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Diss Factsheets

Administrative data

Description of key information

QSAR assessment of Skin sensitising potential using OASIS Times and DEREK

In vitro assessment of skin sensitising potential using Keratinosense assay and DPRA

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation
Remarks:
other: QSAR
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Prediction made with a valid QSAR model; substance was in the applicability domain for the model
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Principles of method if other than guideline:
QSAR prediction made using Derek Nexus: 4.1.0, Nexus: 2.0.0
Type of study:
other: QSAR

The substance was within the applicability domain for the QSAR tool (DEREK). No alerts were identified for skin sensitising potential, thus it was concluded that this substance was unlikely to be a skin sensitiser.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was within the applicability domain for the QSAR tool (DEREK). No alerts were identified for skin sensitising potential, thus it was concluded that this substance was unlikely to be a skin sensitiser.
Endpoint:
skin sensitisation
Remarks:
other: QSAR
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: QSAR prediction made using a valid model; substance is within the applicability domain for the model
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Principles of method if other than guideline:
Prediction of skin sensitising potential using OASIS Times v2.27.16.8
Type of study:
other: QSAR

Butyl Phenyl Ether was assessed for skin sensitising potential using the QSAR tool OASIS Times. Parent compound and metabolites were with the domain of the tool and all predicted to be negative for sensitising potential.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance (and metabolites) was in domain for the QSAR tool and was predicted not to be a sensitiser.
Endpoint:
skin sensitisation: in chemico
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2017
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))
GLP compliance:
yes (incl. QA statement)
Type of study:
direct peptide reactivity assay (DPRA)
Details on the study design:
Study design is in accordance with OECD Guidance: OECD (2015), Test No. 442C: In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA), OECD Publishing, Paris.
Positive control: Cinnamic Aldehyde (CAS 104-55-2) at a concentration of 100 mM in acetonitrile.

Positive control results:
Cinnamic Aldehyde depleted Cysteine and Lysine by 74.6 and 62.52% respectively
Key result
Run / experiment:
other: Definitive
Parameter:
other: % Cysteine Depletion
Value:
0.64
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Key result
Run / experiment:
other: definitive
Parameter:
other: % Lysine depletion
Value:
0.28
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Key result
Run / experiment:
other: Definitive
Parameter:
other: Mean % Cysteine and lysine depletion
Value:
0.46
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Interpretation of results:
GHS criteria not met
Conclusions:
The test material did not deplete Cysteine or Lysine in the DPRA assay. Therefore it is concluded that this substance is unlikely to be a Skin sensitiser
Executive summary:

The Direct Peptide Reactivity Assay was used to assess the skin sensitization potenetial of the test substance Butyl Phenyl Ether (Lot# 22466). The skin sensitization potential of the test substance was evaluated by measuring the depletion of synthetic peptides containing either cysteine or lysine aminoacids following incubation with the test substance, using the protocol that is consistent with the OECD Test Guideline 442C “In Chemico Skin Sensitization: Direct Peptide Reactivity Assay (DPRA)”[1]. Based upon the results of this study, the test substance, Butyl Phenyl Ether, was not classified as a skin sensitizer.


[1]            OECD Test Guideline 442C “In ChemicoSkin Sensitization: Direct Peptide Reactivity Assay (DPRA)”, Adopted 4 February 2015.

 

Endpoint:
skin sensitisation: in vitro
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A non-glp, OECD guideline in vitro assessment of skin sensitising potential
Qualifier:
according to guideline
Guideline:
other: OECD 442D
GLP compliance:
no
Remarks:
THe study was conducted in accordance with the principles of GLP (reporting, data auditing, data retention, GLP qualification fo all equipment and study personel) but was not officially conducted as a GLP study.
Type of study:
activation of keratinocytes
Positive control results:
In the two independent replicates, the positive control compound, cinnamic aldehyde, exhibited a dose-dependent increase in luciferase activity with EC1.5 values of 7.41 and 6.55 µM, respectively. In replicate 1, and 2, cinnamic aldehyde exhibited a maximum luciferase induction (Imax) of 18.49-, and 11.54-fold, relative to the vehicle control. In addition, the average variability in the solvent control wells was below the acceptable 20% in each of the two replicates, thereby demonstrating appropriate assay conduct.
Key result
Run / experiment:
other: Average of 2 replicates
Parameter:
other: Imax Fold Luciferase induction
Value:
1.04
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: Luciferase activity was not induced above 1.5 fold of control
Remarks:
Negative.

Butyl phenyl ether was tested at twelve concentrations ranging from 1 to 2000 µM in two independent assay replicates. 

In replicate 1, and 2, butyl phenyl ether exhibited a maximum luciferase induction (Imax) of 0.96-, and 1.12-fold, relative to the vehicle control. Therefore in both replicates, butyl phenyl ether did not induce luciferase activity above the threshold 1.5-fold. In both replicates, butyl phenyl ether caused cytotoxicity (cell viability < 70%) at 250 µM and higher concentrations. 

Therefore, based on the findings of this study, butyl phenyl ether was considered negative for skin sensitization potential in the in vitro KeratinoSens assay.

Butyl phenyl etherinterpretation criteria

Results

Interpretation

 

Rep-1

Rep-2

Average

 

Imax (relative fold)

0.96

1.12

1.04

 

EC 1.5 (µM)

NA

NA

NA

Potential non-sensitizer

Cell viability at EC 1.5 (%)

NA

NA

NA

 

 

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Butyl Phenyl Ether was cytotoxic in this assay but did not produce an increase in the luciferase activity above 1.5 fold of control at levels that were not cytotoxic.
Consequently this substance was not considered to be a skin sensitiser.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No in vivo skin sensitising potential data are available for butyl phenyl ether therefore two QSAR models and In vitro assays (Keratinosense and DPRA) were used to predict skin sensitising potential in accordance with the AOP for skin sensitising potential.

QSAR predictions:

For both QSAR models (DEREK and OASIS Times) butyl phenyl ether was within the applicability domain for the model, and as such the predictions can be considered to be reliable. Both models predicted that butyl phenyl ether would not be a skin sensitisier.

In vitro:

The in vitro Keratinosense assay butyl phenyl ether failed to induce luciferase activity to greater than 1.5 fold above control in the absence of cytotoxicity.

In the DPRA assay, butyl phenyl ether did not significantly deplete either Cysteine or Lysine (0.64 and 0.28% respectively). Therefore it is concluded that it is unlikely to be a potential sensitiser.

Based on the absence of structural alerts for sensitising potential and the negative in vitro and in chemico assays it is concluded that butyl phenyl ether is not a skin sensitiser and a further in vitro assay to assess sensitising potential was deemed to be unnecessary.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

All assays (in silico, in chemico and in vitro) were negative. Butyl Phenyl Ether is therefore not considered to be a skin sensitiser.