Cyclododeca-1,5,9-triene

Endpoint summary

Description of key information

1988: According to OECd 406; non-GLP; 10-20 guinea pigs; 10%-20% test substance concentration; not sensitizing (K1)

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

Study period:

1988-11-15 to 1988-12-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study was performed prior to the implementation of the LLNA test method.

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:   test group mean 330 g, control group mean 333.5 g
- Number of animals: 20
- 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

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Concentration / amount:

1st application: Induction 10 % intracutaneous
2nd application: Induction 20 % occlusive epicutaneous
3rd application: Challenge 10 % occlusive epicutaneous

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

1st application: Induction 10 % intracutaneous
2nd application: Induction 20 % occlusive epicutaneous
3rd application: Challenge 10 % occlusive epicutaneous

No. of animals per dose:

test group: 20
control group: 10

Details on study design:

ADMINISTRATION/EXPOSURE 
- Induction schedule: single intracutaneous treatment, 1 week later  dermal induction; patch removed after 48 h 
- Challenge schedule: after 2 further weeks, occlusive epicutaneous,  removal of patch after 24 hours, readings after further 24 and 48 hours.
EXAMINATIONS
- Grading system: possible scores 0 - 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

Challenge controls:

vehicle

Positive control substance(s):

not required

Remarks:

not required by 1981 version of Test Guideline

Positive control results:

no positive control included

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10 % preparation of test item in corn oil

No. with + reactions:

2

Total no. in group:

20

Clinical observations:

see"any other information on results"

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10 % preparation of test item in corn oil

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

see"any other information on results"

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

10 % preparation of test item in corn oil

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

see"any other information on results"

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

10 % preparation of test item in corn oil

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

see"any other information on results"

Reading:

1st reading

Group:

positive control

Dose level:

not applicable

No. with + reactions:

0

Total no. in group:

0

Remarks on result:

other: no positive control has been included in the study

RESULTS OF TEST
- Sensitization reaction: 2/20 animals showed a sensitization 24 hours, 1/20 animals 48 hours after challenge   = slight sensitization (no  classification)
- Clinical signs: After intracutaneous application, the following signs  were observed in the places of application:

 FCA treatment: intense erythema and edema as well as necroses; Test substance treatment: slight erythema and edema;
  Vehicle treatment: slight redness
  After removal of the induction patch, severe inflammation with  discharge of matter and in some cases blood was observed in the    FCA  treatment positions.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the test item 1,5,9 -cyclododecatriene showed no dermal sensitization in female guinea pigs. Hence according to the outcome of the study the test item 1,5,9 -cyclododecatriene is not classified regarding dermal sensitisation according to 67/548/EEC and according CLP regulation (1272/2008).

Executive summary:

In a guinea pig maximization test performed with the test 1,5,9 -cyclododecatriene, after intracutane and epidermal inductions and 24 hours as well as 48 hours after epidermal challengen two (48h) and one (24h) 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 1,5,9 -cyclododecatriene showed no dermal sensitization in female guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

To investigate the skin sensitizing potential of the test substance, three studies are available.

A guinea pig maximization test was performed using six male Albino guinea pigs for open induction group, six animals for intradermal induction and 12 males in the control group. In the induction phase, animals in open induction group received a single induction of 0.05 ml undiluted, followed by 10%, 25% (2x), 50% and 25% (5x) in f.a.d on abraded skin. Intradermal induction was performed using 0.05 ml undiluted (open application) followed by 4x 0.1 ml of 1% solution in dimethyl phthalate (intradermal). Challenge was conducted after two weeks rest period on intact and abraded skin. Concentrations used for the challenge were not reported. Results of pilot study revealed rapid and strong irritation. Results of the test revealed no sensitization reactions (1967, K2).

A guinea pig maximization test was performed using ten guinea pigs per dose. One intradermal and one topical test were performed. The test substance was administered as a 0.1% solution in light liquid paraffin. Reactions were read after 24 and 48 hours. No further details reported. Results revealed 10/10 skin sensitization positive reactions both after 24 and 48 hours after intradermal and topical application. With respect to conflicting results obtained in the other two studies described, the most likely explanation given by the authors was that the severe effects were caused by an aggressive impurity and thus the test substance was not classified according to Regulation (EC) 1272/2008 (1968, K4).

A guinea pig maximization test was performed using twenty female Dunkin-Hartley guinea pigs for test groups and ten females in the control group. In the induction phase, animals received a single induction of 10% intracutaneously at first application and 20% epicutaneously under occlusive conditions at second application one week later. The patch was removed after 48 hours. The vehicle used was corn oil. Challenge was conducted after further two weeks using 10% intracutaneously at first application and 20% epicutaneously under occlusive conditions. Removal of the patch was performed after 24 hours and readings were conducted after further 24 and 48 hours. Two out of 20 animals and one animal out of 20 showed a sensitization after 24 hours and 48 hours, respectively. No animals in the control group (0/10) showed a sensitization after any reading. Intense erythema and edema as well as necrosis was observed in the FCA treatment group and slight erythema and edema in the test substance treatment group. Slight redness was observed in the vehicle treatment group. After removal of the induction patch, severe inflammation with discharge of matter and in some cases blood was observed in the FCA treatment groups (1988, K1).  

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.