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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study. Piperazine is one constituent (ca. 15%) of the test substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Principles of method if other than guideline:
14C-piperazine dihydrochloride as aqueous solution was administered as single dose by gavage.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): piperazine dihydrochloride
- Piperazine content is 50%.
Radiolabelling:
yes

Test animals

Species:
pig
Strain:
other: unknown
Sex:
male/female
Details on test animals and environmental conditions:
The animals were at least three month old and in the weight range of 24-52kg.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
300 mg/kg bw
No. of animals per sex per dose:
2 males/2 females
Control animals:
no
Details on dosing and sampling:
The excretion of radiolabeled material in urine and faeces was followed for up to 7 days in two animals, and two were sacrificed 12 and 24 h after dosing for determination of radiolabel in liver, kidney, muscle, fat and skin. By means of TLC, HPLC and LC-MS attempts were made to characterise the labelled material present in urine, faeces and tissue.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Peak plasma concentrations were attained 1 h after administration, followed by rapid disappearence from the blood.
Details on distribution in tissues:
The highest activity was found in kidneys and liver. Elimination of the activity in the kidney was rapid, with only 3% remaining of the 12 h value post dosing. The elimination from the liver, skeleton, muscle, fat and skin was considerably slower with 10, 11, 24, 25% respectively remaining after 7 days in comparison with the 12 h levels.
Details on excretion:
56% of the total activity was eliminated via the urine during 7 days, out of which 46% was excreted in the first 24 h. During the time of observation, 16% was excreted in faeces, while; again, most of the dose, 8%, was eliminated during the first 24 h.
When residues present in cage debris and washes are also included, after 7 days about one fourth of the totally administered amount can be considered as still retained in the body.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
In the urine collected 0-24 hours, 82-83% co-chromatographed with piperazine in HPLC or TLC. By the use of LC-MS for the radioactive residues found in tissue, the validity of the results from the chromatographic analysis could be confirmed. The nature of the labeled conversion products derived from piperazine was not determined, and the proportion of such metabolites in the urine increased with time to reach about 40-50% of the remaining activity in the 144-168 hour urine. In the kidney the fraction unidentified metabolites increased from about 20% at 12 hours post dosing to 80-90% of the remaining activity at 96 hours post dosing. Since carbon dioxide in exhaled air was not collected, minor metabolic conversion of piperazine to this metabolic end product cannot be excluded.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results