Piperazine, compound with phosphoric acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Data source

Reference

Reference 1

Reference Type:

publication

Title:

13-week dietary toxicity study - dogs: piperazine dihydrochloride.

Author:

Rutter HA and Voelker RW

Year:

1975

Bibliographic source:

Final report to Jefferson Chemical Co., Austin TX from Hazleton Laboratories America. 13.

Reference 2

Reference Type:

other: study report

Title:

Committee for Veterinary Medicinal Products - Piperazine - Summary report

Author:

EMEA

Year:

1999

Bibliographic source:

The European Agency for the Evaluation of Medicinal Products Veterinary medicines and Inspections; EMEA/MRL/531/98-FINAL MAY 1999

Reference 3

Reference Type:

other: study report

Title:

European Union Risk Assessment Report : Piperazine

Author:

European Chemicals Bureau

Year:

2005

Bibliographic source:

3rd Priority List Volume: 56;Final Report, 2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from 'The European Agency for the Evaluation of Medicinal Products Veterinary medicines and Inspections'

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Piperazine

EC Number:

203-808-3

EC Name:

Piperazine

Cas Number:

110-85-0

IUPAC Name:

piperazine

Test animals

Species:

dog

Strain:

Beagle

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

intermittent

Doses / concentrations

Remarks:

Doses / Concentrations:
Dosage levels of 92.3 mg/kg feed(3 mg/kg/day) and 369.2 (12.3 mg/kg/day) for the low and intermediate groups and at 1476.8 mg/kg feed(49.7 mg/kg/day) from week 1 through 5 and 3692 mg/kg feed(121.8 mg/kg/d) from week 6 through 13 for the high level group.
Basis:
no data

No. of animals per sex per dose:

Three groups of beagle dogs (4 male and 4 female in each group)

Control animals:

yes

Details on study design:

Since the high dose of 121.8 mg/kg bw/day of piperazine dihydrochloride was not maintained for the entire administration period,the dose of 49.7 mg/kg bw/day of piperazine dihydrochloride (equivalent to 25 mg/kg bw/day of piperazine base)was considered as the NOEL in dogs.

Examinations

Observations and examinations performed and frequency:

No compound related signs of systemic toxicity were observed in any of the test animals with regard to appearance and behaviour,bodyweight changes,ophtalmoscopic finding,organ weights,and gross and microscopic pathology.At 4 weeks and at 13 weeks serum glutamic-oxaloacetic transaminase values fell in the control group whereas they remained constant in treated groups.

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

25 other: mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Induction of mild hepatic involvement in the Beagle dog established.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Upon repeated dose oral administration to beagle dogs, except for some signs of liver toxicity, little evidence of systemic toxicity was observed at the highest tested dose. A NOAEL of 25 mg/kg/day of piperazine base for induction of mild hepatic involvement in the Beagle dog can be established.

Executive summary:

Upon repeated dose oral administration to beagle dogs, except for some signs of liver toxicity, little evidence of systemic toxicity was observed at the highest tested dose. A NOAEL of 25 mg/kg/day of piperazine base for induction of mild hepatic involvement in the Beagle dog can be established.