Cyclododeca-1,5,9-triene

Endpoint summary

Description of key information

Skin

1983: According to OECD 404; pre-GLP; 6 rabbits; undiluted test substance; slightly irritating (K1)

Eye

1983: According to OECD 405; pre-GLP; 6 Small White Russian rabbits; undiluted test substance; no irritant effects (K1)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

other: Small white Russian, Chbb

Details on test animals or test system and environmental conditions:

TEST ANIMALS: 
- Strain: Small white Russian, Chbb-SPF
- Sex: male and female
- Source: Dr. Karl Thomae GmbH, Biberach (Germany)
- Weight at study initiation: 2.2 - 2.7 kg
- Number of animals: 3 males, 3 females
- Feed: K4 complete feed for rabbits (Ssniff, Soest, Germany);
- Water: tap water ad libitum
Environmental conditions:
- Room temperature: 20°C (+/- 1°C);
- Humidity: 60% (+/- 5%);
- Air change: 15 times/hour;
- Light: 12 hour light/dark rhythm;

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

undiluted

Duration of treatment / exposure:

4 hour(s)

Observation period:

1, 24, 48, 72 hours; 6, 8, 11, 14 days after exposure

Number of animals:

6

Details on study design:

ADMINISTRATION/EXPOSURE 
- Area of exposure: ca. 6 cm2
- Occlusion: mull patch, polyethylene film, elastic dressing 
- Postexposure period: 14 days
- Removal of test substance: dist. water
EXAMINATIONS
- Scoring system: OECD; evaluation: VCI notes on safety data sheet
- Examination time points: 1, 24, 48, 72 hours; 6, 8, 11, 14 days;  evaluation based on readings 1-4

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

1.2

Max. score:

8

Remarks on result:

other: additional time point after 1 h

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.61

Max. score:

4

Irritant / corrosive response data:

AVERAGE SCORE
- Erythema: 1.00
- Edema: 0.61

Other effects:

no other effects

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the test item 1,5,9 -cyclododecatrien showed a slightly irritant effect on the skin of male and female rabbits which leads to no classification according to 67/548/EEC and according CLP regulation (1272/2008).

Executive summary:

To test the acute skin irritant effect the test item 1,5,9 -cyclododecatrien was applied to the shaven dorsal skin of 3 male and 3 female rabbits. The product was administered undiluted and the time of exposure in the patch test was 4 hours. According to the study, the test item 1,5,9 -cyclododecatrien showed a slightly irritant effect on the skin of male and female rabbits

.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

other: Small white Russian, Chbb-SPF

Details on test animals or tissues and environmental conditions:

TEST ANIMALS: 
- Strain: Small white Russian, Chbb-SPF
- Sex: male/female
- Source: Dr. Karl Thomae GmbH, Biberach (Germany)
- Weight at study initiation: 2.3 - 2.5 kg
- Number of animals: 3 per sex
- Controls: untreated eye
- Number of animals: 3 males, 3 females
- Feed: K4 complete feed for rabbits (Ssniff, Soest, Germany);
- Water: tap water ad libitum
Environmental conditions:
- Room temperature: 20°C (+/- 1°C);
- Humidity: 60% (+/- 5%);
- Air change: 15 times/hour;
- Light: 12 hour light/dark rhythm;

Vehicle:

unchanged (no vehicle)

Controls:

other: identical animals, left eyes remained untreated

Amount / concentration applied:

undiluted
Amount applied: 0.1 ml

Duration of treatment / exposure:

not rinsed

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

6

Details on study design:

Comment: not rinsed
EXAMINATIONS
- Ophtalmoscopic examination: 1, 24, 48, 72 hours after treatment
- Scoring system: Draize (1959); evaluation: VCI notes on safety data  sheet
- Tool used to assess score: sodium fluorescein / ophthalmic lamp

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

110

Reversibility:

fully reversible within: complete after 6 days

Remarks on result:

other: additional time point after 1 h

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: complete after 6 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: complete after 6 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.5

Max. score:

3

Reversibility:

fully reversible within: complete after 6 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: complete after 6 days

Irritant / corrosive response data:

AVERAGE SCORE
- Cornea: 0.17
- Iris: 0
- Conjunctivae (Redness): 0.50
- Conjunctivae (Chemosis): 0.22
- Overall irritation score: 3/110

Other effects:

REVERSIBILITY: complete after 6 days

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the test item 1,5,9 -cyclododecatrien showed no irritant effects on eyes and mucosa of male and female rabbits which leads to no classification according to 67/548/EEC and according CLP regulation (1272/2008).

Executive summary:

To test the acute irritant effect on eyes and mucosa the test item 1,5,9 -cyclododecatriene was administered undiluted into eyes or eyelid sacs of 3 male and 3 female rabbits. According to the study, the test item 1,5,9 -cyclododecatriene showed no irritant

effect on the eyes and mucosa of male and female rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

Three studies are available investigating the skin irritating potential of the test substance.

Firstly, the skin irritating potential of the test substance was analyzed by using six New Zealand White rabbits. No data on used guideline was available and study was not performed pre-GLP. Animals were exposed to the undiluted test substance applied to intact and abraded skin areas on the back. Observation time points were various and not specified. Average erythema score was minimal in abraded and intact skin of all rabbits. Average edema score was minimal in abraded akin of two rabbits at 24 hours. Effects were completely reversible after one week. Under the conditions chosen, the test substance showed minimal irritant reversible effects on the skin of rabbits which, however, were not sufficient for a classification according to Regulation (EC) 1272/2008 (1961, K2).

 

Secondly, the skin irritating potential of the test substance was analyzed by using rabbits, guinea pigs, and hairless mice. No data on used guideline was available and the study was performed pre-GLP. Animals were exposed to the undiluted test substance applied occlusively (rabbits) and open (rabbits, guinea pigs, mice). Observation time points were not specified. Postexposure period was three weeks for guinea pigs. Very severe irritation was observed for guinea pigs which did not fully recover within 21 days. 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).

The skin irritating potential of the test substance was analyzed by using six Small White Russian rabbits. Animals were exposed for 4 hours to the undiluted test substance applied to a shaved area of ca. 6 cm². The test substance was then removed with distilled water. Observation time points were after 1, 24, 48, 72 hours and 6, 8, 11, and 14 days. Evaluation was based on 1-4 readings. The average scores of erythema, edema and overall irritation score were 1, 0.61 and 1.2, respectively established by combining time points 24/48/72 hours. Under the conditions chosen, the test substance showed a slightly irritant effect on the skin of male and female rabbits which, however, does not lead to a classification according to Regulation (EC) 1272/2008 (1983, K1).

Eye

Three studies are available investigating the eye irritating potential of the test substance.

Firstly, the eye irritating potential of the test substance was analyzed by using rabbits. No data on used guideline was available and the study was performed pre-GLP. Animals were exposed to the undiluted test substance. A single application of 0.1 ml with no specified exposure period was applied to the conjunctivae sac of the right eyes. The total observation period was one week and observation time points were 1, 24, 48, 72 hours and 1 week after treatment. The scoring system used was the one installed by Draize. The overall irritation scores after 1 hour, 24 h, 48 h, 72 h and 1 week were 6.6, 2.3, 1, 1, and 0, respectively (max 110). The test substance produced erythema of the palpebral conjunctiva, obvious swelling of the lids and nicititating mambrane and lacrimation within 1 hour. Effects were completely reversible within one week. The test substance showed only very mild reversible effects on eyes and mucosa of males and females. However, effects were not sufficient for a classification according to Regulation (EC) 1272/2008 (1961, K2).

Secondly, the eye irritating potential of the test substance was analyzed by using rabbits. No data on used guideline was available and the study was performed pre-GLP. No information on exposure period, observation period or concentration used were available. The substance was an immediate irritant but produced only a mild conjunctivitis which faded within 48 hours. Main effects were associated with the eye lids which became red and swollen and exuded a purulent discharge. Blepharitis was still apparent one week after application of the substance. With respect to the conflicting results obtained in other studies, the most likely explanations is that the severe effects were caused by an aggressive impurity (1968, K4).

Six male and female Small White Russian rabbits were exposed to the undiluted test substance. The study was performed according to OECD 4045 and was conducted pre-GLP. The amount applied to rabbit's eyes was 0.1 ml and the exposure period was 72 hours without rinsing. Ophtalmoscopic examinations were performed at 1, 24, 48 and 72 hours after treatment and the scoring system by Draize was used. Scores were evaluated using average time points of 24/48/72 hours. The overall irritation score was 3 (max 110), cornea opacity score was 0.17 (max 4), iris score was 0 (max 2), conjunctivae score was 0.5 (max 3), and chemosis score was 0.22. The test substance showed no irritant effects on eyes and mucosa of male and female rabbits (1983, K1).

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 irritation under Regulation (EC) No. 1272/2008.