(2Z)-7-chloro-2-({[(1S)-2,2-dimethylcyclopropyl]carbonyl}amino)hept-2-enoic acid

Skin sensitisation

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

Test material information

Constituent 1

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.