed and the test sites were gently cleansed of any residual test substance.
- Test groups: 1 at 100% test substance
- Control group: 1 "naive control" group
- Site: applied to the skin of a naive site on the right flank of each test animal
- Concentrations: 100% test substance
- Evaluation (hr after challenge): sites were evaluated for a sensitisation response (erythema) approximately 24 and 48 hours after the challenge application
Challenge controls:
In addition to the test animals, 10 guinea pigs from the same shipment were maintained under identical environmental conditions and were treated with the test substance at challenge only. These animals constituted the "naive control" group.
Positive control substance(s):
yes
Remarks:
Historical positive control data with alpha-Hexylcinnamaldehyde (HCA)

Results and discussion

Positive control results:
Induction Phase
Historical Positive Control Animals (100% HCA): Very faint erythema (0.5) was noted for two positive control sites 24 hours after the second induction application. Very faint to faint erythema (0.5-1) was evident for all sites 24 and/or 48 hours after the third induction application.
Challenge Phase
Historical Positive Control Animals (100% test substance): Two of ten positive control animals exhibited signs of a sensitization response (faint erythema [1]) 24 hours after challenge with very faint erythema noted at all other sites. Very faint erythema (0.5) persisted at five sites through 48 hours.
Historical Positive Control Naïve Control Animals (100% HCA): There was no irritation noted at any positive control naïve control site during the challenge phase.
Historical Positive Control Rechallenge Phase
Historical Positive Control Animals (100% HCA): Three of ten positive control animals exhibited signs of a sensitization response (faint erythema [1]) 24 hours after challenge. Similar indications persisted at two of these sites through 48 hours. Very faint erythema (0.5) was noted for most other sites following challenge.
Historical Positive Control Naïve Control Animals (100% HCA): There was no irritation noted at any positive control naïve control site during the challenge phase.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: challenge and rechallenge phase
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: challenge and rechallenge phase
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
100%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: challenge phase
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: challenge phase
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
100%
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
other: rechallenge phase
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
100%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: rechallenge phase

Any other information on results incl. tables

Induction Phase

Test Animals (100% test substance): There was no dermal irritation observed at any test site during the induction phase.

Challenge Phase

Test Animals (100% test substance): There was no dermal irritation noted at any test site 24 or 48 hours after the challenge application.

Naive Control Animals (100% test substance): There was no dermal irritation noted at any naive control site after the challenge application.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Not a skin sensitizer.
Executive summary:

A dermal sensitisation test was conducted with guinea pigs to determine the potential for the test substance to produce sensitisation after repeated topical applications. Preliminary irritation testing was performed on 4 animals to determine appropriate concentrations of the test substance that could be used for both the induction and challenge phases. The HNIC selected for the challenge phase was 100%.

Twenty healthy test guinea pigs were selected for test and treated with the test substance during the induction and challenge phase. For the induction phase, the undiluted test substance was topically applied to the skin on the left flank of each of the 20 guinea pigs for six hours, once each week for a three-week induction period. Twenty-eight days after the first induction dose, a challenge dose of the test substance was applied to the skin of a naive site on the right flank of all test animals as described above. A naive control group (ten animals) was maintained under the same environmental conditions and treated with the test substance at challenge only. Approximately 24 and 48 hours after each induction and challenge dose, the test and naive control animals were scored for erythema.

Based on the results, none of the test animals (0 of 20) had a positive skin sensitisation response. Therefore, the test substance is not considered a skin sensitizer.