4,4'-ethylenedianiline

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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-ethylenedianiline

EC Number:

210-716-7

EC Name:

4,4'-ethylenedianiline

Cas Number:

621-95-4

Molecular formula:

C14H16N2

IUPAC Name:

4-[2-(4-aminophenyl)ethyl]aniline

Details on test material:

Name of the test substance used in the study report: 4,4'-Diaminodibenzyl
Purity: 100%

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals with a mean weight of about 26.8 g were used for the study.
The animals were identified using cage cards.
For the duration of about one week the animals were housed in Makrolon cages in groups of 5 separately according to sex. During this time the animals were accommodated in fully air-conditioned rooms in which central air conditioning guaranteed a range of 20 - 24°C for temperature and a range of 30 - 70% for relative humidity. Before the start of the treatment the animals were transferred to Makrolon cages, type MI, and housed individually under the same conditions until the end of the test.
The day/night rhythm was 12 hours (12 hours light from 6.00 - 18.00 hours and 12 hours darkness from 18.00 - 6.00 hours).
Standardized pelleted feed (Kliba Haltungsdiaet, Klingentalmuehle AG, Kaiseraugst, Switzerland) and drinking water from bottles were available ad libitum.

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Due to the insolubility of the test substance in water, a 0.5% CMC formulation was selected as the vehicle, which had been demonstrated to be suitable in the in vivo micronucleus test and for which historical data are available.

Details on exposure:

All test substance formulations were prepared immediately before administration.
The amount of substance or volume to be administered was related to the specific weight of the individual animals on the day of the experiment.

Duration of treatment / exposure:

single administration

Frequency of treatment:

single administration

Doses / concentrations

Remarks:

Doses / Concentrations:
75, 150, 300 mg/kg bw
Basis:

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide and vincristine

Examinations

Tissues and cell types examined:

bone marrow cells

Details of tissue and slide preparation:

In a pretest for the determination of the acute intraperitoneal toxicity, 2000 mg/kg body weight recommended as the highest dose according to the EEC Directive 92/69, B 12 and to the OECD Guideline No . 474/U.S. EPA TSCA Guidelines deaths were observed (two out of 10 animals) down to a dose of 400 mg/kg body weight. 200 mg/kg body weight were survived by all animals.
Therefore, a dose of 300 mg/kg body weight was selected as the highest dose in the present cytogenetic study. 150 mg/kg and 75 mg/kg body weight were administered as further doses.

Results and discussion

Additional information on results:

According to the results of the present study, the single intraperitoneal administration of 4,4'-Diaminodibenzyl did not lead to any increase in
the number of polychromatic erythrocytes containing either small or large micronuclei. The rate of micronuclei was always in the same range as that of the negative control in all dose groups and at all sacrifice intervals.
No inhibition of erythropoiesis determined from the ratio of polychromatic to normochromatic erythrocytes was detected.

Applicant's summary and conclusion

Conclusions:

Under the experimental conditions chosen here, the test substance does not have any chromosome-damaging (clastogenic) effect, and there were no indications of any impairment of chromosome distribution in the course of mitosis.