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EC number: 266-104-5 | CAS number: 66069-34-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- other: A company document which reviews several studies
- Adequacy of study:
- key study
- Study period:
- 1976
- 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:
- other company data
- Title:
- Unnamed
- Year:
- 1 976
- Report date:
- 1976
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No information regarding the methods used have been provided in the clinical brochure, this is not the actual study report this is a review of studies which were conducted on the surrogate material (potassium clavulanate).
- GLP compliance:
- not specified
Test material
- Reference substance name:
- potassium clavulanate
- IUPAC Name:
- potassium clavulanate
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- Potassium clavulanate
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- other: various different animals were used including a dog, rat, mouse and monkey
- Strain:
- other: As various animals were used, various species have been used too.
- Sex:
- male/female
Administration / exposure
- Route of administration:
- other: various routes including the oral route, subcutaneous, intravenous and intramuscular
- Vehicle:
- not specified
- Duration and frequency of treatment / exposure:
- no data
Doses / concentrations
- Remarks:
- Doses / Concentrations:
various concentrations were used:
In the urinary excretion studies the animals were tested at concentrations of 100 mg/kg.
In the metabolism studies, the mouse was tested at concentrations of 20, 50 and 100 mg/kg, the rat was tested at concentrations of 100 and 500 mg/kg, the dogs were tested at concentrations of 90 and 500 mg/kg and the monkeys were tested at concentrations of 10 and 100 mg/kg.
- No. of animals per sex per dose / concentration:
- no data available
- Control animals:
- not specified
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Mouse:
Absorption In the mouse appears to be variable. Blood concentrations of between 14 and 29 µg/ml were obtained after oral administration of 100 mg/kg. Subcutaneous administration at the same dose gave blood concentrations roughly five-fold higher than this (80 - 120 µg/ml).
Rat:
After orally dosing the rat with 100 mg/kg, blood concentrations were low, 0.9 to 2.9 µg/ml. Intramuscular administration of 500 mg/kg gave peak blood levels of 200 to 340 µg/ml after 15 to 30 minutes.
Dog:
Blood concentrations in the dog after oral administration of 90 mg/kg gave peak concentrations at 1 hour of between 17 and 33 µg/ml, but vomiting frequently occurs at this dose level. Intramuscular administration at 90 mg/kg resulted in higher blood concentrations, approximately three times greater
than from the corresponding oral dose occurring after 30 minutes. In repeat dose studies at 100 mg/kg similar results have been obtained indicating no accumulation of BRL. 14151.
Monkey:
Oral administration of BRL 14151 at 100 mg/kg to the squirrel monkey gave blood concentrations of 24 - 37 µg/ml. Intramuscular administration of 10 mg/kg produced blood concentrations of 10 to 15 µg/ml. - Details on distribution in tissues:
- Extensive radioactive studies are currently being carried out to determine the route of excretion, the absorption and metabolism of BRL 14151 in the rat, dog, mouse and Rhesus monkey. At present the 14C-BRL 14151 used in these studies has been prepared by a fermentation process.
The information obtained so far indicates that in the rat the absorption of 14C-BRL 14151 or its metabolites after oral administration is greater than that indicated by the non-radioactive studies carried out where only BRL.14151 was measured in urine. The radioactive studies have also indicated that in the rat the bile is currently a minor route of elimination of the 14C-compound or its metabolites and that extensive metabolism of the 14C-BRL.14151 occurs when the compound is administered orally.
- Details on excretion:
- Mouse:
Urinary recovery figures are generally low/moderate (4 - 21% at 100 mg/kg) after oral dosing. After subcutaneous dosing, the urinary excretion is generally two to three fold higher than after the corresponding oral dose.
Rat:
The percentage urinary recovery Is low and extremely variable after oral administration to both Wistar and Sprague Dawley rats, (0.08 - 4.4% Wlstar and 0.5 - 9.6% for Sprague Dawley strain, after 100 mg/kg). Intramuscular administration also gave extremely variable urinary recoveries (ranging from 4 - 55% for Wistar and 8.3 - 77%. Sprague Dawley strain, after 500 mg/kg). A marked sex difference has been observed, female giving high recoveries In high urine volumes, males low recoveries in low urine volumes.
Dog:
Urinary recoveries are extremely variable after both oral and intramuscular dosing, ranging between 2.5 and 63% In separate studies after oral dosing and similar erratic recovery is seen after intramuscular dosing.
Monkey:
Urinary recovery after oral administration of 100 mg/kg was less than seen In the dog and mouse, but not as variable as seen in the rat.
Metabolite characterisation studies
- Metabolites identified:
- not specified
Any other information on results incl. tables
This layer chromatography using non radiolabelled compounds has also been carried out in urine from the dog and the rat. Urine from dogs dosed with BRL 14151 at 100 mg/kg orally and intramuscularly showed a single spot with the same RF value as BRL 14151. The chromatograms from rat urine showed many spots, however BRL 14151 was not positively detected.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): no data
The information obtained so far indicates that in the rat the absorption of 14C-BRL 14151 or its metabolites after oral administration is greater than that indicated by the non-radioactive studies carried out where only BRL.14151 was measured in urine. The radioactive studies have also indicated that in the rat the bile is currently a minor route of elimination of the 14C-compound or its metabolites and that extensive metabolism of the 14C-BRL.14151 occurs when the compound is administered orally. - Executive summary:
Several studies were conducted on a range of species including the rat, dog, mouse and monkey. The studies looked into adsorption, excretion, metabolism and distribution of potassium clavulanate within these animals. The results can be seen below:
Adsorption:
Mouse:
Absorption In the mouse appears to be variable. Blood concentrations of between 14 and 29 µg/ml were obtained after oral administration of 100 mg/kg. Subcutaneous administration at the same dose gave blood concentrations roughly five-fold higher than this (80 - 120 µg/ml).
Rat:
After orally dosing the rat with 100 mg/kg, blood concentrations were low, 0.9 to 2.9 µg/ml. Intramuscular administration of 500 mg/kg gave peak blood levels of 200 to 340 µg/ml after 15 to 30 minutes.
Dog:
Blood concentrations in the dog after oral administration of 90 mg/kg gave peak concentrations at 1 hour of between 17 and 33 µg/ml, but vomiting frequently occurs at this dose level. Intramuscular administration at 90 mg/kg resulted in higher blood concentrations, approximately three times greater
than from the corresponding oral dose occurring after 30 minutes. In repeat dose studies at 100 mg/kg similar results have been obtained indicating no accumulation of BRL. 14151.
Monkey:
Oral administration of BRL 14151 at 100 mg/kg to the squirrel monkey gave blood concentrations of 24 - 37 µg/ml. Intramuscular administration of 10 mg/kg produced blood concentrations of 10 to 15 µg/ml.
Urinary recovery values were low and very variable in all the specieis tested and through all the routes of administration tested (intramuscular and via te oral route).
The following results were obtained from radioactive studies to assess the distribution of potassium clavulanate:
The information obtained so far indicates that in the rat the absorption of 14C-BRL 14151 or its metabolites after oral administration is greater than that indicated by the non-radioactive studies carried out where only BRL.14151 was measured in urine. The radioactive studies have also indicated that in the rat the bile is currently a minor route of elimination of the 14C-compound or its metabolites and that extensive metabolism of the 14C-BRL.14151 occurs when the compound is administered orally.
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