11-oxahexadecan-16-olide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The in vitro Ames test is negative but is without the required TA102 or E.coli strain.

Therefore, QSARs for TA102 in the absence and presence of S9 -mix have been added.

The QSAR predictions (+/- S9) required only sub-categorisation via DNA binding to obtain completely negative prediction giving high confience in the prediction results.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Musk R1, T-02437, No. 148983

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

CELLS USED
- Source of cells: Dr Bruce Ames
- Suitability of cells: Yes

MEDIA USED
- Type and identity of media including CO2 concentration if applicable:
- Properly maintained:: yes

Additional strain / cell type characteristics:

not applicable

Species / strain / cell type:

S. typhimurium TA 1538

Details on mammalian cell type (if applicable):

CELLS USED
- Source of cells: Dr Bruce Ames
- Suitability of cells: Yes

MEDIA USED
- Type and identity of media including CO2 concentration if applicable:
- Properly maintained:: yes

Additional strain / cell type characteristics:

not applicable

Cytokinesis block (if used):

NA

Metabolic activation:

with and without

Metabolic activation system:

Single ip injection of 500 mg Aroclor

Test concentrations with justification for top dose:

Bactericidal affect at the higher test concentrations.
Test concentrations 5 - 25 mg/plate.

Vehicle / solvent:

DMSO

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

methylmethanesulfonate

other: Hycanthone Methanesulfonate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation);

DURATION
- Exposure duration: 3 days treatment

NUMBER OF REPLICATIONS: 3 per concentration


DETERMINATION OF CYTOTOXICITY
- Background lawn on the agar plates.

Rationale for test conditions:

Standard conditions for the OECD 471 guidance.

Evaluation criteria:

Not required as the number of revertants for each tester strain were comparable between the solvent control at all concentrations.

Statistics:

Not required.

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Conclusions:

Incorporation of Musk R1 up to non-inhibitory levels did not increase the number of his+ revertants in any of the five tester strains, either in the presence or absence of the liver microsome activation system.

Executive summary:

Negative in TA1535, TA1537, TA98, TA100 and TA1538 in the absence and presence of S9-mix.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

TA102 in the absence of S9-mix

Type of information:

(Q)SAR

Adequacy of study:

supporting study

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 [Q]SAR Toolbox

2. MODEL (incl. version number)
QSAR Toolbox 3.4.0.17
Database version: 3.8.8/3.1.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 3391-83-1
SMILES: O=C1CCCCCCCCCOCCCCCO1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please see the attached OECD [Q]SAR Toolbox report.

5. APPLICABILITY DOMAIN
These profiles are routinely combined for mutagenicity:
in vitro mutagenicity (Ames test) alerts by ISS.
DNA alerts for AMES by OASIS v.1.4.
DNA binding by OECD.
Organic functional groups.
Structural similarity.
Chemical elements.

The target chemical FALLS within applicability domain.
Very high confidence in the result as indicated by the p-value.

6. ADEQUACY OF THE RESULT
Negative Ames in the absence of S9 with strain TA102 with very high confidence.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

supporting study

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 [Q]SAR Toolbox

2. MODEL (incl. version number)
QSAR Toolbox 3.4.0.17
Database version: 3.8.8/3.1.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 3391-83-1
SMILES: O=C1CCCCCCCCCOCCCCCO1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please see the attached OECD [Q]SAR Toolbox report.

5. APPLICABILITY DOMAIN
These profiles are routinely combined for mutagenicity:
in vitro mutagenicity (Ames test) alerts by ISS.
DNA alerts for AMES by OASIS v.1.4.
DNA binding by OECD.
Organic functional groups.
Structural similarity.
Chemical elements.

The target chemical FALLS within applicability domain.
Very high confidence in the result as indicated by the p-value.

6. ADEQUACY OF THE RESULT
Negative Ames in the presence of S9 with strain TA102 with very high confidence.