Dimethyl sulphate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Evaluation of the rodent micronucleus assay in the screening of IARC carcinogens (groups 1, 2A and 2B) the summary report of the 6th collaborative study by CSGMT/JEMS MMS. Collaborative Study of the Micronucleus Group Test. Mammalian Mutagenicity Study.

Author:

Morita T, Asano N, Awogi T, Sasaki YF, Sato S, Shimada H, Sutou S, Suzuki T, Wakata A, Sofuni T, Hayashi M

Year:

1997

Bibliographic source:

Mutat Res 389: 3-122.

Reference 2

Reference Type:

publication

Title:

Erratum to 'Evaluation of the rodent micronucleus assay in th screening of IARC carcinogens (Groups 1, 2A amd 2B). the summary report of the 6th collaborative study by CSGMT/JEMS MMS'

Author:

Morita et al.

Year:

1997

Bibliographic source:

Mutation Research 391 (1997) 259-267

Materials and methods

Principles of method if other than guideline:

Method: other

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl sulphate

EC Number:

201-058-1

EC Name:

Dimethyl sulphate

Cas Number:

77-78-1

Molecular formula:

C2H6O4S

IUPAC Name:

dimethyl sulfate

Details on test material:

- Name of test material (as cited in study report): dimethyl sulphate (purchased at Aldrich Chem. Co., Inc. USA)
- Analytical purity: 99%
- Lot/batch No.: 00621CX
no additional details provided

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: 8- to 10-week old male CD-1 mice
no additional details provided

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: olive oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Highest dose used in the first study corresponded to maximum tolerable dose. No additional details

Duration of treatment / exposure:

once or twice (24-hour interval)

Frequency of treatment:

Animals were dosed by oral gavage once or twice (positive control only once by i.p. injection)

Post exposure period:

peripheral blood reticulocytes were evaluated for micronucleus 24, 48, and 72 hours after dosing.

Doses / concentrations

Remarks:

Doses / Concentrations:
First study: 57, 113, and 223 mg/kg applied once; confirmation study: 57 and 113 mg/kg applied twice
Basis:
actual ingested

No. of animals per sex per dose:

First study: 5 males mice/group; confirmation study: 5-10 male mice/group

Control animals:

other: yes, concurrent vehicle; a sample from each animal immediately before treatment (0 hour sample) was additionally used as the negative control

Positive control(s):

mitomycin C
- Justification for choice of positive control(s): known positive control substance
- Route of administration: single i.p. injection
- Doses / concentrations: 0.5 mg/kg

Examinations

Tissues and cell types examined:

peripheral blood sampled at 0, 24, 48 or 72 hours

Details of tissue and slide preparation:

Micronucleated reticulocyte frequencies were based on the observation of at least 1000 reticulocytes/animal.

Evaluation criteria:

Statistical analysis: 3-step procedure (citations in the reference) and Cochran-Armitage trend test.

Statistics:

When both statistical evaluations were significant, the data was declared positive

Results and discussion

Test results

Sex:

male

Genotoxicity:

positive

Remarks:

see Table 1

Toxicity:

no effects

Remarks:

Maximum tolerated dose was used

Vehicle controls validity:

not applicable

Negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

-

Any other information on results incl. tables

Table 1: Percent of micronucleated reticulocytes:

Sampling time (hours)	Percent (%) of micronucleated reticulocytes at the indicated dose levels in the first study: sampling single oral dose			Percent (%) of micronucleated reticulocytes at the indicated dose levels in the confirmation study: sampling oral dose (mg/kg), twice
	57 mg/kg	113 mg/kg	225 mg/kg	57 mg/kg	113 mg/kg
0	0.14	0.16	0.18	0.12	0.11
24	0.28	0.25	0.33	0.38	0.33
48	0.20	0.30	0.23	0.30	0.23
72	0.18	0.30	0.18	0.20	0.18