[2R-(2α,3Z,5α)]-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, compound with tert-butylamine (1:1)

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1983 - 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Potassium clavulanate

IUPAC Name:

Potassium clavulanate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

2 test materials were tested within this study, these were as follows:
BRL 25000 : Lot No. C.T. 10715 (839 ug/mg as free acid) (568 ug/mg as amoxicillin free acid and 271 ug/mg as BRL 14151K free acid).

BRL 14151K : Lot No. C.T. 10716 (819 ug/mg as free acid). The drug concentrations and doses used when performing the tests are all expressed as weights of free acid.

Method

Species / strain

Species / strain 1

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

TA1535 , TA1537 and TA1538 (all provided vy Dr. Tsuneo Kada, National Institute of Genetics),

TA100, TA98 (provided by Dr. Kunie Yoshikaea, National Institute of Hygenic Sciences)

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

E. coli WP2

Details on mammalian cell type (if applicable):

E. coli WP2 (hcr-) (provided by Dr. Kunie Yoshikawa, National Institute of Hygenic Sciences)

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

TA98 and TA 100 - the following concentrations were used 0, 5, 10, 20, 30, 40, 50mcg
TA1535, TA1537, TA 1538 and E coli Wp2 hcr: 0, 100, 150, 200, 250, 300 and 350 mcg

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-methyl-N'-nitro-N-nitroguanidine (MNNG) , 4-nitroguinoline-1-oxide (4NQO), 9-aminoacridine (9AA), 2-(2-furyl)-3-(5-nitro- 2-furyl)-acrylamide (AF2) and 2-aminoanthracene (2AA) were used as positive controls depending on the bacterial strain.

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Test results 3

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Additional information on results:

There were no significant differences between the solvent control results and the BRL 25000 and BRL 14151K results for the six test strains of Salmonella typhimurium and E. coli with or without S9 mix.

Any other information on results incl. tables

Please see tables 1 to 4 which are located in the attached background information section.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

In Ames test. the numbers of revertant colonies showed no major differences from the negative controls for either BRL 25000 and BRL 14151K. No mutations were induced in any of the test strains. There were also no effects for either compound in the metabolic activation method by adding 59 mix. Therefore. it is assumed that BRL 25000 and BRL 14151K do not induce genetic mutations either in the presence or absence of metabolic activation.

Executive summary:

BRL 25000 and BRL 14151K were tested for induction of gene mutation and chromosomal aberration. BRL 25000 and BRL14151K did not induce revertant colonies against Salmonella typhimurium TA1535, TA1537, TA1538, TA100 and TA98 and E. coli WP2 hcr- with and without S9 mix.