12-aminododecanoic acid

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion

Remarks:

other: QSAR

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

30 June 2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Calculation done according to a scientifically valid (Q)SAR 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

Deviations:

no

Principles of method if other than guideline:

"Nonlinear ANN QSAR Model for Dermal Irritation", Model Version 10.10.2010

GLP compliance:

no

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

Test system

Details on study design:

The 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
-undec-10-enoic acid
-11-aminoundecanoic acid

Considerations on structural analogues:
The structural analogues are rather similar to the studied compound. The key features in the structure for the studied compound are the two polar functional groups at either end of the aliphatic chain, resulting in a relatively low logP and high water solubility values. Similar compounds with just one polar group at the end of a long chain appear as stronger irritants. 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 irritation is a difficult endpoint due to the multitude of possible chemical mechanisms in addition to the variations of permeability, the individual response of test animals may reduce accuracy as well. 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 85 %

The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5):
Skin corrosion/irritation is believed to be underpinned by two aspects – reactivity and permeability. Different mechanisms based on chemical reactivity (depending on the chemical’s tendency to behave as an electron donor or acceptor) have been proposed/described. While some models have been designed that rely on the frontier orbital energies, logP, pKa and softness-hardness descriptors, the present model contains a variety of hydrogen bonding and charged surface area (describing the active sites of the molecule) descriptors to characterize the reactivity of the compounds with the epidermis. The complex nature of the ANN model does not allow direct interpretation of the descriptors addressed to the property. However, investigation of the trends in descriptor and endpoint values allows the finding of some trends. It can be roughly estimated that with the increase (slight negative correlation between the descriptors) of count of H-acceptor sites (AM1), HBCA H-bonding charged surface area (AM1), FHACA Fractional HACA (HACA/TMSA) (AM1) the property the PII values increase.

Results and discussion

Any other information on results incl. tables

The substance was predicted to have no skin irritation effects.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The model predicts that the test material will not cause significant erythema/eschar or oedema, and also that no inflammation will persist to the end of the observation period. The test material can therefore be considered 'not irritating'.

Executive summary:

The model predicts that the test material will not cause significant erythema/eschar or oedema, and also that no inflammation will persist to the end of the observation period. The test material can therefore be considered 'not irritating'.

The predicted value corresponds to "no category" classification as defined in Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP Regulation).