5(or 6)-methyl-7(or 8)-(1-methylethyl)bicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-04-04 to 2000-04-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

8-isopropyl-6-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

EC Number:

267-308-7

EC Name:

8-isopropyl-6-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Cas Number:

67845-30-1

Molecular formula:

C13H20O

IUPAC Name:

8-isopropyl-6-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Constituent 2

Reference substance name:

7-isopropyl-5-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

EC Number:

299-795-7

EC Name:

7-isopropyl-5-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Cas Number:

93904-56-4

Molecular formula:

C13H20O

IUPAC Name:

7-isopropyl-5-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

impurity 1

Reference substance name:

rel-(1S,2R,4R)-1-isopropyl-4-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Cas Number:

36208-34-1

Molecular formula:

C13H20O

IUPAC Name:

rel-(1S,2R,4R)-1-isopropyl-4-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Test material form:

liquid

Specific details on test material used for the study:

Identification: Lierral
Description: colourless to pale yellow liquid
Batch Number: 9000365675
Purity: 99.5%
Stability of test article: Stable under storage conditions; expiration date: 20-Dec-2000
Storage conditions: In the original container, at room temperature (range of 20 +/- 3 °C), away from direct sunlight

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 16 weeks (male) and 14 weeks (females)
- Weight at study initiation: 2.7 to 3.1 kg
- Housing: Animals were housed individually in stainless steel cages, with autoclaved wood and haysticks for gnawing.
- Diet (e.g. ad libitum): Pelleted standard rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water ad libitum in drinking water bowls
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 % (relative)
- Air changes (per hr): 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): An automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the light cycle.

IN-LIFE DATES: From: 2000-04-04 To: 2000-04-25

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm² (10 x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was again clipped. The test material was put on a surgical gauze patch (ca. 2.5 x 2.5 cm). This gauze patch was applied to approximately 6 cm² of the intact skin of the clipped area.
- Type of wrap if used: The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): When the dressing was removed, the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
- Time after start of exposure: 4 hours

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31 1992 (shown below) at approximately 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after the removal of the dressing, gauze patch and test material.

ERYTHEMA AND ESCHAR FORMATION
0 = No erythema
1 = Very slight erythema
2 = Well-defined erythema
3 = Moderate to severe erythema
4 = Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema) reading

OEDEMA FORMATION
0 = No oedema
1 = Very slight oedema (barely perceptible)
2 = Slight oedema (edges of area well-defined by definite raising)
3 = Moderate oedema (edges raised approximately 1 mm)
4 = Severe oedema (raised more than 1 mm and extending beyond the area of exposure)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean score at 24, 48 and 72 hours

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean score at 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean score at 24, 48 and 72 hours

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all 3 animals

Time point:

other: mean score at 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: No oedema was seen at any time point in any animal

Irritant / corrosive response data:

Very slight to well-defined erythema was observed in all animals at the 1 hour observation which persisted until the 48 hour reading (one animal) or diminished at day 7 (one animal) or day 14 (one animal). No oedema was observed within the 14 days after treatment. Slight to moderate scaling appeared at the 7 day reading in all animals and disappeared at the 14 day reading.
All skin reactions were clear within 14 days after treatment.
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 were observed in the animals during the study and no mortality occurred.
No staining by the test material of the treated skin was observed.

Any other information on results incl. tables

Table 1: Skin Irritation Scores - Individual Values

Animal Number	Sex	Evaluation Interval	Erythema	Oedema
1 2 3	M F F	1 hour	1 2 2	0 0 0
1 2 3	M F F	24 hours	1 2 2	0 0 0
1 2 3	M F F	48 hours	1 2 2	0 0 0
1 2 3	M F F	72 hours	0 2 1	0 0 0
1 2 3	M F F	7 days	0 1 0	0 0 0
1 2 3	M F F	10 days	0 1 0	0 0 0
1 2 3	M F F	14 days	0 0 0	0 0 0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the test material was found to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The skin irritation potential of the test material was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 404 and EU Method B.4.

The primary skin irritation potential was investigated by topical semi-occlusive application of 0.5 mL of the test material to the clipped left flank of three young adult New Zealand White rabbits. The duration of 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 scores of each animal at the 24, 48 and 72 hour time points were used in calculating the mean values for each type of lesion.

Very slight to well-defined erythema was observed in all animals at the 1 hour observation which persisted until the 48 hour reading (one animal) or diminished at day 7 (one animal) or day 14 (one animal). No oedema was observed within the 14 days after treatment. Slight to moderate scaling appeared at the 7 day reading in all animals and disappeared at the 14 day reading.

Local signs (mean values from 24 to 72 hours) consisted of grade 1.44 erythema and grade 0.00 oedema. All skin reactions were clear within 14 days after treatment. The test material caused no 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 study, the test material was found to be not irritating to the skin of New Zealand White rabbits.