Reaction mass of 6-butyl-3,6-dihydro-2,4-dimethyl-2H-pyran and 2-butyl-3,6-dihydro-4,6-dimethyl-2H-pyran and 2-butyltetrahydro-6-methyl-4-methylene-2H-pyran

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:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

no TA102 strains used

Principles of method if other than guideline:

As OECD 471 (1983) required to test Salmonella typhimurium TA1535, TA1537, TA98 and TA100 only, there is no deviation from the guideline.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-butyl-3,6-dihydro-4,6-dimethyl-2H-pyran

EC Number:

246-099-6

EC Name:

2-butyl-3,6-dihydro-4,6-dimethyl-2H-pyran

Cas Number:

24237-01-2

Molecular formula:

C11H20O

IUPAC Name:

2-butyl-4,6-dimethyl-3,6-dihydro-2H-pyran

Constituent 2

Reference substance name:

6-butyl-3,6-dihydro-2,4-dimethyl-2H-pyran

EC Number:

246-098-0

EC Name:

6-butyl-3,6-dihydro-2,4-dimethyl-2H-pyran

Cas Number:

24237-00-1

Molecular formula:

C11H20O

IUPAC Name:

6-butyl-2,4-dimethyl-3,6-dihydro-2H-pyran

Constituent 3

Reference substance name:

2-butyltetrahydro-6-methyl-4-methylene-2H-pyran

EC Number:

246-101-5

EC Name:

2-butyltetrahydro-6-methyl-4-methylene-2H-pyran

Cas Number:

24237-02-3

Molecular formula:

C11H20O

IUPAC Name:

2-butyl-6-methyl-4-methylenetetrahydro-2H-pyran

Specific details on test material used for the study:

Material Identification (as stated in the report) : Gyrane St. 2
Sample received on 2nd, December 1985
Dilutions of the test substance were made with ethanol just prior to use.

Method

Target gene:

- Salmonella typhimurium TA1535, TA1537, TA98 and TA100

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9-mix induced by Aroclor 1254

Test concentrations with justification for top dose:

Preliminary test with TA98, without S9-mix: 8.5, 85, 850, 8500 and 85000 µg/plate

Main study: TA1535, TA1537, TA1538, TA98 and TA100:
Without and with S9-mix: 10.49, 31.48, 94.44, 283.33 and 850 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Dilutions of the test substance were made with ethanol just prior to use.

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

ethanol

Positive controls:

yes

Positive control substance:

other: 2-nitrofluorene 1.0 µg/plate in DMSO for TA98 and TA1538

Remarks:

without S9

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

ethanol

Positive controls:

yes

Positive control substance:

other: Sodium azide 1.0 µg/plate in water for TA1535 and TA100

Remarks:

without S9

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

ethanol

Positive controls:

yes

Positive control substance:

other: 9-aminoacridine 80 µg/plate in DMSO for TA1537

Remarks:

without S9

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

ethanol

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene 2.0 µg/plate in DMSO for all tester strains

Remarks:

with S9

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at the highest dose level µg/plate without S9 only

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium, other: TA1537, TA 1538, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

At 850 µg/plate

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

From the above findings it is concluded that Gyrane St 2. did not show any mutagenic activity in the Salmonella/mammalian microsome mutagenicity test under the conditions employed in this evaluation.

Executive summary:

The genetic toxicity of Gyrane was assessed at toxic concentrations of ≤ 850 µg/plate using S. typhimurium TA100, TA1535, TA98, TA1537 and TA1538 strains, in accordance with OECD 471 guideline and according to GLP principles. All strains showed cytotoxicity at the highest tested concentrations.

All bacterial strains showed negative responses with and without metabolic activation. Based on the results of this study, the substance Gyrane is not mutagenic in the Salmonella typhimurium reverse mutation assay.