Methanesulfonic acid, 1,1'-(1,6-hexanediyldiimino)bis[1-oxo-, sodium salt (1:2)

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

The study was performed to investigate the potential of 1,1’-(1,6-Hexanediyldiimino)bis[1- oxo-methanesulfonic acid], sodium salt (1:2) to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse.

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Methansulfonic acid (1,6-hexanediyl-diimino)bis[1-oxo, disodium salt

EC Number:

690-526-2

Cas Number:

38632-47-2

Molecular formula:

C8H14S2N2O8.Na2

IUPAC Name:

Methansulfonic acid (1,6-hexanediyl-diimino)bis[1-oxo, disodium salt

Details on test material:

Identity: 1,1'-(1,6-Hexanediyldiimino)bis[1-oxo-methanesulfonic acid], sodium salt (1:2)
Purity: 91.4 % (dose calculation not adjusted to purity)
Stability in Solvent: Stable for a maximum of 8 days

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Duration of treatment / exposure:

24/48 hours

Frequency of treatment:

The animals received the test item, the vehicle or the positive control substance once intraperitoneally.

Post exposure period:

24 hours after administration animals (all doses) respectively 48 hours after treatment (only the highest dose of the test item) animals were sacrificed and the bone marrow cells were collected for micronuclei analysis.

Doses / concentrations

Remarks:

Doses / Concentrations:
24 h preparation interval: 250, 500, and 1000 mg/kg b.w.; 48 h preparation interval: 1000 mg/kg b.w..
Basis:
nominal conc.

No. of animals per sex per dose:

Seven males per test group were evaluated for the occurrence of micronuclei

Control animals:

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

Bone marrow cells were collected for micronuclei analysis.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

see "Any information on results incl. tables"

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

The test item was dissolved in sterile water, which was also used as vehicle control. The application volume of 10 mL/kg b.w. was administered once intraperitoneally (i.p.). 24 hours after administration animals (all doses) respectively 48 hours after treatment

(only the highest dose of the test item) animals were sacrificed and the bone marrow cells were collected for micronuclei analysis.

Seven males per test group were evaluated for the occurrence of micronuclei. Per animal at least 2000 polychromatic erythrocytes (PCEs) were scored for micronuclei.

To describe a cytotoxic effect due to the treatment with the test item the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and reported as the number of PCEs per 2000 erythrocytes.

Based on lethality observed in the pre-experiments the following dose levels of the test item were investigated:

24 h preparation interval: 250, 500, and 1000 mg/kg b.w..

48 h preparation interval: 1000 mg/kg b.w..

The highest dose was estimated by a pre-experiment to be suitable.

After the treatment with the test item, the number of PCEs was not substantiallydecreased as compared to the mean value of PCEs of vehicle control thus indicating that 1,1’-(1,6-Hexanediyldiimino)bis[1-oxo-methanesulfonic acid], sodium salt (1:2) did not exert any cytotoxic effects in the bone marrow. In all dose groups ruffled fur was observed for at least up to six hours after treatment. Additionally, ruffled fur was observed in the highest dose group up to 48 hours.

In comparison to the corresponding vehicle control values there was no statistically significant and/or biologically relevant increase in the frequency of the detected micronuclei at any preparation interval and dose level after administration of the test item.

The mean values of micronuclei observed after treatment with 1,1’-(1,6- Hexanediyldiimino)bis[1-oxo-methanesulfonic acid], sodium salt (1:2) were below to the value of the respective vehicle control group and within the historical vehicle control range. Additionally no dose dependence was observed.

The positive control cyclophosphamide administered also intraperitoneally showed a substantial and biologically relevant increase of induced micronucleus frequency.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

The study was performed to investigate the potential of 1,1’-(1,6-Hexanediyldiimino)bis[1- oxo-methanesulfonic acid], sodium salt (1:2) to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse.

The test item was dissolved in sterile water, which was also used as vehicle control. The application volume of 10 mL/kg b.w. was administered once intraperitoneally (i.p.). 24 hours after administration animals (all doses) respectively 48 hours after treatment

(only the highest dose of the test item) animals were sacrificed and the bone marrow cells were collected for micronuclei analysis.

Seven males per test group were evaluated for the occurrence of micronuclei. Per animal at least 2000 polychromatic erythrocytes (PCEs) were scored for micronuclei.

To describe a cytotoxic effect due to the treatment with the test item the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and reported as the number of PCEs per 2000 erythrocytes.

Based on lethality observed in the pre-experiments the following dose levels of the test item were investigated:

24 h preparation interval: 250, 500, and 1000 mg/kg b.w..

48 h preparation interval: 1000 mg/kg b.w..

The highest dose was estimated by a pre-experiment to be suitable.

After the treatment with the test item, the number of PCEs was not substantiallydecreased as compared to the mean value of PCEs of vehicle control thus indicating that 1,1’-(1,6-Hexanediyldiimino)bis[1-oxo-methanesulfonic acid], sodium salt (1:2) did not exert any cytotoxic effects in the bone marrow. In all dose groups ruffled fur was observed for at least up to six hours after treatment. Additionally, ruffled fur was observed in the highest dose group up to 48 hours.

In comparison to the corresponding vehicle control values there was no statistically significant and/or biologically relevant increase in the frequency of the detected micronuclei at any preparation interval and dose level after administration of the test item.

The mean values of micronuclei observed after treatment with 1,1’-(1,6- Hexanediyldiimino)bis[1-oxo-methanesulfonic acid], sodium salt (1:2) were below to the value of the respective vehicle control group and within the historical vehicle control range. Additionally no dose dependence was observed.

The positive control cyclophosphamide administered also intraperitoneally showed a substantial and biologically relevant increase of induced micronucleus frequency.

In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse.

Therefore, 1,1’-(1,6-Hexanediyldiimino)bis[1-oxo-methanesulfonic acid], sodium salt (1:2) was negative in this micronucleus assay.