Naphtha (petroleum), steam-cracked middle arom.

Genetic toxicity: in vitro

Administrative data

Endpoint:

genetic toxicity in vitro, other

Remarks:

Type of genotoxicity: other: gene mutation, chromosome aberration, aneuploidy, DNA damage and/or repair.

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, animal experimental study, published in peer reviewed literature. Limitations or minor restrictions in design/reporting but otherwise adequate for assessment.

Data source

Reference

Reference Type:

publication

Title:

Benzene-, catechol-, hydroquinone- and phenol-induced cell transformation, gene mutations, chromosome aberrations, aneuploidy, sister chromatid exchanges and unscheduled DNA synthesis in Syrian hamster embryo cells

Author:

Tsutsui T, Hayashi N, Maizumi H, Huff J and Barrett JC

Year:

1997

Bibliographic source:

Mutation Research Vol 373 PP 113-123

Materials and methods

Principles of method if other than guideline:

Benzene was examined for its ability to induce cell transformation and genotoxic effects using the same mammalian cells (Syrian hamster embryo cells) in culture.

GLP compliance:

not specified

Type of assay:

other: cell transformation and gene mutation assays, chromosome aberrations and chromosome number, sister chromatid exchanges and unscheduled DNA synthesis.

Test material

Test material information

Constituent 1

Reference substance name:

Benzene

EC Number:

200-753-7

EC Name:

Benzene

Cas Number:

71-43-2

Molecular formula:

C6H6

IUPAC Name:

benzene

Details on test material:

- Name of test material (as cited in study report): Benzene
- Supplier: National Institute of Environmental Health Sciences, Research Triangle Park, NC.

Method

Species / strain

Species / strain / cell type:

other: Syrian hamster embryo cells

Details on mammalian cell type (if applicable):

CELL LINE: SHE cell cultures were established from 13 day gestation foetuses from inbred Syrian hamsters, strain LSH/ss, 1990; LAK (Lakeview Hamster Colony, Newfield, NJ) and stored frozen. Secondary cultures were initiated from the frozen stocks, and all experiments were performed with tertiary cultures in a humidified atmosphere with 10% CO2 in air at 37°C.

MEDIA: IBR Dulbecco's modified Eagle's reinforced medium (Biolab, Northbrook, IL) supplemented with 0.37% NaHCO3 and 10% foetal bovine serum (FBS: GIBCO, Grand Island, NY).

Metabolic activation:

without

Test concentrations with justification for top dose:

see below

Controls

Negative solvent / vehicle controls:

yes

Statistics:

Statistical analysis was performed by x2 test

Results and discussion

Test results

Species / strain:

other: Syrian hamster embryo cells

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Any other information on results incl. tables

Cell growth:

Benzene (10-100 µM) had little effect on cell growth

Cell transformation and gene mutation assays:

Treatment at 30-100µM for 48 h elicited a slight reduction in cell survival (ca 75% of control). Exposure to benzene for 48 h resulted in morphological transformation of SHE cells. The frequency of transformation increased with increasing dose. TG-resistant and ouabain-resistant mutations were induced by benzene at two loci (hprt and Na⁺/K⁺- ATPase).

Chromosome aberrations and chromosome number:

There was no treatment-related effect on numbers of aberrations.

Benzene (100 µM) increased the percentage of aneuploid metaphases in the near-diploid range from 3% after 24-h treatment to 11% after 48-h treatment. Slight induction of aneuploidy in the near-diploid range was observed in cultures treated for 48 h with benzene (10 to 30 µM). No significant increase in the number of metaphases with a tetraploid and a near-tetraploid number of chromosomes was induced by treatment for 24 and 48 h with benzene.

Sister chromatid exchanges:

There was no effect on sister chromatid exchange induction at concentrations of 10-3000 µM.

Unscheduled DNA synthesis:

There was no treatment-related effect on the induction of UDS.

Applicant's summary and conclusion

Conclusions:

Interpretation of results:
positive cell transformation, gene mutation, aneuploidy
negative chromosome aberrations, sister chromatid exchanges and unscheduled DNA synthesis

Benzene induces cell transformation and genotoxic effects. In this series of studies using Syrian hamster embryo cells, it was positive for cell transformation, gene mutation and aneuploidy and it was negative for chromosome aberrations, sister chromatid exchanges and unscheduled DNA synthesis.

Executive summary:

Benzene induces cell transformation and genotoxic effects. In this series of studies using Syrian hamster embryo cells, it was positive for cell transformation, gene mutation and aneuploidy and it was negative for chromosome aberrations, sister chromatid exchanges and unscheduled DNA synthesis.