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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The paper by Ohuchida et al. was published 1994 in a Japanese journal as part of a series of publications on Tazobactam. Only the summary and the Tables are provided in English. Therefore the evaluation restricts to the English parts of the paper. The report provides in the summary and the relevant Table 1 only few details on the method used. Missing information, which might appear in the Japanese text, are: Purity of the test substance; no evidence of the compliance with GLP; no evidence of an independent repetition of the experiment; etc. The results are also consistent with those of an other Ames study, see below. There is enough weight of evidence to state that Tazobactam acid is not to genotoxic in the Ames-test, even if a lot of details of the method is missing in the legible description of the study.
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The paper by Ohuchida et al. was published 1994 in a Japanese journal as part of a series of publications on Tazobactam. Only the summary and the Tables are provided in English. Therefore the evaluation restricts to the English parts of the paper. The report provides in the summary and the relevant Table 5 only few details on the method used. Missing information, which might appear in the Japanese text, are: Purity of the test substance; evidence of the compliance with GLP; etc.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
Some details of the methods can not be evaluated due to language problems.
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
other: Chinese hamster lung cells.
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
0 - 2.5 - 5.0 - 10 mM
Negative solvent / vehicle controls:
yes
Remarks:
saline
Positive controls:
yes
Remarks:
mitomycin C; N-nitrosodimethylamine
Details on test system and experimental conditions:
DURATION
- Treatment time (h) / expression time (h) in the 4 experiments were:
24 / 0 without S9 mix,
48 / 0 without S9 mix,
6 / 18 without S9 mix,
6 / 18 with S9 mix

NUMBER OF CELLS EVALUATED: 200 cells were scored for chromosome aberrations.

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: not stated.
Key result
Species / strain:
other: Chinese hamster lung cells
Metabolic activation:
with and without
Genotoxicity:
negative
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
The test substance was negative in each of the 4 experiments.
Executive summary:

An in vitro chromosome aberrations study with Chinese hamster lung cells with and without addition of an external metabolising system was performed. Treatment and expression times were varied in 4 experiments.

The test substance was negative in each of the 4 experiments

Data source

Reference
Reference Type:
publication
Title:
Mutagenicity tests of tazobactam/piperacillin, tazobactam and piperacillin.
Author:
Ohuchida A; Taniguti A; Kouchi Y; Maeda Y; Kashihara A; Omae S
Year:
1994
Bibliographic source:
J Toxicol Sci 1994 Oct; Vol 19, Suppl 2: pp 263-80.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Some details of the methods can not be evaluated due to language problems.
Principles of method if other than guideline:
The paper includes 3 mutagenicity tests. One of them is a reverse mutation assay in bacteria with 4 strains of S. typhimurium and the E. coli strain WP2uvrA. The described method in the summary and the details recognised from the relevant Table 1 show a procedure much similar to the present OECD-Guideline 471. Missing information, which might appear in the Japanese text, are: Purity of the test substance; no evidence of the application of GLP; no evidence of an independent repetition of the experiment.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name in the publication: (+)-(2S, 3S, 5R)-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide.
No further details are provided in the English text. The Japanese text of the publication obviously contains some information.

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
10 to 1000 µg/plate
Controls
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)
NUMBER OF REPLICATIONS: 3 per concentration.

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
only with S9 mix
Vehicle controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
The test substance was not mutagenic to Samonella typhimurium strains TA1535, TA1537, TA98 and TA100 and E. coli strain WP2uvrA with and without metabolic activation.
Executive summary:

An Ames test was performed with Salmonella strains TA100, TA1535, TA98 , TA1537 and the E. coli strain WP2uvrA.

Positive control substances were genotoxic. The test substance was not genotoxic in the performed assay, with and without an external metabolizing system.