Cyclopropanemethanol, 1-methyl-2-[(1,2,2-trimethylbicyclo[3.1.0]hex-3-yl)methyl]-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 10 September 1997 to 29 September 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1S,2S)-, rel-

Molecular formula:

C15H26O

IUPAC Name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1S,2S)-, rel-

Constituent 2

Reference substance name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1R,2R)-, rel-

Molecular formula:

C15H26O

IUPAC Name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1R,2R)-, rel-

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Javanol
- Physical state: Pale yellow viscous liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH - Birkendorferstrasse 65 - D-88397 Biberach/Riss
- Age at study initiation: 15 weeks
- Weight at study initiation:
Male: 2873 g
Female: 3020 and 3184 g
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, ad libitum
- Water (e.g. ad libitum):Community tap water from Itingen, ad libitum
- Acclimation period: four days under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-115
- Photoperiod (hrs dark / hrs light): 12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Test material was used undiluted.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours, 7 days and 14 days after treatment

Number of animals:

3 (one male, two females)

Details on study design:

TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used:
semi-occlusive dressing (surgical gauze patch (ca. 2.5 cm x 2.5 cm) - The dressing was wrapped around the abdomen and anchored with tape).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water
- Time after start of exposure:
4 hours

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours - 7 days and 14 days

SCORING SYSTEM:
- Method of calculation:The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test item.

EEC COMMISSION DIRECTIVE 92/69/EEC, JULY 31, 1992
Grading of Skin Reactions
ERYTHEMA AND ESCHAR FORMATION
No erythema ...................................................................................................................................... 0
Very slight erythema ......................................................................................................................... l
Well-defined erythema ...................................................................................................................... 2
Moderate to severe erythema ............................................................................................................ 3
Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema)
reading .............................................................................................................................................. 4
OEDEMA FORMATION
No oedema ........................................................................................................................................ 0
Very slight oedema (barely perceptible) ........................................................................................... 1
Slight oedema (edges of area well-defined by definite raising). ........................................................ 2
Moderate oedema ( edges raised approximately 1 mm) ..................................................................... 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) ..................... 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal: 19

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

edema score

Basis:

animal: 20

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

edema score

Basis:

animal: 21

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

erythema score

Basis:

animal: 19

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

erythema score

Basis:

animal: 20

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

erythema score

Basis:

animal: 21

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 1.78. Very slight reddening and very slight swelling were noted in two animals after 24 hours and in all animals from 48 hours to 7 days after application. All findings were reversible after 14 days. Local signs (mean values from 24 to 72 hours) consisted of grade 0.89 erythmea and grade 0.89 edema. No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity or mortality occurred.
No staining by the test article of the treated skin observed.
Body weights were within normal range of viability.

Any other information on results incl. tables

Skin irritation scores - individual values:

Animal number	Sex	Evaluation Interval	Erythema	Oedema	Cumulative
					Score	Mean
19 20 21	M F F	1 hour	0 0 0	0  0 0	0.00 0.00 0.00	0.00
19 20 21	M F F	24 hours	0 1 1	0 1 1	0.00 2.00 2.00	1.33
19 20 21	M F F	48 hours	1 1 1	1 1 1	2.00 2.00 2.00	2.00
19 20 21	M F F	72 hours	1 1 1	1 1 1	2.00 2.00 2.00	2.00
19 20 21	M F F	7 days	1 1 1	1 1 1	2.00 2.00 2.00	2.00
19 20 21	M F F	14 days	0 0 0	0 0 0	0.00 0.00 0.00	0.00

Skin irritation scores - mean values of 24, 48 and 72 hours

nimal Number	Sex	Erythema	N	Oedema	N	Primary Skin Irritation Score
19 20 21	M F F	0.67 1.00 1.00	3 3 3	0.67 1.00 1.00	3 3 3	1.78

N = number of available data points

Skin irritation scores - assessment

Evaluated intervals	Erythema	Oedema
24 hours 48 hours 72 hours	Not Irritating	Not irritating

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria, Javanol is considered to be 'not irritating' to rabbit skin.

Executive summary:

A key dermal irritation study was performed according to OECD guideline 404 (adopted 1992), EEC Commission Directive 92/69/EEC (1992) and in compliance with GLP.

The primary skin irritation potential of the test article was investigated by a topical application of 0.5 ml to 6cm2 intact dorsal skin of each of three young adult New Zealand White rabbits. The duration of the treatment was 4 hours.The scoring of skin reactions was performed 1, 24, 48 and 72 hours as well as 7 and 14 days after removal of the dressing. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of data points. The primary eye irritation score was 1.78 (max 8.0). Local signs (mean values from 24 to 72 hours) consisted of grade 0.89 erythema and grade 0.89 edema.

Very slight reddening and swelling were noted in two animals after 24 hours and in all animals from 48 hours to 7 days after application. All findings were reversible after 14 days.

The test article did not cause staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Under the conditions of the this test, Javanol is not considered to be a skin irritant.

Based upon the test results and in accordance to the Regulation (EC) No 1272/2008 (CLP) and Globally Harmonized System of Classification and Labeling of Chemicals (GHS), Javanol is not classified.