[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)

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

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

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The information used is from a document which summarises many investigations on the substance potassium clavulanate, the document looks into the toxicity of potassium clavulanate in a range of different species by both oral and parenteral routes. The document reviews the results of many study reports and very little information regarding the methods has been included which is why a klimisch reliability of 4 has been given.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Limit test:

no

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:

The toxicity of BRL 14151 has been studied in different animal species. Wide species differences have been seen however in all species the renal tube appears to be a target organ of toxicity.

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
100 and 500 mg/kg

No. of animals per sex per dose:

no data

Control animals:

not specified

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The following effects were seen in the 100 and 500 mg/kg group:

Renal effects were manifested by changes in plasma electrolytes, reduction in albumin/globulin ratio: decreased urinary osmolarity and marginal proteinuria.

Anaemia with Heinz bodies, splenomegaly and reticulocyte response in females at 500 mg/kg, less marked changes in males.

Slightly increased osmotic fragility (500 mg/kg), apparent after 8 days. Reversible after 14 day regression period.

Applicant's summary and conclusion

Conclusions:

Male and female rats have been dosed at 500 mg/kg and 100 mg/kg per day subcutaneously for 14 days with a regression period of 14 days in the high dose animals.

The following effects were seen in the 100 and 500 mg/kg group:
Renal effects were manifested by changes in plasma electrolytes, reduction in albumin/globulin ratio: decreased urinary osmolarity and marginal proteinuria.

Executive summary:

Male and female rats have been dosed at 500 mg/kg and 100 mg/kg per day subcutaneously for 14 days with a regression period of 14 days in the high dose animals. The following effects were seen in the 100 and 500 mg/kg group: Renal effects were manifested by changes in plasma electrolytes, reduction in albumin/globulin ratio: decreased urinary osmolarity and marginal proteinuria.