1,3-propanesultone

Genetic toxicity: in vivo

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

Test material information

Constituent 1

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:

1,2λ⁶-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