2-methoxy-2-methylbutane

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-compliant near-guideline study, no restrictions, fully adequate for assessment.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1995

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2-methoxy-2-methylbutane

EC Number:

213-611-4

EC Name:

2-methoxy-2-methylbutane

Cas Number:

994-05-8

Molecular formula:

C6H14O

IUPAC Name:

2-methoxy-2-methylbutane

Details on test material:

- Name of test material (as cited in study report): MRD-89-374
- Physical state: colourless liquid
- Analytical purity: 93%
- Lot/batch No.: 1

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 Breeding Laboratories
- Age at study initiation: 7 weeks
- Weight at study initiation: 23-38 gram
- Housing: single
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: 19 days


ENVIRONMENTAL CONDITIONS
- Temperature: 68-76°F
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

corn oil

Details on exposure:

Negative control and TAME treated animals formed three different sample time groups (24, 48 and 72 hours), consisting of five mice of each sex per group. Animals dosed with cyclophosphamide were taken at 24 hours only.

The doses were selected based on a preliminary toxicity test in which there was mortality still at 1000 mg/kg dose, 750 mg/kg was found to be the highest non-toxic concentration.

Duration of treatment / exposure:

single intraperitoneal injection

Frequency of treatment:

single intraperitoneal injection

Post exposure period:

24, 48 and 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
150, 375 or 750 mg/kg body weight
Basis:
other: single i.p. dose

No. of animals per sex per dose:

10 (5/sex/dose)

Control animals:

yes, concurrent vehicle

Positive control(s):

Positive control (cyclophosphamide, 40 mg/kg bw) mice were sampled at 24 hours only.

Examinations

Tissues and cell types examined:

Both femurs from each animal were removed and bone marrow was recovered.

Details of tissue and slide preparation:

Bone marrow as suspended in fetal bovine serum. Following centrifugation to pellet the tissue, the supernatant was drawn off, the pellet resuspended and the suspension spread on slides and dried (two slides were prepared per animal). Prior to microscopic evaluation, the slides were stained using acridine orange.

Evaluation criteria:

Bone marrow smears were prepared from femurs:
- 1000 polychromatic erythrocytes (PCE) were examined for micronuclei;
- the ratio of PCE and normochromatic erythrocytes (NCE) was calculated from 1000 erythrocytes.

Statistics:

A standard one way analysis of variance and regression analysis were performed.

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

Additional information on results:

All mice survived to scheduled termination. No increase in micronucleus frequency was observed at any dose level. Overt marrow toxicity was not observed (measured by a decrease in the percentage of PCEs). The percentages of PCEs observed were within the normal range.