Allyltributylphosphonium chloride

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

Study Completion Date: 3rd May, 2018

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
Nexus DEREK

2. MODEL (incl. version number)

Predictions for individual constituents were performed using the following QSAR models:
• Nexus DEREK v 6.0.1
• OECD QSAR Toolbox v 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Constituent
SMILES
Allyltributylphosphonium chloride
[Cl-].CCCC[P+](CCCC)(CCCC)CC=C
Prop-1-en-1-yltributylphosphonium chloride
[Cl-].CCCC[P+](CCCC)(CCCC)C=CC
Sulfolane
C1CCCS1(=O)=O


4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Following QSAR models were applied to predict the Skin Sensitisation potential for the individual constituents in the
mixture of Allyltribuylphosphonium chloride, Prop-1-en-1-yltributylphosphonium chloride and Sulfolane :
Nexus DEREK
DEREK predicts the skin sensitisation potential of a substance based on the triggered structural alerts for this
endpoint. If the substance is a sensitiser, DEREK also provides the EC3 value. The report also provides detailed
information about each triggered alert.
OECD QSAR Toolbox v4.2
The latest version of the OECD QSAR Toolbox facilitates the profiling of a query substane based on the following
skin sensitisation relevant profilers incorporated into its interface

5. APPLICABILITY DOMAIN

See attached document

6. ADEQUACY OF THE RESULT
These QSAR models has been designed to be used for regulatory purposes and based on the QSAR results, this report predicts the consensus endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the OECD Guideline for Testing of Chemicals No. 429: Skin Sensitisation

Data source

Reference

Reference 1

Reference Type:

other: QSAR

Title:

Nexus DEREK v 6.0.1

Year:

2018

Bibliographic source:

DEREK predicts the skin sensitisation potential of a substance based on the triggered structural alerts for this endpoint.

Reference 2

Reference Type:

other: QSAR

Title:

OECD QSAR Toolbox v4.2

Year:

2018

Bibliographic source:

The latest version of the OECD QSAR Toolbox facilitates the profiling of a query substane based on the following skin sensitisation relevant profilers incorporated into its interface

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSAR R.6

Principles of method if other than guideline:

These QSAR models has been designed to be used for regulatory purposes and based on the QSAR results, this report predicts the consensus endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the OECD Guideline for Testing of Chemicals No. 429: Skin Sensitisation.

Test material

Test material information

Constituent 1

Reference substance name:

Allyltributylphosphonium chloride

EC Number:

216-231-7

EC Name:

Allyltributylphosphonium chloride

Cas Number:

1530-48-9

Molecular formula:

C15H32P.Cl

IUPAC Name:

tributyl(prop-2-en-1-yl)phosphanium chloride

impurity 1

Reference substance name:

Tributyl-1-propen-1-yl-phosphonium chloride

Molecular formula:

C15H32P.Cl

IUPAC Name:

Tributyl-1-propen-1-yl-phosphonium chloride

impurity 2

Reference substance name:

Tetrahydrothiophene 1,1-dioxide

EC Number:

204-783-1

EC Name:

Tetrahydrothiophene 1,1-dioxide

Cas Number:

126-33-0

Molecular formula:

C4H8O2S

IUPAC Name:

tetrahydrothiophene 1,1-dioxide

Specific details on test material used for the study:

Constituent SMILES
Allyltributylphosphonium chloride [Cl-].CCCC[P+](CCCC)(CCCC)CC=C
Prop-1-en-1-yltributylphosphonium chloride [Cl-].CCCC[P+](CCCC)(CCCC)C=CC
Tetrahydrothiophene 1,1-dioxide C1CCCS1(=O)=O

Results and discussion

Positive control results:

No alert found

In vitro / in chemico

Results

Key result

Run / experiment:

other: QSAR

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

Results with OECD QSAR Toolbox v4.2

Following profiling results were derived for all the three constituents. All the below-listed profilers provided the same results for these constituents. 

OECD QSAR Toolbox v4.2 Profilers for Skin Sensitisation
Profilers
General Mechanistic
Protein binding potency GSH	Not possible to classify according to these rules (GSH)
Protein binding potency Cys (DPRA 13%)	DPRA less than 9% (DPRA 13%) >> No protein binding alert
Protein binding by OASIS	No alert found
Protein binding by OECD	No alert found
Protein binding potency Lys (DPRA 13%)	DPRA less than 9% (DPRA 13%) >> No protein binding alert
Endpoint Specific
Keratinocyte gene expression	Not possible to classify according to these rules
Protein binding alerts for skin sensitization by OASIS	No alert found
Protein binding alerts for skin sensitization according to GHS	No alert found
Protein Binding Potency h-CLAT	No alert found

 

As per the profiling results, all the three mono-consituents were be predicted as non-sensitising to the skin.

Results with Nexus DEREK

 

No structural alerts were triggered for skin sensitisation forof Allyltribuylphosphonium chloride.Results for Prop-1-en-1-yltributylphosphonium chloride were considered the same as that for Allyltribuylphosphonium chloride as both these substances are position isomers.

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Combining the results derived for individual constituents using multiple QSAR models, mixture of Allyltribuylphosphonium chloride, Prop-1-en-1-yltributylphosphonium chloride and Tetrahydrothiophene 1,1-dioxide is predicted as a non-sensitising to the skin.