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Description of key information

Modern in-vitro and historical human studies do not indicate any imune response or potential sensitisation

The substance is widely used is cosmetics and dermal reactions will be recorded.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Remarks:
Keratin
Type of information:
experimental study
Adequacy of study:
key study
Study period:
48 hour exposure
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Guideline study performed 2017 to GLP
Qualifier:
according to
Guideline:
OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
Version / remarks:
KeratinoSensTM cell line (test system)
GLP compliance:
yes (incl. certificate)
Type of study:
activation of keratinocytes
Justification for non-LLNA method:
In-vitro alternative
Specific details on test material used for the study:
46560D15
Details on study design:
The KeratinoSensTM cell line (test system) is an immortalized adherent cell line derived from HaCaT human keratinocytes, stably transfected with a selectable plasmid containing the luciferase gene under the transcriptional control of the Anti-oxidant Response Element (ARE) from a gene that is known to be up-regulated by contact sensitisers. The luciferase signal reflects the activation by sensitisers of endogenous Nrf2 dependent genes, and the dependence of the luciferase signal in the recombinant cell line on Nrf2 has been demonstrated. This allows quantitative measurement (by luminescence detection) of luciferase gene induction, using well established light producing luciferase substrates, as an indicator of the activity of the Nrf2 transcription factor in cells
Positive control results:
Valid results with Effect > EC1.5 limit for positive response. At the highest concentration of positive control the response was 15 fold induction
Key result
Parameter:
other: Luciferase activity
Run / experiment:
Test materials
Value:
< 1.263
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
Response in range 0.91 - 1.26, with highest response at 25mg/l of material tested (ca 10 mg/l actives)
At 50 mg/l there was significant cytotoxicty and 100% complete cytotoxicty (20 and 40mg/l actives)
Interpretation of results:
GHS criteria not met
Conclusions:
The luciferase inihibition was below the limits considered to cause a positive response for sensitisation with a score of < 1.5.
The test was run up to the limit of cytotoxicty and is considered valid
The positive control gave a high response of 15.
Executive summary:

The substance is not considered to be sensitising on the basis of this study.

Endpoint:
skin sensitisation: in chemico
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 hour exposure
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Guideline study performed to GLP in 2017. Quality criteria met.
Qualifier:
according to
Guideline:
OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
Version / remarks:
EURL ECVAM DB-ALM Protocol No. 154 (Direct Peptide Reactivity Assay for Skin Sensitisation Testing).
GLP compliance:
yes (incl. certificate)
Type of study:
other: Relative percent peptide depletion
Justification for non-LLNA method:
In-vitro to avoid use of animals
Specific details on test material used for the study:
Batch 46560D15
Light yellow liquid
Details on study design:
The DPRA covers the molecular initiating event of the skin sensitisation Adverse Outcome Pathway (AOP) by quantifying the reactivity to synthetic peptides containing either Lysine or Cysteine. Peptide depletion values are used to categorise to discriminate between skin sensitisers and non-sensitisers.
Cinnamic Aldehyde (>95% purity) used as positive control
Key result
Parameter:
other: Peptide loss
Run / experiment:
Mean of triplicate tests on both peptides
Value:
ca. 1.7
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

The test item produced 1.745% mean Cysteine and Lysine peptide depletion, therefore, using the Cysteine 1:10 / Lysine 1:50 prediction model, the test item was classified as a Non-Sensitiser with No or Minimal Reactivity.

Each test was performed in triplicate on each protein;

The test material led to a range of depletion in Cysteine of 0 - 7.4% and in Lysine, 0% depletion in all replicates.

Interpretation of results:
GHS criteria not met
Conclusions:
A neam deplation rate of 1.745% is well inside the range of 0 - 6.38% depletion used for negative response.
The positive control gave a result of 56 - 67% in the highest band for positive response.
Executive summary:

The test item produced 1.745% mean Cysteine and Lysine peptide depletion, therefore, using the Cysteine 1:10 / Lysine 1:50 prediction model, the test item was classified as a Non-Sensitiser with No or Minimal Reactivity. A single HPLC analysis for both the Cysteine and the Lysine peptide was considered sufficient for the test item as the result was unequivocal.

Each test was performed in triplicate on each protein; the test material led to a range of depletion in Cysteine of 0 - 7.4% and in Lysine, 0% depletion in all replicates.

The concentrations tested were adjusted to reflect the actives and take into account the use of a water-based commercial grade material. As this metho relies on a molar ratio with reagents, the mean molecular weight was used knowing the general proportion of components in the UVCB substance.

Justification for classification or non-classification