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Toxicological information

Genetic toxicity: in vitro

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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

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 / strainopen allclose all
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 / 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 resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
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.