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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
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
publication
Title:
Evaluation of the rodent mieronueleus assay in the screening of IARC carcinogens (Groups 1, 2A and 2B) The summary report of the 6th collaborative study by CSGMT/JEMS - MMS
Author:
Morita, T. et al.
Year:
1997
Bibliographic source:
Mutation Research 389 3-122

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
not applicable
GLP compliance:
not specified
Type of assay:
other: micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-propanesultone
EC Number:
214-317-9
EC Name:
1,3-propanesultone
Cas Number:
1120-71-4
Molecular formula:
C3H6O3S
IUPAC Name:
1,2lambda6-oxathiolane-2,2-dione

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Diet (ad libitum): commercial pellets
- Water (ad libitum): yes

ENVIRONMENTAL CONDITIONS
- no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- saline
Duration of treatment / exposure:
- animals were treated with the test substance twice (24 h intervall) and peripheral blood was collected up to 72 h after last treatment
Frequency of treatment:
- twice (24 h intervall)
Post exposure period:
- 24, 48, 72 h
Doses / concentrations
No. of animals per sex per dose:
- 5 male mice per dose
Control animals:
yes
Positive control(s):
- Mitomycin C
- Route of administration: ip
- Doses / concentrations: 0.5 mg/kg (single dose)

Examinations

Tissues and cell types examined:
- peripheral blood reticulocytes were used for analyses
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
- The highest dose was fixed by the preliminary dose-finding test (based on mortality)

METHOD OF ANALYSIS:
- Micronucleated reticulocyte frequencies were based on the observation of at least 1000 polychromatic reticulocytes
Statistics:
When the control data were acceptable, the increase in micronucleus frequency against the concurrent negative control data were evaluated using a conditional binomial test and the dose response relationship using the Cochran-Armitage trend test were evaluated. When these were both significant, the data was declared positive. If neither step showed significance, the data was judged negative. All other cases were called inconclusive.

Results and discussion

Test results
Key result
Sex:
male
Genotoxicity:
positive
Toxicity:
yes
Remarks:
can be assumed, since the highest dose tested was fixed by a preliminary dose-finding test
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Summary of the micronucleus assay results:

% micronucleated reticulocytes

 

dose

0 h

24 h

48 h

72 h

mg/kg bw

mean SD

mean SD

p

mean SD

p

mean SD

p

 

 

 

 

 

 

 

 

9

0.08± 0.04

 

0.17± 0.10

 

0.151

 

0.10± 0.13

 

0.500

 

0.08± 0.10

 

0.623

 

18

0.10± 0.11

 

0.23± 0.10

 

0.058

0.10± 0.11

 

0.613

0.07± 0.05

 

0.828

36

0.12± 0.08

 

0.87± 0.53

 

< 0.001

0.63± 0.16

 

< 0.001

0.28± 0.16

 

0.032

72

0.10± 0.09

 

1.92± 0.99

 

< 0.001

1.68± 0.50

 

< 0.001

0.27± 0.14

 

0.026

p: value of the pairwise comparison

Applicant's summary and conclusion