12-oxahexadecan-16-olide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

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

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial forward mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

12-oxahexadecan-16-olide

EC Number:

229-755-6

EC Name:

12-oxahexadecan-16-olide

Cas Number:

6707-60-4

Molecular formula:

C15H28O3

IUPAC Name:

1,6-dioxacycloheptadecan-7-one

Test material form:

liquid

Specific details on test material used for the study:

Test material name (as stated in the report): CERVOLIDE
Batch No.: VE00445215
Expiry date: 07 June 2018

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Test concentrations with justification for top dose:

CERVOLIDE was tested in the tester strains TA1535, TA1537, TA98, TA100 and WP2uvrA
with concentrations of 5.4, 17, 52, 164, 512, 1600 and 5000 μg/plate in the absence and
presence of 5% (v/v) S9-mix.

Vehicle / solvent:

Saline and DMSO

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: ICR-191

Results and discussion

Test results

Key result

Species / strain:

other: TA1535, TA1537, TA98, TA100 and WP2uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

All bacterial strains showed negative responses over the entire dose-range, i.e. no significant

dose-related increase in the number of revertants in two independently repeated experiments.

The negative control values were within the laboratory historical control data ranges.

The strain-specific positive control values were within the laboratory historical control data

ranges indicating that the test conditions were adequate and that the metabolic activation

system functioned properly, except the responses for TA1535 (presence of S9-mix) and

TA1537 (absence of S9-mix) in the second experiment. The purpose of the positive control is

as a reference for the test system, where a positive response is required to check if the test

system functions correctly. Since the values were more than 10 and 342 times greater than

the concurrent solvent control values for the tester strains TA1535 and TA1537, respectively,

these deviations in the mean plate counts of the positive controls had no effect on the results

of the study.

Applicant's summary and conclusion

Conclusions:

In conclusion, based on the results of this study it is concluded that CERVOLIDE is not
mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli
reverse mutation assay.

Executive summary:

All bacterial strains showed negative responses over the entire dose-range, i.e. no significant

dose-related increase in the number of revertants in two independently repeated experiments.

The negative control values were within the laboratory historical control data ranges.

The strain-specific positive control values were within the laboratory historical control data

ranges indicating that the test conditions were adequate and that the metabolic activation

system functioned properly, except the responses for TA1535 (presence of S9-mix) and

TA1537 (absence of S9-mix) in the second experiment. The purpose of the positive control is

as a reference for the test system, where a positive response is required to check if the test

system functions correctly. Since the values were more than 10 and 342 times greater than

the concurrent solvent control values for the tester strains TA1535 and TA1537, respectively,

these deviations in the mean plate counts of the positive controls had no effect on the results

of the study.

In conclusion, based on the results of this study it is concluded that CERVOLIDE is not

mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli

reverse mutation assay.