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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:
September - November 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
(3Z,6Z)-3,7,11-trimethyldodeca-1,3,6,10-tetraene
Cas Number:
28973-99-1
Molecular formula:
C15H24
IUPAC Name:
(3Z,6Z)-3,7,11-trimethyldodeca-1,3,6,10-tetraene
Constituent 2
Chemical structure
Reference substance name:
(E)-1-methyl-4-(6-methylhepta-2,5-dien-2-yl)cyclohex-1-ene
Cas Number:
25532-79-0
Molecular formula:
C15H24
IUPAC Name:
(E)-1-methyl-4-(6-methylhepta-2,5-dien-2-yl)cyclohex-1-ene
Constituent 3
Chemical structure
Reference substance name:
(Z)-1-methyl-4-(6-methylhepta-2,5-dien-2-yl)
Cas Number:
29837-07-8
Molecular formula:
C15H24
IUPAC Name:
(Z)-1-methyl-4-(6-methylhepta-2,5-dien-2-yl)
Constituent 4
Chemical structure
Reference substance name:
(E)-7,11-dimethyl-3-methylenedodeca-1,6,10-triene
EC Number:
242-582-0
EC Name:
(E)-7,11-dimethyl-3-methylenedodeca-1,6,10-triene
Cas Number:
18794-84-8
Molecular formula:
C15H24
IUPAC Name:
7,11-dimethyl-3-methylenedodeca-1,6,10-triene
Constituent 5
Chemical structure
Reference substance name:
(E)-1-methyl-4-(6-methylhept-5-en-2-ylidene)
Cas Number:
53585-13-0
Molecular formula:
C15H24
IUPAC Name:
(E)-1-methyl-4-(6-methylhept-5-en-2-ylidene)
Constituent 6
Chemical structure
Reference substance name:
(Z)-1-methyl-4-(6-methylhept-5-en-2-ylidene)
Cas Number:
13062-00-5
Molecular formula:
C15H24
IUPAC Name:
(Z)-1-methyl-4-(6-methylhept-5-en-2-ylidene)
Constituent 7
Chemical structure
Reference substance name:
1-methyl-4-(6-methylhepta-1,5-dien-2-yl)
Cas Number:
869843-05-0
Molecular formula:
C15H24
IUPAC Name:
1-methyl-4-(6-methylhepta-1,5-dien-2-yl)
Constituent 8
Chemical structure
Reference substance name:
(3Z,6E)-3,7,11-trimethyldodeca-1,3,6,10-tetraene
Cas Number:
26560-14-5
Molecular formula:
C15H24
IUPAC Name:
(3Z,6E)-3,7,11-trimethyldodeca-1,3,6,10-tetraene
Constituent 9
Chemical structure
Reference substance name:
(Z)-7,11-dimethyl-3-methylenedodeca-1,6,10-triene
Cas Number:
28973-97-9
Molecular formula:
C15H24
IUPAC Name:
(Z)-7,11-dimethyl-3-methylenedodeca-1,6,10-triene
Constituent 10
Chemical structure
Reference substance name:
1-methyl-4-(6-methylhept-5-en-2-yl)cyclohexa-1,4-diene
Cas Number:
72345-84-7
Molecular formula:
C15H24
IUPAC Name:
1-methyl-4-(6-methylhept-5-en-2-yl)cyclohexa-1,4-diene
Constituent 11
Chemical structure
Reference substance name:
2,6,10-trimethyldodeca-2,6,9,11-tetraene
EC Number:
207-948-6
EC Name:
2,6,10-trimethyldodeca-2,6,9,11-tetraene
Cas Number:
502-61-4
Molecular formula:
C15H24
IUPAC Name:
3,7,11-trimethyldodeca-1,3,6,10-tetraene
Constituent 12
Chemical structure
Reference substance name:
Likely sesquiterpene hydrocarbons
Cas Number:
n/a
Molecular formula:
C15H24
IUPAC Name:
Likely sesquiterpene hydrocarbons
Test material form:
liquid
Details on test material:
UVCB substance
Specific details on test material used for the study:
Batch number 9000458190
Stability of test item Stable under storage conditions
Expiry date 04-FEB-2004
Storage conditions In the original container, in the refrigerator (range of 2-8 °C), away from direct sunlight
Safety precautions Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Source: Elevage scientifiaue des Dombes F-01400 Chatillon sur Chalaronne / France
Number of animal per test: 3 (Animals of both sexes were used)
Age at treatment: 12 weeks for mal and 11 weeks for females
Identification: by unique cage number and corresponding ear number
Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
Allocation: Male No 73 and Females Nos 74 and 75
Husbandry
Conditions: Standard laboratory conditions
Air-conditioned with target ranges for romm temperature 17-23°C, relative humidity 30-70% and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occured, usually following room cleaning. These transiet variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.
Accomodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Woodblocks and haysticks 4646 were provided for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC lab.
Water: Community tap water from Fullinsdorf, ad libitum. Results for bacteriological, chemical and contaminant analyses are archived at RCC lab.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours as well as 7, 10 and 14 days after removal of the dressing
Number of animals:
3
Details on study design:
Four days before treatment, one flank was clipped with an electric clipper, exposing an area of approximately 100 cm2. The skin of the animals was examined one day before treatment, and regrown fur of all animals was again clipped.
Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, 0.5 ml of bisabolene was placed on a surgical gauze patch (ca. 4cm x 4cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.
The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at the time.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 73
Time point:
24/48/72 h
Score:
3
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 74
Time point:
24/48/72 h
Score:
2.67
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 75
Time point:
24/48/72 h
Score:
2.33
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 73
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 74
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 75
Time point:
24/48/72 h
Score:
1.33
Reversibility:
fully reversible
Irritant / corrosive response data:
Very slight to well-defined erythema was apparent at the test site of all animals at the first examination, 1 hour after removal of the dressing.
Well-defined to moderate/severe erythema was present in all animals after up to 7 days after removal of the dressing.
The severity of the erythema gradually decreased and was no longer evident after 14 days after treatment, the end of the observation period of all animals.
Very slight to slight swelling was observed in all animals from 1 to 72 hours after treatment.
Scaling was evident in all animals from 7 days after treatment and was still present at termination of the test.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occured.
No staining by the test item of the treated skin was observed (coloration).
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin (corrosion).
The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Based upon the results of this study, BISABOLENE is considered to be Irritating to Skin.
Executive summary:

The primary skin irritation potential of Bisabolene was investigated by topical semi-occlusive application of 0.5 ml to the intact left flank of each of three young adult New Zealand White rabbits. The duration of the treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after removal of the dressing.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

The mean erythema/eschar score of the three animals was 3.00, 2.67 and 2.33 respectively and the mean oedema score was 1.00, 1.00 and 1.33 respectively.

The application of Bisabolene to the skin resulted in moderate/severe and prolonged signs of irritation such as erythema, oedema and scaling. Both the erythema and oedema were reversible and were no longer evident at termination of the test. Scaling was however still apparent at the test site of all animals 14 days after treatment, the end of observation period for all animals. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals.

Based upon the results of this study, BISABOLENE is considered to be Irritating to Skin.

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