4,4'-oxydi(benzenesulphonohydrazide)

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

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed in accordance with the OECD guideline 474, and in compliace with GLP standard.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

not specified

Principles of method if other than guideline:

NA

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-oxydi(benzenesulphonohydrazide)

EC Number:

201-286-1

EC Name:

4,4'-oxydi(benzenesulphonohydrazide)

Cas Number:

80-51-3

Molecular formula:

C12H14N4O5S2

IUPAC Name:

4-[4-(hydrazinesulfonyl)phenoxy]benzene-1-sulfonohydrazide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): 4,4'-oxybis(benzenesulfonyl hydrazide)
- Analytical purity: no data
- Purity test date: 97.6%
- Lot/batch No.: 08929DR

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 8 weeks
- Weight at study initiation: 28.5 - 36.0 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: MC (methyl cellulose)
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: no data
- Amount of vehicle (if gavage or dermal): 0.5% MC
- Type and concentration of dispersant aid (if powder): no data
- Lot/batch no. (if required): 126H0394
- Purity: no data

Details on exposure:

no data

Duration of treatment / exposure:

two treatments at 24 hour intervals

Frequency of treatment:

duplicate treatments (positive control group was dosed once)

Post exposure period:

24 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 375, 750 and 1500 mg/kg bw/day
Basis:

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide.H2O
- Justification for choice of positive control(s): no data
- Route of administration: intraperitoneal injection
- Doses / concentrations: 70mg/kg

Examinations

Tissues and cell types examined:

erythrocytes

Details of tissue and slide preparation:

no data

Evaluation criteria:

At least 2,000 polychromatic erythrocytes per animals were scored for the incidence of micronuclei.
There are several criteria for determining a positive result, such as a dose-related increase in the number of micronucleated cells or a clear increase in the number of micronucleated cells in a single dose group at a single sampling time.

Statistics:

To compare the results of the control and treatment groups, Kruskal-Wallis’ H-test was carried out. If this result was significant, Dunnett’s t-test was conducted to find out significance. If there was a significant difference, Cochran-Armitage trend test was conducted to confirm the dose-dependency. Mann-Whitney’s U-test was carried out to compare the results of the control and positive controls.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not examined

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

All animals dosed with OBSH exhibited similar PCE/(PCE + NCE) ratios and MNPCE frequencies compared to those of negative control animals (p > 0.01). All frequencies of MNPCE in the negative control groups fell within acceptable ranges, while the positive control groups induced clear increase in the frequencies of MNPCE.

Any other information on results incl. tables

Table. Summary of PCE/(PCE+NCE) ratio and MNPCE frequency

Treatment group	Dose (mg/kg)	No. of Animal	PCE/(PCE+NCE) (mean±S.D.)	MNPCE per2,000 PCE (mean±S.D.)
Vehicle(0.5 % methyl cellulose)	0	6	0.43 ( 0.11	0.67 ( 0.82
OBSH	375	6	0.47 ( 0.04	0.67 ( 0.82
	750	6	0.47 ( 0.05	1.00 ( 0.89
	1,500	6	0.45 ( 0.03	1.33 ( 0.82
Cyclophosphamide	70	6	0.37( 0.04	75.50 ( 22.41*

*: Significant difference from the control at p < 0.01

MNPCE; Micronucleated polychromatic erythrocyte,

PCE; Polychromatic erythrocyte,

NCE; Normochromatic erythrocyte,

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
The genetic toxicity in vivo of OBSH was evaluated in a Mammalian erythrocyte micronucleus test. The test was performed in accordance with the OECD guideline 474. It was concluded that OBSH did not induce micronuclei in the mice bone marrow cells.

Executive summary:

The genetic toxicity in vivo of OBSH was evaluated in a Mammalian erythrocyte micronucleus test. The test was performed in accordance with the OECD guideline 474.

All animals dosed with OBSH exhibited similar PCE/(PCE + NCE) ratios and MNPCE frequencies compared to those of negative control animals (p > 0.01). All frequencies of MNPCE in the negative control groups fell within acceptable ranges, while the positive control groups induced clear increase in the frequencies of MNPCE.

It was concluded that OBSH did not induce micronuclei in the mice bone marrow cells.