Styrax benzoin, ext.

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Result published in peer-reviewed journal, only results available with no method, guideline etc.

Qualifier:

no guideline available

Principles of method if other than guideline:

A maximisation pre-test was performed in human volunteers under 48 h closed patch.

GLP compliance:

not specified

Species:

other: human volunteer

Type of coverage:

occlusive

Vehicle:

other: petrolatum

Amount / concentration applied:

4% w/w

Duration of treatment / exposure:

48 h

Number of animals:

5 male and 5 female volunteers

Details on study design:

Human maximisation pre-test

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: individual scores not mentioned

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: individual scores not mentioned

Interpretation of results:

study cannot be used for classification

Conclusions:

The constituent was not irritating to human skin (Belsito, 2007).

Executive summary:

A maximisation pre-test was conducted in human volunteers to determine the skin irritation potential of the constituent. Based on the limited results published, the constituent was not irritating to human skin (Belsito, 2007).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Only results available with no method, guideline etc.

Qualifier:

no guideline available

Principles of method if other than guideline:

A skin irritation study was conducted with undiluted test substance at intact or abraded rabbit skin under occlusion and observed for 24 h.

GLP compliance:

not specified

Species:

rabbit

Type of coverage:

occlusive

Preparation of test site:

abraded

Remarks:

as well as intact skin

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

24 h

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: individual scores not available

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: individual scores not available

Conclusions:

Based on study conditions, the constituent was irritant to rabbit skin.

Executive summary:

A skin irritation study was conducted with undiluted test substance at intact or abraded rabbit skin under occlusion and observed for 24 h. Based on study conditions, the constituent was irritating to rabbit skin (Opdyke, 1979).

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Result published in peer-reviewed journal, only results available with no method, guideline etc.

Qualifier:

no guideline available

Principles of method if other than guideline:

Irritation evaluated during an associated LD50 study.

GLP compliance:

not specified

Species:

rabbit

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Number of animals:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: individual scores not available

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: individual scores not available

Conclusions:

Based on study conditions, the constituent was irritant to rabbit skin.

Executive summary:

A skin irritation study was performed as part of an acute toxicity study in rabbits. Based on study conditions, the constituent was irritating to rabbit skin (Bickers, 2005).

Reference 4

Endpoint:

skin irritation / corrosion, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and 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 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 skin irritation was 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 of most conservative estimate for hazard assessment.

GLP compliance:

no

Species:

rabbit

Irritation / corrosion parameter:

other: QSAR prediction

Run / experiment:

Cinnamic acid

Remarks on result:

positive indication of irritation

Irritation / corrosion parameter:

other: QSAR prediction

Run / experiment:

Coniferyl cinnamate

Remarks on result:

no indication of irritation

Irritation / corrosion parameter:

other: QSAR prediction

Run / experiment:

p-coumaryl cinnamate

Remarks on result:

no indication of irritation

Interpretation of results:

study cannot be used for classification

Conclusions:

Based on the QSAR prediction from Toxtree v3.1, the skin irritation potential predictions for the major constituents ranged from corrosive to skin to not irritating to skin.

Executive summary:

The skin irritation potential for the test substance were predicted using the expert rule-based decision tree of the Toxtree v3.1 program. Since the test substance is a UVCB, the skin irritation 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. SMILES codes were used as the input parameter. The skin irritation potential predictions for the major constituents ranged from corrosive to skin to not irritating to skin (Ideaconsult Ltd., 2019).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Result published in peer-reviewed journal, only results available with limited details on method and no guideline details.

Qualifier:

no guideline available

Principles of method if other than guideline:

In an eye irritation study, the test substance was instilled at 0.1–1% in distilled water into one eye of rabbits and observations were made for up to 24 h.

GLP compliance:

not specified

Species:

rabbit

Vehicle:

water

Amount / concentration applied:

0.1-1%

Observation period (in vivo):

24 h

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: eye irritation observed up to 24 h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: eye irritation observed up to 24 h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: eye irritation observed up to 24 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: eye irritation observed up to 24 h

Conclusions:

Based on study conditions, the test substance was not irritating to rabbit eye.

Executive summary:

An eye irritation study was performed in rabbits. The test substance was instilled at 0.1–1 % in distilled water into one eye of rabbits and the observations were made up to 24 h. Based on study conditions, the test substance was not irritating to rabbit eye (Bickers, 2005).

Reference 2

Endpoint:

eye irritation, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and 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 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 eye irritation potential was 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 of the most conservative estimate for hazard assessment.

GLP compliance:

no

Species:

rabbit

Irritation parameter:

other: QSAR prediction

Run / experiment:

Cinnamic acid

Remarks on result:

other: unknown prediction

Irritation parameter:

other: QSAR prediction

Run / experiment:

Coniferyl cinnamate

Remarks on result:

other: unknown prediction

Irritation parameter:

other: QSAR prediction

Run / experiment:

p-coumaryl cinnamate

Remarks on result:

other: unknown prediction

Interpretation of results:

study cannot be used for classification

Conclusions:

The eye irritation potential predictions for the major constituents are unknown or cannot be predicted

Executive summary:

The eye irritation potential for the test substance were predicted using the expert rule-based decision tree of the Toxtree v3.1 program. Since the test substance is a UVCB, the eye irritation 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. SMILES codes were used as the input parameter. The eye irritation potential predictions for the major constituents are unknown or cannot be predicted (Ideaconsult Ltd., 2019).

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Experimental

Constituent 2 (Cinnamic acid)

A skin irritation study was conducted with undiluted test substance at intact or abraded rabbit skin under occlusion and observed for 24 h. Based on study conditions, the constituent was irritating to rabbit skin (Opdyke, 1979).

A skin irritation study was performed as part of an acute toxicity study in rabbits. Based on study conditions, the constituent was irritating to rabbit skin (Bickers, 2005).

Constituent 4 (Cinnamyl cinnamate):

A maximisation pre-test was conducted in human volunteers to determine the skin irritation potential of the constituent. Based on the limited results published, the constituent was not irritating to human skin (Belsito, 2007).

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

The skin irritation potential for the test substance were predicted using the expert rule-based decision tree of the Toxtree v3.1 program. Since the test substance is a UVCB, the skin irritation 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. SMILES codes were used as the input parameter. The skin irritation potential predictions for the major constituents ranged from corrosive to skin to not irritating to skin (Ideaconsult Ltd., 2019).

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 skin irritation result (in case of cinnamic acid), the substance is considered to be irritating to skin.

Eye irritation

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

The eye irritation potential for the test substance were predicted using the expert rule-based decision tree of the Toxtree v3.1 program. Since the test substance is a UVCB, the eye irritation 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. SMILES codes were used as the input parameter. The eye irritation potential predictions for the major constituents are unknown or cannot be predicted (Ideaconsult Ltd., 2019).

Experimental

Constituent 4 (Cinnamayl cinnamate):

An eye irritation study was performed in rabbits. The test substance was instilled at 0.1–1 % in distilled water into one eye of rabbits and the observations were made up to 24 h. Based on study conditions, the test substance was not irritating to rabbit eye (Bickers, 2005).

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 considering the limitation of the experimental value (only tested upto 1%) (in case of cinnamyl cinnamate), the eye irritation potential of the substance cannot be predicted/determined at the moment.

Justification for classification or non-classification

Based on the experimental data and QSAR predictions for skin irritation for the four major constituents of the substance, the substance is considered to be irritating to skin and therefore, warrants classification as Skin irrit 2 (H315: ) according to EU CLP (1272/2008) criteria.

Based on the experimental data and QSAR predictions for eye irritation for the four major constituents of the substance, no classification could be assigned according to EU CLP (1272/2008) criteria.