Potassium 2-hydroxy-5-nitrobenzoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion

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

Year:

2014

Report date:

2015

Materials and methods

Principles of method if other than guideline:

Estimated by using ACD/Percepta QSAR model and Toxtree decision rule system.

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

The prediction results of skin irritation are illustrated in the following Table .

ACD/Percepta prediction	Toxtree prediction	Consensus prediction
SKIN IRRITANT Reliable	NOT SKIN IRRITANT	SKIN IRRITANT Reliable

ACD/Percepta model for skin irritation estimates the potential of a chemical to cause skin irritation in a standard rabbit Draize test. It calculates the probability for a chemical to cause moderate or above irritation to skin of rabbit at a standard dose of 100 and 500 mg, respectively. It lists all the rules that are applicable and are used in the calculation, it highlights the structural fragments corresponding to the listed rules on the molecule of interest and it provides a list of up to five most similar structures from the training set with the experimental values of their standard Draize test result and references.

ACD/Percepta Probability to cause moderate or stronger rabbit skin irritation	ACD/Percepta prediction	Reliability assessment
0.91	SKIN IRRITANT	RELIABLE

ACD/Percepta predicted 2-hydroxy-5-nitrobenzoic acid as skin irritant, with a probability to cause skin irritation equal to 0.91, since it identified two structural alerts: 1) monocarboxyacid without basic groups; 2) a small (McGowanVolume < 1.42) compound possessing aromatic hydroxy group and no basic fragments. Compounds containing monocarboxyacids without basic groups in the molecule are highly probable irritants of the rabbit's skin and 50 such compounds out of the 65 in ACD/Percepta database (77%) exhibit moderate or stronger rabbit skin irritation. Compounds containing a small (McGowanVolume < 1.42) compound possessing aromatic hydroxy group and no basic fragments will most likely irritate rabbit's skin and 35 such compounds out of the 44 in ACD/Percepta database (80%) exhibit moderate or stronger rabbit skin irritation.

Together with the prediction, ACD/Percepta displays up to 5 most structurally similar structures from the training set along with experimental skin irritation data. The structural similarity is evaluated by a fragmental approach. The information on the structurally similar compounds in the training set is used to further assess the reliability of the prediction, since it illustrates how the test compound, i.e. 2-hydroxy-5-nitrobenzoic acid, is represented in the training set. The five mostly similar compounds from the training set, illustrated in Table, exhibit consistent experimental data, being all of them irritants. Thus, the prediction was considered reliable.

5-(2,4-Dichlorophenoxy)-2 -nitrobenzoic acid, potassium saltResult: Slightly irritatingDescription: Registry of Toxic Effects of Chemicals Substances

Acetic acid, (2,4-dichloro-6 -nitrophenyl) esterResult: Slightly irritatingDescription: Registry of Toxic Effects of Chemicals Substances

2-NitrophenolResult: Slightly irritatingDescription: European Chemicals Bureau New Chemicals Database

p-Nitrobenzoic acidResult: IrritatingDescription: European Chemicals Bureau New Chemicals Database

AcifluorfenResult: Moderately IrritatingDescription: Tomlin, C.D.S. (ed.). The Pesticide Manual – World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994

Toxtree predicts the skin irritation caused by a chemical according to the EU risk phrases (R34: Causes burns; R35: Causes severe burns; R38: Irritating to skin). Toxtree predicts the skin irritation caused by a chemical based on physicochemical property exclusion rules and structural inclusion rules. Physicochemical exclusion rules depend on: molecular weight, LogP, melting point, water solubility, lipid solubility and surface tension. Toxtree prediction for the target compound is illustrated in the Table .

Toxtree exclusion rules	Toxtree inclusion rules	Toxtree prediction
All Melting Point > 200°C	-	NOT SKIN IRRITANT

Toxtree predicted the target 2-hydroxy-5-nitrobenzoic acid as not skin irritant since it fulfils the exclusion rule related to compounds containing all type of atoms and with a melting point > 200°C (EPISuite/MPBPVP experimental 229.5°C). A detailed assessment of the reliability of the prediction is not provided.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The skin irritation potential of the target chemical was predicted employing two different in silico approaches: the QSAR statistical model as provided by ACD/Percepta 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. Since Toxtree prediction is not supported by a detailed assessment of its reliability and following a precautionary approach, based on ACD/Percepta prediction, it was concluded that the target 2-hydroxy-5-nitrobenzoic acid is SKIN IRRITANT, and the prediction is reliable.