Dec-9-en-1-ol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Genetic Toxicity in vitro:

According to the TG OECD 471, the Bacterial Reverse Mutation Assay was carried out under GLP conditions and indicated that the test item did not cause a positive mutagenic response with any of the tester strains in either the presence or absence of Aroclor-induced rat liver S9.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 November 2016 - 05 January 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

tryptophan
histidine

Species / strain / cell type:

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

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

1.50, 5.00, 15.0, 50.0, 150, 500, 1500 and 5000 μg per plate.
Based upon the Initial Toxicity-Mutation Assays results, the maximum dose tested in the confirmatory mutagenicity assay was 5000 μg per plate.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility of the test substance and compatibility with the target cells.

Untreated negative controls:

yes

Remarks:

Historical Negative Control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

On all strains, with S9 activation

Untreated negative controls:

yes

Remarks:

Historical Negative Control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

On TA98, without S9 activation

Untreated negative controls:

yes

Remarks:

Historical Negative Control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

On TA100 and TA1535, without S9 activation

Untreated negative controls:

yes

Remarks:

Historical Negative Control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

On TA1537, without S9 activation

Untreated negative controls:

yes

Remarks:

Historical Negative Control

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

On WP2 uvrA, without S9 activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium
- Cell density at seeding (if applicable): 0.3x10^9 cells per milliliter

NUMBER OF REPLICATIONS: triplicate

Evaluation criteria:

For the test substance to be evaluated positive, it must cause a dose-related increase in the mean revertants per plate of at least one tester strain over a minimum of two increasing concentrations of test substance as specified below:
Strains TA1535 and TA1537:
Data sets will be judged positive if the increase in mean revertants at the peak of the dose response is equal to or greater than 3.0-times the mean vehicle control value and above the corresponding acceptable vehicle control range.
Strains TA98, TA100 and WP2 uvrA:
Data sets will be judged positive if the increase in mean revertants at the peak of the dose response is equal to or greater than 2.0-times the mean vehicle control value and above the corresponding acceptable vehicle control range.
An equivocal response is a biologically relevant increase in a revertant count that partially meets the criteria for evaluation as positive. This could be a dose-responsive increase that does not achieve the respective threshold cited above or a non-dose responsive increase that is equal to or greater than the respective threshold cited. A response was evaluated as negative if it was neither positive nor equivocal.
Toxicity:
A minimum of four non-toxic dose levels will be required to evaluate assay data. A dose level is considered toxic if it causes a >50% reduction in the mean number of revertants per plate relative to the mean vehicle control value (this reduction must be accompanied by an abrupt dose-dependent drop in the revertant count) or a reduction in the background lawn. In the event that four non-toxic dose levels are achieved, the affected portion of the essay will be repeated with an appropriate change in dose levels.

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

See attachment for result tables.
Initial Toxicity-Mutation Assays
Dose levels:1.50, 5.00, 15.0, 50.0, 150, 500, 1500 and 5000 μg per plate in DMSO
In the initial toxicity-mutation assay (B1), no precipitate was observed. Toxicity was observed beginning at 500 or 1500 μg per plate. Non-dose responsive increases of 1.6-, 1.7- and 2.1-fold (maximum increases) were observed with tester strains TA98 in the absence of S9 activation and WP2 uvrA in the presence and the absence of S9 activation. The increases with tester strains TA98 in the absence of S9 activation and WP2 uvrA in the presence of S9 activation were within the 95% Historical Control Limit (HCL) for each test condition. The increase with WP2 uvrA in the absence of S9 activation was just outside the 95% HCL, but the increase observed occurred at a toxic dose level and was not dose responsive.
Tester strain TA98 in the presence of S9 activation was counted, but the data was not reported or evaluated for mutagenicity due to the presence of intermediate colonies (pin prick-like colonies).
No positive mutagenic responses were observed with any of the tester strains except with TA98 in the presence of S9 activation. Based upon these results, the maximum dose tested in the confirmatory mutagenicity assay was 5000 μg per plate.
In the retest of initial toxicity-mutation assay (B2), the dose levels tested were 1.50, 5.00, 15.0, 50.0, 150, 500, 1500 and 5000 μg per plate. No precipitate was observed. Toxicity was observed beginning at 1500 μg per plate.
No positive mutagenic response was observed with tester strain TA98 in the presence of S9 activation.

Sterility Results
No contaminant colonies were observed on the sterility plates for the vehicle control, the test substance dilutions or the S9 and Sham mixes.

Conclusions:

All criteria for a valid study were met as described in the protocol. The results of the Bacterial Reverse Mutation Assay indicate that, under the conditions of this study, the test item did not cause a positive mutagenic response with any of the tester strains in either the presence or absence of Aroclor-induced rat liver S9.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

Genetic Toxicityin vitro:

According to the TG OECD 471, the Bacterial Reverse Mutation Assay was carried out under GLP conditions and indicated that the test item did not cause a positive mutagenic response with any of the tester strains in either the presence or absence of Aroclor-induced rat liver S9.