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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in chemico
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
GLP compliance:
no
Remarks:
GLP equivalent
Type of study:
direct peptide binding assay

Test material

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

In chemico test system

Details on study design:
The Direct peptide reactivity Assay (DPRA) is an in chemico test to determine the reactivity of test a
substance towards peptides.
This assay has been validated for a broad range of low-molecular weight chemicals and it was found
to detect reactive 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 was dissolved in acetonitrile and mixed with a Cysteine- and a
Lysine-containing peptide according to the standard operating procedure of the DPRA. One study
with three replicates was conducted. After 24 h incubation time, peptide depletion induced by was determined by HPLC-UV.

Results and discussion

In vitro / in chemico

Results
Key result
Parameter:
other: Average depletion Cys-and Lys-peptide
Value:
14.6
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The result of the DPRA assay should be used as part of an integrated approach for testing and
assessment (IATA). A parallel test in the KeratinoSens™ assay may indicate whether congruent
results are obtained by both test methods. According to a detailed analysis on large set of
chemicals, two congruent results in these two tests give a good prediction of the sensitizer hazard
[3-5] particularly when predicting human data, while an additional test in a dendritic cell line
assessing expression of surface markers may be needed in case of discordant results.
GR-86-6599 was reactive with the Cys-peptide (27.8% depletion) and classified into the LOW
reactivity class according to the prediction model. It is therefore considered a sensitizer according to
the prediction model of the DPRA. Additional analysis with LC-MS indicated that it indeed formed a
covalent adduct with the test peptide.