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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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:
The study was conducted before the requirement of LLNA method was mandated.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
Freund's complete adjuvant test
Justification for non-LLNA method:
The study was conducted before the requirement of LLNA method was mandated.
Species:
guinea pig
Sex:
male/female
Vehicle:
other: acetone
Concentration / amount:
10% w/w
Vehicle:
other: acetone
Concentration / amount:
10% w/w
No. of animals per dose:
10
Positive control substance(s):
not specified
Key result
Group:
test chemical
Dose level:
10%
Remarks on result:
positive indication of skin sensitisation
Key result
Group:
negative control
Dose level:
0%
Remarks on result:
no indication of skin sensitisation
Key result
Group:
positive control
Dose level:
10%
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
study cannot be used for classification
Conclusions:
Under the study conditions, the test substance is considered to be weak to moderate skin sensitiser in guineapigs.
Executive summary:

A study was conducted to determine the skin sensitisation potential according to the Modified Freund's Complete Adjuvant test method. The test substance was applied at 10% in acetone in both induction as well as challenge phases. Under the study conditions, the test substance is considered to be weak to moderate skin sensitiser in guineapigs (Bickers, 2005).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
Freund's complete adjuvant test
Justification for non-LLNA method:
The study was conducted before the requirement of LLNA was mandated.
Species:
guinea pig
Sex:
male/female
Vehicle:
other: acetone
Concentration / amount:
3%
Vehicle:
other: acetone
Concentration / amount:
10%
Vehicle:
other: acetone
Concentration / amount:
3%
Vehicle:
other: acetone
Concentration / amount:
10%
Positive control substance(s):
not specified
Key result
Group:
test chemical
Dose level:
3% and 10%
Remarks on result:
other: weak sensitisation effects, no further detail provided
Key result
Group:
negative control
Dose level:
0%
Remarks on result:
other: no details provided
Key result
Group:
positive control
Dose level:
No details
Remarks on result:
other: no details provided
Endpoint:
skin sensitisation, other
Remarks:
Derek Nexus v6.0.1 profiling
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:
1. SOFTWARE : Derek Nexus

2. MODEL (incl. version number): version 6.0.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Constituent 1 (p-coumaryl cinnamate): Oc1ccc(C=CCOC(=O)C=Cc2ccccc2)cc1
Constituent 2 (cinnamic acid): C1=CC=C(C=C1)C=CC(=O)O
Constituent 3 (coniferyl cinnamate): COc1cc(C=CCOC(=O)C=Cc2ccccc2)ccc1O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: skin sensitisation
The alert has demonstrated the following predictive performance:
1) Cronin and Basketter data set: 1 compound activates this alert of which 0 are reported positive (po
sitive predictivity: 0%)
2) Gerberick et al data set: 0 compounds activate this alert
3) Contact Dermatitis data set: 0 compounds activate this alert
1) A collection of guinea pig maximisation test data for 216 compounds from the following reference:
Cronin MTD and Basketter DA. Multivariate QSAR analysis of a skin sensitization database. SAR
and QSAR in Environmental Research, 1994, 2, 159-179, available at "http://dx.doi.org/10.1080/1
0629369408029901".
2) A collection of local lymph node assay data for 318 compounds derived from the following refer
ences: (i) Gerberick GF, Ryan CA, Kern PS, Schlatter H, Dearman RJ, Kimber I, Patlewicz GY and
Basketter DA. Compilation of historical local lymph node data for evaluation of skin sensitization alte
rnative methods. Dermatitis, 2005, 16, 157-202. Downloaded from "http://www.inchemicotox.org/result
s/" (3 September 2010); (ii) Kern PS, Gerberick GF, Ryan CA, Kimber I, Aptula A and Basketter DA.
Local lymph node data for the evaluation of skin sensitization alternatives: a second compilation. D
ermatitis, 2010, 21, 8-32, available at "http://dx.doi.org/10.2310/6620.2009.09038".
3) A collection of local lymph node assay data for 137 compounds published in Contact Dermatitis
which have been extracted from Vitic Nexus (13 September 2012).
In assessing predictive performance, it should be noted that:
- Mammalian skin sensitisation predictions in Derek associated with a reasoning level of equivocal or
above have been considered positive;
- Predictions do not take into account (i) the tautomeric forms of compounds or (ii) the individual
components of mixtures;
- Compounds have been considered positive for skin sensitisation if they have been classified as ex
treme, strong or moderate sensitisers;
- Compounds classified as weak sensitisers have been excluded from the analysis;
- No account has been taken of other skin sensitisation alerts which may also be present in some
compounds;
- Information from the data sets may have been used previously as supporting evidence for the
derivation of some alerts;
- Some compounds may be present in more than one of the data sets analysed.

5. APPLICABILITY DOMAIN
The test substance was found to fall in the applicability domain of this method and results are
adequate for the purpose of classification and labeling and/or risk assessment.
Qualifier:
according to guideline
Guideline:
other: ECHA REACH Guidance on QSARs and grouping of chemicals (R.6)
GLP compliance:
no
Key result
Run / experiment:
other: Constituent 1 (p-coumaryl cinnamate)
Parameter:
other: skin sensitisation in mammal
Remarks on result:
other: alerts identified (439 substituted phenol and 481 alpha beta unsaturated ester), moderate sensitiser
Key result
Run / experiment:
other: Constituent 2 (cinnamic acid)
Parameter:
other: Skin sensitisation in mammal
Remarks on result:
other: non-sensitiser (misclassified or unclassified features)
Key result
Run / experiment:
other: Constituent 3 (cinnamyl cinnamate)
Parameter:
other: skin sensitisation in mammal
Remarks on result:
other: alerts identified (481 alpha beta unsaturated ester and 845 1,2-dihydroxybenzene derivative), moderate sensitiser
Interpretation of results:
study cannot be used for classification
Conclusions:
DEREK NEXUS tool v6.0.1 prediction for the major constituents of the test substance was performed in order to identify structural alerts related to skin sensitisation. The profiling indicated equivocal results.
Executive summary:

DEREK NEXUS tool v6.0.1 prediction for the three major constituents of the test substance was performed in order to identify structural alerts related to skin sensitisation. The profiling indicated two constituents to be moderate sensitiser and one constituent to be non-sensitiser (Lhasa Ltd., 2019).

Endpoint:
skin sensitisation, other
Remarks:
Skin Sensitization model (CAESAR) 2.1.6 profiling
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:
1. SOFTWARE : Skin Sensitization model CAESAR

2. MODEL (incl. version number): version 2.1.6

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:

Constituent 1 (p-coumaryl cinnamate): Oc1ccc(C=CCOC(=O)C=Cc2ccccc2)cc1
Constituent 2 (cinnamic acid): C1=CC=C(C=C1)C=CC(=O)O
Constituent 3 (coniferyl cinnamate): COc1cc(C=CCOC(=O)C=Cc2ccccc2)ccc1O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: skin sensitisation
Accuracy: accuracy of prediction for similar molecules found in the training set is good.
Concordance for similar molecules: similar molecules found in the training set have experimental values that agree with the predicted
value.
Model descriptor's range check: descriptors for this compound have values inside the descriptor range of the compounds of the
training set.
Atom centered fragments similarity check: all atom centered fragment of the compound have been found in the compounds of the training
set.

5. APPLICABILITY DOMAIN
The test substance was found to fall in the applicability domain of this method and results are
adequate for the purpose of classification and labeling and/or risk assessment.
Qualifier:
according to guideline
Guideline:
other: ECHA REACH Guidance on QSARs and grouping of chemicals (R.6)
GLP compliance:
no
Key result
Run / experiment:
other: Constituent 1 (p-coumaryl cinnamate)
Parameter:
other: skin sensitisation
Remarks on result:
other: sensitiser
Key result
Run / experiment:
other: Constituent 2 (cinnamic acid)
Parameter:
other: skin sensitisation
Remarks on result:
other: sensitiser
Key result
Run / experiment:
other: Constituent 3 (coniferyl cinnamate)
Parameter:
other: skin sensitisation
Remarks on result:
other: sensitiser
Interpretation of results:
study cannot be used for classification
Conclusions:
The profiling indicated all three constituents to be sensitisers
Executive summary:

VEGA CAESAR tool v2.1.6 prediction for the three major constituents of the test substance was performed in order to identify structural alerts related to skin sensitisation. The profiling indicated all three constituents to be sensitisers (VEGA-QSAR, 2019).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Skin sensitisation:

Experimental data

Consitituent 2 (cinnamic acid):

A study was conducted to determine the skin sensitisation potential according to the Modified Freund's Complete Adjuvant test method. The test substance was applied at 10% in acetone in both induction as well as challenge phases. Under the study conditions, the test substance is considered to be weak to moderate skin sensitiser in guineapigs (Bickers, 2005).

Constituent 4 (cinnamyl cinnamate):

A study was conducted to determine the skin sensitisation potential according to the Modified Freund's Complete Adjuvant test method. The test substance was applied at 3 or 10% in acetone in both induction as well as challenge phases. Under the study conditions, the test substance is considered to be weak skin sensitiser in guineapigs (Bickers, 2005).

QSAR data

DEREK NEXUS prediction for three major constituents (p-coumaryl cinnamate, cinnamic acid and coniferyl cinnamate):

DEREK NEXUS tool v6.0.1 prediction for the three major constituents of the test substance was performed in order to identify structural alerts related to skin sensitisation. The profiling indicated two constituents to be moderate sensitiser and one constituent to be non-sensitiser (Lhasa Ltd., 2019).

VEGA CAESAR tool v2.1.6 prediction for the three major constituents of the test substance was performed in order to identify structural alerts related to skin sensitisation. The profiling indicated all three constituents to be sensitisers (VEGA-QSAR, 2019).

Overall, based on the available evidence from in silico (prediction from DEREK NEXUS v6.0.1 and VEGA-CAESAR 2.1.6) together with in vivo studies on four major constituents (which constitutes more than 96% of the composition), the test substance was overall concluded to be moderately sensitising to skin.

Justification for classification or non-classification

Therefore, based on the available weight of evidence from in silico and in vivo studies with the four major constituents of the substance (which constitutes more than 96% of the composition), the test substance warrants Skin sens. 1B classification for skin sensitisation according to EU CLP (Regulation 1272/2008/EC) criteria.