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Toxicological information

Genetic toxicity: in vitro

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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:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Inducibility of chromosome aberrations by steroid hormones in cultured chinese hamster ovary cells
Author:
Kochhar T.S.
Year:
1985
Bibliographic source:
Toxicology Letters 29, 201-206 (1985)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
CHO cells used in the current investigation were routinely grown in 75cm² Corning plastic flasks in 10 ml of McCoy’s 5a medium supplemented with 10% fetal calf serum and antibiotics consisting of penicillin-G, (100 U/ml) and streptomycin, (100 µg/ml). The cultures were incubated in an atmosphere of 5% CO2 in air. To test the effect of steroid hormones, cultures were set up 24 h prior to the treatment by seeding approx. 1.6 x 10 to 6 cells per flask. Treatments were given by exposing the cultures to test compounds dissolved in DMSO and suspended in the culture medium for 12 h. The control cultures contained 0.5% of DMSO and were incubated under identical conditions. The procedure for the preparation of chromosomes to score for the abnormalities
is described in Experientia, 38 (1982) 845-846.
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Estrone
EC Number:
200-164-5
EC Name:
Estrone
Cas Number:
53-16-7
Molecular formula:
C18H22O2
IUPAC Name:
3-hydroxyestra-1,3,5(10)-trien-17-one
Specific details on test material used for the study:
The test material was procured from Sigma, St. Louis, MO.

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
The CHO cells were obtained from Environmental Health Research and Testing, Lexington, KY. The cells were not used at a passage level of more than 15 after cloning, and were thawed routinely from liquid nitrogen storage and maintained by transferring twice a week.
Metabolic activation:
not specified
Test concentrations with justification for top dose:
10 to minus five M; 5 x 10 to minus five M; 10 to minus 4 M
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
no

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
not applicable
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
not examined

Applicant's summary and conclusion

Conclusions:
positive
Executive summary:

The effect of steroid hormones on the chromosomes of cultured Chinese hamster ovary (CHO) cells was studied. It was noticed that estradiol-17fl, estrone, estriol and ethynyl estradiol were effective in producing various types of chromosome aberrations. The percentage of these abnormalities increased with increasing concentrations of steroids used.