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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Justification for type of information:
This endpoint record is part of a Weight of Evidence approach comprising an in vivo study (this record) and three QSAR predictions. All data sources agree in the estimated eye irritation potential (i.e., Eye Irritation Category 2 according to EC 1272/2008 as amended) as further explained in the provided endpoint summary.
Cross-referenceopen allclose all
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source
Justification for type of information:
This endpoint record is part of a Weight of Evidence approach comprising an in vivo study and three QSAR predictions (one of which is this record). All data sources agree in the estimated eye irritation potential (i.e., Eye Irritation Category 2 according to EC 1272/2008 as amended) as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reference:
Composition 0
Guideline:
other: QSAR prediction
Principles of method if other than guideline:
Derek v1.1
Prediction report is attached in IUCLID
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: CC2(C1CCC(CC1)(N([N+]2=O)[O-])C)C
Irritation parameter:
other: QSAR eye irritation/corrosion
Remarks on result:
other: No alerts were issued by the model.
Interpretation of results:
study cannot be used for classification
Remarks:
part of a Weight of Evidence approach as further explained in the provided endpoint summary
Conclusions:
No alerts for eye irritation were issued by the model.
Executive summary:

The Derek nexus model for eye irritation/corrosion was used. No alerts for eye irritation were issued by the model. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
This endpoint record is part of a Weight of Evidence approach comprising an in vivo study and three QSAR predictions (one of which is this record). All data sources agree in the estimated eye irritation potential (i.e., Eye Irritation Category 2 according to EC 1272/2008 as amended) as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reference:
Composition 0
Guideline:
other: QSAR prediction
Principles of method if other than guideline:
Times v.2.28.1.6
Toolbox prediction report is attached in IUCLID
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: O=[N+]1C(C2CCC(N1[O-])(CC2)C)(C)C
Irritation parameter:
other: QSAR eye irritation model
Remarks on result:
other: No known structural alerts were issued by the model, which indicates that the test substance is not corrosive via any mechanism considered by this model.
Interpretation of results:
study cannot be used for classification
Remarks:
part of a Weight of Evidence approach as further explained in the provided endpoint summary
Conclusions:
No known structural alerts were issued by the model, which indicates that the test substance is not corrosive via any mechanism considered by this model.
Executive summary:

The Times model for in vivo eye irritation was used. No known structural alerts were issued by the model, which indicates that the test substance is not corrosive via any mechanism considered by this model. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
This endpoint record is part of a Weight of Evidence approach comprising an in vivo study and three QSAR predictions (one of which is this record). All data sources agree in the estimated eye irritation potential (i.e., Eye Irritation Category 2 according to EC 1272/2008 as amended) as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reference:
Composition 0
Guideline:
other: QSAR prediction
Principles of method if other than guideline:
BIOVIA Discovery Studio v4.5
Prediction report is attached in IUCLID
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: O=[N+]1C(C2CCC(N1[O-])(CC2)C)(C)C
Irritation parameter:
other: QSAR eye irritation model
Remarks on result:
positive indication of irritation
Remarks:
Prediction: Moderate
Interpretation of results:
study cannot be used for classification
Remarks:
part of a Weight of Evidence approach as further explained in the provided endpoint summary
Conclusions:
The model predicts that the test substance will be a moderate irritant.
Executive summary:

The BIOVIA model for ocular irritancy was used. The model predicts that the test substance will be a moderate irritant. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Specific details on test material used for the study:
Haskell No. 9864

Test animals / tissue source

Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Albino

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
10 mg solid test material
Duration of treatment / exposure:
20 secs after treatment, treated eye of one of the test animals was washed. Treated eye of other test animal was not washed.
Observation period (in vivo):
At 1 and 4 hrs after treatment then again at 1, 2, and 3 days
Number of animals or in vitro replicates:
2
Details on study design:
10 mg of solid test material was placed into the right conjunctival sac of each of two albino rabbits. Twenty seconds after contact, one treated eye was washed with tap water for one minute. The treated eye of the other rabbit was not washed. Observations of the cornea, iris and conjunctive. were made with a hand-slit lamp at one and four hours and at one, two, and three days. A biomicroscope and 5% aqueous fluorescein stain were used at examinations after the day of treatment.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
2 animals
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
no corneal effect reported
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
2 animals
Time point:
other: 1hr, 4 hrs, 24 hrs, 48 hrs, 72 hrs
Remarks on result:
not determinable because of methodological limitations
Remarks:
no corneal effect reported
Irritation parameter:
iris score
Basis:
mean
Remarks:
2 animals
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
no iritic effect reported
Irritation parameter:
iris score
Basis:
mean
Remarks:
2 animals
Time point:
other: 1hr, 4 hrs, 24 hrs, 48 hrs, 72 hrs
Remarks on result:
not determinable because of methodological limitations
Remarks:
no iritic effect reported
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
2 animals
Time point:
24/48/72 h
Remarks on result:
no indication of irritation
Remarks:
Mild redness 4 hours - 2 day; slight discharge 1-4 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
2 animals
Time point:
other: 1hr, 4 hrs, 24 hrs, 48 hrs, 72 hrs
Remarks on result:
not determinable because of methodological limitations
Remarks:
Mild redness 4 hours - 2 day; slight discharge 1-4 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
2 animals
Time point:
other: 1hr, 4 hrs, 24 hrs, 48 hrs, 72
Remarks on result:
not determinable because of methodological limitations
Remarks:
Mild redness 4 hours - 2 day; slight discharge 1-4 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
2 animals
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
Mild redness 4 hours - 2 day; slight discharge 1-4 hours
Irritant / corrosive response data:
The test substance produced transient mild to minimal conjunctival irritation with no corneal or iritic effect in unwashed and washed rabbit eyes. Both eyes were normal within 4 hours to 3 days. Only temporary mild to minimal ocular effects occurred; however, as in the case of all chemicals, eye contact with this material should be avoided. In case of eye contact, good hygienic practice would be to flush copiously with water.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
part of a Weight of Evidence approach as further explained in the provided endpoint summary
Conclusions:
The test substance produced transient mild to minimal conjunctival irritation with no corneal or iritic effect in unwashed and washed rabbit eyes. Both eyes were normal within 4 hours to 3 days. Only temporary mild to minimal ocular effects occurred; however, as in the case of all chemicals, eye contact with this material should be avoided. In case of eye contact, good hygienic practice would be to flush copiously with water.