[No public or meaningful name is available]

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-fluoro-4-methyl-1,3,2-dioxaphospholane

Cas Number:

16415-09-1

Molecular formula:

C3H6FO2P

IUPAC Name:

2-fluoro-4-methyl-1,3,2-dioxaphospholane

Method

Species / strain

Species / strain / cell type:

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

Remarks:

Salmonella typhimurium(S. typhimurium) strains(TA98, TA100, TA1535 and TA1537) and tryptophan requiring Escherichia coli(E. coli) strain(WP2 uvrA(pKM101))

Metabolic activation:

with and without

Metabolic activation system:

[S9 fraction]
Species : Rat
Sex : Male
Strain : Sprague-Dawley
Supplier : Molecular Toxicology, Inc.
Storage condition : Freeze(-15 °C below)
Product No. : 11-01L
Lot No. : 4365
Inductive material : Aroclor 1254-induced rat liver S-9

[S9 cofactor]
Name : Cofactor Ⅰ
Manufacturer : Genogen Co., Ltd.
Lot No. : 201215-I, 210203-I
Storage condition : Deep freeze(-70±20 °C)

Test concentrations with justification for top dose:

Dose levels: 6.9, 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 μg/plate

In result of dose range finding study, turbidity and precipitation of test substance were not observed at all dose in the all strains in the treatment mixture. Also, when revertants were counted at the end of the incubation period, precipitation was not observed at all dose in the all strains. There was no cytotoxicity or increases in mean number of revertants at all dose in the all strains both in the presence and absence of the metabolic activation system.
In the positive control group, increases of mean number of revertant was observed more than twice compared to the negative control group.
According to results of dose range finding study, the highest dose in the main study was selected as 5000 μg/plate and serially diluted to consist of five dose levels(61.7, 185.2, 555.6, 1666.7 and 5000 μg/plate) by the common ratio of 3.

Vehicle / solvent:

Dimethyl sulfoxide(DMSO)

Controls

Negative solvent / vehicle controls:

yes

Remarks:

Dimethyl sulfoxide(DMSO)

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

other: N-Methyl-N’-nitro-N-nitrosoguanidine

Evaluation criteria:

If the test substance meets the following criteria, it was judged as negative.
- When there is no dose-dependent increase of mean number of revertants in the test substance-treated group and mean number of revertants is less than 2 times the number of negative control group.

If the test substance meets all the following criteria, it was judged to be positive.
Regardless of the application of the metabolic activation system to the test substance exposure, the test substance was judged to induce a reverse mutation in the bacteria strains when the following results are obtained in at least one strain. At this time, biological relevance was considered.
- When there is dose-dependent increase of mean number of revertants in the test substance-treated group.
- When mean number of revertants in the test substance-treated group is 2 times or more than the number of revertants in negative control group at one or more dose.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

All validity criteria of this test were fulfilled. No increases in mean number of revertants were observed at all dose in the all strains both in the presence and absence of the metabolic activation system compared to the negative control group.
In conclusion, the test substance, FCCA-04, was considered as not having reverse mutagenic potential on bacterial strains under the present study conditions.