Diethyl sulphate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OTS 798.5900 (In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)

Deviations:

no

GLP compliance:

yes

Type of assay:

sister chromatid exchange assay in mammalian cells

Test material

Test material information

Constituent 1

Reference substance name:

Diethyl sulphate

EC Number:

200-589-6

EC Name:

Diethyl sulphate

Cas Number:

64-67-5

Molecular formula:

C4H10O4S

IUPAC Name:

diethyl sulfate

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

S9 liver homogenate prepared from Aroclor l2S4-1nduced, Sprague-Dawley male rats

Test concentrations with justification for top dose:

A maximum concentration of 20 x 10-3% by volume was chosen as the top dose level for examination baaed on cytotoxicity data from the CHO mutation test (in the same battery). Higher concentrations were expected to produce delays in the mitotic cycle and to decrease the number of cells with SCE staining.

A 16-fold range of diethyl sulfate concentrations from 20X10-3% to 1.25X10-3% (by volume) was examined for SCE induction.

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

N-dimethylnitrosamine

ethylmethanesulphonate

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Treatment of CHO cells with diethyl sulfate over a 16-fold range of concentrations indicated a significant potential for mutagenic activity without the addition of an active S9, metabolic activation system. Evidence of a dose-related effect was evident and the test substance can be considered to be an active mutagen under the test conditions.