Piperonyl acetate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6 (QSPR model adapted specifically from OECD 471 test guideline)

Principles of method if other than guideline:

Multiple Quantitative Structure Activity Relationship (QSAR) models were used to predict the Ames mutagenicity of the test item Piperonyl acetate. 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 chemcials No. 471: Bacterial Reverse Mutation Test.
The in silico study aims to predict the Ames Mutagenicity of the test item using the following QSAR models:
* Nexus DEREK v6.0.1
* OECD QSAR Toolbox v4.2 (profiling results)
* Danish QSAR Database

Type of assay:

other: QSAR prediction

Test material

Test material information

Constituent 1

Reference substance name:

Piperonyl acetate

EC Number:

206-312-5

EC Name:

Piperonyl acetate

Cas Number:

326-61-4

Molecular formula:

C10H10O4

IUPAC Name:

(2H-1,3-benzodioxol-5-yl)methyl acetate

impurity 1

Reference substance name:

Piperonyl alcohol

EC Number:

207-808-4

EC Name:

Piperonyl alcohol

Cas Number:

495-76-1

Molecular formula:

C8H8O3

IUPAC Name:

1,3-benzodioxol-5-ylmethanol

Specific details on test material used for the study:

SMILES/ O=C(OCc(ccc(OCO1)c12)c2)C

Method

Species / strain

Species / strain / cell type:

other: S. typhimurium

Remarks:

QSAR prediction

Results and discussion

Test results

Key result

Species / strain:

other: S. typhimurium (in vitro)

Metabolic activation:

not specified

Genotoxicity:

positive

Remarks:

QSAR prediction

Cytotoxicity / choice of top concentrations:

not specified

Remarks:

QSAR prediction

Vehicle controls validity:

not specified

Remarks:

QSAR prediction

Untreated negative controls validity:

not specified

Remarks:

QSAR prediction

True negative controls validity:

not specified

Remarks:

QSAR prediction

Positive controls validity:

not specified

Remarks:

QSAR prediction

Any other information on results incl. tables

* Results with OECD QSAR Toolbox v4.2:

 

Profiler	Result
DNA alerts for AMES by OASIS	AN2: Shiff base formation after aldehyde release   SN1: nucleophilic attack after carbenium ion formation   SN2: Acylation and nucleophilic substitution at sp3 carbon atom
in vitro mutagenicity (Ames test) alerts by ISS	No alert found

 

As per the profiling results, the query substance was predicted as mutagenic.

 

 

* Results with Nexus DEREK: 

Mutagenicity in vitro in bacterium, Escherichia coli and Salmonella typhimurium is INACTIVE: No misclassified or unclassified features.

 

* Results with Danish QSAR Database:

 

 

Model	Prediction
SciQSAR	Inconclusive

Leadscope	Inconclusive
Case Ultra	Non-mutagenic (inside the applicability domain)
Battery	Non-mutagenic (outside the applicability domain)

Applicant's summary and conclusion

Conclusions:

A test battery was performed using 6 differents QSAR models for reverse mutagenicity on bacteria (Ames test). One of them pointed out a mutagenic potential of the test item, this constitues an alert leading to futher investigations. An in vitro Ames test will be performed to confirm this alert for mutagenic potential.