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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no data on positve control)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 1981
Deviations:
yes
Remarks:
(no data on positive control)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The described guinea pig maximisation test according to OECD 406 was conducted in 1991 before the guidance for the LLNA (OECD429, first adopted in 2002) was available, and before the method was fully established and validated. And since the result of the guinea pig maximisation test is considered to be scientifically valid, the test was not repeated also taking into account exposure and animal welfare considerations.

Test material

Constituent 1
Chemical structure
Reference substance name:
Octa-1,7-diene
EC Number:
223-054-9
EC Name:
Octa-1,7-diene
Cas Number:
3710-30-3
Molecular formula:
C8H14
IUPAC Name:
octa-1,7-diene

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White, Dunkin Hartley, BOR DHPW (SPF)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa. Winkelmann, Versuchstierzucht GmbH & Co KG, Borchen, Germany
- Age at study initiation: young adult animals
- Mean weight at study initiation: test group: 354 g; control group 1: 360 g; control group 2: 363 g
- Housing: max. 5 animals/cage (Macrolon type IV)
- Diet: Ssniff G 4 Alleindiaet fuer Meerschweinchen (Fa. Ssniff, Spezialfutter GmbH, Soest, Germany)
- Water: tap water; ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 12 Nov 1990 To: 21 Dec 1990

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
- Induction, intradermal: 5% (only test group)
- Induction, epicutaneous: 100% (only test group)
- First challenge: 100% (test group and control group 1)
- Second challenge: 25% (test group and control group 2)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
- Induction, intradermal: 5% (only test group)
- Induction, epicutaneous: 100% (only test group)
- First challenge: 100% (test group and control group 1)
- Second challenge: 25% (test group and control group 2)
No. of animals per dose:
- Test group: 20
- Control group 1: 10
- Control group 2: 10
Details on study design:
RANGE FINDING TESTS:
A range finding test was performed in order to determine a test concentration, which is well-tolerated after intradermal induction and to determine a test concentration for epicutaneous induction, which is the highest to cause mild-to-moderate skin irritation. Furthermore, the highest non-irritant dose for epicutaneous challenge was determined within the range finding test:

- Intradermal application: Several concentrations of the test substance in vehicle (0.25%, 0.5%, 1%, 2.5%, 5% and 10% (w/w)) were injected intradermally in the left flank of 2 animals, respectively. Evaluation was performed 24 h post-application. The test substance at a concentration of 10% in vehicle caused moderate edema and erythema formation. Intradermally injections of 0.25 - 5% test substance in vehicle resulted in well defined erythema and moderate edema formation. Thus, a cocentration of 5% was chosen for the intradermal induction.

- Epicutaneous application: Each of 4 animals were treated dermally with test substance concentrations of 2.5%, 25% and 50% (w/w) in vehicle as well as 100% under occlusive conditions for 24 h (two patches on the right and left flank of each animal, respectively). Evaluation was performed directly as well as 24 h and 48 h after patch removal. No primary skin irritation was observed in any animal at any applied dose. Thus 100% was chosen as concentration for dermal induction and challege in the main study. For the dermal induction a pre-treatment with sodium dodecyl sulphate was perfomed in order to create a local irritation.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 hours (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections; 0.1 mL/injection):
Injection 1: a 1:1 mixture FCA/water
Injection 2: test substance in vehicle
Injection 3: test substance in a 1:1 mixture FCA/vehicle

Epicutaneous: test substance (2 x 4 cm² patch; occlusive) after pre-treatment with 10% SDS in vaseline 24 h before the epicutaneous induction application

- Control group 1 and 2 (3 pairs of injections; 0.1 mL/injection):
Injection 1: a 1:1 mixture FCA/water
Injection 2: vehicle
Injection 3: a 1:1 mixture FCA/vehicle

Epicutaneous: vehicle (2 x 4 cm² patch; occlusive) after pre-treatment with 10% SDS in vaseline 24 h before the epicutaneous induction application

- Site: shoulder region (shaved area: 4 x 6 cm) for intradermal and epicutaneous induction
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal: 5%, epicutaneous: 100%


B. CHALLENGE EXPOSURE
- No. of exposures: 2 (challenge and rechallenge)
- Day of challenge: 21 (challenge) and 28 (rechallenge)
- Exposure period: 24 h (2 x 2 cm² patch; occlusive)
- Test groups: 0.1 - 0.4 mL test substance (challenge and rechallenge)
- Control group 1: 0.1 - 0.4 mL test substance (only challenge)
- Control group 2: 0.1 - 0.4 mL test substance (only rechallenge)
- Site: left flank for challenge and right flank for rechallenge
- Concentration: 100% (challenge) and 25% (rechallenge)
- Evaluation: 24 h and 48 h after patch removal

Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction: intradermal: 5%, dermal: 100%; Challenge: 100%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: intradermal: 5%, dermal: 100%; Challenge: 100%. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction: intradermal: 5%, dermal: 100%; Challenge: 100%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: intradermal: 5%, dermal: 100%; Challenge: 100%. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group 1
Dose level:
Induction: intradermal: 0%, dermal: 0%; Challenge: 100%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control group 1. Dose level: Induction: intradermal: 0%, dermal: 0%; Challenge: 100%. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control group 1
Dose level:
Induction: intradermal: 0%, dermal: 0%; Challenge: 100%
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: control group 1. Dose level: Induction: intradermal: 0%, dermal: 0%; Challenge: 100%. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction: intradermal: 5%, dermal: 100%; Challenge: 100%; Rechallenge: 25%
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: intradermal: 5%, dermal: 100%; Challenge: 100%; Rechallenge: 25%. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction: intradermal: 5%, dermal: 100%; Challenge: 100%; Rechallenge: 25%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: intradermal: 5%, dermal: 100%; Challenge: 100%; Rechallenge: 25%. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
other: control group 2
Dose level:
Induction: intradermal: 0%, dermal: 0%; Challenge: 0%; Rechallenge: 25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: other: control group 2. Dose level: Induction: intradermal: 0%, dermal: 0%; Challenge: 0%; Rechallenge: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
other: control group 2
Dose level:
Induction: intradermal: 0%, dermal: 0%; Challenge: 0%; Rechallenge: 25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: control group 2. Dose level: Induction: intradermal: 0%, dermal: 0%; Challenge: 0%; Rechallenge: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

All animals in the test and control groups gained body weight normally until day 28. Thereafter (day 28 - day 31), a slight decrease in body weight was noted in 8 animals of the test group. Furthermore, 8 animals of the test group showed impaired body weight gain. However, since the effects on body weight were also noted in the control animals (14 animals with slightly decreased body weight and 2 animals with impaired body weight gain), it was not considered substance-related.

No systemic effects were noted during the course of the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
2/20 animals of the test group and 0/10 animals of the control group showed positive reactions after rechallenge in a guinea pig maximisation test. Thus, classification for skin sensitisation is not warranted.