1,4,4-trimethyl-2,3-diazabicyclo[3.2.2]non-2-ene 2,3-dioxide

Eye irritation

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

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 for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

Reason / purpose for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

Reason / purpose for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

Guideline:

other: QSAR prediction

Principles of method if other than guideline:

Derek v1.1
Prediction report is attached in IUCLID

GLP compliance:

no

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.

Cross-reference 2

Reason / purpose for cross-reference:

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 for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

Reason / purpose for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

Reason / purpose for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

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

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.

Cross-reference 3

Reason / purpose for cross-reference:

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 for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

Reason / purpose for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

Reason / purpose for cross-reference:

reference to other study

Remarks:

part of a Weight of Evidence approach

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

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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,4,4-trimethyl-2,3-diazabicyclo[3.2.2]non-2-ene 2,3-dioxide

EC Number:

251-833-3

EC Name:

1,4,4-trimethyl-2,3-diazabicyclo[3.2.2]non-2-ene 2,3-dioxide

Cas Number:

34122-40-2

Molecular formula:

C10H18N2O2

IUPAC Name:

1,4,4-trimethyl-2,3-diazabicyclo[3.2.2]non-2-ene-2,3-diium-2,3-bis(olate)

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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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.