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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation, other
Remarks:
other: In Vitro KeratinoSens
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study done to guideline and following the principles of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD TG 442d
Deviations:
no
GLP compliance:
no
Remarks:
Study following the principles of GLP.
Type of study:
other: KeratinoSens

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
impurity
Type:
impurity
Type:
impurity
Test material form:
liquid

In vitro test system

Details on study design:
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. This assay has been validated for a broad range of low-molecular weight chemicals 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. It was validated by ECVAM and proposed to be used as part of an integrated approach for testing and assessment (IATA).
The test substance JASMONYL was dissolved in DMSO and tested according to the standard operating procedure of the KeratinoSensTM assay at 12 concentrations in three repetitions, each time in three replicates. After 48 h incubation time, luciferase induction and cellular viability at each
of the concentrations were determined.

In vivo test system

Test animals

Species:
other: in vitro
Strain:
other: human keratinocyte culture HaCaT.
Sex:
not specified
Details on test animals and environmental conditions:
In vitro test

Study design: in vivo (non-LLNA)

Induction
Route:
other: In vitro test
Challenge
Route:
other: In vitro test
No. of animals per dose:
IN vitro test.
Positive control substance(s):
yes
Remarks:
Cinnamic aldehyde

Results and discussion

Positive control results:
Cinnamic aldehyde was run in all three repetitions. Here the detailed results for this positive control are reported in Table 8 and Figure 5. Cinnamic aldehyde needs to be positive for a run to be accepted (i.e. induction > 1.5 fold). This was the case in all three repetitions. The induction at 64 μM
and the EC 1.5 for cinnamic aldehyde were also calculated. The targets are: (i) Average induction in the three replicates for cinnamic aldehyde at 64 μM should be between 2 and 8, and (ii) the EC 1.5 value should be between 7 μM and 30 μM. At least one of these two numerical criteria must be met in order to accept a repetition. In the experiments performed here both criteria were fulfilled in all three repetitions. Thus all three repetitions were valid for the positive control.

In vitro / in chemico

Results
Key result
Remarks on result:
no indication of skin sensitisation
Other effects / acceptance of results:
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.

Any other information on results incl. tables

The result of the KeratinoSens™ assay should be used as part of an integrated approach for testing and assessment (IATA)[9]. A parallel test in the DPRA may indicate whether congruent results are obtained by both test methods. According to a detailed analysis on large set of substances, two congruent results in these two tests give a good prediction of the sensitizer hazard [5, 7, 18], in particular when comparing against human data, while an additional test in a dendritic cell line assessing expression of surface markers may be needed in case of discordant results. 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.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
JASMONYL is considered a non-sensitizer according to the prediction model of the KeratinoSens™ assay.