Ethanol, 2-amino-, reaction products with ammonia, by-products from

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Original reference in Japanese, study summary and tables in English.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

Samples of bone marrow were taken onle once (24 h).

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-aminoethylamino)ethanol

EC Number:

203-867-5

EC Name:

2-(2-aminoethylamino)ethanol

Cas Number:

111-41-1

Molecular formula:

C4H12N2O

IUPAC Name:

2-[(2-aminoethyl)amino]ethanol

Details on test material:

- Name of test material (as cited in study report): N-(Aminoethyl)ethanolamin (AEEA)
- Analytical purity: 99.9 %

Test animals

Species:

mouse

Strain:

other: Crj:BDF1

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- solvent used: water

Duration of treatment / exposure:

- animals received single doses of AEEA dissolved in water

Post exposure period:

- 24 hours after dosing the animals were killed

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 500; 1000; 2000 mg/kg bw
Basis:
other: gavage

No. of animals per sex per dose:

5

Control animals:

other: solvent

Positive control(s):

- Cyclophosphamide
- Route of administration: oral per gavage
- Concentration: 50 mg/kg bw

Examinations

Tissues and cell types examined:

- Bone marrow blood cells were prepared

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
- Bone marrow blood cells were prepared, stained (acridine orange), and analysed for the occurrence of micronucleated polychromatic
erythrocytes (MNPCE) 


METHOD OF ANALYSIS:
- 2000 polychromatic erythrocytes (PCE) per animal counted
- The proportion of polychromatic erythrocytes in 500 erythrocytes was also recorded(PCE/500 ERY)
- results were expressed as percentage of MNPCE/PCE and the percentage of PCE/ERY.

Statistics:

A statistical evaluation was performed. The method applied is not known because it is not described in the English section of the paper.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

The percentage of micronucleated cells per 2000 polychromatic cells, and the percentage of polychromatic cells per 500 erythrocytes was as follows (means +/- SD):

Group	% MNPCE/PCE	% PCE/ERY
Solvent	0.19 ± 0.05	55.5 ± 5.5
AEEA
500 mg/kg  bw	0.19 ± 0.10	55.3 ± 3.6
1000 mg/kg  bw	0.11 ± 0.04	57.0 ± 5.3
2000 mg/kg  bw	0.23 ± 0.14	51.5 ± 3.9
Pos. Control: CPA 50 mg/kg bw	1.82 ± 0.43 ***	48.7 ± 2.7

 

MNPCE: micronucleated polychromatic erythrocytes 
PCE: polychromatic erythrocytes

*** = p < 0 .001 compared to the solvent control

The frequency of micronucleated immature erythrocytes was not significantly increased in males or females up to the dose of 2000 mg/kg bw by oral gavage and animals killed after 24 h after treatment. Inhibition of bone marrow cell proliferation was not observed under the test conditions.

Applicant's summary and conclusion

Executive summary:

In a Crj:BDF1 mouse bone marrow micronucleus assay 5 animals/sex/dose were treated by gavage with AEEA (99.9 % a.i.) at doses of 0, 500, 1000, or 2000  mg/kg bw.  Bone marrow cells were harvested 24 hours post-treatment. The vehicle was water. 

There were no signs of toxicity during the study. The positive control (CPA) induced the appropriate response. There was not a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow up to the dose of 2000 mg/kg bw after treatment time.

This study is classified as acceptable and satisfies the requirement for Test Guideline OECD 474 for in vivo cytogenetic mutagenicity data.