6-(cyclohexylamino)-3-methyl-3H-dibenz[f,ij]isoquinoline-2,7-dione

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in chemico

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE: OECD QSAR Toolbox

2. MODEL (incl. version number): Toolbox Version 4.4

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: CN1C(=O)C=C2c3ccccc3C(=O)c3c(NC4CCCCC4)ccc1c23

4. CAS Smiles relation: not applicable

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2021

Materials and methods

Principles of method if other than guideline:

- Software tool(s) used including version: QSAR Toolbox version 4.4
- Model(s) used: QSAR Toolbox

GLP compliance:

no

Type of study:

other:

Test material

Test material information

Constituent 1

Reference substance name:

6-(cyclohexylamino)-3-methyl-3H-dibenz[f,ij]isoquinoline-2,7-dione

EC Number:

244-320-0

EC Name:

6-(cyclohexylamino)-3-methyl-3H-dibenz[f,ij]isoquinoline-2,7-dione

Cas Number:

21295-57-8

Molecular formula:

C23H22N2O2

IUPAC Name:

10-(cyclohexylamino)-14-methyl-14-azatetracyclo[7.7.1.0²,⁷.0¹³,¹⁷]heptadeca-1(16),2,4,6,9,11,13(17)-heptaene-8,15-dione

Test material form:

solid

Details on test material:

Purity: 94.2%

In chemico test system

Details on the study design:

The QSAR Toolbox is a software for grouping chemicals into categories and filling gaps in (eco)toxicity data needed for assessing the hazards of chemical. The model focuses on intrinsic properties of chemicals (mechanism or mode of action, (eco-)toxicological effects). It enables robust hazard assessment through mechanistic comparisons without testing.

Results and discussion

In vitro / in chemico

Results

Results 1

Run / experiment:

run/experiment 1

Parameter:

other: Protein binding potency h-CLAT

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

other: no indication of skin sensitisation, no alert found

Results 2

Run / experiment:

run/experiment 1

Parameter:

other: Protein binding potency Cys and Lys (DPRA 13%)

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

other: no indication of skin sensitisation, no protein binding alert

Results 3

Run / experiment:

other: 1

Parameter:

other: Protein binding by OECD

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

other: Acylation; Acylation >> Direct Acylation Involving a Leaving group; Acylation >> Direct Acylation I

Other effects / acceptance of results:

Protein binding by OASIS: No alert found
Protein binding alerts for skin sensitisation by OASIS: No alert found
Protein binding alerts for skin sensitisation according to GHS: No alert found
Protein binding potency GSH: Not possible to classify according to these rules (GSH)
Keratinocyte gene expression: Very high gene expression; Very high gene expression >> Substituted para- and ortho-phenylenediamines, aminophenols and benzenediols
Skin sensitisation for DASS: Positive
The customized profiler “Skin sensitization for DASS” is developed for Defined approaches (DA) purposes and it is part of the “Skin sensitization for defined approaches” automated workflow. The profiler combines application of the endpoint specific “Protein binding alerts for skin sensitization by OASIS” profiler with the Autoxidation and Skin metabolism simulators. Thus, it can identify the presence or absence of protein binding alerts in the parent chemical and predicted metabolites.
No alert was found by the profiler Protein binding alerts for skin sensitisation by OASIS for the parent compound. Therefore, the result of the DASS profiler is not relevant for the target compound.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The substance is within the applicability domain of the following profilers in the OECD Toolbox 4.4, i.e. Protein binding by OASIS: no alert found,
Protein binding alerts for skin sensitisation according to GHS: No alert found
Protein binding by OECD: Acylation; Acylation >> Direct Acylation Involving a Leaving group; Acylation >> Direct Acylation Involving a Leaving group >> Acetates,
Protein binding potency Cys (DPRA 13%): No protein binding alert,
Protein binding potency Lys (DPRA 13%): Non-conjugated mono- and diketones (non reactive),
Protein binding potency h-CLAT: No alert found,
Protein binding potency GSH: not possible to classify according to these rules (GHS),
Keratinocyte gene expression Very high gene expression; Very high gene expression >> Substituted para- and ortho-phenylenediamines, aminophenols and benzenediols

Executive summary:

The structure activity relationship of the registered substance was investigated by using the OECD Toolbox 4.4 (released 2020). Alerts for protein binding are found by 2 (2 out of 9) by the QSAR Toolbox 4.4 profilers (Protein binding by OECD: Acylation; Acylation >> Direct Acylation Involving a Leaving group; Acylation >> Direct Acylation Involving a Leaving group >> Acetates; Keratinocyte gene expression Very high gene expression; Very high gene expression >> Substituted para- and ortho-phenylenediamines, aminophenols and benzenediols).