2-methoxyethanol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Number of mice and metaphases counted less than recommended. Some information missing (e.g. verification that xenobiotic reaches target site) is not necessary as this is a well studied material. Other data missing is not regarded as rendering the study unreliable. Broadly follows requirements of guideline.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Evaluation of the clastogenic effect of 2-methoxyethanol in mice

Author:

Au W, Morris, DL, Legator MS

Year:

1993

Bibliographic source:

Mut Res, 300, 273-9.

Reference 2

Reference Type:

publication

Title:

Toxicity and genotoxicity of 2-methoxyethanol in vitro and in vivo

Author:

Au WW, Ahmed AE, Chiewchanwit T, Hsie AW, Ma H, Moslen MT

Year:

1996

Bibliographic source:

Occup Hyg vol 2, 177-86

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

, see rational for reliability above.

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

2-methoxyethanol

EC Number:

203-713-7

EC Name:

2-methoxyethanol

Cas Number:

109-86-4

Molecular formula:

C3H8O2

IUPAC Name:

2-methoxyethanol

Details on test material:

- Analytical purity: No data on purity
- Technical grade supplied by Aldrich Chemical Company.

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague-Dawley, Houston
- Age at study initiation: Young mice
- Weight at study initiation: 20-25g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period: 1 week.


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: sterile isotonic saline

Duration of treatment / exposure:

Single dose, dose rate of 10ml/kg.

Frequency of treatment:

Due to the labour intensive nature of the experiment, not all dose levels were included in all harvests, although positive and negative controls were included in each. Not all doses were carried out simultaneously. Mice were implanted with a 50mg BrDU tablet then subject to methoxyethanol treatment.

Post exposure period:

16 hour after treatment, the mice were treated i.v. with viniblastine sulphate to arrest mitosis. The animals were then sacrificed by cervical dislocation and bone marrow cells harvested from the femur.

Doses / concentrations

Remarks:

Doses / Concentrations:
1200, 1400, 1600, 1900 mg/kg
Basis:

No. of animals per sex per dose:

3

Control animals:

other: vehicle only

Positive control(s):

Positive control was cyclophosphamide.

Examinations

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
Cells were washed, treated with methanol/acetic acid then stained with the technique of Goto (Chromosome, 66, 351, 1977)

Evaluation criteria:

50 metaphase cells per mouse were analysed for chromosome aberrations and 100 cells to obtain the proliferation index. The proliferation index was calculated based on the observed frequency of metaphase cells showing the first, second or third cell-cycle staining pattern.

Statistics:

Fischer exact one tail test.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Methoxyethanol induced a reduction of proliferation indices compared to controls but did not induce chromosome aberrations. The positive control induced both cell cycle delays and chromosome aberrations. The NOAEL and LOAEL are in this case both greater than 2500mg/kg.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Methoxyethanol induced a reduction of proliferation indices compared to controls but did not induce chromosome aberrations. This result can be used to support address the weaknesses in the in vitro chromosome abberation data (lack of metabolic activation.)

Executive summary:

In a chromosome aberration study in mice, a single treatment of 2-Methoxyethanol did not induce chromosomal aberrations in the bone marrow of mice treated by gavage (at doses up to 1900 mg/kg) or by intravenous injection.