Styrax benzoin, ext.

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

no guideline followed

Principles of method if other than guideline:

An acute oral toxicity study was conducted with the constituent in rats. The consitutent was orally administered to 10 animals per dose and observed for mortality.

GLP compliance:

not specified

Test type:

other: no information

Species:

rat

Route of administration:

oral: unspecified

No. of animals per sex per dose:

10 animals per dose

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 200 mg/kg bw

Based on:

test mat.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral LD50 of the constituent in rats was 4200 mg/kg bw.

Executive summary:

An acute oral toxicity study was conducted with the constituent in rats. The consitutent was orally administered to 10 animals per dose. Based on the results of th study, the acute oral LD50 of the constituent in rats was determined to be 4200 mg/kg bw (Belsito, 2007).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

no guideline followed

Principles of method if other than guideline:

An acute oral toxicity study was conducted with the constituent in rats. The consitutent was orally administered to 10 animals per dose and observed for mortality.

GLP compliance:

not specified

Species:

rat

Sex:

male/female

Route of administration:

oral: unspecified

No. of animals per sex per dose:

10 animals per dose

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 570 mg/kg bw

Based on:

test mat.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Based on the results of th study, the acute oral LD50 of the constituent in rats was determined to be 3570 mg/kg bw (Bickers, 2005).

Executive summary:

An acute oral toxicity study was conducted with the constituent in rats. The consitutent was orally administered to 10 animals per dose. Based on the results of th study, the acute oral LD50 of the constituent in rats was determined to be 3570 mg/kg bw (Bickers, 2005).

Reference 3

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.

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

Species:

rat

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 499 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

QSAR from three major constituents (p-Coumaryl cinnamate, cinnamic acid and coniferyl cinnamate):

The acute oral toxicity LD50 values for the test substance in rats 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 parameters. The acute oral 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.

Constituent 2 (Cinnamic acid):

An acute oral toxicity study was conducted with the constituent in rats. The consitutent was orally administered to 10 animals per dose. Based on the results of th study, the acute oral LD50 of the constituent in rats was determined to be 3570 mg/kg bw (Bickers, 2005).

Constituent 4 (Cinnamyl cinnamate):

An acute oral toxicity study was conducted with the constituent in rats. The consitutent was orally administered to 10 animals per dose. Based on the results of the study, the acute oral LD50 of the constituent in rats was determined to be 4200 mg/kg bw (Belsito, 2007).

Justification for classification or non-classification

Therefore, considering the available weight of evidences from the four major constituents of the substance (which constitutes approximately 96% w/w of the substance) and giving preference to experimental value over the predicted LD50 value (in case of cinnamic acid), the acute oral LD50 estimate would be greater than 2000 mg/kg bw. Therefore, no classification is warranted for acute toxicity according to EU CLP (1272/2008/EC) criteria.