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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vitro
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
GLP compliance:
yes (incl. certificate)
Type of study:
other: LuSens Assay

Test material

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

Results and discussion

Positive control results:
EGDMA (120 µM) was used as positive control. The viability was above 70 % and a dis-tinct increase in luciferase induction above 2.5 fold in comparison to the solvent control was detected. This luciferase induction is well within the historical data range of the posi-tive control.

In vitro / in chemico

Resultsopen allclose all
Key result
Parameter:
other: Induction of Luciferase(fold)
Run / experiment:
experiment I
Value:
> 1.5
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: In the Luciferase assay, a dose-dependent effect was detected. At the concentrations 804 µM to 2000 µM the luciferase induction was above the threshold of 1.5 fold in com-parison to the solvent control.
Key result
Parameter:
other: Relative Viability (%)
Run / experiment:
experiment I
Value:
>= 83
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Key result
Parameter:
other: Induction of Luciferase(fold)
Run / experiment:
Experiment II
Value:
> 1.5
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: In the Luciferase assay, a dose-dependent effect was detected. At the concentrations 558 µM to 2000 µM the luciferase induction was above the threshold of 1.5 fold in com-parison to the solvent control.
Key result
Parameter:
other: Relative Viability (%)
Run / experiment:
experiment II
Value:
>= 76.9
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Each valid experiment (i.e. meeting all acceptance criteria, according to the procedure described above) is interpreted as follows:
A test compound is considered to have the potential to activate the Nrf2 transcription factor if the luciferase induction is above or equal to 1.5 fold compared to the vehicle control in 2 (or more than) consecutive non-cytotoxic (relative viability ≥ 70 %) tested concentrations whereby at least three tested concentrations must be non-cytotoxic in two independent valid experiments.
A test compound is considered not to have the potential to activate the Nrf2 transcription factor if the effects mentioned above are not observed.

In order to come to a conclusion on the skin sensitization hazard of a substance, a mini-mum of two valid and independent experiments needs to indicate a positive or negative result according to the above-described criteria. If the first two experiments come to the same result (i.e. either being negative or being positive) no further testing is required. In case that the first two experiments give discordant results (i.e. one is negative and the other is positive), a third independent experiment needs to be conducted to complete the study. The skin sensitizing potential (corresponding to the potential to activate the Nrf2 transcription factor) of a test substance is determined by the result of the majority of the repetitions of an experiment. If two of two or two of three experiments are negative/positive, the substance is considered as negative/positive.

The luciferase induction was above 1.5 fold in more than 2 consecutive non-cytotoxic test item concentrations in experiment I and II.
Therefore, the test item (R)-3,7-dimethyl-1,6-octadien-3-ol is considered to have the poten-tial to activate the Nrf2 transcription factor (sensitizing potential) under the conditions of the LuSens test