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

Endpoint summary

Description of key information

Based on a Weight of Evidence approach, the substance is predicted to be a non-sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 two QSAR predictions. All data sources agree in the estimated skin sensitization potential (i.e., non-sensitizing 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 same study

Remarks:

skin irritation results

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

no

Type of study:

intracutaneous test

Justification for non-LLNA method:

The guinea pig skin sensitization test results were existing data and were not commissioned for the purposes of REACH.

Specific details on test material used for the study:

Haskell No. 9864

Species:

guinea pig

Strain:

not specified

Sex:

male

Details on test animals and environmental conditions:

Albino males

Route:

intradermal

Vehicle:

other: saline

Concentration / amount:

0.1 mL of a 1% solution (wt/vol) of test material in 0.9% saline

Day(s)/duration:

3 wks

Adequacy of induction:

not specified

Route:

intradermal

Vehicle:

propylene glycol

Concentration / amount:

0.05 mL each of a 50% and a 5% suspension (wt/vol) of test material in propylene glycol

Day(s)/duration:

48 hours

Adequacy of challenge:

not specified

No. of animals per dose:

9

Details on study design:

To test for the sensitization potential, a series of four sacral intradermal injections was given, one each week over a three-week period, which consisted of 0.1 ml of a 1% solution (wt/vol) of test material in 0.9% saline. Following a two-week rest period, the test animals were challenged for sensitization by applying, and lightly rubbing in 1 drop (approx. 0.05 mL) each of a 50% and a 5% suspension (wt/vol) of test material in propylene glycol on the shaved intact shoulder skin. A group of 10 previously unexposed guinea pigs received similar applications at the time of challenge to provide a direct comparison of the challenge reactions on skin of similar age.

Challenge controls:

A group of 10 previously unexposed guinea pigs received similar applications at the time of challenge to provide a direct comparison of the challenge reactions on skin of similar age.

Reading:

2nd reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50% suspension (wt/vol)

No. with + reactions:

3

Total no. in group:

6

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50% suspension (wt/vol)

No. with + reactions:

0

Total no. in group:

9

Reading:

2nd reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5% suspension (wt/vol)

No. with + reactions:

0

Total no. in group:

9

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5% suspension (wt/vol)

No. with + reactions:

0

Total no. in group:

9

Reading:

2nd reading

Hours after challenge:

24

Group:

negative control

Dose level:

5% suspension (wt/vol)

No. with + reactions:

0

Total no. in group:

0

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

50% suspension (wt/vol)

No. with + reactions:

0

Total no. in group:

0

Reading:

2nd reading

Hours after challenge:

24

Group:

positive control

Dose level:

5% suspension (wt/vol)

No. with + reactions:

0

Total no. in group:

0

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

50% suspension (wt/vol)

No. with + reactions:

0

Total no. in group:

0

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 material produced mild irritation in three test guinea pigs and one control guinea pig when applied at challenge to the shaved intact skin of male albino guinea pigs as a 50% suspension in propylene glycol. No irritation was produced by a 5% suspension. No sensitization was observed at challenge; however, the material is a mild skin irritant. However, this study has limitations: induction did not have 3 pairs of intradermal injections and did not have topical application. Also, it is unclear whether the highest induction dose was the highest to cause mild to moderate skin irritation. Coverage information was not provided, and skin reaction observed during the induction period was not reported.

Reference 2

Endpoint:

skin sensitisation: in vitro

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 two QSAR predictions (one of which is this record). All data sources agree in the estimated skin sensitization potential (i.e., non-sensitizing 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

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

Parameter:

other: QSAR skin sensitization model

Remarks on result:

no indication of skin sensitisation

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 is predicted to be a non-sensitiser.

Executive summary:

The Times model for skin sensitisation was used. The test substance is predicted to be a non-sensitiser. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reference 3

Endpoint:

skin sensitisation: in vitro

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 two QSAR predictions (one of which is this record). All data sources agree in the estimated skin sensitization potential (i.e., non-sensitizing 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

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

Parameter:

other: QSAR skin sensitisation

Remarks on result:

no indication of skin sensitisation

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 is predicted to be a non-sensitiser.

Executive summary:

The BIOVIA model for skin sensitisation was used. The test substance is predicted to be a non-sensitiser. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation was assessed as part of a Weight of Evidence approach comprising an in vivo study and two QSAR predictions. The in vivo study has limitations: induction did not have 3 pairs of intradermal injections and did not have topical application; unclear whether the highest induction dose was the highest to cause mild to moderate skin irritation; coverage information was not provided; and skin reaction observed during the induction period was not reported. This in vivo study reported that no sensitization was observed at challenge. The BIOVIA model for skin sensitisation predicted the test substance to be a non-sensitizer. The TIMES model for skin sensitisation predicted the test substance to be a non-sensitizer.

Based on a Weight of Evidence comprising an in vivo study and two QSAR predictions, TAOBN can be conservatively considered to be a non-skin sensitizer which does not meet the criteria for classification as a skin sensitizer according to CLP (EC 1272/2008 as amended).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on a Weight of Evidence approach, the substance is predicted to be a moderate eye irritant meeting the criteria for classification as an eye irritant Category 2 according to CLP (EC 1272/2008 as amended).