12-aminododecanoic acid

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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

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

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.

The substance was predicted to be a non-sensitiser.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In the key study, the test material was predicted to be a non-sensitiser (ss = 0.0) according to a five scale classification: (non-sensitisers, weak sensitisers, moderate sensitisers, strong sensitisers, very-strong sensitisers).

Migrated from Short description of key information:
The test material was found to be a non-sensitiser.

Justification for selection of skin sensitisation endpoint:
The key study is a QSAR, conducted in accordance with REACH guidance on QSARs R.6, May/July 2008; it uses the validated "Nonlinear ANN QSAR Model for Skin Sensitisation (GMPT)", Model Version 10.10.2010
In accordance with the criteria of Klimisch (1997) it may be awarded a reliability score of 2 and is considered to be an accurate reflection of the test material.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin sensitisation

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for skin sensitisation.