Oxaceprol

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:

2000-02-02 to 2001-08-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Test guideline 3

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Test guideline 4

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Oxaceprol

EC Number:

251-780-6

EC Name:

Oxaceprol

Cas Number:

33996-33-7

Molecular formula:

C7H11NO4

IUPAC Name:

1-acetyl-4-hydroxy-L-proline

Test material form:

solid: crystalline

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Kyowa Hakko Kogyo Co., Ltd. / lot 000703

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Solubility and stability of the test substance in the solvent/vehicle: highly soluble

Method

Target gene:

Histidine mutation: His C3076, His D3052, His G46
Additional mutations: LPS (rfa), Repair (uvrB), R-factor (plasmid pKM 101)

Species / strain

Species / strain / cell type:

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

Remarks:

WP2uvrA-

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

Preliminary toxicity study: 0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 1500 and 5000 µg/plate
Range finding study: 50, 150, 1500 and 5000 µg/plate
Main study: 50, 150, 1500 and 5000 µg/plate Justification for top dose: Results of preliminary study and range finding study

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: Oxaceprol is highly soluble in water

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

other: In addition, historical values

Details on test system and experimental conditions:

METHOD OF APPLICATION: (plate incorporation); preincubation

DURATION
- Exposure duration: 48 h

SELECTION AGENT (mutation assays): base pair substituation and frameshift type

NUMBER OF REPLICATIONS: 3 per concentration

Evaluation criteria:

The test material may be considered positive in the test system if the following criteria is met:

The test material should have induced a reproducible, dose-reated and statistically [Dunnett's method of linear regression (5)] significant increase in the revertant count in at least one strain of bacteria.

Results and discussion

Test results

Key result

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2uvrA-

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

not valid

Additional information on results:

From the results obtained in the experiments it appeared that incubation of the test substance with the bacteria did not increase the number of his+ revertants with S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100 and WP2uvrA-, either in the absence or in the presence of the S-9 mix.

The test substance appeared not to be toxic.

The positive controls used in the present assays gave the expected strong increase in the number of his+ revertants, both in the absence and in the presence of the S-9 mix.

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Applicant's summary and conclusion

Conclusions:

Oxaprenol is considered to be non-mutagenic under the condistions of the test.

Executive summary:

The potential of causing genetic toxicity by Oxaceprol was investigated in a Stuy according to OECD 471 (Ames-test).

From the results obtained in the experiments it appeared that incubation of the test substance with the bacteria did not increase the number of his+ revertants with S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100 and WP2uvrA-, either in the absence or in the presence of the S-9 mix.

The test substance appeared not to be toxic.

The positive controls used in the present assays gave the expected strong increase in the number of his+ revertants, both in the absence and in the presence of the S-9 mix.