2-[(2-[2-(dimethylamino)ethoxy]ethyl)methylamino]ethanol

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:

1992-11-03 to 1992-11-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Experimental study was run under GLP conditions and according to OECD guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

other: EEC Annex V Commitee (EEC 1984)

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Test material form:

liquid

Specific details on test material used for the study:

- Name of test mtarial (as cited in study report): Texacat ZF-10
- Chemical name: 2-[(2-[2-(dimethylamino)ethoxyethyl)methylamino]ethanol
- Physical appearance: clear colorless liquid
- Analytical purity: 98.3%
- Lot/batch No.: 18610791 (U186-1-0791)
- Expiration date of the lot/batch: February 1994
- Storage condition of test material: room temperature in the dark

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent, UK
- Age at study initiation: 35 days
- Weight at study initiation: 22-24g
- Assigned to test groups randomly: yes
- Fasting period before study:
- Diet (e.g. ad libitum): free access to pelleted Biosure LAD 1 rodent diet
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Air changes (per hr): 30
- Photoperiod (hrs dark / hrs light): artificial light for 12 hours per day

Administration / exposure

Route of administration:

oral: gavage

Details on exposure:

Dose : orally by intragastric gavage
Volume : 20ml/kg bw
Fast period : overnight prior to and for 2 hours after oral dosing.

Duration of treatment / exposure:

Single acute dose

Doses / concentrations

Dose / conc.:

1 408 mg/kg bw/day (nominal)

No. of animals per sex per dose:

40 males and 40 females

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Positive control(s):

Mitomycin C, batch number 4530740N, obtained from BDH Limited.
Concentration : 0.6 mg/ml

Examinations

Tissues and cell types examined:

Bone marrow smear from femus.
Examination of erythrocytes

Details of tissue and slide preparation:

Sampling times : 24, 48 and 72 hours after treatment.

Evaluation criteria:

Evaluation of clinical signs and mortalities
Count of micronucleated polychromatic and normochromatic erythrocytes.
Examination of at least 1000 erythrocytes for each animal and assessment of the ratio of polychromatic to normochromatic erythrocytes

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

not valid

Additional information on results:

RESULTS OF PRELIMINARY TOXICITY TEST
PHASE I :
- Dose range: 320, 800, 2000, 5000 mg/kg
PHASE II :
- Dose range: 594, 792, 1056, 1408 mg/kg

Following the dosing in Phase II, any mortality or clinical signs of reaction during the experiment were recorded for a period of 72 hours.
The maximum tolerated dose was estimated to be approximately 1408 mg/kg. This dosage was therfore chosen for use in the micronucleus test.

RESULTS OF DEFINITIVE STUDY
Texacat ZF-10 failed to cause any significant decresae in the ratio of polychromatic to normochromatic erythrocytes.

Any other information on results incl. tables

The positive control with Mitomycin C did not reveal any statistically significant decreases in the ratio of polychromatic to normochromatic erythrocytes. It should be noted that even very cytotoxic compounds such as mitomycine C do not always produce a substantial decrease in this ratio as early as the 24 hours sampling time because of the lag caused by erythrocyte maturation.

Applicant's summary and conclusion

Conclusions:

Since the test substance did not cause any substantial increase in the incidence of micronucleated polychromatic erythrocytes or any substantial decrease in the p/n ratio, it is concluded that the test substance did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered orally in the in vivo test procedure.