1,4-dioxane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals

Author:

Galloway SM, Armstrong MJ, Reuben C, Colman S, Brown B, Cannon C, Bloom AD, Nakamura F, Ahmed M, Duk S, Rimpo J, Margolin BH, Resnick MA, Anderson B and Zeiger E

Year:

1987

Bibliographic source:

Environ. Mol. Mutag. 10 (Suppl.10), 1-37.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Galloway SM, Bloom AD, Resnick M, Margolin BH, Nakamura F, Archer P, Zeiger E (1985): Development of a standard protocol for in vitro cytogenetic testing with Chinese hamster ovary cells: Comparison of results for 22 compounds in two laboratories. Environ Mutagen 7:1-51.

GLP compliance:

no

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

1,4-dioxane

EC Number:

204-661-8

EC Name:

1,4-dioxane

Cas Number:

123-91-1

Molecular formula:

C4H8O2

IUPAC Name:

1,4-dioxane

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

S9 mix from male SD rats induced with Aroclor 1254

Test concentrations with justification for top dose:

1,050-10,500 µg/mL

Vehicle / solvent:

no data

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

mitomycin C

other: triethylenemelamine

Details on test system and experimental conditions:

No specific details were reported regarding exposure duration.
Cells were collected by mitotic shake-off. Slides were stained with Giemsa and coded and 100 cells were scored from each of the three highest dose groups having sufficient metaphases for analysis. All types of aberrations were recorded separately, but for data analysis they were grouped into categories of simple (breaks and terminal deletions), "complex" (exchanges and rearrangements), other (includes pulverized chromosomes), and total. Gaps and endoreduplications were recorded but were not included in the totals. Aberrations in polyploidy cells were not scored but used metaphases with 19-23 chromosomes (the modal number being 21).

Evaluation criteria:

The evidence for a dose relation and the absolute increase over the solvent control at each dose was examined. A lineair regression analysis of the percentage of cells with abberations vs the log-dose was used as the test for trend. To examine absolute increases over control levels at each dose, a binomial sample assumption was used.

Statistics:

P values were adjusted by Dunnet's method, and criterion for a positive response was P<= 0.05

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

True negative controls validity:

not applicable

Positive controls validity:

valid