2-ethylhexan-1-ol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Significant methodological deficiencies. Only males examined. Low number of cells examined (50 metaphases instead of 100 per animal; mitotic index in 100 cells instead of 1000 cells).

Data source

Reference

Reference 1

Title:

No information

Author:

EPA

Year:

1980

Bibliographic source:

Document No. 86-87000603, Microfiche No. OTS0515130

Report date:

1980

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Principles of method if other than guideline:

cytogenetics assay was performed according to a modification of the procedures described by Kilian et al [1977]

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexan-1-ol

EC Number:

203-234-3

EC Name:

2-ethylhexan-1-ol

Cas Number:

104-76-7

Molecular formula:

C8H18O

IUPAC Name:

2-ethylhexan-1-ol

Details on test material:

- Analytical purity: >99.7%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, NY, USA
- Weight at study initiation: 150-190 g
- Assigned to test groups randomly: yes, randomly assigned to five groups of five animals each.
- Housing: in an American Association for the Accreditation of Laboratory Animal Care (AAALAC)-accredited facility. Rats were housed three to four per cage during the quarantine period and one per cage during treatment. Hardwood chips were used as bedding
- Diet: certified laboratory chow, ad libitum
- Water: ad libitum
- Acclimation period: 10-14 days prior to testing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12-hr light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil
- Concentration of test material in vehicle: 5 ml/kg/day

Duration of treatment / exposure:

5 days

Frequency of treatment:

daily

Post exposure period:

6 hours after the last dose rats were sacrificed

Doses / concentrations

Remarks:

Doses / Concentrations:
0.02, 0.07, 0.2 ml/kg day
Basis:

No. of animals per sex per dose:

5 males per dose

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Doses: 0.5 ml/kg
- single intraperitoneal (IP) injection one day prior sacrifice

Examinations

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
The dose levels, the highest of which represented approximately one-tenth of the five-day LD50, were based on a preliminary five-day dose-finding study for each test material.

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
The rats were sacrificed by carbon dioxide asphyxiation six hr after the last dose.

DETAILS OF SLIDE PREPARATION:
The femurs were removed, and the bone marrow flushed into Hanks' balanced salt solution. After centrifugation at 600-800g for 8-10 min, the cells were treated with 0.075 M KCl for 20-30 min at 37°C. The cells were again centrifuged and washed twice with 5 ml of Carnoy's fixative. The cells were resuspended in 5 ml of Carnoy's fixative and allowed to stand overnight at 4°C. The cells were then centrifuged and resuspended to opalescence in fresh Carnoy's fixative. Two to five slides were prepared from each animal. Slides were stained with Giemsa and permanently mounted.

METHOD OF ANALYSIS:
A minimum of 50 metaphase spreads from each animal was scored for chromatid and chromosomal gaps, breaks, and fragmentation, structural rearrangements, and ploidy [Cohen and Hirschorn, 1971; Kilian et al, 1977; Legator et al, 1973].
Spreads were selected for evaluation by systematic scanning of slides. Only cells which appeared intact with the chromosomes spread symmetrically, with no other metaphase cells intruding into the vicinity, and which contained no less than 36 chromosomes, were scored. In addition, the mitotic index (mitosis/100 cells) was recorded for each test animal.

Results and discussion

Test results

Sex:

male

Any other information on results incl. tables

Of the 50 metaphase bone marrow cells examined from each animal, no significant 
increase in chromatid and chromosome breaks or structural rearrangements
was noted. 
The mitotic index was unaffected by 2-ethylhexanol. 

 

Applicant's summary and conclusion

Conclusions:

According to the authors the dose levels tested did not induce detectable chromosomal aberrations after oral administration, or change the mitotic index. However, the number of cells examined is too low to comply with current test guidelines.