Potassium 2-hydroxy-5-nitrobenzoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

other: in silico predictions

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2015

Materials and methods

Principles of method if other than guideline:

Estimated by employing Toxtree decision rule system and Vega QSAR.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium 2-hydroxy-5-nitrobenzoate

EC Number:

807-692-0

Cas Number:

54234-73-0

Molecular formula:

C7 H4 O5 N K

IUPAC Name:

Potassium 2-hydroxy-5-nitrobenzoate

Details on test material:

In silico predictions for salt substances, require the removal of the counter ion and the subsequent neutralization. This procedure is needed to calculate the descriptors used to make the predictions. The procedure of removing the counter ion and subsequent neutralization was discussed and confirmed by several experts, both academic and regulators (European Agency for chemicals, ECHA) and is therefore the procedure commonly used for the in silico predictions of salt substances. Thus, for modelling purposes, the chemical structures of benzoic acid, 2-hydroxy-5-nitro-,potassium salt (1:1) has been processed by removal of the counter ion and subsequent neutralization.

Results and discussion

Any other information on results incl. tables

Toxtree predicts the skin sensitization according to decision rules based on the identification of Structural Alerts (SA) for skin sensitization as defined by Enoch SJ et al. (Enoch SJ, Madden JC, Cronin MT, Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach, SAR QSAR Environ Res. 2008; 19(5-6):555-78). As one or more SAs embedded in a molecular structure are recognised, the system flags the potential skin sensitization activity of the chemical. The methodology used to capture this information is based on series of SMARTS (Smiles ARbitary Target Specification) patterns (www.daylight.com) defining the rules. Thus, chemicals which contain a given reactive fragment are then assigned to the reactivity domain that the fragment belongs to. It is important to realize that a chemical may be assigned to one of the electrophilic reactivity domains even if it is a non-sensitizer. The SMARTS rules aim to identify potential electrophilic fragments and therefore identify a potential hazard associated with a compound. However, the best approach is to firstly classify the chemicals into potential reactivity domains and then perform further analysis within the domains in order to be able to predict skin sensitization. Toxtree predicted the target 2-hydroxy-5-nitrobenzoic acid as not skin sensitizers, since it did not identify any skin sensitization reactivity domain alert. A detailed assessment of the reliability of the prediction is not provided.

Vega model predicts skin sensitization by an Adaptive Fuzzy Partition (AFP) model, which produces as output two values 1 (positive) and O (negative) that represent the belonging degree respectively to the sensitizer and non-sensitizer classes. The compound is assigned to the class having this degree value higher than 0.5. The applicability domain of the predictions is assessed using an Applicability Domain Index (ADI) that has values from 0 (worst case) to 1 (best case). An ADI value greater than 0.9 means that the predicted substance is into the applicability domain of the model; ADI value lower than 0.7 means that the predicted substance is out of the applicability domain of the model, while an ADI value between 0.7 and 0.9, means that the predicted substance could be out of the Applicability Domain of the model. Vega predicted the target 2-hydroxy-5-nitrobenzoic acid as not skin sensitizers, and the prediction is reliable (ADI = 0.91).

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The skin sensitization of the target 2-hydroxy-5-nitrobenzoic acid was predicted employing two different in silico approaches: the QSAR statistical model as provided by Vega and the decision rule system provided by Toxtree. The two predictors were employed in order to apply a consensus approach to enhance the reliability of the prediction. In the consensus assessment only reliable predictions are to be taken into account. In the case of the target 2-hydroxy-5-nitrobenzoic acid, the two predictors were in agreement leading to the conclusion that the target 2-hydroxy-5-nitrobenzoic acid is NOT SKIN SENSITIZER, and the prediction is reliable.