12-aminododecanoic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

other: QSAR

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

21 June 2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Calculation done according to a scientifically valid QSAR model.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2010

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

"Nonlinear ANN QSAR Model for Skin Sensitisation (GMPT)", Model Version 10.10.2010

GLP compliance:

not specified

Remarks:

(not reported)

Type of study:

other: QSAR calculation

Test material

Test material information

Constituent 1

Reference substance name:

12-aminododecanoic acid

EC Number:

211-754-7

EC Name:

12-aminododecanoic acid

Cas Number:

693-57-2

Molecular formula:

C12H25NO2

IUPAC Name:

12-aminododecanoic acid

Details on test material:

SMILES: O=C(O)CCCCCCCCCCCN (not used for prediction)
InChI: 1 S/C12H25NO2/c13-11-9-7-5-3-1-2-4-6-8-10-21(14)15/h1-11, 13H2,(H, 14, 15) (not used for prediction)

3D Mol file used for prediction

In vivo test system

Study design: in vivo (non-LLNA)

Details on study design:

Applicability domain (OECD principle 3)
Domains:
- descriptor domain
All descriptor values for 12-aminododecanoic acid fall in the applicability domain (training set value ± 30%).
-structural fragment domain
12-aminododecanoic acid is structurally rather similar to the training set compounds; the training set contains long aliphatic chains, carboxylic acid and amine functionalities. The training set contains compounds of similar size to the studied compound.
-mechanism domain
12-aminododecanoic acid is considered to be in the same mechanistic domain(s) as the molecules in the training set.
 
Structural Analogues
- 4-aminobenzoic acid
-dodecanedioic acid
-11-aminoundecanoic acid

Considerations on structural analogues:
The structural analogues are rather similar to the studied compound. None of them has strong electrophilic groups/centres present in their structure that would indicate skin sensitizing capability which is in accordance with the generally accepted mechanistic interpretation. The analogues are considered to be within the same mechanistic domain as the studied molecule.

The uncertainty of the prediction (OECD principle 4)
The training set is not from one lab but a collection from several. However, previous and present successful modelling supports its consistency. The statistical quality of the model supports reliable predictions. Skin sensitization is a difficult endpoint due to the multitude of possible mechanisms and the individual response of test animals. The studied compound is similar to the training set compounds, adding to prediction reliability. All structural analogues were evaluated correctly within the present model.

The prediction reliability is estimated as 82 %

The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5):
Skin sensitization is believed to be underpinned by mechanisms based on chemical reactivity (with the chemical behaving as an electrophile), in most cases binding covalently to a skin protein leading it to becoming antigenic. It has been agreed that the key to predicting likely sensitization potential is being able to predict electrophilic reactivity and proelectrophilicity. The present model includes a number of chemical reactivity descriptors accounting for these effects. One of the most important descriptors is the HOMO–LUMO energy gap which accounts for the stability and reactivity of the molecule. The importance of this molecular feature was confirmed also by other authors (related to the mechanism of action). Other carbon, oxygen and hydrogen reactivity descriptors contribute to the frontier orbital energy gap descriptor.

Results and discussion

Any other information on results incl. tables

The substance was predicted to be a non-sensitiser.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information ss = 0.0 Criteria used for interpretation of results: EU

Conclusions:

The test material was predicted to be a non-sensitiser.

Executive summary:

The test material was predicted to be a non-sensitiser according to five scale classification: (non-sensitisers, weak sensitisers, moderate sensitisers, strong sensitisers, very-strong sensitisers). Following EU CLP criteria (Xi R43), if measured experimentally, the predicted value would correspond to “no category” in the CLP classification system.