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Toxicological information

Genetic toxicity: in vivo

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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

Referenceopen allclose all

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 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

Reference
Name:
Unnamed
Type:
Constituent
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 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

Applicant's summary and conclusion