Styrax benzoin, ext.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 acute oral toxicity were predicted for three major constituents (cinnamic acid, p-coumaryl cinnamate and conferyl cinnamate), which corresponds to more than 90% of the composition, followed by the selection lowest value for hazard assessment.

GLP compliance:

no

Test type:

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

Test animals

Species:

rat

Results and discussion

Effect levels

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 2 499 - ca. 5 225 mg/kg bw

Based on:

other: major constituents (p-coumaryl cinnmate, cinnamic acid, confieryl cinnamate)

Remarks on result:

other: predicted acute oral LD50 values

Any other information on results incl. tables

Results

TEST - Acute oral
Name	SMILES	Consensus model LD50 (mg/kg bw)	Mean absolute error (MAE) for entire external and training datasets	Mean absolute error (MAE) for most similar chemicals with Similarity coefficient ≥ 0.5	Domain evaluation
p-Coumaryl cinnamate	Oc1ccc(C=CCOC(=O)C=Cc2ccccc2)cc1	5225	0.43 and 0.34	0.27 and 0.25	ID - external and training dataset
Cinnamic acid	C1=CC=C(C=C1)C=CC(=O)O	2499*	-	-	-
Coniferyl cinnamate	COc1cc(C=CCOC(=O)C=Cc2ccccc2)ccc1O	4216	0.43 and 0.34	0.35 and 0.25	ID - external and training dataset
As per the T.E.S.T Guide, currently no definition of model domain is available. However, confidence in predicted value is increased, if the MAE (mean absolute error) values for similar chemicals (≥0.5) is lower or equal to the MAE for the external and training dataset, which were determined to be 0.43 and 0.34, respectively.

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

Applicant's summary and conclusion

Conclusions:

Using the Consensus method of the T.E.S.T. v4.2.1 program, the acute oral rat LD50 values predictions for the major constituents ranged from 2499 to 5225 mg/kg bw, indicating low toxicity potential.

Executive summary:

The rat acute oral toxicity LD50 value for the test substance were predicted using the Consensus method of the T.E.S.T. v4.2.1 program. Since the test substance is a UVCB, the acute oral LD50 values were predicted 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 parameter. The acute oral rat LD50 values predictions for the major constituents ranged from 2499 to 5225 mg/kg bw (US EPA, 2019), indicating low acute toxicity. Applicability domain evaluation was performed by checking the descriptor and structural fragment domains of the individual QSAR methods (i.e., FDA, hierarchical 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. However, the confidence in predicted value is increased, as the MAE (mean absolute error) values for similar chemicals (≥0.5) were found to be lower than the MAE for the entire external and training datasets. Therefore, the acute oral LD50 value predictions for the two constituents based on Consensus method are considered to be reliable with restrictions.