Decane-1,10-diol

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:

November - December 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1983

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Decane-1,10-diol

EC Number:

203-975-2

EC Name:

Decane-1,10-diol

Cas Number:

112-47-0

Molecular formula:

C10H22O2

IUPAC Name:

decane-1,10-diol

Method

Target gene:

n/a

Species / strain

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

n/a

Additional strain / cell type characteristics:

not applicable

Cytokinesis block (if used):

n/a

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S9 mix

Test concentrations with justification for top dose:

30 - 5000 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

other: 2-aminoanthracene (all strains with S9)

Details on test system and experimental conditions:

Five dose levels of test item ranging up to a maximum of 5000 µg/plate in the absence and in the presence of metabolic activation were spaced at helf-log intervals.
In the test #1, the plate incorporation method was used. And in the test #2, the preincubation method was used.

Rationale for test conditions:

The following criteria must be met for the mutagenicity assay to be considered valid :
-in the solvent control, each tester strain culture must exhibit a characteristic mean number of spontaneous revertants
-to ensure that appropriate numbers of bacteria are plated, overnight culture titers must be in excess of 10^8 bacteria/ml
-the mean of each positive control must exhibit a significant increase on the number of revertants over the mean value of the respective vehicle control
-normally, at least four non-toxic dose levels are required to evaluate the assay data

Evaluation criteria:

For a test compound to be considered positive, it must (in two independent experiments) cause at least a doubling in the mean revertants per plate of at least one tester strain. This increase must be accompanied by a dose response towards increasing concentrations of the test article. A test article that does not meet these criteria will be called non-mutagenic in bacteria. Single increases in revertant frequencies, which are not dose-related and not reqroducible in two independent tests are considered non-relevant. If however these increases do occur in both tests, this will be taken as an indication of a mutagenic effect.

Statistics:

no

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

see below

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

see below

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

see below

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

Excessive toxicity, incdicated by a reduced growth or total absence of the bacterial background lawn, was detectable with :
-TA100 at 5000 µg/plate (without S9, preincubation test)
-TA1535 at 5000 µg/plate (+/-S9, plate incorporation test) and at 3000 (without S9, preincubation test)
-TA1537 at 5000 µg/plate (+/-S9, plate incorporation test) and at 100, 3000 (without S9, preincubation test) and at 3000 (with S9, preincubation test)

All four bacterial strao,ns exhibited a positive mutagenic response with the positive controls test both with and without metabolic activation by S9 mix. Negative (sovent) controls were also tested with each strain, and the mean numbers of spontaneous revertants were considered acceptable.
In both experiments, no indication of test compound induced mutagenicity was observed with either one of the four tester TA98, TA100, TA1535 and TA1537 with or without metabolic activation.
All criteria for a valid study were met as described.

Applicant's summary and conclusion

Conclusions:

Decane-1.10-diol did not induce a mutagenic effect in S.typhimurium. It is therefore not considered to ba a bacterial mutagen.

Executive summary:

Decane-1,10 -diol was tested for its ability to induce reverse mutations in an in vitro bacterial system. Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were treated with the test compound by the Ames test plate incorporation (test #1) as well as the preincubation method (test #2). Five dose levels covering the range between 30 and 5000 µg/plate, in triplicate both with and without the addition of a metabolising system (Aroclor 1254 induced rat liver S9 mix) were employed.

All four bacterial strains exhibited mutagenic responses to the appropriate positive control substances. Solvent controls also tested with each strain and the mean mumbers of spontaneous revertants were in an acceptable range.

Mutagenic activity of the test compound to one or more of the tester strains was not observed in either experiment with and without metabolic activation.

It is therefore concluded, taht decane-1,10 -diol is not a bacterial mutagen.