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Description of key information

Eye irritation/corrosion:

Irritating to eyes (WoE, Kr.2).

Skin corrosion/irritation:

Irritating to skin (RS, K).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
ALPHA PINENE EPOXIDE MULTICONSTITUENT is substance multiconstituent composed by the two isomers ALPHA PINENE EPOXIDE DEXTRO (CAS No.32162-27-9) and ALPHA PINENE EPOXIDE LAEVO (CAS No. 19894-99-6). Therefore, data on ALPHA PINENE EPOXIDE LAEVO can be extrapolated to ALPHA PINENE EPOXIDE MULTICONSTITUENT.
Reason / purpose for cross-reference:
read-across source
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: JEGARD, 22120 Yffiniac, France
- Housing: individual housing on floor grid.
- Diet: complete pelleted rabbit maintenance diet ERGILAP
- Acclimation period: at least 5 days
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL of the test item was applied
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: clipped skin from the dorsal area of the trunk
- Type of wrap used: Undiluted test item was applied to the clipped skin then covered with a gauze (2.5 x 2.5 cm) held in place by means of a 5 x 5 cm wide "Micropore" fastening tape. Then the trunk of the animals was wrapped with a 10 cm wide stretch tape (varicose vein tape) fastened by adhesive tape of the same width, placed in such way so as not to hinder respiratory movements.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h
- Residual test substance was removed using coton wool moistened with water.

SCORING SYSTEM: According to OECD Guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72h
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 72h
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 72h
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 72h
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the test item is classified as "R38: irritating to skin" according to the Directive 67/548/EEC and Category 2 "H315 Cause skin reaction" to the CLP Regulation (EC) N° 1272 /2008.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
28-09-2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
Derek Nexus: 6.1.0, Nexus: 2.3.0, Lhasa Ltd.

2. MODEL (incl. version number)
Derek KB 2020 1.0. Version 1.0. Last Modified Date: 26/03/2020 09:28:54. Certified by: Lhasa Limited, Leeds, Yorkshire, UK.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: CC(C)(O)C1CCC(C)(O)CC1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
No QMRF is currently available for this irritation endpoints from the model developer. See attached documentation from Nexus Derek discussing irritation endpoints.

5. APPLICABILITY DOMAIN
See attached report

6. ADEQUACY OF THE RESULT
See attached report
Qualifier:
no guideline followed
Principles of method if other than guideline:
QSAR study result
GLP compliance:
no
Species:
other: not applicable
Strain:
other: not applicable
Vehicle:
other: not applicable
Controls:
other: not applicable
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
not applicable
Duration of post- treatment incubation (in vitro):
not applicable
Number of animals or in vitro replicates:
not applicable
Irritation parameter:
other: QSAR result
Remarks on result:
positive indication of irritation
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
DEREK Nexus evaluation showed alerts for eye irritation/corrosion.
Executive summary:

DEREK software ( Derek Nexus: 6.1.0, Nexus: 2.3.0, Lhasa Ltd.) was used to predict the eye irritation/corrosion potential  of (1α,2β,4β,6α)-2,2,7-trimethyl-3-oxatricyclo[4.1.1.02,4]octane

The query structure does match structural alerts or examples for eye irritation/corrosion in Derek. 

 DEREK Nexus evaluation showed alerts for eye irritation. Therefore, the test substance is considered as irritating to eyes and classified into category 2, H319 according to CLP and UN GHS criteria.

Endpoint:
eye irritation, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
10-10-2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
1. SOFTWARE
Toxtree

2. MODEL (incl. version number)
Toxtree v3.1.0
Profiler applied: Eye irritation and corrosion

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: CC(C)(O)C1CCC(C)(O)CC1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
No QMRF is currently available for this endpoint from the model developer. Toxtree documentation discussing irritation profilers have been provided.

5. APPLICABILITY DOMAIN
See attached report

6. ADEQUACY OF THE RESULT
See attached report
Qualifier:
no guideline followed
Principles of method if other than guideline:
QSAR analysis.
GLP compliance:
no
Species:
other: not applicable.
Strain:
other: not applicable.
Vehicle:
other: Not applicable
Controls:
other: not applicable
Amount / concentration applied:
Other: not applicable.
Duration of treatment / exposure:
Other: not applicable.
Observation period (in vivo):
Other: not applicable.
Duration of post- treatment incubation (in vitro):
Other: not applicable.
Number of animals or in vitro replicates:
Other: not applicable.
Details on study design:
QSAR analysis
Irritation parameter:
other: Toxtree prediction
Remarks on result:
other: Alerts for skin irritation. Therefore the test substance is considered as irritating to eyes.
Other effects / acceptance of results:
Other effects / acceptance of results
Evaluation for eye irritation: unknown. Structural alerts were identified for skin irritation/corrosion for the test substance using Toxtree v3.1.0.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Toxtree evaluation showed alerts for skin irritation/corrosion. The test substance is considered as irritating to eyes (Worst case).
Executive summary:
 

Toxtree v3.1.0 was used to predict the eye irritation/corrosion potential of (1α,2β,4β,6α)-2,2,7-trimethyl-3-oxatricyclo[4.1.1.02,4]octane.

The query structure are unknown for eye irritation.Toxtree evaluation showed alerts for skin irritation/corrosion. Therefore, the test substance is considered as irritating to eyes and classified into category 2, H319 according to CLP and UN GHS criteria (Worst case).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Dermal irritation/corrosion:

In a primary dermal irritation study performed according to OECD Guideline 404 and in compliance with GLP, three New Zealand albino rabbits were dermally exposed to 0.5 mL of undiluted EPOXY ALPHA PINENE GAUCHE under a semi-occlusive patch for 4 h on clipped skin. After removal of the dressings, irritation was scored as outlined in the OECD Guideline 404 at 1, 24, 48 and 72 h after exposure.

The application of the test item produced one hour after patch removal, in all animals, the outbreak of well defined erythema with slight to moderate edema. During the first 72 hours, erythematous reactions were maintained or decreased in the rabbits and the oedematous reactions decreased in all the rabbits. The reversibility of this cutaneous reactions was complete within 8 days for one rabbit and 9 days for the 2 others.

Mean scores over 24, 48 and 72 h for each animal were 2.0, 1.3 and 2.0 for erythema and 2.3, 1.3 and 2.3 for edema.

Under the test conditions, the test item was classified in Category 2 "H315 Cause skin reaction" to the CLP Regulation (EC) No 1272 /2008.

Eye irritation/corrosion:

Two QSARs predictions are available and considered as WoE (Kr.2).

1- DEREK software ( Derek Nexus: 6.1.0, Nexus: 2.3.0, Lhasa Ltd.) was used to predict the eye irritation/corrosion potential  of the test substance. The results are PLAUSIBE. The test substance is considered as irritating to eyes.

2- Toxtree v3.1.0 was used to predict the eye irritation/corrosion potential of the test substance. Toxtree evaluation showed alerts for skin irritation/corrosion. However the query structure are unknown for eye irritation evaluation. Therefore, the test substance is considered as irritating to eyes as worst case.

Based on the results of these two QSARs evaluation, the test substance is considered as irritating to eyes and classified into category 2, H319 according to CLP and UN GHS criteria.

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 and to the GHS.

Self classification:

Dermal irritation:

In an in vivo skin irritation study conducted on (-)-alpha-pinene, an optical isomer present in the substance, results of irritation led to classification as irritating to skin. Therefore, in a read across approach, the substance was classified in Category 2 "H315 Causes skin irritation" according to the CLP Regulation (EC) No. 1272/2008.

 

Eye irritation:

Based on the available data, the test substance is classified as irritant to eyes into category 2, H319 according to the Regulation (EC) No. 1272/2008 (CLP) and the GHS.

 

Respiratory irritation:

No data was available regarding respiratory irritation.