2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion

Remarks:

other: in silico predictions

Type of information:

(Q)SAR

Adequacy of study:

key 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:

2014

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:

methyl 3-[(2-methoxy-2-oxoethyl)sulfamoyl]thiophene-2-carboxylate

EC Number:

600-780-8

Cas Number:

106820-63-7

Molecular formula:

C9H11NO6S2

IUPAC Name:

methyl 3-[(2-methoxy-2-oxoethyl)sulfamoyl]thiophene-2-carboxylate

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

other: ACD/Percepta Probability to cause moderate or stronger rabbit skin irritation

Value:

ca. 0.3

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
NOT SKIN IRRITANT Little Reliable	NOT SKIN IRRITANT	NOT SKIN IRRITANT Little Reliable

ACD/Percepta 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
0.30	NOT SKIN IRRITANT	LITTLE RELIABLE

ACD/Percepta predicted 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester as not skin irritant, with a probability to cause skin irritation equal to 0.30. In fact, no structural fragments corresponding to the listed rules that are associated to skin irritation have been identified. However, this prediction is considered of little reliability since the target compound is not represented in the model training set (no training compounds with similarity greater than 0.5 with respect to the target were found).

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
Group CNS LogKow < 0.5Group CNS Melting Point > 120°CGroup CNS Melting Point > 50°C	No	NOT SKIN IRRITANT

Toxtree predicted 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester as not skin irritant, since it fulfils three exclusion rules and does not meet any inclusion rule. In more details, three exclusion rules are fulfilled. The target belongs to the structural class made of chemicals containing Carbon (C), Hydrogen (H), Oxygen (O), Nitrogen (N) and Sulphur (S) atoms with a LogKow < 0.5, a melting point > 50°C and a melting point > 120°C. In addition, no structural inclusion rule were met. Therefore Toxtree predicted the target 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester as not skin irritant. A detailed assessment of the reliability of the prediction is not provided.

Applicant's summary and conclusion

Interpretation of results:

not 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. Despite Toxtree didn’t provide a detailed assessment of the reliability of the prediction, ACD/Percepta and Toxtree were in agreement leading to the consensus prediction that target compound, i.e. 2-Thiophenecarboxylic acid, 3-[[(2-methoxy-2-oxoethyl)amino]sulfonyl]-, methyl ester, is NOT SKIN IRRITANT. Since Toxtree does not provide a reliability assessment of its prediction, based on the little reliability of ACD/Percepta prediction, the consensus prediction is considered of little reliability.