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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 April 2007 - 9 May 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
-
EC Number:
482-330-9
EC Name:
-
Cas Number:
144020-22-4
Molecular formula:
C17H26O
IUPAC Name:
1-[(1E,5Z,9Z)-2,5,10-trimethylcyclododeca-1,5,9-trien-1-yl]ethan-1-one; 1-[(1R)-2,5,10-trimethylcyclododeca-2,5,9-trien-1-yl]ethan-1-one; 1-[(1R)-4,9-dimethyl-12-methylidenecyclododeca-4,8-dien-1-yl]ethan-1-one; 1-[(1S)-2,5,10-trimethylcyclododeca-2,5,9-trien-1-yl]ethan-1-one; 1-[(1S)-4,9-dimethyl-12-methylidenecyclododeca-4,8-dien-1-yl]ethan-1-one

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England
- Age at study initiation: 12 to 13 weeks of age
- Weight at study initiation: 2.47 – 2.81 kg
- Housing: The rabbits were housed individually in plastic cages with perforated floors
- Diet: Each rabbit was offered 125 g of a standard laboratory rabbit diet (Rabbit Diet Pellets (GD) supplied by Highgate Farm) per day. The animals were given a dietary supplement of hay
- Water: ad libitum
- Acclimation period: one to three weeks prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20°C
- Humidity (%): 40 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
other: additional site was similarly treated with the exception of the test substance
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
15 days
Number of animals:
3 males
Details on study design:
TEST SUBSTANCE PREPARATION
The substance was applied as such.

TEST SITE
On the day before application of the test substance, hair was removed with clippers from the dorsolumbar region of each rabbit exposing an appropriate sized area of skin.

APPLICATION
Approximately 0.5 mL of the test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad secured with ‘blenderm’ surgical tape to intact skin sites on three animals. An additional site was similarly treated with the exception of test substance and acted as a control.
A single animal (number 60) received three exposures (of three minutes, one or four hours duration) in a step-wise manner and acted as a preliminary screen. In the absence of a severe effect on removal of the dressings the next exposure was initiated.
For exposures of one hour or more each treatment site was covered with cotton wool and "Tubigrip" elasticated bandage dressing for the duration of the exposure period. The animals were returned to their cages immediately after treatment.

REMOVAL OF TEST SUBSTANCE
Yes, at the end of the exposure period using lukewarm tap water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

OBSERVATIONS
- Mortality/Viability: Daily
- Toxicity: Daily
- Body Weight: Prior to treatment (day 1)
- Necropsy: Not applicable
- Irritation: Examination of the treated skin was made on removal of the dressings (for 3 minute or one hour exposures) and approximately 1, 24, 48 and 72 hours, seven and 14 days later.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECDTG 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Animal #1
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Animal #2
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Animal #3
Irritation parameter:
edema score
Basis:
animal: #1, #2 and #3.
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: All animals
Irritant / corrosive response data:
- No Mortality.
- There was no sign of toxicity or ill health in any rabbit during the observation period.
- Dermal response: Very-slight or well-defined erythema was evident in all animals throughout the first 72 hours after bandage removal and in one case on Day 8. Exfoliation was present in all animals seven days after bandage removal persisting in one case one week later.

Applicant's summary and conclusion

Interpretation of results:
other: Not irritant according to EU CLP (1272/2008 and its amendments)
Conclusions:
The substance does not cause skin irritation but is a mild skin irritant according to GHS in the OECD TG 404 test.
Executive summary:

Skin irritation potential of the substance was carried out according to OECD TG 404 and GLP. Three rabbits received a single four hour, semi-occlusive, dermal administration of approximately 0.5 mL of the test substance as supplied and were observed for 15 days. There was no sign of toxicity or ill health in any rabbit during the observation period. Very-slight or well-defined erythema was evident in all animals throughout the first 72 hours after bandage removal and in one case on Day 8. Exfoliation was present in all animals seven days after bandage removal persisting in one case one week later.  The Primary Irritation Index was calculated to be 1.7. Based on the results of this study, the substance is not a skin irritant.