Registration Dossier

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:
other: Guideline study with acceptable restrictions: No positive control (not required by 1981 version of Test Guideline)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A skin sensitization test according to OECD 406 has already excisted since 1990 and is sufficient for evaluation of the skin sensitisation potential of the test substance.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
cis,cis-1,5-cyclooctadiene of Hüls AG.
Produced May / June 1989; purity > 99.5 %

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS: 
- Strain: Dunkin-Hartley (Bor: DHPW)
- Sex: female
- Source: F. Winkelmann, Borchen (Germany)
- Weight at study initiation: 360 g (mean test); 351 g (mean control)
- Controls: 10 animals; treatment: vehicle
Environmental conditions:
- Feed: G4 diet for guinea pigs (Ssniff; Soest, Germany)
- Water: tap water ad libitum
- Room temperature: 20°C (+/- 1°C)
- Humidity: 60% (+/- 5%)
- Air change: 15 times/hour
- Light-dark rhythm: 12 hours light/dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: corn oil
Concentration / amount:
1st application: Induction 5 % intracutaneous
2nd application: Induction 100 % occlusive epicutaneous
3rd application: Challenge 100 % occlusive epicutaneous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: corn oil
Concentration / amount:
1st application: Induction 5 % intracutaneous
2nd application: Induction 100 % occlusive epicutaneous
3rd application: Challenge 100 % occlusive epicutaneous
No. of animals per dose:
20
Details on study design:
ADMINISTRATION/EXPOSURE 
- Induction schedule:   
day 0 injection,   
day 6 induction of slight to moderate irritation (10 % sodium dodecyl  sulfate in petrolatum)   
days 7-9 patch treatment (48 hours)
- Injection details: 0.1 ml each at 6 positions on shoulders:   
2 x Freund's Complete Adjuvant / deionized water (50:50)   
2 x test substance 5 % in corn oil   
2 x test substance 5 % in Freund's Complete Adjuvant / corn oil (50:50)   simultaneous and symmetrical application of each solution   
controls: corn oil instead of test substance
- Challenge schedule: 2 weeks after end of induction, patch treatment for  24 hours
- Concentrations used for challenge:   
100 % with filter paper on left side   readings 24 and 48 hours after removal of patch
- Rechallenge: no
- Positive control: no
EXAMINATIONS
- Grading system: 
possible scores 0 / 1 / 2 / 3         
0 % of animals scored > 0: no sensitization    
1 -  8 % of animals scored > 0: very slight sensitization    
9 - 28 % of animals scored > 0: slight sensitization   
29 - 64 % of animals scored > 0: distinct sensitization   
65 - 80 % of animals scored > 0: severe sensitization   
81 -100 % of animals scored > 0: extreme sensitization
- Pilot study: skin irritation
Challenge controls:
vehicle
Positive control substance(s):
not required
Remarks:
not required by 1981 version of Test Guideline

Study design: in vivo (LLNA)

Statistics:
no data

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 %
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: 100 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
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: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100 %
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: 100 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
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: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

RESULTS OF PILOT STUDY: 100 % test substance caused no dermal irritation
RESULTS OF TEST
- Sensitization reaction: 
  0/20 animals positive at 24 hours and at 48 hours = no sensitization
  no animals positive in control group
  no skin reaction upon corn oil treatment on opposite side (both groups)

- Clinical signs: 
  1st induction, FCA application sites (all): severe erythema, edema, and  

necrosis
  1st induction, test substance application sites: distinct erythema and  edema
  1st induction, vehicle application sites: slight erythema and edema
  2nd induction, test and control groups:
    1 hour after patch removal: erythema over the entire application  area, 

severe and partly bleeding inflammation with edema (wounds), partly  eschar 

formation, slight inflammation of the other injection sites,  agitation of 

the animals and scratching in the application area.
    24 hours after patch removal: formation of eschar on inflamed  injection 

areas.
- Other: Mean body weight gain 128 g in test group, 116 g in control  

group = expected range.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of this guinea pig maximization test, the test item 1,5 -Cyclooctadien showed no dermal sensitization in
male guinea pigs.
Executive summary:

In a guinea pig maximization test according to OECD 406 performed with the test item 1,5 -cyclooctadiene, after intracutane and epidermal inductions and 24 hours as well as 48 hours after epidermal challenge, no one of the 20 animals examined in this study showed positive response regarding dermal sensitization.

Under the conditions of this guinea pig maximization test, the test item 1,5 -cyclooctadien showed no dermal sensitization in male guinea pigs.