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Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414, Fuellinsdorf, Switzerland
- Age at study initiation: 8-9 weeks
- Weight at study initiation: Males: 375-473g, Females: 376-495g
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard 342 Kliba, Batch 33/86 and 34/87 guinea pig breeding/ maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen ad libitum
- Acclimation period: One week under test conditions after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
PRELIMINARY STUDY:
- Intradermal injections (0.1 mL/site) at concentrations of 0.1, 0.3, 0.5, 1, 3 and 5 % of the test article.
- Epidermal applications: 3, 5, 10 and 25 % of the test article.
MAIN STUDY:
- Induction: Intradermal injections: 5 %, Epidermal applications: 25%
- Challenge: 25%
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
PRELIMINARY STUDY:
- Intradermal injections (0.1 mL/site) at concentrations of 0.1, 0.3, 0.5, 1, 3 and 5 % of the test article.
- Epidermal applications: 3, 5, 10 and 25 % of the test article.
MAIN STUDY:
- Induction: Intradermal injections: 5 %, Epidermal applications: 25%
- Challenge: 25%
No. of animals per dose:
Ten animals (5 males, 5 females) were treated with the vehicle alone and 20 animals (10 males, 10 females) were treated with the test article.
Details on study design:
- Preliminary study: Intradermal injections (0.1 mL/site) were made into the clipped flank of two guinea-pigs at concentrations of 0.1, 0.3, 0.5, 1, 3 and 5 % of the test article in physiological saline. The resulting dermal reactions were assessed 24 hours later.
Topical applications: Patches of filter paper ( 2 x 2 cm) were saturated with concentrations of 3, 5, 10 and 25 % of the test article in physiological saline and applied to the clipped and shaved flanks of each of four guinea-pigs. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wrapped around the trunk and covered with impervious adhesive tape. The dressings were removed after an exposure period of 24 hours and the reaction sites were assessed for erythema and edema on a numerical basis. Further examination of the sites were performed 24 and 48 hours after removal of the dressings.
- Main study: induction: Intradermal injections: An area of dorsal skin from the scapular region (approximately 6 x 8 cm) was clipped free of hair. Three pairs of intradermal injections (0.1 mL/site) were made at the border of a 4 x 4 cm area in the clipped region as follows: 1) Freunds' complete adjuvant 50:50 with physiological saline for injection. 2) The test article, diluted to 5 % with physiological saline. 3) The test article at the concentration used in (2), emulsified in a 50:50 mixture of Freunds' complete adjuvant, and the vehicle used in (2).
Topical applications: One week after the injections, the scapular area was again clipped and shaved free of hair. A 4 x 4 cm patch of filter paper was saturated with the test article (25 %) and placed over the injection sites of the test animals. The patch was covered by aluminum 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 approximately 48 hours.

- Main study: challenge: The test and control guinea-pigs were challenged two weeks after the topical induction application. Hair was clipped and shaved from a 5 x 5 cm area on the left flank of each guinea-pig. A 2 x 2 cm patch of filter paper was saturated with a non-irritant concentration (25%) of the test article and applied to the flank in a similar method to that used for the topical application. The dressings were removed approximately 24 hours later. The sites were assessed for erythema and edema using the arbitrary scale as described under preliminary study. The control animals were treated with the vehicle alone.
- Main study: rechallenge: A second challenge was performed two weeks after the first challenge. The method was similar to that described for the first challenge with the exception that the right flanks of all the guinea-pigs were used. The control animals were treated with the test article in the same concentration as the animals of the test group to avoid false positive results.
Challenge controls:
The control animals were treated as described above.
Positive control substance(s):
yes
Remarks:
A control group is tested twice a year with dinitro-chloro-benzol as a sensitivity check of the guinea pig strain. The last test was performed during February 1987.
Positive control results:
100% reaction after the first challenge procedure.
Reading:
1st reading
Hours after challenge:
24
Group:
negative 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: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative 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: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
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: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
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: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0
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: 0. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0
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: 0. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
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: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
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: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Mortality: No deaths occured during the study

Local symptoms: For both the vehicle control as the test article, the application area around the injections 1 and 3 were found to show edema and erythema from day 2 to 4. Starting with day 5 to 10 necroses were observed and exfoliation from day 11 to 19. Additional necroses from day 20 to 30 and exfoliation from day 31 to 39 (termination).

Systemic symptoms: Male No. 265 (control group) showed severe emaciation from day 18 to 39 (termination).

Body weights: With the exception of male No. 265, the body weight gain of all animals was not affected during the test procedure.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not a sensitizer.
Executive summary:

In a GLP compliant sensitivity study using the Maximization-Test, performed according to OECD guideline 406, guinea pigs were treated with the test substance. Twenty animals were treated with the test substance and ten animals with only the vehicle (physiological saline). The concentrations of the test substance used in the main study were determined by the results of the preliminary study. The intradermal induction of sensitization in the test group was performed using 5% of the test substance in both the vehicle and adjuvant/vehicle mixture. One week later this was boosted by the topical application of the test substance at 25% concentration over the injection sites. Animals of the control group were treated in the same manner but the selected vehicle was used. Two weeks after the second induction all animals were challenged by topical application of the test substance at 25% concentration followed by a rechallenge two weeks later. No sensitisation was observed in any animals during both the challenge and the rechallenge. Therefore it can be concluded that the test substance is not a sensitizer.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a GLP compliant sensitivity study using the Maximization-Test, performed according to OECD guideline 406, guinea pigs were treated with the test substance (RCC 1987). Twenty animals were treated with the test substance and ten animals with only the vehicle (physiological saline). The concentrations of the test substance used in the main study were determined by the results of the preliminary study. The intradermal induction of sensitization in the test group was performed using 5% of the test substance in both the vehicle and adjuvant/vehicle mixture. One week later this was boosted by the topical application of the test substance at 25% concentration over the injection sites. Animals of the control group were treated in the same manner but the selected vehicle was used. Two weeks after the second induction all animals were challenged by topical application of the test substance at 25% concentration followed by a rechallenge two weeks later. No sensitisation was observed in any animals during both the challenge and the rechallenge. Therefore it can be concluded that the test substance is not a sensitizer.


Migrated from Short description of key information:
The test substance is not a sensitizer.

Justification for selection of skin sensitisation endpoint:
Only one study available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the findings in the skin sensitisation study, the test substance does not need to be classified according to the Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008