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Description of key information

An in vivo study was published in 2001 describing a test design equivalent to OECD Guideline 406 (Guinea Pig Maximisation Test)

The results for esculin were as follows:

0% sensitisation was observed at 0.01 M,

25% sensitistation rate was observed at 0.1 M

As the sensitistion rate is below 30% no classification is required according to CLP.

In addition an OECD Guideline 442D study was conducted (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method).

In the first and second experiments, no significant luciferase induction > 1.5 was found in the tested concentration range. Therefore, no EC1.5 value could be calculated. Under the condition of this study the test item is therefore considered as non sensitiser.

A second in vitro study (OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))) shows

Co-elution of esculin with the lysine peptide peak was observed and cannot be used for evaluation. A low reactivity towards the synthetic cystein peptides at 100 mM stock solution was observed. The mean depletion of the cysteine peptide was > 13.89% (14.09%) and is therefore in the borderline range.

Based on the results of the in vivo study we conclude that no classification according to CLP is required.

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:
other: publication
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
available reference with in vivo study
Species:
guinea pig
Strain:
Hartley
Sex:
female
Route:
intradermal
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.1 M
Day(s)/duration:
6
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: ethanol
Concentration / amount:
0.1 M
Day(s)/duration:
2
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, open
Vehicle:
other: ethanol
Concentration / amount:
0.01 M
Day(s)/duration:
2
Adequacy of challenge:
not specified
No. of animals per dose:
12
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.1 M
No. with + reactions:
3
Total no. in group:
12
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.01 M
No. with + reactions:
0
Total no. in group:
12
Interpretation of results:
GHS criteria not met
Conclusions:
0% sensitisation was observed at 0.01M,
25% sensitistation rate was observed at 0.1 M
As the sensitistion rate is below 30% no classification is required according to CLP.
Endpoint:
skin sensitisation: in vitro
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Mai 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
Version / remarks:
February 04, 2015
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
activation of keratinocytes
Key result
Parameter:
other: luciferase induction
Run / experiment:
first experiment
Value:
< 1.5
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Key result
Parameter:
other: luciferase induction
Run / experiment:
second experiment
Value:
< 1.5
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Interpretation of results:
GHS criteria not met
Executive summary:

In the first and second experiments, nosignificant luciferase induction > 1.5 was found in the tested concentration range. Therefore, no EC1.5value could be calculated. Under the condition of this study the test item is therefore considered as non sensitiser.

Endpoint:
skin sensitisation: in vitro
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
GLP compliance:
yes (incl. certificate)
Type of study:
direct peptide binding assay
Specific details on test material used for the study:
Dose Groups
Solvent control
Test Item: 100 mM stock solution
Positive Control: 100 mM stock solution
Key result
Parameter:
other: Mean Cysteine Peptide Depletion
Remarks:
in %
Value:
14.09
Positive controls validity:
valid
Key result
Parameter:
other: Mean Lysine Peptide Depletion
Remarks:
in %
Value:
1.68
Positive controls validity:
valid
Conclusions:
In the present study Aesculin was dissolved in DMF. Based on a molecular weight of 367.31 g/mol a 100 mM stock solution was prepared.
For the 100 mM stock solution of the test item no turbidity or precipitation was observed when diluted with the cysteine peptide solution and lysine peptide solution.
Co-elution of the test item with the lysine peptide peak was observed. The peak area determined in the co-elution controls corresponds to 0.0185 mM of lysine peptide. Therefore, the given peak areas and corresponding lysine peptide values can only be considered as an estimation of the peptide depletion and cannot be used for evaluation.
The 100 mM stock solution of the test item showed low reactivity towards the synthetic peptides. The mean depletion of the cysteine peptide was > 13.89% (14.09%). Based on the prediction model 2 the test item can be considered as sensitiser.
The 100 mM stock solution of the positive control (cinnamic aldehyde) showed high reactivity towards the synthetic peptides. The mean depletion of both peptides was 65.32%. The controls confirmed the validity of the study for both, the cysteine and lysine run.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Justification for classification or non-classification