2-(2-oxopyrrolidin-1-yl)butyramide

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

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: “Commission Directive 2000132/EC, L1362000, Annexe 4D, dated May 19,2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Batch: C02421-1620
Purity: 98.6%

Method

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9 liver fractions of rats, induced with phenobarbital/ ß-naphthoflavone.

Test concentrations with justification for top dose:

Concentration range in the main test (with metabolic activation): 33 ... 5000 µg/plate
Concentration range in the main test (without metabolic activation): 33 ... 5000 µg/plate

Vehicle / solvent:

Solvent: Deionised water

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

(> 5000 µg/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No toxic effects, evident as a reduction in the number of revertants, occurred in the test groups with and without metabolic activation.

The plates incubated with the test item showed normal background growth up to 5000 pglplate with and without S9 mix in all strains used.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with ucb 6474 at any concentration level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

The number of colonies did not quite reach the lower limit of our historical control data in strain TA 1535 (solvent control, exp. 1,without S9 mix) and in strain WP2 uvrA (negative control, exp. 11,with S9 mix). Since these deviations are rather small, these effects are considered to be based upon biologically irrelevant fluctuations in the number of colonies and have no detrimental impact on the outcome of the study.

The historical range of negative controls was exceeded with metabolic activation in strains TA 98 (exp. 11)and TA 100 (exp. l), also the historical range of solvent controls was exceeded with metabolic activation in strain TA 100 (exp. I and II), Since these deviations are rather small, these effects are considered to be based upon biologically irrelevant fluctuations in the number of colonies and have no detrimental impact on the outcome of the study

The historical range of positive controls was exceeded without metabolic activation in strains TA 1535 (exp. 11)and TA 100 (exp. 11).This effect indicates the sensitivity of the strains rather than compromising the assay. Appropriate reference mutagens were used as positive controls. They showed a distinct increase in induced revertant colonies.

All acceptability criteria of the assay were met during the study.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

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

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pairchanges or frameshifts in the genome of the strains used. Therefore, ucb 6474 is considered to be non-mutagenic in this Bacterial Reverse Mutation Assay with Sa/mone//a fyphimurium strains TA 98, TA 100, TA 1535, and TA 1537, and the Escherichia coli strain WP2 uvrA.