Registration Dossier

Diss Factsheets

Administrative data

Description of key information

According to the prediction model of the KeratinoSens™ assay, the test substance is rated as non-sensitizer.

 

FOLROSIA was non-reactive and classified into the MINIMAL reactivity class according to the prediction model. It is therefore considered a non-sensitizer according to the prediction model of the DPRA.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
December 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
Deviations:
no
GLP compliance:
no
Type of study:
direct peptide reactivity assay (DPRA)
Justification for non-LLNA method:
In vitro testing sufficient to conclude on the sensitization potential of Folrosia.
Details on the study design:
Skin sensitizing chemicals have the ability to covalently modify skin proteins or to be biotically or abiotically activated to become protein-reactive. Chemical-modified proteins are recognized by the immune system as foreign and trigger a specific T-cell mediated immune response.
A key step in the skin sensitization process is therefore the formation of a covalent adduct between the skin sensitizer and endogenous proteins and/or peptides in the skin. Based on this well established toxicity mechanism, the most straightforward approach to predict skin sensitization
involves the measurement of the reactivity of a test compound towards peptides and proteins (reviewed in [8]). Gerberick et al. [2, 6] therefore developed a peptide depletion assay using different heptapeptides (later coined the DPRA or ‘direct peptide reactivity assay’) to assess a chemicals
ability to react with and deplete a test peptide. Depletion is measured as the loss of the peptide signal as determined by HPLC-UV.
Parameter:
other: Average depletion Cys-and Lys-peptide
Value:
2.6
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Interpretation of results:
GHS criteria not met
Executive summary:

FOLROSIA was non-reactive and classified into the MINIMAL reactivity class according to the prediction model. It is therefore considered a non-sensitizer according to the prediction model of the DPRA.

Endpoint:
skin sensitisation: in vitro
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
December 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: OECD TG 442d
Deviations:
no
Principles of method if other than guideline:
The KeratinoSensTM assay is a cell-based assay with a reporter cell line to detect potential skin sensitizers by their ability to induce the Nrf2-response [2].
This assay has been validated for a broad range of low-molecular weight chemicals [2-8] and it was found to respond to skin sensitizers from a broad range of so called applicability domains, i.e. chemicals reacting with proteins by different mechanisms.
GLP compliance:
no
Type of study:
other: KeratinoSens assay
Justification for non-LLNA method:
In vitro method sufficient to conclude on the sensitization potential
Details on the study design:
Cells are grown for 24 h in 96-well plates. The medium is then replaced with medium containing a final level of 1% of the solvent DMSO containing the test substance. Each compound is tested at 12 concentrations in the range from 0.98 to 2000 μM. Each test plate contains six wells with the solvent control, 1 well with no cells for background value and 5 wells with a dose response of the positive control cinnamic aldehyde. In each repetition, three parallel replicate plates are run with this same set-up, and a forth parallel plate is prepared for cytotoxicity determination.
Key result
Remarks on result:
no indication of skin sensitisation
Remarks:
NEGATIVE
Interpretation of results:
GHS criteria not met
Executive summary:

No induction of the luciferase above the threshold of 1.5 was noted in all three repetitions. According to the prediction model of the KeratinoSens™ assay, the test substance is rated as non-sensitizer.

This is also clearly supported by the analysis of the dose-response curve in Figure 4 with overall no induction of the luciferase reporter gene to be observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Justification for classification or non-classification