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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation, other
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 and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:

1. SOFTWARE:

- Vega
- Toxtree
- Derek Nexus


2. MODEL (incl. version number)

- Vega = Virtual models for evaluating the properties of chemicals within a global architecture - Ver 1.1.3
- Toxtree = Ideaconsult, version 2.6.13
- Derek Nexus Lhasa Limited

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:

O=C(N\C(=C/CCCCCl)C(=O)O)[C@H]1CC1(C)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL

These above mentioned tools were selected according to the OECD Guidance Documents on the Validation of (Q)SAR models:

- Document on the validation of (Quantitative) Structure Activity Relationship models. OECD Series on testing and Assessment N° 69. ENV/JM/MONO(2007)2.
- EnochSJ, Madden JC, Cronin MT (2008) Identification of mechanism of toxic action for skin sensitisation using a SMARTS pattern based approach, SAR QSAR Environ Res. 19(5-6):555-78

5. APPLICABILITY DOMAIN

- Vega: Applicability Domain Index (ADI) from 0 (not reliable) to 1( fully reliable)
- Toxtree: Based on Structural alerts (SA).
- Derek Nexus: The prediction is generated by applying expert knowledge rules in toxicology.

6. ADEQUACY OF THE RESULT

- Vega: Sensitizer with prediction: Low reliable.
- Toxtree: Identifies two alerts.
- Derek Nexus: Skin sensitisation is Plausible.


From the evaluation of the results of each software, the target compound was predicted to be a SENSITIZER for the skin and the final prediction was assessed as Moderate Reliable.




Data source

Reference
Reference Type:
other: In silico prediction
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD Series on Testing and Assessment No 69
Version / remarks:
ENV/JM/MONO(2007)2
Deviations:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
(2Z)-7-chloro-2-({[(1S)-2,2-dimethylcyclopropyl]carbonyl}amino)hept-2-enoic acid
EC Number:
618-065-4
Cas Number:
877674-77-6
Molecular formula:
C13H20ClNO3
IUPAC Name:
(2Z)-7-chloro-2-({[(1S)-2,2-dimethylcyclopropyl]carbonyl}amino)hept-2-enoic acid

Results and discussion

In vitro / in chemico

Results
Parameter:
other: QSAR prediction
Remarks:
It's not a In vitro/In chemico study
Remarks on result:
other: QSAR prediction
Remarks:
Skin Sensitiser

In vivo (non-LLNA)

Results
Reading:
other: QSAR prediction-It's not an In vivo(non-LLNA) study
Remarks on result:
other: QSAR Prediction
Remarks:
Skin Sensitiser

In vivo (LLNA)

Results
Parameter:
other: QSAR prediction
Remarks:
It's not an In Vivo (LLNA)study
Remarks on result:
other: QSAR prediction
Remarks:
Skin Sensitiser

Any other information on results incl. tables

This study was designated to generate estimated "in silico" (non - testing) data to be used for the hazard assessment of the substance.

The table below shows the result obtained.

 Endpoint:  Prediction call  Reliability Assessment
  SKIN SENSITISATION, LLNA Skin Sensitizer    Moderate Reliable

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
SKIN SENSITISATION,LLNA:

-Prediction Call : Skin sensitizer;
-reliability Assessment: Moderate Reliable
Executive summary:

The skin sensitization of the target compound was predicted employing two different in silico approaches:

the QSAR statistical model as provided by Vega and the decision rule system provided by Toxtree and Derek

Nexus. The three predictors were employed in order to apply a weight of evidence (WoE) approach to enhance the reliability of the prediction. In the weight of evidence assessment only reliable predictions are to

be taken into account. In the case of the target (2Z)-7-chloro-2-({[(1S)-2,2-

dimethylcyclopropyl]carbonyl}amino)hept-2-enoic acid, Vega predicted the target compound as sensitizer

but the prediction was assessed as low reliable, Toxtree identified two alerts and Derek Nexus predicted the

skin sensitisation as PLAUSIBLE. Thus the target compound (2Z)-7-chloro-2-({[(1S)-2,2-

dimethylcyclopropyl]carbonyl}amino)hept-2-enoic acid was predicted as sensitizer for the skin and the

prediction was assessed as moderate reliable.