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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The paper 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 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.

Data source

Reference
Reference Type:
publication
Title:
A six-months intravenous repeated dose toxicity study of Tazobactam/Piperacillin and Tazobactam in dogs
Author:
Hayashi T, Yada H, Blair M, Laughlin KA, Blanchard GL, Tucek PV, Geil RG
Year:
1994
Bibliographic source:
J Toxicol Sci 19 Suppl II (1994) 177-197

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD 409
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
dog
Sex:
male/female

Administration / exposure

Route of administration:
intravenous
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 months.
1 month recovery period.
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
40 mg/kg bw/day
Dose / conc.:
80 mg/kg bw/day
Dose / conc.:
160 mg/kg bw/day
No. of animals per sex per dose:
4 in the low dose group, 6 in the other dosed groups and the control.
Control animals:
yes

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No mortality.

No relevant effects on clinical findings, body weight, food consumption, haematology, serum biochemistry, urinalysis, ophthalmology, electrocardiography, necropsy, organ weight.

Histopathology: Deposition of PAS-positive aggregates in liver cells of high dosed animals. Electron micrography of hepatocytes: Glycogen granules in cytoplasm and increased smooth endoplasmatic reticulum. Changes disappeared after 1 month recovery.

NOAEL: 40 mg/kg/day.

Applicant's summary and conclusion

Conclusions:
NOAEL: 40 mg/kg/day.
Executive summary:

No mortality.

No relevant effects on clinical findings, body weight, food consumption, haematology, serum biochemistry, urinalysis, ophthalmology, electrocardiography, necropsy, organ weight.

Histopathology: Deposition of PAS-positive aggregates in liver cells of high dosed animals. Electron micrography of hepatocytes: Glycogen granules in cytoplasm and increased smooth endoplasmatic reticulum. Changes disappeared after 1 month recovery.

NOAEL: 40 mg/kg/day.