2-Propenoic acid, 2-methyl-, hydroxybutyl ester

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 13, 2006 to Januray 29, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to OECD method and in accordance with GLP. Study material is well characterized.

Data source

Reference

Reference Type:

other: Unnamed report

Title:

Unnamed

Year:

2007

Report date:

2007

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)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Test material form:

liquid

Method

Target gene:

five histidine-requiring strains

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium: TA1535, TA1537, TA98, TA100, TA102

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix(2.5%) from Aclor 1254-induced rat liver

Test concentrations with justification for top dose:

For genotoxicity experiment concentrations (with & without metabolic activation) used:

The dose ranges were determined in a preliminary toxicity assay.

Concentration range in the main test 1 & 2 (with and without metabolic activation): 50,150, 500, 1500 and 5000 µg/plate using direct plate method.

Vehicle / solvent:

solvent- dimethyl sulphoxide

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Remarks:

(vehicle controls used in parallel with the test material)

Positive controls:

yes

Positive control substance:

mitomycin C

Controls 2

Untreated negative controls:

yes

Positive controls:

other: 2-Aminoanthracene: 1 ug/plate(TA100), 2.0 ug/plate (TA 98,TA1535&TA1537 without S-9.

Controls 3

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Controls 4

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Controls 5

True negative controls:

yes

Positive control substance:

benzo(a)pyrene

Controls 6

True negative controls:

yes

Positive control substance:

other: 1,8 dihydroxyanthraquinone at 10 ug/plate for T102

Details on test system and experimental conditions:

Toxicity: no precipitation was noted in any test concentration

Evaluation criteria:

Evaluation criteria: test article would be considered mutagenic if:
the increase in the number of revertants is concentration-related;
at one concentration tested (at least), the number of revertant colonies is equal to or greater than twice the number of spontaneous revertants
the positive responses described above were reproducible in an independent assay.

Statistics:

Mean and standard deviation of the plate counts for each treatment were determined

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No toxicologically significant increase in the frequency of revertant colonies were recorded for any of the bacterial strains with any dose of the test material with and without metabolic activation. Small increases in revertant colony frequency was observed for bacterial strains T100 ( without s9) at 500 and 1500 ug/plate in the second experiment. The increases were considered to be of no biological relevance because there was no evidence of dose response relationship or reproducibility. Inn addition, the revertant counts at 500 and 1500 ug/plate were within in house control ranges for the strain and the fold increases were only 1.17 and 1.27 times the concurrent vehicle control at 500 and 1500 ug/plate,respectively.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Observations: All positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with and without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9 mix were validated.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
ambiguous without metabolic activation

No dose-related and reproducible increases in revertant colony frequency were observed in any tester strains at any concentration, both with and without S9. The test substance was not genotoxic in the Ames test