Styrax benzoin, ext.

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction from an well known and acknowledged tool. See below under 'Overall remarks, attachments' for applicability domain and 'attached background material section' for methodology.

Data source

Reference

Reference 1

Reference Type:

other: Guidance

Title:

Unnamed

Year:

2017

Report date:

2017

Reference 2

Reference Type:

other: User Guide

Title:

User’s guide for T.E.S.T. (version 4.2) (Toxicity Estimation Software Tool) - A program to estimate toxicity from molecular structure.

Author:

United States Environment Protection Agency (US EPA)

Year:

2016

Bibliographic source:

Toxicity Estimation Software Tool for Microsoft® Windows, v 4.2.1, United States Environmental Protection Agency, Washington, DC, USA (https://www.epa.gov/chemical-research/toxicity-estimation-software-tool-test)

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs: Chapter R.6. QSARs and grouping of chemicals

Principles of method if other than guideline:

Since the test substance is a UVCB, the mutagenicity potential was predicted for the three major constituents (cinnamic acid, p-coumaryl cinnamate and coniferyl cinnamate), which correspond to more than 90% of the composition.

GLP compliance:

no

Type of assay:

other: QSAR prediction

Test material

Test material information

Constituent 1

Reference substance name:

Styrax benzoin, ext.

EC Number:

284-557-7

EC Name:

Styrax benzoin, ext.

Cas Number:

84929-79-3

Molecular formula:

Not available as the substance is a UVCB

IUPAC Name:

Resin of Styrax benzoin, Styracaceae, extraction from gum with medium chain triglycerides and isolation with HPLC

Results and discussion

Test results

Key result

Species / strain:

other: QSAR prediction from TEST v4.2.1

Remarks:

Ames Mutagenicity Test

Metabolic activation:

not specified

Genotoxicity:

negative

Remarks:

predicted for all three major constituents

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Any other information on results incl. tables

Results

TEST - Ames Mutagenicity Test
Name	SMILES	Mutagenicity value	Mutagenicity result	Prediction statistics for similar chemicals - External and Training Dataset
				Concordance	Sensitivity	Specificity
p-Coumaryl cinnamate	Oc1ccc(C=CCOC(=O)C=Cc2ccccc2)cc1	0.11	Negative	0.90 and 0.80	0.80 and 0.50	1 and 0.88
Cinnamic acid	C1=CC=C(C=C1)C=CC(=O)O	0.00*	Negative	-	-	-
Coniferyl cinnamate	COc1cc(C=CCOC(=O)C=Cc2ccccc2)ccc1O	0.16	Negative	0.80 and 0.80	0.67 and 0.50	1 and 0.88

*Experimental result available. So no need to perfprm domain evaluation.

In general, if the concordance is greater than or equal to 0.8, the model is considered to be valid. In addition both the leave-one-out sensitivity and specificity must be at least 0.5 to avoid using models which are heavily biased to predict either active or inactive scores.

For more details on results, kindly refer the attached background material section of the IUCLID.

Applicant's summary and conclusion

Conclusions:

Based on the negative mutagenicity predictions for the major constituents using the Consensus method of the T.E.S.T. v4.2.1 program, the test substance is overall considered to be non-mutagenic.

Executive summary:

The mutagenicity potential of the test substance was predicted using the Consensus method of the T.E.S.T. v4.2.1 program. Since the test substance is a UVCB, the mutagenicity predictions were performed for the three major constituents (cinnamic acid, p-coumaryl cinnamate and coniferyl cinnamate), which correspond to more than 90% of the composition. SMILES codes were used as the input parameters. All three constituents were predicted to be negative for mutagenicity (US EPA, 2019), indicating that the test substance can be overall considered to be non-mutagenic. Applicability domain evaluation was performed by checking the descriptor and structural fragment domains of the individual QSAR methods (i.e., FDA, hierarchical clustering and nearest neighbour methods) underlying Consensus model predictions. Since an experimental value could be identified for cinnamic acid, the domain evaluation of the remaining two constituents indicated that they were within both descriptor and structural fragment domains of the FDA and hierarchical clustering methods, but not completely within domain for the structural fragments identified for the three nearest neighbours. Further, the prediction accuracy of the binary toxicity endpoints, can be evaluated in terms of the fraction of compounds that are predicted accurately and are described based on three statistical parameters: concordance, sensitivity, and specificity. In general, if the concordance is greater than or equal to 0.8, the model is considered to be valid. And both the leave-one-out sensitivity and specificity must be at least 0.5 to avoid using models which are heavily biased to predict either active or inactive scores. Based on respective scores for the three statistical parameters, which were above the required cut-offs the mutagenicity predictions for the 2 constituents can be considered to be accurate. Therefore, considering the applicability domain and prediction accuracy evaluations, the mutagenicity predictions for the two constituents based on Consensus method are overall considered to be reliable.