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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro DNA damage and/or repair study
Remarks:
Type of genotoxicity: other: SCE
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
March, 1985 - July, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Well executed and reported study subjected to peer review and conducted according to modern standards, including GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Principles of method if other than guideline:
No guidelines are cited in the source document. A detailed description of the SCE protocol is presented by Galloway et al. (1985, 1987). Briefly, Chinese hamster ovary cells were incubated with study compound or solvent (dimethylsulfoxide) as described in (c) and (d) below, and cultured for sufficient.
time to reach second metaphase division. Cells were then collected by mitotic shake-off, fixed, air-dried, and stained.
GLP compliance:
yes
Remarks:
NTP follows GLP as a matter of policy
Type of assay:
sister chromatid exchange assay in mammalian cells

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Not provided in source report.

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
Arochlor 1254 induced liver homogenate from SD rats
Test concentrations with justification for top dose:
0.0, 0.16, 0.50, 1.60, 5.00, 16.00, 50.0 ug/ml
Vehicle / solvent:
dimethylsulfoxide (DMSO)
Controls
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
Migrated to IUCLID6: mitomycin
Details on test system and experimental conditions:
A detailed description of the SCE protocol is presented by Galloway et al. (1985, 1987). Briefly, Chinese hamster ovary cells were incubated with study compound or solvent (dimethylsulfoxide) as described in (c) and (d) below, and cultured for sufficient time to reach second metaphase division. Cells were then collected by mitotic shake-off, fixed, air-dried, and stained.

In the absence of S9, cells were incubated with study compound or solvent for 2 h at 37°C. Then BrdU was added and incubation was continued for 24 h. Cells were washed, fresh medium containing BrdU and colcemid was added, and incubation was continued for 2-3 h.

In the presence of S9, cells were incubated with study compound or solvent for 2 h at 37°C. The cells were then washed, and medium containing BrdU was added. Cells were incubated for a further 26 h, with colcemid present for the final 2-3 h. S9 was from the livers of Aroclor 1254-induced male Sprague Dawley rats.
Statistics:
Trend test

Results and discussion

Test resultsopen allclose all
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

See pp B-4 and B-5 of attached study report.

Applicant's summary and conclusion

Conclusions:
t-BP-induced sister-chromatid exchange in Chinese hamster ovary cells in vitro, only in the absence of S9 fraction.
Executive summary:

t-BP-induced sister-chromatid exchange in Chinese hamster ovary cells in vitro, only in the absence of S9 fraction.