Gasoline, pyrolysis, hydrogenated

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The assay follows the principles of the guidelines, modified specifically for gaseous materials. Deviations are considered acceptable for drawing conclusions.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

An improved system for exposure of cultured mammalian cells to gaseous compounds in the chromosomal aberration assay

Author:

Asakura M, Sasaki T, Sugiyama T, Arito H, Fukushima S and Matsushima T

Year:

2008

Bibliographic source:

Mutation Research 652, 122-130

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

yes

Principles of method if other than guideline:

System comprised 12 square culture vessels, a device for preparation of air containing test gas, and positive and negative control gases at target concentrations and for supplying these gases to the culture vessels, and a roller apparatus in an incubator. Chinese hamster lung cells (CHL/IU) were grown on one side of the inner surface of the square culture vessel in MEM medium. Immediately prior to exposure, the medium was changed to modified MEM. Air in the culture vessel was replaced with air containing test gas, positive or negative control gas. Then, the culture vessels were rotated at 1.0 rpm. The monolayered culture cells were exposed to test gas during about 3/4 rotation at upper positions and alternatively immersed into the culture medium during about 1/4 rotation at lower positions.

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

1,3-butadiene

IUPAC Name:

1,3-butadiene

Details on test material:

- Name of test material (as cited in study report): 1,3-Butadiene
- Supplier: Sumitomo-Seika Chemicals Co. Ltd., Tokyo, Japan.
- Physical state: gas
- Analytical purity: >95%

Method

Target gene:

not applicable

Species / strain

Species / strain / cell type:

mammalian cell line, other: A clonal sub-line derived from the lung of a newborn female Chinese hamster (CHL/IU)

Details on mammalian cell type (if applicable):

Type and identity of media: Cells were cultured in Eagle’s MEM supplemented with 10% heat-inactivated CS, grown in a monolayer and, for exposure, modified MEM (m-MEM containing 10% CS, NaHCO3 0.22 g/L, 1 M NaOH 1 ml/L and 10 mM HEPES

Metabolic activation:

with and without

Metabolic activation system:

A post-mitochondrial supernatant fraction of liver homogenates (S9) from the phenobarbital- and 5,6-benzoflavone-pretreated rat

Test concentrations with justification for top dose:

0 – 20% atmosphere of 1,3-butadiene for 6h

Vehicle / solvent:

air

Controls

Controls 1

Positive controls:

yes

Positive control substance:

other: Vinyl chloride and methyl chloride

Remarks:

+/- S9 mix

Controls 2

Untreated negative controls:

yes

Details on test system and experimental conditions:

See below

Evaluation criteria:

see below

Statistics:

none

Results and discussion

Test results

Species / strain:

mammalian cell line, other: A clonal sub-line derived from the lung of a newborn female Chinese hamster (CHL/IU)

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

other: Reduction in Growth Index was measured

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

none

Any other information on results incl. tables

The frequency of structural abberrations was increased in a dose-related manner after 6 hour exposure to gaseous 1,3-butadiene with and without metabolic activation. The frequency of structural aberrations was similar in the presence and absence of metabolic activation. 

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive with metabolic activation
positive without metabolic activation

Exposure of (CHL/IU) cells to gaseous 1,3-butadiene for 6 hours induced structural aberrations in the presence and absence of metabolic activation.

Executive summary:

1,3 -butadiene was tested in a chromosomal aberration assay in an improved system for the exposure of cultured mammalian cells to gaseous compounds. Exposure to 1,3-butadiene for 6 hours induced a dose-related increase in structural aberrations, with and without S9 metabolic activation.