Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed equivalent or similar to OECD 404 guideline, but predating GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Observations were not continued until day 14 to detemine the reversibility of the effects.
GLP compliance:
no
Remarks:
Study performed around/just before the time GLP was introduced in Europe, but internal QA statement.

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 5-[(2R)-butan-2-yl]-2-[(1R,2R)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2R)-butan-2-yl]-2-[(1R,2S)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2R)-butan-2-yl]-2-[(1S,2R)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2R)-butan-2-yl]-2-[(1S,2S)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2S)-butan-2-yl]-2-[(1S,2R)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2S)-butan-2-yl]-2-[(1S,2S)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane
EC Number:
700-927-7
Molecular formula:
C17H30O2
IUPAC Name:
Reaction mass of 5-[(2R)-butan-2-yl]-2-[(1R,2R)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2R)-butan-2-yl]-2-[(1R,2S)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2R)-butan-2-yl]-2-[(1S,2R)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2R)-butan-2-yl]-2-[(1S,2S)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2S)-butan-2-yl]-2-[(1S,2R)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane and 5-[(2S)-butan-2-yl]-2-[(1S,2S)-2,4-dimethylcyclohex-3-en-1-yl]-5-methyl-1,3-dioxane
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): PM 968
- Physical state: liquid
- Description: clear, colourless solution
- Storage condition of test material: no data available.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: commercial supplier
- Age at study initiation: no data available
- Weight at study initiation: no data available
- Housing: individually
- Diet: free access to pelleted food
- Water: free access to water
- Acclimation period: no data available

ENVIRONMENTAL CONDITIONS
- No data available.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated skin of each animal serves as its own control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
8
Details on study design:
STUDY DESIGN
The test is designed to investigate the irritant effects of a single application of a substance under semi-occlusive conditions. A standard substance (Geraniol) was applied for comparative purposes; no untreated control animals are used. The untreated skin of each animal serves as its own control.

TEST SITE
Three to four days prior to testing, the dorsal areas of the trunks of the animals were clipped to identify those which are in telogen (non-growth phase of the hair cycle) and which have no skin blemishes. Of these suitable rabbits, at least three and normally eight are selected for the test. A final clipping of the test animals is made approximately 24 hours before testing.

The test substance was applied to the skin of one flank, using a gauze patch of 25x25 mm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the patches were removed and excess substance wiped from the skin with a damp tissue.

OBSERVATIONS
- Irritation: The animals were observed for signs of erythema and oedema and the response graded at 30 to 60 minutes, and then at 24, 48 and 72 hours after patch removal.


SCORING SYSTEM:
Dermal irritation is graded and recorded according to the system described in OECD 404. Further observations may be needed, as necessary, to establish reversibility. In addition to the observation of irritation, any serious lesions such as corrosion (irreversible destruction of skin tissue) and other
toxic effects are fully described.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: #1 and #7
Time point:
other: mean of 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal: #2 and #8
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
4
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal: #4, #5 and #6
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal: #3, #5 and #8
Time point:
other: mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal: #4 and #7
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
4
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
no data
Irritant / corrosive response data:
The substance showed very slight to well-defined erythema 72 hours after patch removal in 7 animals. In one animal erythema was fully reversible within 72 hours.
The substance showed very slight oedema 72 hours after patch removal in 3 animals. In 4 animals oedema was fully reversible within 48 hours and in 1 animal the irritation effects were fully reversible within 72 hours.
No data is available after 72 hours. 7 animals still had very slight erythema, in addition 3 of these still had very slight oedema.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was tested in a skin irritation test in rabbits equivalent or similar to OECD 404 guideline and GLP principles. The substance is considered to be not irritating.
Executive summary:

The substance was tested in a skin irritation test in rabbits equivalent or similar to OECD 404 guideline and GLP principles.

The substance showed very slight to well-defined erythema 72 hours after patch removal in 7 animals. In one animal the erythema effects were fully reversible within 72 hours. In addition, the substance showed very slight oedema 72 hours after patch removal in 3 animals. In 4 animals the oedema was fully reversible within 48 hours and in 1 animal the erythema was fully reversible within 72 hours though observations were not continued until day 14 to detemine the reversibility of the effects. The scores averaged over 3 days do not indicate skin irritation and in several animals the effects were reversible within 72 hours. Therefore, the substance is not considered to be irritating to skin. In addition, the substance has no reactive functional groups and it also has a high log Kow limiting dermal absorption and this absorption is needed for skin irritation.