N,N,4-trimethylpiperazine-1-ethylamine

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Evaluation of the genotoxic potential of alkyleneamines

Author:

Leung

Year:

1993

Bibliographic source:

Mutation Research, 320 (1994) 31-43

Materials and methods

Principles of method if other than guideline:

The assay (Heddle et al., 1983) was based on the procedures developed by Schmid et al. (1975) to screen chemicals for clastogenic potential (See section References)

GLP compliance:

no

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

2-piperazin-1-ylethylamine

EC Number:

205-411-0

EC Name:

2-piperazin-1-ylethylamine

Cas Number:

140-31-8

Molecular formula:

C6H15N3

IUPAC Name:

2-(piperazin-1-yl)ethan-1-amine

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6-8 weeks old

Administration / exposure

Route of administration:

intraperitoneal

Frequency of treatment:

single administration

Post exposure period:

Sampling times:
30h post administration
48h post administration
72h post administration

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

175 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

350 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

560 mg/kg bw/day (nominal)

Control animals:

yes

Positive control(s):

Triethylenemelamine at 0.3 mg/kg bw

Examinations

Tissues and cell types examined:

Micronuclei in peripheral, polychromatic erythrocytes from blood samples collected from the tail vein

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: Test doses were selected from a preliminary range-finding test to determine approximate toxicity of the test materials.

DETAILS OF SLIDE PREPARATION: Micronuclei in peripheral, polychromatic erythrocytes were stained with Furr's R-66 Giemsa diluted in phosphate buffer (Gallupudi and Kamra, 1974). Slides were coded and read blindly to prevent bias. The polychromatic : normochromatic erythrocytes ratio for approximately 1000 total cells was calculated.

Evaluation criteria:

A positive result was concluded if at least one statistically significant increase above vehicle control was observed with an indication of a dose-related effect.

Statistics:

Data were compared for significant differences using the Fisher's Exact Test.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Remarks:

at 30, 48 and 72h sampling times

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

With AEP, there was no increase at either the 48- or 72-h sample periods. Of the 3 dose levels, only the middle one (350 mg/kg), and only at the 30-h post-injection sample interval, produced a single statistically significant increase in the number of micronuclei.
 

Any other information on results incl. tables

 INDUCTION OF MICRONUCLEUS IN PERIPHERAL ERYTHROCYTES OF SWISS-WEBSTER MICE INJECTED INTRAPERITONEALLY WITH ALKYLENEAMINES

	Water	TEM	AEP
	10	0.3	175	350	560
	mg/kg	mg/kg	mg/kg
30 hours post dosing
Male	4.2±1.6	24.0±6.4^b	3.0±1.4	5.0±1.6	2.8±1.8
Female	1.4±1.7	17.0±5.3^b	2.0±1.6	4.0±1.9 a	1.8±1.3
48 hours post dosing
Male	2.4±0.9	-	3.8±3.4	2.0±1.4	1.2±1.6
Female	1.8±0.8	-	2.8±1.1	2.8±0.8	1.4±2.0
72 hours post dosing
Male	2.4±2.2	-	4.2±2.5	2.0±1.2	2.2±1.3
Female	1.2±1.3	-	1.8±1.6	1.6±0.9	2.2±1.8

TEM, triethylenemelamine.

Statistical analysis employed the Fisher's Exact text (1-tailed):ap < 0.01; b p < 0.001.

Applicant's summary and conclusion

Conclusions:

In this micronucleus study with Swiss-Webster mice, no clastogenic activity was observed with AEP in male and female mice.