Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
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: Data taken from EU risk assessment of piperazine. Piperazine is one constituent (ca. 15%) of the test substance.

Data source

Reference
Reference Type:
publication
Title:
Study to evaluate the potential to induce micronuclei in the bone marrow of treated mice
Author:
Marshall, R.R.
Year:
1987
Bibliographic source:
Cited in the EC Risk Assessment Report for Piperazine, vol. 56, 2005

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In accordance with Salamone, Heddle Stuart, Katz, Mutat. Res., 74, 347 - 356, 1980
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): piperazine phosphate
- The piperazine content ist 42%.

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
Carboxymethylcellulose in distilled water
Duration of treatment / exposure:
single dose
Frequency of treatment:
single dose
Post exposure period:
24, 48 and 72 h
Doses / concentrations
Remarks:
Doses / Concentrations:
5000 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
2 mice /sex
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide oral administration at 80 mg/kg bw to 5 male and 5 female mice.

Examinations

Tissues and cell types examined:
erythrocytes from bone marrow

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
Mice treated with piperazine phosphate exhibited ratios of polychromatic erythrocytes (PCE) to normochromatic erythrocyte (NCE), and frequencies of micronucleated PCE and NCE which were similar to negative controls.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Piperazine phosphate did not induce micronuclei in the polychromatic or normochromatic erythrocytes of the bone marrow of mice administered at 5000 mg/kg bw.
Executive summary:

In a micronucleus assay CD-1 mice were dosed orally with 5000 mg piperazine phosphate per kg bodyweight. No significant increase in the level of micronuclei of polychromatic or normochromatic erythrocytes of the bone marrow could be detected.