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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Key study: Test method equivalent to OECD 471. The test substance was not mutagenic to S. typhimurium strains TA1535, TA1537, TA98, TA100 and E. coli WP2uvrA with and without metabolic activation.

Supporting study: Test method equivalent to OECD 471.The test substance was not mutagenic to S. typhimurium strains TA98, TA100, TA102 with and without metabolic activation.

Supporting study: Test method equivalent to OECD 473. The substance did not produce significant increases in chromosome aberrations to Chinese hamster lung cells with and without metabolic activation.

Link to relevant study records
Reference
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.
Reason / purpose:
reference to same study
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
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
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.
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
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Supporting study: Test method similar to OECD 474. The substance did not produce significant increases in the formation of micronucleous in CD-1 mouse after intravenous administration.

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
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 Tables 8 and 9 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
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
not specified
Type of assay:
micronucleus assay
Species:
mouse
Strain:
CD-1
Sex:
male
Route of administration:
intravenous
Frequency of treatment:
once
Post exposure period:
24, 48 and 72 h in the pilot test.
48 h in the definitive test.
Remarks:
Doses / Concentrations:
625 to 5000 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
5 males per dose.
Control animals:
yes
Positive control(s):
MMC,; i.p. administration of 2 mg/kg; analysis 24 h after administration.
Tissues and cell types examined:
Femoral marrow was analysed for red blood cells, polychromatic erythrocytes, micronuclei containing polychromatic erythrocytes.
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
only slight effect
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The frequency of micronuclei containing polychromatic erythrocytes was between 0.0.2 and 0.17 %.
Conclusions:
Tazobactam is considered not to have an in vivo mutagenic potential, in this test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Although 3 studies are only partly legible, because they were written in Japanese, and because the publication do not give extensive information on the methods used, there is enough weight of evidence that Tazobactam acid can be considered at present as non-mutagenic.

Justification for classification or non-classification

Based on the available information, the substance is not classified for genotoxicity according to CLP Regulation (EC) No 1272/2008.